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Clinical Trial Results:
A Phase Ib, Randomized, Observer-Blind, Multicenter, Factorial-Design Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Injections of Trivalent Inactivated Influenza Vaccine with or without a Second Influenza B Strain in Combination with or without One of Three Different Doses of Adjuvant in Healthy Children, Ages 6 to <36 Months.

Summary
EudraCT number	2008-002602-20
Trial protocol	FI BE
Global end of trial date	30 Mar 2009

Results information
Results version number	v2(current)
This version publication date	29 Jul 2016
First version publication date	12 Apr 2015
Other versions	v1 (removed from public view)
Version creation reason	Correction of full data set Required for the re-QC project because of the EudraCT system glitch and possible updates to results may be required. Moreover, a change in system user for this study is necessary.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

V104P2

ISRCTN number

US NCT number

NCT00848887

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Vaccines and Diagnostics S.r.l.

Sponsor organisation address

Via Fiorentina, 1, Siena, Italy, 53100

Public contact

Posting Director, Novartis Vaccines and Diagnostics, RegistryContactVaccinesUS@novartis.com

Scientific contact

Posting Director, Novartis Vaccines and Diagnostics, RegistryContactVaccinesUS@novartis.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

02 Nov 2010

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

30 Mar 2009

Was the trial ended prematurely?

Main objective of the trial

To Evaluate: A.Noninferiority of study vaccine to the pediatric trivalent influenza vaccine (TIV) formulated with MF59 at ½ dose of the marketed adult adjuvanted vaccine, Fluad B.Superiority of study vaccine to TIV formulated with ½MF59 Fluad C.Superiority of study vaccine formulation to non adjuvanted pediatric marketed comparator Vaxiprip (cTIV) D.Similarity of antibody response to single vaccination for any formulation to two 0.25mL vaccination of an aTIV/aQIV+½MF59 & TIV/QIV+0MF59 E.Increase in antibody responses of B strain (Malaysia) (B_MY) on addition of B_MY to TIV/QIV F.Increase in cross-reactive antibody responses to A/H3N2, A/H1N1 and B strain(Florida) (B-FL) on addition of B_MY to TIV/QIV G.Increase in cross-reactive antibody responses to B_MY on increase in antigen dose in TIV H.Immunogenicity of study vaccine formulations according to the EMEA recommendation I.MF59 dose-response trend in antibody responses J.Safety and tolerability of study vaccine formulations

Protection of trial subjects

This trial was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with Good Clinical Practice (GCP), and the applicable regulatory requirement(s) for the country in which the trial was conducted according to International Conference on Harmonisation (ICH) guidelines, and applicable Standard Operating Procedures (SOPs).

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Oct 2008

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 208

Country: Number of subjects enrolled

Finland: 202

Worldwide total number of subjects

410

EEA total number of subjects

410

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

304

Children (2-11 years)

106

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants were enrolled from two study center.

Screening details

All enrolled subjects were included in the trial.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

A_7.5TIV+0MF59

Arm description

Subjects who received 2 doses of non adjuvanted trivalent influenza vaccine (TIV - 7.5μg per antigen) on day 1 and day 29.

Arm type

Active comparator

Investigational medicinal product name

Nonadjuvanted Trivalent influenza vaccine(TIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.25 mL of TIV was administered by IM injection.

B_15TIV+0MF59

Arm description

Subjects who received 2 doses of non adjuvanted trivalent influenza vaccine (TIV - 15μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

Nonadjuvanted Trivalent influenza vaccine(TIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.5 mL dose of TIV was administered by IM injection.

C_7.5QIV+0MF59

Arm description

Subjects who received 2 doses of non adjuvanted quadravalent influenza vaccine (QIV - 7.5μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

Nonadjuvanted Quadravalent influenza vaccine(QIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.25 mL dose of TIV was administered by IM injection.

D_15QIV+0MF59

Arm description

Subjects who received 2 doses of non adjuvanted quadravalent influenza vaccine (QIV - 15μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

Nonadjuvanted Quadravalent influenza vaccine(QIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.5 mL dose of TIV was administered by IM injection.

Q_7.5cTIV+0MF59

Arm description

Subjects who received 2 doses of non adjuvanted trivalent influenza vaccine (cTIV - 7.5μg per antigen) on day 1 and day 29.

Arm type

Active comparator

Investigational medicinal product name

Nonadjuvanted Trivalent influenza vaccine(cTIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.25 mL dose of TIV was administered by IM injection.

E_7.5aTIV+⅛MF59

Arm description

Subjects who received 2 doses of ⅛ MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 7.5μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

adjuvanted Trivalent influenza vaccine (aTIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.25 mL dose of TIV was administered by IM injection.

F_7.5aQIV+⅛MF59

Arm description

Subjects who received 2 doses of ⅛MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 7.5μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

adjuvanted Quadravalent influenza vaccine (aQIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.25 mL dose of TIV was administered by IM injection.

G_7.5aTIV+¼MF59

Arm description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 7.5μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

adjuvanted Trivalent influenza vaccine (aTIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.25 mL dose of TIV was administered by IM injection.

H_15aTIV+¼MF59

Arm description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 15μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

adjuvanted Trivalent influenza vaccine (aTIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.5 mL dose of aTIV was administered by IM injection.

I_7.5aQIV+¼MF59

Arm description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV – 7.5μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

adjuvanted Quadravalent influenza vaccine (aQIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.25 mL dose of aQIV was administered by IM injection.

J_15aQIV+¼MF59

Arm description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 15μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

adjuvanted Quadravalent influenza vaccine (aQIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.5 mL dose of TIV was administered by IM injection.

K_7.5aTIV+½MF59

Arm description

Subjects who received 2 doses of ½MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 7.5μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

adjuvanted Trivalent Influenza Vaccine (aTIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.25 mL dose of TIV was administered by IM injection.

L_15aTIV+½MF59

Arm description

Subjects who received 2 doses of ½MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 15μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

adjuvanted Trivalent Influenza Vaccine (aTIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.5 mL dose of aTIV was administered by IM injection.

M_7.5aQIV+½MF59

Arm description

Subjects who received 2 doses of ½ MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 7.5μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

adjuvanted Quadravalent Influenza Vaccine (aQIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.25 mL dose of aQIV was administered by IM injection.

N_15aQIV+½MF59

Arm description

Subjects who received 2 doses of ½ MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 15μg per antigen) on day 1 and day 29.

Arm type

Experimental

Investigational medicinal product name

adjuvanted Quadravalent Influenza Vaccine (aQIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.5 mL dose of TIV was administered by IM injection.

O_15aTIV+fullMF59

Arm description

Subjects who received one dose of full MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 15μg per antigen) on day 1.

Arm type

Experimental

Investigational medicinal product name

adjuvanted Trivalent Influenza Vaccine (aTIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Single dose of 0.5 mL dose of TIV was administered by IM injection.

P_15aQIV+fullMF59

Arm description

Subjects who received one dose of full MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 15μg per antigen) on day 1.

Arm type

Experimental

Investigational medicinal product name

adjuvanted Quadravalent Influenza Vaccine (aQIV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Single dose of 0.5 mL dose of aQIV was administered by IM injection.

Number of subjects in period 1	A_7.5TIV+0MF59	B_15TIV+0MF59	C_7.5QIV+0MF59	D_15QIV+0MF59	Q_7.5cTIV+0MF59	E_7.5aTIV+⅛MF59	F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59	H_15aTIV+¼MF59	I_7.5aQIV+¼MF59	J_15aQIV+¼MF59	K_7.5aTIV+½MF59	L_15aTIV+½MF59	M_7.5aQIV+½MF59	N_15aQIV+½MF59	O_15aTIV+fullMF59	P_15aQIV+fullMF59
Started	25	22	25	28	26	24	23	23	21	24	24	27	23	22	25	26	22
Completed	24	22	24	25	26	24	21	22	19	22	24	27	22	22	25	24	22
Not completed	1	0	1	3	0	0	2	1	2	2	0	0	1	0	0	2	0
Consent withdrawn by subject	-	-	1	2	-	-	2	-	2	1	-	-	1	-	-	1	-
Adverse Events	-	-	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-
Lost to follow-up	-	-	-	-	-	-	-	1	-	1	-	-	-	-	-	1	-
Unable to Classify	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

Baseline characteristics

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Reporting group title

A_7.5TIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted trivalent influenza vaccine (TIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

B_15TIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted trivalent influenza vaccine (TIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

C_7.5QIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted quadravalent influenza vaccine (QIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

D_15QIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted quadravalent influenza vaccine (QIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

Q_7.5cTIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted trivalent influenza vaccine (cTIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

E_7.5aTIV+⅛MF59

Reporting group description

Subjects who received 2 doses of ⅛ MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

F_7.5aQIV+⅛MF59

Reporting group description

Subjects who received 2 doses of ⅛MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

G_7.5aTIV+¼MF59

Reporting group description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

H_15aTIV+¼MF59

Reporting group description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

I_7.5aQIV+¼MF59

Reporting group description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV – 7.5μg per antigen) on day 1 and day 29.

Reporting group title

J_15aQIV+¼MF59

Reporting group description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

K_7.5aTIV+½MF59

Reporting group description

Subjects who received 2 doses of ½MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

L_15aTIV+½MF59

Reporting group description

Subjects who received 2 doses of ½MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

M_7.5aQIV+½MF59

Reporting group description

Subjects who received 2 doses of ½ MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

N_15aQIV+½MF59

Reporting group description

Subjects who received 2 doses of ½ MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

O_15aTIV+fullMF59

Reporting group description

Subjects who received one dose of full MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 15μg per antigen) on day 1.

Reporting group title

P_15aQIV+fullMF59

Reporting group description

Subjects who received one dose of full MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 15μg per antigen) on day 1.

Reporting group values	A_7.5TIV+0MF59	B_15TIV+0MF59	C_7.5QIV+0MF59	D_15QIV+0MF59	Q_7.5cTIV+0MF59	E_7.5aTIV+⅛MF59	F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59	H_15aTIV+¼MF59	I_7.5aQIV+¼MF59	J_15aQIV+¼MF59	K_7.5aTIV+½MF59	L_15aTIV+½MF59	M_7.5aQIV+½MF59	N_15aQIV+½MF59	O_15aTIV+fullMF59	P_15aQIV+fullMF59	Total
Number of subjects	25	22	25	28	26	24	23	23	21	24	24	27	23	22	25	26	22	410
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	16	18	17	23	20	15	15	17	17	18	19	18	17	16	20	23	15	304
Children (2-11 years)	9	4	8	5	6	9	8	6	4	6	5	9	6	6	5	3	7	106
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Age continuous
Units: months
arithmetic mean (standard deviation)	20 ( 7 )	15 ( 8.8 )	18 ( 8.9 )	15.2 ( 7.8 )	16.1 ( 8.5 )	18.5 ( 9.3 )	17 ( 9 )	16.4 ( 7.4 )	15.4 ( 7.6 )	16.6 ( 8.8 )	16 ( 9.4 )	19 ( 9.4 )	18.3 ( 8.7 )	16.3 ( 9 )	15.4 ( 9.2 )	14.2 ( 7.1 )	17.8 ( 8.7 )	-
Gender categorical
Units: Subjects
Female	14	6	9	13	13	11	14	13	13	13	12	11	15	13	12	15	6	203
Male	11	16	16	15	13	13	9	10	8	11	12	16	8	9	13	11	16	207

End points

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Reporting group title

A_7.5TIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted trivalent influenza vaccine (TIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

B_15TIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted trivalent influenza vaccine (TIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

C_7.5QIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted quadravalent influenza vaccine (QIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

D_15QIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted quadravalent influenza vaccine (QIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

Q_7.5cTIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted trivalent influenza vaccine (cTIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

E_7.5aTIV+⅛MF59

Reporting group description

Subjects who received 2 doses of ⅛ MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

F_7.5aQIV+⅛MF59

Reporting group description

Subjects who received 2 doses of ⅛MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

G_7.5aTIV+¼MF59

Reporting group description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

H_15aTIV+¼MF59

Reporting group description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

I_7.5aQIV+¼MF59

Reporting group description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV – 7.5μg per antigen) on day 1 and day 29.

Reporting group title

J_15aQIV+¼MF59

Reporting group description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

K_7.5aTIV+½MF59

Reporting group description

Subjects who received 2 doses of ½MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

L_15aTIV+½MF59

Reporting group description

Subjects who received 2 doses of ½MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

M_7.5aQIV+½MF59

Reporting group description

Subjects who received 2 doses of ½ MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

N_15aQIV+½MF59

Reporting group description

Subjects who received 2 doses of ½ MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

O_15aTIV+fullMF59

Reporting group description

Subjects who received one dose of full MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 15μg per antigen) on day 1.

Reporting group title

P_15aQIV+fullMF59

Reporting group description

Subjects who received one dose of full MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 15μg per antigen) on day 1.

Subject analysis set title

All enrolled population

Subject analysis set type

Intention-to-treat

Subject analysis set description

All subjects who were enrolled in the study irrespective of whether or not they were randomized. An analysis of the “All Enrolled Population” was not planned.

Subject analysis set title

Per Protocol Set (PPS) (Visit-1) Day 1

Subject analysis set type

Per protocol

Subject analysis set description

All enrolled subjects who received the vaccinations correctly, provided evaluable serum samples at the relevant time points (visit 1), and had no major protocol violation as defined prior to unblinding. A major deviation was defined as a protocol deviation considered to have a significant impact on the immunogenicity result of the subject. In case of randomization errors, subjects were analyzed as treated in the PPS.

Subject analysis set title

Per Protocol Set (PPS) (Visit-3) Day 29

Subject analysis set type

Per protocol

Subject analysis set description

All enrolled subjects who received the vaccinations correctly, provided evaluable serum samples at the relevant time points (Visit-3), and had no major protocol violation as defined prior to unblinding. A major deviation was defined as a protocol deviation considered to have a significant impact on the immunogenicity result of the subject. In case of randomization errors, subjects were analyzed as treated in the PPS.

Subject analysis set title

Per Protocol Set (PPS) (Visit-5) Day 50

Subject analysis set type

Per protocol

Subject analysis set description

All enrolled subjects who received the vaccinations correctly, provided evaluable serum samples at the relevant time points (Visit-5), and had no major protocol violation as defined prior to unblinding. A major deviation was defined as a protocol deviation considered to have a significant impact on the immunogenicity result of the subject. In case of randomization errors, subjects were analyzed as treated in the PPS.

Subject analysis set title

Safety Set

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects enrolled who received at least one study vaccination and provided post-baseline safety data.

Subject analysis set title

A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in healthy subjects aged 6 to <36 months who received non adjuvanted trivalent/quadravalent influenza vaccine (TIV/QIV - 7.5μg per antigen).

Subject analysis set title

B_15TIV+0MF59 + D_15QIV+0MF59

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in healthy subjects aged 6 to <36 months who received non adjuvanted trivalent /quadravalent influenza vaccine (TIV/QIV - 15μg per antigen).

Subject analysis set title

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in healthy subjects aged 6 to <36 months who received eighth MF59 dose adjuvanted trivalent/quadravalent influenza vaccine (aTIV/aQIV - 7.5μg per antigen).

Subject analysis set title

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in healthy subjects aged 6 to <36 months who received quarter MF59 dose adjuvanted trivalent/quadravalent influenza vaccine (aTIV/aQIV - 7.5μg per antigen).

Subject analysis set title

H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in healthy subjects aged 6 to <36 months who received quarter MF59 dose adjuvanted trivalent/quadravalent influenza vaccine (aTIV/aQIV - 15μg per antigen).

Subject analysis set title

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in healthy subjects aged 6 to <36 months who received half MF59 dose adjuvanted trivalent /quadravalent influenza vaccine (aTIV/aQIV - 7.5μg per antigen)

Subject analysis set title

A_7.5TIV+0MF59 + B_15TIV+0MF59

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in subjects who received non adjuvanted 7.5μg and 15 μg per antigen trivalent influenza vaccine (TIV) on day 1 and day 29.

Subject analysis set title

G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in subjects who received quarter MF59 dose adjuvanted, 7.5μg and 15μg per antigen trivalent influenza vaccine(aTIV) on day 1 and day 29.

Subject analysis set title

K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in subjects who received half MF59 dose adjuvanted, 7.5μg and 15μg per antigen trivalent influenza vaccine (aTIV) on day 1 and day 29.

Subject analysis set title

L_15aTIV+½MF59 + N_15aQIV+½MF59

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in subjects received half MF59 Dose adjuvanted, 15μg per antigen trivalent/quadravalent influenza vaccine (aTIV/aQIV - 15μg per antigen) on day 1 and day 29.

Subject analysis set title

O_15aTIV+fullMF59 + P_15aQIV+fullMF59

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in subjects who received full MF59 dose adjuvanted trivalent/quadravalent influenza vaccine (aTIV/aQIV - 15μg per antigen) on day 1 and day 29.

Subject analysis set title

AEGK

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in subjects who received non adjuvanted/ eighth/ quarter/ half adjuvanted 7.5μg per antigen trivalent influenza vaccine (aTIV). (A_7.5TIV+0MF59+ E_7.5aTIV+⅛MF59 + G_7.5aTIV+¼MF59 + K_7.5aTIV+½MF59)

Subject analysis set title

BHL

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in subjects who received non adjuvanted/ eighth/ quarter/ half adjuvanted 15 μg per antigen trivalent influenza vaccine (aTIV). (B_15TIV+0MF59 + H_15aTIV+¼MF59 + L_15aTIV+½MF59)

Subject analysis set title

CFIM

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in subjects who received non adjuvanted/ eighth/ quarter/ half adjuvanted 7.5μg per antigen quadravalent influenza vaccine (aTIV). (C_7.5QIV+0MF59 + F_7.5aQIV+⅛MF59 + I_7.5aQIV+¼MF59 + M_7.5aQIV+½MF59)

Subject analysis set title

DJN

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in subjects who received non adjuvanted/ eighth/ quarter/ half adjuvanted 15μg per antigen quadravalent influenza vaccine (aTIV). (D_15QIV+0MF59 + J_15aQIV+¼MF59 + N_15aQIV+½MF59)

Subject analysis set title

AGK

Subject analysis set type

Per protocol

Subject analysis set description

Study vaccine combinations in subjects who received non adjuvanted/ quarter/ half adjuvanted 7.5μg per antigen trivalent influenza vaccine (TIV/aTIV) on day 1 and day 29. (A_7.5TIV+0MF59 + G_7.5aTIV+¼MF59 + K_7.5aTIV+½MF59)

Subject analysis set title

Slope (log10) inc. 95% CI

Subject analysis set type

Per protocol

Subject analysis set description

Dose-response relationship for MF59 using a linear regression analysis with dose and day 50 antibody titers to log base 10.

Subject analysis set title

Slope incl. 95% CI

Subject analysis set type

Per protocol

Subject analysis set description

Dose-response relationship for MF59 using a linear regression analysis with dose and day 50 antibody titers.

Primary: 1. To assess non-inferiority of study vaccine formulations to the pediatric trivalent influenza vaccine (TIV - 7.5μg per antigen) formulated with MF59 at half the dose of the marketed adult adjuvanted vaccine.

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End point title

1. To assess non-inferiority of study vaccine formulations to the pediatric trivalent influenza vaccine (TIV - 7.5μg per antigen) formulated with MF59 at half the dose of the marketed adult adjuvanted vaccine.

End point description

To assess immunogenicity in terms of Geometric Mean Titer (GMT) in order to evaluate whether any of the study vaccine formulations is noninferior to the pediatric trivalent influenza vaccine (TIV - 7.5μg per antigen) formulated with MF59 at half the dose of the marketed adult adjuvanted vaccine, Fluad for three strains.

End point type

Primary

End point timeframe

Day 1, Day 29 and Day 50

End point values	A_7.5TIV+0MF59 + C_7.5QIV+0MF59	B_15TIV+0MF59 + D_15QIV+0MF59	E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59	H_15aTIV+¼MF59 + J_15aQIV+¼MF59	K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59
Number of subjects analysed	49	49	44	44	44	49
Units: Titers
geometric mean (confidence interval 95%)
A/H1N1 (Day 1)	6.4 (4.7 to 8.72)	6.54 (4.8 to 8.91)	8.15 (5.88 to 11)	8.41 (6.07 to 12)	7.83 (5.66 to 11)	7.7 (5.65 to 10)
A/H1N1 (Day 29) (N=37,43,37,35,33,41)	14 (7.76 to 24)	12 (7.2 to 21)	109 (62 to 193)	118 (65 to 212)	149 (81 to 272)	118 (69 to 203)
A/H1N1 (Day 50) (N= 37,42,36,34,33,40)	57 (37 to 85)	69 (47 to 102)	533 (351 to 810)	481 (313 to 740)	576 (372 to 892)	529 (356 to 787)
A/H3N2 (Day1)	7.38 (5.22 to 10)	7.22 (5.11 to 10)	7.96 (5.53 to 11)	9.54 (6.62 to 14)	6.8 (4.72 to 9.79)	8.44 (5.97 to 12)
A/H3N2 (Day 29) (N=37,43,37,35,33,41)	19 (12 to 30)	12 (7.52 to 18)	91 (57 to 145)	114 (71 to 184)	112 (68 to 183)	150 (96 to 232)
A/H3N2 (Day 50) (N= 37,42,36,34,33,40)	73 (50 to 106)	60 (42 to 86)	518 (354 to 758)	496 (335 to 734)	503 (338 to 748)	608 (423 to 872)
B_FL (Day 1)	5.37 (4.8 to 6)	5.29 (4.73 to 5.92)	6.23 (5.54 to 7.02)	6.33 (5.63 to 7.13)	5.16 (4.58 to 5.81)	5.8 (5.18 to 6.49)
B_FL (Day 29) (N=37,43,37,35,33,41)	8.45 (5.64 to 13)	6.74 (4.63 to 9.8)	9.37 (6.26 to 14)	13 (8.29 to 19)	8.45 (5.51 to 13)	9.59 (6.53 to 14)
B_FL (Day 50) (N= 37,42,36,34,33,40)	13 (9.45 to 18)	11 (7.98 to 15)	61 (43 to 84)	61 (43 to 86)	69 (49 to 98)	81 (59 to 112)

A/H1N1: Day 1 (AC:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of non adjuvanted 7.5μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen TIV and QIV, adjuvanted with ½ MF59 dose for strain A/H1N1 on day 1. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5 aTIV+½MF59 + M_7.5 aQIV+½MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

P-value

= 0.16

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.08

Notes
[1] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 1 (BD:KM)

Statistical analysis description

Non-inferioriority of study vaccine combinations of non adjuvanted 15μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg /antigen TIV and QIV, adjuvanted with ½MF59 dose for strain A/H1N1 on day 1. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5 aTIV+½MF59 + M_7.5 aQIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

P-value

= 0.14

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

1.32

Notes
[2] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 1 (EF:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ⅛ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H1N1 on day 1. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF591 + M_7.5aQIV+½MF593)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

P-value

= 0.023

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.66

Notes
[3] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 1 (GI:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen TIV and QIV, adjuvanted with ½ MF59 dose for strain A/H1N1 on day 1. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF591 + M_7.5aQIV+½MF593)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.016

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.71

A/H1N1: Day 1 (HJ:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 15μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H1N1 on day 1. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.034

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.59

A/H1N1: Day 29 (AC:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of non adjuvanted 7.5μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg /antigen aTIV and aQIV, adjuvanted with ½MF59 dose for strain A/H1N1 on Day 29. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.053

upper limit

0.26

A/H1N1: Day 29 (BD:KM)

Statistical analysis description

Non-inferioriority of study vaccine combinations of non adjuvanted 15μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½MF59 dose for strain A/H1N1 on day 29. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.049

upper limit

0.22

A/H1N1: Day 29 (EF:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ⅛ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H1N1 on day 29. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF591 + M_7.5aQIV+½MF593)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.21

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

2.03

A/H1N1: Day 29 (GI:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H1N1 on day 29. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.16

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

2.22

A/H1N1: Day 29 (HJ:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 15μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H1N1 on day 29. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

P-value

= 0.064

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

2.84

Notes
[4] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 50 (AC:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of non adjuvanted 7.5μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H1N1 on day 50. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF593)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

0.19

Notes
[5] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 50 (BD:KM)

Statistical analysis description

Non-inferioriority of study vaccine combinations of non adjuvanted 15μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg /antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H1N1 on day 50. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.075

upper limit

0.23

Notes
[6] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 50 (EF:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ⅛ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H1N1 on day 50. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF591 + M_7.5aQIV+½MF593)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.082 ^[7]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.79

Notes
[7] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 50 (GI:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/ antigen TIV and QIV influenza vaccine, adjuvanted with ¼MF59 dose influenza vaccines to that of 7.5μg/ antigen TIV and QIV, adjuvanted with ½MF59 dose for strain A/H1N1 on Day 50. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF591 + M_7.5aQIV+½MF593)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

P-value

= 0.15

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.63

Notes
[8] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 50 (HJ:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 15μg/antigen TIV and QIV influenza vaccine, adjuvanted with ¼MF59 dose influenza vaccines to that of 7.5μg/antigen TIV and QIV, adjuvanted with ½MF59 dose for strain A/H1N1 on Day 50. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

P-value

= 0.053

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.97

Notes
[9] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (AC:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of non adjuvanted 7.5μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½MF59 dose for strain A/H3N2 on day 1. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5 aTIV+½MF59 + M_7.5 aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

P-value

= 0.14

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.42

Notes
[10] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (BD:KM)

Statistical analysis description

Non-inferioriority of study vaccine combinations of non adjuvanted 15μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H3N2 on day 1. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

P-value

= 0.16

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.4

Notes
[11] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (EF:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ⅛MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H3N2 on day 1. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF591 + M_7.5aQIV+½MF593)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

P-value

= 0.091

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.56

Notes
[12] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (GI:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H3N2 on day 1. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

P-value

= 0.021

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.87

Notes
[13] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (HJ:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 15μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H3N2 on day 1. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF591 + M_7.5aQIV+½MF593)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[14]

P-value

= 0.024

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

1.33

Notes
[14] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29 (AC:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of non adjuvanted 7.5μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg /antigen aTIV and aQIV, adjuvanted with ½MF59 dose for strain A/H3N2 on day 29. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.065

upper limit

0.24

Notes
[15] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29 (BD:KM)

Statistical analysis description

Non-inferioriority of study vaccine combinations of non adjuvanted 15μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H3N2 on day 29. (B_15 TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF591 + M_7.5aQIV+½MF593)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[16]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.077

Confidence interval

level

95%

sides

2-sided

lower limit

0.042

upper limit

0.14

Notes
[16] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29 (EF:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ⅛ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H3N2 on day 29. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[17]

P-value

= 0.61

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

1.16

Notes
[17] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29 (GI:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H3N2 on day 29. (G_7.5 aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5 aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

P-value

= 0.35

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.46

Notes
[18] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29 (HJ:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 15μg/ antigen TIV and QIV influenza vaccine, adjuvanted with ¼MF59 dose influenza vaccines to that of 7.5μg/antigen TIV and QIV, adjuvanted with ½MF59 dose for strain A/H3N2 on day 29. (H_15aTIV+¼MF59+ J_15aQIV+¼MF59 : K_7.5aTIV+½MF591+ M_7.5aQIV+½MF593)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

P-value

= 0.37

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

1.45

Notes
[19] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 50 (AC:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of non adjuvanted 7.5μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H3N2 on day 50. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.071

upper limit

0.2

Notes
[20] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 50 (BD:KM)

Statistical analysis description

Non-inferioriority of study vaccine combinations of non adjuvanted 15μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen TIV and QIV, adjuvanted with ½MF59 dose for strain A/H3N2 on day 50. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF593)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.099

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

0.16

Notes
[21] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 50 (EF:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen TIV and QIV influenza vaccine, adjuvanted with ⅛MF59 dose influenza vaccines to that of 7.5μg / antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H3N2 on day 50. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF591+ M_7.5aQIV+½MF593)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.18

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.44

A/H3N2: Day 50 (GI:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain A/H3N2 on day 50. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5 aTIV+½MF591 + M_7.5 aQIV+½MF593)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.23

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

1.39

A/H3N2: Day 50 (HJ:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 15μg/ antigen TIV and QIV influenza vaccine, adjuvanted with ¼MF59 dose influenza vaccines to that of 7.5μg/antigen TIV and QIV, adjuvanted with ½MF59 dose for strain A/H3N2 on day 50. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF591 + M_7.5aQIV+½MF593)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

P-value

= 0.22

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

1.42

Notes
[22] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (AC:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of non adjuvanted 7.5μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen TIV and QIV, adjuvanted with ½MF59 dose for strain B_FL on day 1. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.29

Notes
[23] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (BD:KM)

Statistical analysis description

Non-inferioriority of study vaccine combinations of non adjuvanted 15μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½MF59 dose for strain B_FL on day 1. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[24]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.07

Notes
[24] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (EF:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ⅛ MF59 dose influenza vaccines to that of 7.5μg/antigen TIV and QIV, adjuvanted with ½ MF59 dose for strain B_FL on day 1. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[25]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

1.27

Notes
[25] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (GI:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½MF59 dose for strain B_FL on day 1. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.29

B_FL: Day 1 (HJ:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 15μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain B_FL on day 1. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.05

B_FL: Day 29 (AC:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of non adjuvanted 7.5μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain B_FL on day 29. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[26]

P-value

= 0.17

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.54

Notes
[26] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29 (BD:KM)

Statistical analysis description

Non-inferioriority of study vaccine combinations of non adjuvanted 15μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain B_FL on day 29. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v B_15TIV+0MF59 + D_15QIV+0MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[27]

P-value

= 0.43

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

1.2

Notes
[27] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29 (EF:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ⅛ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain B_FL on day 29. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[28]

P-value

= 0.092

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

1.7

Notes
[28] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29 (GI:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain B_FL on day 29. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.01

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.31

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

2.3

B_FL: Day 29 (HJ:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 15μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain B_FL on day 29. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.17

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.57

B_FL: Day 50 (AC:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of non adjuvanted 7.5μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain B_FL on day 50. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.25

Notes
[29] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 50 (BD:KM)

Statistical analysis description

Non-inferioriority of study vaccine combinations of non adjuvanted 15μg/antigen TIV and QIV influenza vaccine, to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain B_FL on day 50. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[30]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.086

upper limit

0.21

Notes
[30] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 50 (EF:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ⅛ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½ MF59 dose for strain B_FL on day 50. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[31]

P-value

= 0.33

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.18

Notes
[31] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 50 (GI:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg/antigen TIV and QIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen TIV and QIV, adjuvanted with ½ MF59 dose for strain B_FL on day 50. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.32

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.19

B_FL: Day 50 (HJ:KM)

Statistical analysis description

Non-inferiority of study vaccine combinations of 15μg/antigen aTIV and aQIV influenza vaccine, adjuvanted with ¼ MF59 dose influenza vaccines to that of 7.5μg/antigen aTIV and aQIV, adjuvanted with ½MF59 dose for strain B_FL on day 50. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.16

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.36

Primary: 2. To assess non-inferiority of 7.5 μg QIV formulated with half MF59 to 7.5μg and 15μg TIV and QIV groups.

Top of page

End point title

2. To assess non-inferiority of 7.5 μg QIV formulated with half MF59 to 7.5μg and 15μg TIV and QIV groups. ^[32]

End point description

To assess non-inferiority of the 7.5 μg aQIV formulated with half MF59 in terms of GMTs, the 7.5μg and 15μg TIV groups of the same adjuvant concentration were combined, while the QIV groups for the second B-strain, B_Malaysia (B_MY). The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1, Day 29 and Day 50

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

End point values	C_7.5QIV+0MF59	D_15QIV+0MF59	E_7.5aTIV+⅛MF59	F_7.5aQIV+⅛MF59	I_7.5aQIV+¼MF59	J_15aQIV+¼MF59	M_7.5aQIV+½MF59	A_7.5TIV+0MF59 + B_15TIV+0MF59	G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59	K_7.5aTIV+½MF59 + L_15aTIV+½MF59
Number of subjects analysed	24	28	23	21	22	24	22	46	42	47
Units: Titers
geometric mean (confidence interval 95%)
B_MY(Day1)	5 (4.86 to 5.14)	5 (4.87 to 5.13)	5 (4.86 to 5.14)	5.17 (5.02 to 5.32)	5 (4.86 to 5.15)	5.15 (5.01 to 5.29)	5 (4.86 to 5.15)	5 (4.9 to 5.1)	5 (4.9 to 5.11)	5.07 (4.97 to 5.18)
B_MY(Day 29)	6.39 (5.24 to 7.79)	5 (4.2 to 5.95)	6.22 (5.16 to 7.51)	6.06 (5 to 7.35)	5.83 (4.81 to 7.07)	6.55 (5.4 to 7.94)	6.22 (5.16 to 7.51)	5 (4.39 to 5.69)	5.45 (4.72 to 6.3)	5.79 (5.07 to 6.61)
B_MY(Day50)	11 (7.12 to 16)	9.68 (6.58 to 14)	10 (6.85 to 16)	42 (28 to 64)	63 (42 to 96)	63 (41 to 96)	70 (47 to 106)	5.74 (4.34 to 7.6)	11 (8.33 to 16)	14 (11 to 19)

B_MY:Day 1 (AB:M)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg and 15μg/antigen non-adjuvanted TIV to that of 7.5μg/antigen QIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 1. (A_7.5TIV+0MF59 + B_15TIV+0MF59 : M_7.5aQIV+½MF593)

Comparison groups

M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[33]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.04

Notes
[33] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (C:M)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen non-adjuvanted QIV to that of 7.5μg/antigen QIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 1. (C_7.5QIV+0MF59 : M_7.5aQIV+½MF593)

Comparison groups

C_7.5QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[34]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[34] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (D:M)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/ antigen non-adjuvanted QIV to that of 7.5μg/antigen QIV, adjuvanted with ½MF59 dose for strain B/Malaysia (B_MY) on day 1. (D_15 QIV+0MF59 : M_7.5 aQIV+½MF593)

Comparison groups

D_15QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[35]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[35] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (E:M)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen aTIV, adjuvanted with ⅛ MF59 dose to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 1. (E_7.5aTIV+⅛MF59 : M_7.5 aQIV+½MF593)

Comparison groups

E_7.5aTIV+⅛MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[36]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[36] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (F:M)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen aQIV, adjuvanted with ⅛ MF59 dose to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 1. (F_7.5aQIV+⅛MF59 : M_7.5aQIV+½MF593)

Comparison groups

F_7.5aQIV+⅛MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[37]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.08

Notes
[37] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY:Day 1 (GH:M)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg and 15μg/ antigen adjuvanted ¼ MF59 dose aTIV and aQIV to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 1. (G_7.5 aTIV+¼MF59 + H_15aTIV+¼MF59 : M_7.5aQIV+½MF593)

Comparison groups

M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[38]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[38] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (I:M)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen aQIV, adjuvanted with ¼ MF59 dose to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 1. (I_7.5aQIV+¼MF59 : M_7.5aQIV+½MF593)

Comparison groups

I_7.5aQIV+¼MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[39]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[39] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (J:M)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen AQIV, adjuvanted with ¼ MF59 dose to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 1. (J_15aQIV+¼MF59 : M_7.5aQIV+½MF593)

Comparison groups

J_15aQIV+¼MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[40]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.07

Notes
[40] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY:Day 1 (KL:M)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg and 15μg/antigen adjuvanted ½ MF59 dose aTIV to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 1. (K_7.5aTIV+½MF59 + L_15aTIV+½MF59 : M_7.5aQIV+½MF593)

Comparison groups

M_7.5aQIV+½MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[41]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

1.05

Notes
[41] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY:Day 29 (AB:M)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg and 15μg/antigen non-adjuvanted TIV to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 29. (A_7.5TIV+0MF59 + B_15TIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[42]

P-value

= 0.059

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

1.01

Notes
[42] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29 (C:M)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen non-adjuvanted QIV to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 29. (C_7.5QIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

C_7.5QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[43]

P-value

= 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.35

Notes
[43] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY:Day 29 (D:M)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen non-adjuvanted QIV to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 29. (D_15QIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

D_15QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[44]

P-value

= 0.082

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

1.04

Notes
[44] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29 (E:M)

Statistical analysis description

Comparison groups

E_7.5aTIV+⅛MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[45]

P-value

= 0.002

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.3

Notes
[45] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29 (F:M)

Statistical analysis description

Comparison groups

F_7.5aQIV+⅛MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[46]

P-value

= 0.003

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.27

Notes
[46] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29 (GH:M)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg and 15μg/antigen adjuvanted ¼ MF59 dose aTIV and aQIV to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 29. (G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59 : M_7.5aQIV+½MF593)

Comparison groups

M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[47]

P-value

= 0.013

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.11

Notes
[47] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY:Day 29 (I:M)

Statistical analysis description

Comparison groups

I_7.5aQIV+¼MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[48]

P-value

= 0.007

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.23

Notes
[48] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29 (J:M)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen aQIV, adjuvanted with ¼ MF59 dose to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 29. (J_15aQIV+¼MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[49]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.38

Notes
[49] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29 (KL:M)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen aQIV, adjuvanted with ¼ MF59 dose to that of 15μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 29. (K_7.5aTIV+½MF59 + L_15aTIV+½MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[50]

P-value

< 0.003

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.17

Notes
[50] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 50 (AB:M)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg and 15μg/antigen non-adjuvanted aTIV to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 50. (A_7.5TIV+0MF59 + B_15TIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[51]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.082

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

0.13

Notes
[51] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY:Day 50 (C:M)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen non-adjuvanted QIV to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 50. (C_7.5QIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

C_7.5QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[52]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.086

upper limit

0.27

Notes
[52] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 50 (D:M)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen non-adjuvanted QIV to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 50. (D_15 QIV + 0MF59 : M_7.5 aQIV+ ½MF59)

Comparison groups

D_15QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[53]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.079

upper limit

0.24

Notes
[53] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 50 (E:M)

Statistical analysis description

Comparison groups

E_7.5aTIV+⅛MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[54]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.083

upper limit

0.26

Notes
[54] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 50 (F:M)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen QIV, adjuvanted with ⅛MF59 dose to that of 7.5μg/antigen QIV, adjuvanted with ½MF59 dose for strain B/Malaysia (B_MY) on day 50. (F_7.5QIV+⅛MF59 : M_7.5aQIV+½MF593)

Comparison groups

F_7.5aQIV+⅛MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[55]

P-value

= 0.64

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

1.08

Notes
[55] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 50 (GH:M)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg and 15μg/antigen adjuvanted ¼ MF59 dose aTIV and aQIV to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 50. (G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[56]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.097

upper limit

0.27

Notes
[56] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 50 (I:M)

Statistical analysis description

Comparison groups

I_7.5aQIV+¼MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[57]

P-value

= 0.16

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.61

Notes
[57] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 50 (J:M)

Statistical analysis description

Comparison groups

J_15aQIV+¼MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[58]

P-value

= 0.17

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

1.61

Notes
[58] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 50 (KL:M)

Statistical analysis description

Non-inferiority of study vaccine combinations of 7.5μg and 15μg/antigen adjuvanted ½ MF59 dose aTIV to that of 7.5μg/antigen aQIV, adjuvanted with ½ MF59 dose for strain B/Malaysia (B_MY) on day 50. (K_7.5aTIV+½MF59 + L_15aTIV+½MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[59]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.12

upper limit

0.33

Notes
[59] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

Primary: 3. To evaluate superiority of any of the study vaccine formulations to the pediatric trivalent influenza vaccine (TIV - 7.5μg per antigen) formulated with MF59 at half the dose of the marketed adult adjuvanted vaccine, Fluad.

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End point title

3. To evaluate superiority of any of the study vaccine formulations to the pediatric trivalent influenza vaccine (TIV - 7.5μg per antigen) formulated with MF59 at half the dose of the marketed adult adjuvanted vaccine, Fluad.

End point description

To assess immunogenicity in terms of GMT in order to evaluate whether any of the study vaccine formulations is superior to the pediatric trivalent influenza vaccine (TIV - 7.5μg per antigen) formulated with MF59 at half the dose of the marketed adult adjuvanted vaccine, Fluad. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1, Day 29 and Day 50

End point values	A_7.5TIV+0MF59 + C_7.5QIV+0MF59	B_15TIV+0MF59 + D_15QIV+0MF59	E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59	H_15aTIV+¼MF59 + J_15aQIV+¼MF59	K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59	L_15aTIV+½MF59 + N_15aQIV+½MF59
Number of subjects analysed	49	49	44	44	44	45	49
Units: Titers
geometric mean (confidence interval 95%)
A/H1N1 (Day 1)	6.4 (4.7 to 8.72)	6.54 (4.8 to 8.91)	8.15 (5.88 to 11)	8.41 (6.07 to 12)	7.83 (5.66 to 11)	7.7 (5.65 to 10)	7.58 (5.49 to 10)
A/H1N1 (Day 29) (N=37,43,37,35,33,37,41)	14 (7.76 to 24)	12 (7.2 to 21)	109 (62 to 193)	118 (65 to 212)	149 (81 to 272)	118 (69 to 203)	220 (124 to 390)
A/H1N1 (Day 50) (N=37,42,36,34,33,36,40)	57 (37 to 85)	69 (47 to 102)	533 (351 to 810)	481 (313 to 740)	576 (372 to 892)	529 (356 to 787)	718 (473 to 1092)
A/H3N2 (Day 1)	7.38 (5.22 to 10)	7.22 (5.11 to 10)	7.96 (5.53 to 11)	9.54 (6.62 to 14)	6.8 (4.72 to 9.79)	8.44 (5.97 to 12)	6.6 (4.6 to 9.46)
A/H3N2 (Day 29) (N=37,43,37,35,33,37,41)	19 (12 to 30)	12 (7.52 to 18)	91 (57 to 145)	118 (65 to 212)	112 (68 to 183)	150 (96 to 232)	163 (103 to 259)
A/H3N2 (Day 50) (N=37,42,36,34,33,36,40)	73 (50 to 106)	60 (42 to 86)	518 (354 to 758)	496 (335 to 734)	503 (338 to 748)	608 (423 to 872)	559 (382 to 819)
B_FL (Day 1)	5.37 (4.8 to 6)	5.29 (4.73 to 5.92)	6.23 (5.54 to 7.02)	6.33 (5.63 to 7.13)	5.16 (4.58 to 5.81)	5.8 (5.18 to 6.49)	5.48 (4.88 to 6.16)
B_FL (Day 29) (N=37,43,37,35,33,37,41)	8.45 (5.64 to 13)	6.74 (4.63 to 9.8)	9.37 (6.26 to 14)	13 (8.29 to 19)	8.45 (5.51 to 13)	9.59 (6.53 to 14)	18 (12 to 27)
B_FL (Day 50) (N=37,42,36,34,33,36,40)	13 (9.45 to 18)	11 (7.98 to 15)	61 (43 to 84)	61 (43 to 86)	69 (49 to 98)	81 (59 to 112)	101 (72 to 141)

A/H1N1: Day 1 (AC:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[60]

P-value

= 0.8

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.29

Notes
[60] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 1 (BD:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5 TIV+½MF59 + M_7.5QIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[61]

P-value

= 0.77

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

1.32

Notes
[61] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 1 (EF:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[62]

P-value

= 0.4

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.66

Notes
[62] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 1 (GI:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[63]

P-value

= 0.35

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.71

Notes
[63] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 1 (HJ:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[64]

P-value

= 0.47

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.59

Notes
[64] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 1 (LN:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

L_15aTIV+½MF59 + N_15aQIV+½MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[65]

P-value

= 0.53

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.54

Notes
[65] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (AC:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (A_7.5 TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[66]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.053

upper limit

0.26

Notes
[66] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (BD:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[67]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.049

upper limit

0.22

Notes
[67] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (EF:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[68]

P-value

= 0.58

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

2.03

Notes
[68] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (GI:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[69]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

2.22

Notes
[69] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (HJ:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[70]

P-value

= 0.29

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

2.84

Notes
[70] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (LN:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

L_15aTIV+½MF59 + N_15aQIV+½MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[71]

P-value

= 0.061

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

4.1

Notes
[71] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (AC:KM)

Statistical analysis description

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[72]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

0.19

Notes
[72] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (BD:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5QIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[73]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.075

upper limit

0.23

Notes
[73] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (EF:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[74]

P-value

= 0.49

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.79

Notes
[74] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (GI:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[75]

P-value

= 0.62

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.63

Notes
[75] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (HJ:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[76]

P-value

= 0.39

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.97

Notes
[76] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (LN:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

L_15aTIV+½MF59 + N_15aQIV+½MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[77]

P-value

= 0.15

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.36

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

2.42

Notes
[77] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (AC:KM)

Statistical analysis description

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[78]

P-value

= 0.71

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.42

Notes
[78] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (BD:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2, and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with 0, ⅛, or ¼MF59 with 7.5μg aTIV/aQIV + ½MF59. (B_15 TIV + 0MF59+ D_15 QIV + 0MF59:K_7.5 TIV+ ½MF59+ M_7.5 QIV+ ½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[79]

P-value

= 0.73

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.4

Notes
[79] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (EF:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[80]

P-value

= 0.59

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.56

Notes
[80] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (GI:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[81]

P-value

= 0.32

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.87

Notes
[81] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (HJ:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[82]

P-value

= 0.8

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

1.33

Notes
[82] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (LN:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[83]

P-value

= 0.83

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.29

Notes
[83] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (AC:KM)

Statistical analysis description

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[84]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.065

upper limit

0.24

Notes
[84] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (BD:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5TIV+½MF59 + M_7.5QIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[85]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.077

Confidence interval

level

95%

sides

2-sided

lower limit

0.042

upper limit

0.14

Notes
[85] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (EF:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (E_7.5TIV+⅛MF59 + F_7.5QIV+⅛MF59 : K_7.5TIV+½MF59 + M_7.5QIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[86]

P-value

= 0.94

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

1.16

Notes
[86] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (GI:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[87]

P-value

= 0.79

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.46

Notes
[87] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (HJ:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[88]

P-value

= 0.81

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

1.45

Notes
[88] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (LN:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

L_15aTIV+½MF59 + N_15aQIV+½MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[89]

P-value

= 0.39

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

2.07

Notes
[89] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (AC:KM)

Statistical analysis description

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[90]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.071

upper limit

0.2

Notes
[90] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (BD:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5TIV+½MF59 + M_7.5QIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[91]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.099

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

0.16

Notes
[91] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (EF:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (E_7.5TIV+⅛MF59 + F_7.5QIV+⅛MF59 : K_7.5TIV+½MF59 + M_7.5QIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[92]

P-value

= 0.73

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.44

Notes
[92] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (GI:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2, and B/Florida 06 was assessed by comparing 7.5μg TIV/QIV and 15μg TIV/QIV each formulated with 0, ⅛, or ¼MF59 with 7.5μg TIV/QIV + ½MF59. (G_7.5 aTIV+ ¼MF59 + I_7.5 aQIV+ ¼MF59:K_7.5 aTIV+ ½MF59 + M_7.5 aQIV+ ½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[93]

P-value

= 0.77

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

1.39

Notes
[93] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (HJ:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[94]

P-value

= 0.76

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

1.42

Notes
[94] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (LN:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+ ½MF59)

Comparison groups

L_15aTIV+½MF59 + N_15aQIV+½MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[95]

P-value

= 0.62

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.56

Notes
[95] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 1 (AC:KM)

Statistical analysis description

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[96]

P-value

= 0.83

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.08

Notes
[96] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 1 (BD:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[97]

P-value

= 0.87

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.07

Notes
[97] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 1 (EF:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[98]

P-value

= 0.19

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

1.27

Notes
[98] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 1 (GI:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[99]

P-value

= 0.14

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.29

Notes
[99] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 1 (HJ:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[100]

P-value

= 0.92

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.05

Notes
[100] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 1 (LN:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

L_15aTIV+½MF59 + N_15aQIV+½MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[101]

P-value

= 0.75

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.11

Notes
[101] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 29 (AC:KM)

Statistical analysis description

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[102]

P-value

= 0.67

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.54

Notes
[102] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 29 (BD:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[103]

P-value

= 0.9

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

1.2

Notes
[103] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 29 (EF:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[104]

P-value

= 0.53

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

1.7

Notes
[104] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 29 (GI:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[105]

P-value

= 0.17

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.31

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

2.3

Notes
[105] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 29 (HJ:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[106]

P-value

= 0.67

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.57

Notes
[106] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 29 (LN:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

L_15aTIV+½MF59 + N_15aQIV+½MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[107]

P-value

= 0.014

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.86

Confidence interval

level

95%

sides

2-sided

lower limit

1.07

upper limit

3.25

Notes
[107] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 50 (AC:KM)

Statistical analysis description

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[108]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.25

Notes
[108] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 50 (BD:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5TIV+½MF59 + M_7.5QIV+½MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[109]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.086

upper limit

0.21

Notes
[109] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 50 (EF:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF59 + M_7.5QIV+½MF59)

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[110]

P-value

= 0.9

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.18

Notes
[110] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 50 (GI:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[111]

P-value

= 0.89

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.19

Notes
[111] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 50 (HJ:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[112]

P-value

= 0.75

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.36

Notes
[112] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL: Day 50 (LN:KM)

Statistical analysis description

The superiority of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 was assessed by comparing 7.5μg TIV/aTIV/QIV/aQIV and 15μg TIV/aTIV/QIV/aQIV each formulated with nonadjuvanted/eighth/quarter adjuvanted MF59 with 7.5μg aTIV/aQIV+½MF59. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[113]

P-value

= 0.18

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.24

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.96

Notes
[113] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

Primary: 4. To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV + ½MF59 group.

Top of page

End point title

4. To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV + ½MF59 group. ^[114]

End point description

Evaluating the superiority of GMTs against the second B strain (Malaysia) B_MY, the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV+½MF59 group. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1, Day 29 and Day 50

Notes
[114] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

End point values	C_7.5QIV+0MF59	D_15QIV+0MF59	E_7.5aTIV+⅛MF59	F_7.5aQIV+⅛MF59	I_7.5aQIV+¼MF59	J_15aQIV+¼MF59	M_7.5aQIV+½MF59	N_15aQIV+½MF59	A_7.5TIV+0MF59 + B_15TIV+0MF59	G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59	K_7.5aTIV+½MF59 + L_15aTIV+½MF59
Number of subjects analysed	24	28	23	21	22	24	22	25	46	42	47
Units: Titers
geometric mean (confidence interval 95%)
B_MY (Day 1)	5 (4.87 to 5.14)	5 (4.88 to 5.13)	5 (4.87 to 5.14)	5.17 (5.02 to 5.32)	5 (4.86 to 5.14)	5.15 (5.01 to 5.29)	5 (4.86 to 5.14)	5 (4.87 to 5.13)	5 (4.9 to 5.1)	5 (4.9 to 5.1)	5.07 (4.98 to 5.17)
B_MY (Day 29) (N= 17,22,19,18,18,19,21,40,32,38)	6.39 (5.18 to 7.87)	5 (4.16 to 6.01)	6.22 (4.16 to 7.58)	6.06 (4.95 to 7.43)	5.83 (4.76 to 7.15)	6.55 (5.34 to 8.02)	6.22 (5.11 to 7.58)	7.19 (5.96 to 8.68)	5 (4.36 to 5.73)	5.45 (4.68 to 6.35)	5.79 (5.03 to 6.65)
B_MY (Day 50)(N= 18,21,18,18,18,17,19,21,40,32,36)	11 (7.12 to 16)	9.68 (6.58 to 14)	9.68 (6.58 to 16)	42 (28 to 64)	63 (42 to 96)	63 (41 to 96)	70 (47 to 106)	70 (48 to 103)	5.74 (4.34 to 7.59)	11 (8.33 to 16)	14 (11 to 19)

B_MY: Day 1 (AB:M)

Statistical analysis description

To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV + ½MF59 group for Day 1. (A_7.5TIV+0MF59 + B_15TIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[115]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.03

Notes
[115] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (C:M)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[116]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[116] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (D:M)

Statistical analysis description

Comparison groups

D_15QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[117]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[117] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (E:M)

Statistical analysis description

Comparison groups

E_7.5aTIV+⅛MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[118]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[118] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (F:M)

Statistical analysis description

To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV+½MF59 group for day 1. (F_7.5 aQIV+⅛MF59 : M_7.5aQIV+½MF59)

Comparison groups

F_7.5aQIV+⅛MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[119]

P-value

= 0.53

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.08

Notes
[119] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (GH:M)

Statistical analysis description

To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV+½MF59 group for day 1. (G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[120]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.04

Notes
[120] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (I:M)

Statistical analysis description

To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV+½MF59 group for day 1. (I_7.5aQIV+¼MF59 : M_7.5aQIV+½MF59)

Comparison groups

I_7.5aQIV+¼MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[121]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[121] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (J:M)

Statistical analysis description

Comparison groups

J_15aQIV+¼MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[122]

P-value

= 0.071

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.07

Notes
[122] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (KL:M)

Statistical analysis description

To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV+½MF59 group for day1. (K_7.5 aTIV+ ½MF59 + L_15 aTIV+ ½MF59:M_7.5 aQIV+ ½MF59)

Comparison groups

M_7.5aQIV+½MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[123]

P-value

= 0.2

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

1.05

Notes
[123] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (N:M)

Statistical analysis description

To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV+½MF59 group for day 1. (N_15aQIV+½MF59 : M_7.5aQIV+½MF59)

Comparison groups

N_15aQIV+½MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[124]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[124] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (AB:M)

Statistical analysis description

To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV + ½MF59 group for Day 29. (A_7.5TIV+0MF59 + B_15TIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[125]

P-value

= 0.96

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.02

Notes
[125] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (C:M)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[126]

P-value

= 0.43

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.37

Notes
[126] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (D:M)

Statistical analysis description

Comparison groups

D_15QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[127]

P-value

= 0.94

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

1.05

Notes
[127] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (E:M)

Statistical analysis description

Comparison groups

E_7.5aTIV+⅛MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[128]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.32

Notes
[128] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (F:M)

Statistical analysis description

Comparison groups

F_7.5aQIV+⅛MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[129]

P-value

= 0.57

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.29

Notes
[129] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (GH:M)

Statistical analysis description

To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV + ½MF59 group for Day 29. (G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[130]

P-value

= 0.85

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.12

Notes
[130] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (I:M)

Statistical analysis description

Comparison groups

I_7.5aQIV+¼MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[131]

P-value

= 0.67

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.24

Notes
[131] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (J:M)

Statistical analysis description

Comparison groups

J_15aQIV+¼MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[132]

P-value

= 0.36

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.4

Notes
[132] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (KL:M)

Statistical analysis description

To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV + ½MF59 group for day 29. (K_7.5aTIV+½MF59 + L_15aTIV+½MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[133]

P-value

= 0.72

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.18

Notes
[133] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (N:M)

Statistical analysis description

Comparison groups

N_15aQIV+½MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[134]

P-value

= 0.15

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.52

Notes
[134] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (AB:M)

Statistical analysis description

To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV + ½MF59 group for day 50. (A_7.5TIV+0MF59 + B_15TIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[135]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.082

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

0.13

Notes
[135] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (C:M)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[136]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.086

upper limit

0.27

Notes
[136] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (D:M)

Statistical analysis description

Comparison groups

D_15QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[137]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.079

upper limit

0.24

Notes
[137] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (E:M)

Statistical analysis description

Comparison groups

M_7.5aQIV+½MF59 v E_7.5aTIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[138]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.083

upper limit

0.26

Notes
[138] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (F:M)

Statistical analysis description

Comparison groups

F_7.5aQIV+⅛MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[139]

P-value

= 0.96

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

1.08

Notes
[139] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (GH:M)

Statistical analysis description

To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV + ½MF59 group for day 50. (G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[140]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.097

upper limit

0.27

Notes
[140] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (I:M)

Statistical analysis description

Comparison groups

I_7.5aQIV+¼MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[141]

P-value

= 0.64

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.61

Notes
[141] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (J:M)

Statistical analysis description

Comparison groups

J_15aQIV+¼MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[142]

P-value

= 0.65

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

1.6

Notes
[142] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (KL:M)

Statistical analysis description

To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV + ½MF59 group for day 50. (K_7.5aTIV+½MF59 + L_15aTIV+½MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[143]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.12

upper limit

0.33

Notes
[143] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (N:M)

Statistical analysis description

Comparison groups

N_15aQIV+½MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[144]

P-value

= 0.51

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.74

Notes
[144] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

Primary: 5. Evaluating the superiority of the antibody responses in terms of GMTs to the study vaccines (combining TIV/QIV/ aTIV/aQIV of identical antigen and adjuvant dose) to that of the marketed pediatric trivalent influenza vaccine Vaxigrip (7.5μg cTIV+0MF59).

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End point title

5. Evaluating the superiority of the antibody responses in terms of GMTs to the study vaccines (combining TIV/QIV/ aTIV/aQIV of identical antigen and adjuvant dose) to that of the marketed pediatric trivalent influenza vaccine Vaxigrip (7.5μg cTIV+0MF59). ^[145]

End point description

To evaluate the superiority of the antibody responses (GMTs) to the study vaccines (combining TIV/QIV/aTIV/aQIV of identical antigen and adjuvant dose) to that of the marketed pediatric trivalent influenza vaccine Vaxigrip (7.5μg cTIV+0MF59) for A/H1N1, A/H3N2 and first B-strain. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1, Day 29 and Day 50

Notes
[145] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

End point values	Q_7.5cTIV+0MF59	A_7.5TIV+0MF59 + C_7.5QIV+0MF59	B_15TIV+0MF59 + D_15QIV+0MF59	E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59	H_15aTIV+¼MF59 + J_15aQIV+¼MF59	K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59	L_15aTIV+½MF59 + N_15aQIV+½MF59
Number of subjects analysed	26	49	49	44	44	44	49	45
Units: Titers
geometric mean (confidence interval 95%)
A/H1N1 (Day 1)	9.74 (6.37 to 15)	6.4 (4.7 to 8.72)	6.54 (4.8 to 8.91)	8.15 (5.88 to 11)	8.41 (6.07 to 12)	7.83 (5.66 to 11)	7.7 (5.65 to 10)	7.58 (5.49 to 10)
A/H1N1 (Day 29) (N=23,37,43,37,35,33,41,37)	42 (20 to 86)	14 (7.76 to 24)	12 (7.2 to 21)	109 (62 to 193)	118 (65 to 212)	149 (81 to 272)	118 (69 to 203)	220 (124 to 390)
A/H1N1 (Day 50) (N=24,37,42,36,34,33,40,36)	261 (157 to 437)	57 (37 to 85)	69 (47 to 102)	533 (351 to 810)	481 (313 to 740)	576 (372 to 892)	529 (356 to 787)	718 (473 to 1092)
A/H3N2 (Day 1)	5 (3.11 to 8.03)	7.38 (5.22 to 10)	7.22 (5.11 to 10)	7.96 (5.53 to 11)	9.54 (6.62 to 14)	6.8 (4.72 to 9.79)	8.44 (5.97 to 12)	6.6 (4.6 to 9.46)
A/H3N2 (Day 29) (N=23,37,43,37,35,33,41,37)	22 (12 to 39)	19 (12 to 30)	12 (7.52 to 18)	91 (57 to 145)	114 (71 to 184)	112 (68 to 183)	150 (96 to 232)	163 (103 to 259)
A/H3N2 Day 50) (N=24,37,42,36,34,33,40,36)	133 (83 to 211)	73 (50 to 106)	60 (42 to 86)	518 (354 to 758)	496 (335 to 734)	503 (338 to 748)	608 (423 to 872)	559 (382 to 819)
B_FL (Day 1)	5.87 (5.03 to 6.84)	5.37 (4.8 to 6)	5.29 (4.73 to 5.92)	6.23 (5.54 to 7.02)	6.33 (5.63 to 7.13)	5.16 (4.58 to 5.81)	5.8 (5.18 to 6.49)	5.48 (4.88 to 6.16)
B_FL (Day 29) (N=23,37,43,37,35,33,41,37)	11 (6.46 to 18)	8.45 (5.64 to 13)	6.74 (4.63 to 9.8)	9.37 (6.26 to 14)	13 (8.29 to 19)	8.45 (5.51 to 13)	9.59 (6.53 to 14)	18 (12 to 27)
B_FL (Day 50) (N=24,37,42,36,34,33,40,36)	24 (16 to 36)	13 (9.45 to 18)	11 (7.98 to 15)	61 (43 to 84)	61 (43 to 86)	69 (49 to 98)	81 (59 to 112)	101 (72 to 141)

A/H1N1: Day 1 (AC:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[146]

P-value

= 0.94

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

1.11

Notes
[146] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 1 (BD:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[147]

P-value

= 0.93

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.14

Notes
[147] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 1 (EF:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[148]

P-value

= 0.74

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

1.43

Notes
[148] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 1 (GI:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[149]

P-value

= 0.71

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.47

Notes
[149] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 1 (HJ:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2/B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (H_15aTIV+¼MF59 + J_15QIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[150]

P-value

= 0.79

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.37

Notes
[150] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 1 (KM:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[151]

P-value

= 0.81

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.34

Notes
[151] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 1 (LN:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[152]

P-value

= 0.82

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

1.33

Notes
[152] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (AC:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : Q_7.5 cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[153]

P-value

= 0.99

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.13

upper limit

0.83

Notes
[153] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (BD:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (B_15TIV+0MF59 + D_15QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[154]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.12

upper limit

0.72

Notes
[154] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (EF:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[155]

P-value

= 0.021

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.03

upper limit

6.56

Notes
[155] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (GI:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[156]

P-value

= 0.015

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.81

Confidence interval

level

95%

sides

2-sided

lower limit

1.11

upper limit

7.15

Notes
[156] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (HJ:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (H_15aTIV+¼MF59 + J_15QIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[157]

P-value

= 0.004

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

3.55

Confidence interval

level

95%

sides

2-sided

lower limit

1.38

upper limit

9.14

Notes
[157] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (KM:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[158]

P-value

= 0.013

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.82

Confidence interval

level

95%

sides

2-sided

lower limit

1.14

upper limit

6.98

Notes
[158] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 29 (LN:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[159]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

5.26

Confidence interval

level

95%

sides

2-sided

lower limit

2.09

upper limit

Notes
[159] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (AC:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[160]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.22

Confidence interval

level

95%

sides

2-sided

lower limit

0.11

upper limit

0.42

Notes
[160] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (BD:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (B_15TIV+0MF59 + D_15QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[161]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.14

upper limit

0.5

Notes
[161] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (EF:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[162]

P-value

= 0.017

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.04

Confidence interval

level

95%

sides

2-sided

lower limit

1.05

upper limit

3.95

Notes
[162] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (GI:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[163]

P-value

= 0.037

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

3.59

Notes
[163] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (HJ:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (H_15aTIV+¼MF59 + J_15QIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[164]

P-value

= 0.011

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.12

upper limit

4.32

Notes
[164] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (KM:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[165]

P-value

= 0.017

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.02

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

3.87

Notes
[165] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1: Day 50 (LN:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[166]

P-value

= 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.75

Confidence interval

level

95%

sides

2-sided

lower limit

1.42

upper limit

5.33

Notes
[166] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (AC:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2/B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[167]

P-value

= 0.097

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.48

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

2.65

Notes
[167] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (BD:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[168]

P-value

= 0.11

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

2.6

Notes
[168] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (EF:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for Day 1. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[169]

P-value

= 0.064

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.59

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

2.89

Notes
[169] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (GI:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (G_7.5 aTIV+¼MF59 + I_7.5aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[170]

P-value

= 0.017

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.91

Confidence interval

level

95%

sides

2-sided

lower limit

1.05

upper limit

3.47

Notes
[170] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (HJ:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[171]

P-value

= 0.16

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.36

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

2.47

Notes
[171] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (KM:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[172]

P-value

= 0.04

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

3.03

Notes
[172] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (LN:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[173]

P-value

= 0.18

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

2.39

Notes
[173] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (AC:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : Q_7.5 cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[174]

P-value

= 0.65

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

1.82

Notes
[174] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (BD:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (B_15TIV+0MF59 + D_15QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[175]

P-value

= 0.95

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.54

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

1.11

Notes
[175] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (EF:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (E_7.5 aTIV+⅛MF59 + F_7.5 aQIV+⅛MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[176]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

4.23

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

8.95

Notes
[176] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (GI:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[177]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

5.3

Confidence interval

level

95%

sides

2-sided

lower limit

2.48

upper limit

Notes
[177] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (HJ:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : Q_7.5 cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[178]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

5.19

Confidence interval

level

95%

sides

2-sided

lower limit

2.41

upper limit

Notes
[178] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (KM:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[179]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

6.93

Confidence interval

level

95%

sides

2-sided

lower limit

3.32

upper limit

Notes
[179] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 29 (LN:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[180]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

7.56

Confidence interval

level

95%

sides

2-sided

lower limit

3.57

upper limit

Notes
[180] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (AC:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2/B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[181]

P-value

= 0.97

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

Notes
[181] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (BD:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (B_15TIV+0MF59 + D_15QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[182]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.25

upper limit

0.82

Notes
[182] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (EF:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[183]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

3.91

Confidence interval

level

95%

sides

2-sided

lower limit

2.14

upper limit

7.13

Notes
[183] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (GI:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[184]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

3.74

Confidence interval

level

95%

sides

2-sided

lower limit

2.03

upper limit

6.88

Notes
[184] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (HJ:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (H_15aTIV+¼MF59 + J_15QIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[185]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

3.79

Confidence interval

level

95%

sides

2-sided

lower limit

2.05

upper limit

Notes
[185] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (KM:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[186]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

4.58

Confidence interval

level

95%

sides

2-sided

lower limit

2.54

upper limit

8.27

Notes
[186] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 50 (LN:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[187]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

4.22

Confidence interval

level

95%

sides

2-sided

lower limit

2.31

upper limit

7.71

Notes
[187] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 1 (AC:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[188]

P-value

= 0.82

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.11

Notes
[188] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 1 (BD:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[189]

P-value

= 0.86

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.09

Notes
[189] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 1 (EF:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[190]

P-value

= 0.27

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.29

Notes
[190] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 1 (GI:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[191]

P-value

= 0.22

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

1.31

Notes
[191] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 1 (HJ:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[192]

P-value

= 0.9

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.07

Notes
[192] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 1 (KM:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[193]

P-value

= 0.55

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.2

Notes
[193] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 1 (LN:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[194]

P-value

= 0.75

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.13

Notes
[194] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 29 (AC:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : Q_7.5 cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[195]

P-value

= 0.77

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

1.5

Notes
[195] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 29 (BD:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (B_15 TIV+0MF59 + D_15QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[196]

P-value

= 0.93

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

1.18

Notes
[196] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 29 (EF:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[197]

P-value

= 0.66

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

1.67

Notes
[197] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 29 (GI:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[198]

P-value

= 0.32

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

2.25

Notes
[198] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 29 (HJ:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (H_15aTIV+¼MF59 + J_15QIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[199]

P-value

= 0.76

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.53

Notes
[199] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 29 (KM:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[200]

P-value

= 0.64

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.69

Notes
[200] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 29 (LN:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[201]

P-value

= 0.064

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

3.18

Notes
[201] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 50 (AC:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2/B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[202]

P-value

= 0.99

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.54

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

0.92

Notes
[202] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 50 (BD:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (B_15TIV+0MF59 + D_15QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[203]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.45

Confidence interval

level

95%

sides

2-sided

lower limit

0.27

upper limit

0.75

Notes
[203] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 50 (EF:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[204]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.51

Confidence interval

level

95%

sides

2-sided

lower limit

1.48

upper limit

4.24

Notes
[204] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 50 (GI:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[205]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.52

Confidence interval

level

95%

sides

2-sided

lower limit

1.48

upper limit

4.29

Notes
[205] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 50 (HJ:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (H_15aTIV+¼MF59 + J_15QIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[206]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.86

Confidence interval

level

95%

sides

2-sided

lower limit

1.68

upper limit

4.89

Notes
[206] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 50 (KM:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2/B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[207]

P-value

= 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

3.37

Confidence interval

level

95%

sides

2-sided

lower limit

2.01

upper limit

5.65

Notes
[207] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 50 (LN:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strainsA/H1N1, A/H3N2, B strain (Florida), the 7.5μg and 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[208]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

4.18

Confidence interval

level

95%

sides

2-sided

lower limit

2.47

upper limit

7.07

Notes
[208] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

Primary: 6. Superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined TIV/QIV+½MF59 group.

Top of page

End point title

6. Superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined TIV/QIV+½MF59 group. ^[209]

End point description

To assess immunogenicity in terms of GMT in order to evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined TIV/QIV+½MF59 group. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1, Day 29 and Day 50

Notes
[209] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

C_7.5QIV+0MF59

D_15QIV+0MF59

Q_7.5cTIV+0MF59

E_7.5aTIV+⅛MF59

F_7.5aQIV+⅛MF59

I_7.5aQIV+¼MF59

J_15aQIV+¼MF59

M_7.5aQIV+½MF59

N_15aQIV+½MF59

A_7.5TIV+0MF59 + B_15TIV+0MF59

G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects analysed

Units: Titers

geometric mean (confidence interval 95%)

B_MY (Day 1)

5 (4.87 to 5.13)

5 (4.88 to 5.12)

5 (4.88 to 5.13)

5 (4.87 to 5.13)

5.17 (5.03 to 5.31)

5 (4.87 to 5.14)

5.15 (5.02 to 5.28)

5 (4.87 to 5.14)

5 (4.88 to 5.13)

5 (4.91 to 5.09)

5 (4.9 to 5.1)

5.07 (4.98 to 5.17)

B_MY (Day 29) (N= 17,22,23,19,18,18,18,40,32)

6.39 (5.23 to 7.8)

5 (4.19 to 5.96)

5 (4.21 to 5.94)

6.22 (5.15 to 7.52)

6.06 (4.99 to 7.37)

5.83 (4.8 to 7.09)

6.55 (5.39 to 7.96)

6.22 (5.15 to 7.52)

7.19 (6 to 8.61)

5 (4.39 to 5.7)

5.45 (4.71 to 6.31)

5.79 (5.06 to 6.62)

B_MY (Day 50) (N= 18,21,24,18,18,18,17,40,32)

11 (7.24 to 16)

9.68 (6.68 to 14)

5.37 (3.8 to 7.59)

10 (6.97 to 15)

42 (28 to 63)

63 (43 to 95)

63 (42 to 94)

70 (48 to 101)

5.74 (4.39 to 7.51)

11 (8.44 to 15)

14 (11 to 19)

B_MY: Day 1 (AB:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (A_7.5TIV+0MF59 + B_15TIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[210]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.03

Notes
[210] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (C:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (C_7.5 QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

C_7.5QIV+0MF59 v Q_7.5cTIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[211]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[211] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (D:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg /15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (D_15aQIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[212]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.03

Notes
[212] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (E:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (E_7.5aTIV+⅛MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v E_7.5aTIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[213]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[213] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (F:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (F_7.5QIV+⅛MF59 : Q_7.5cTIV+0MF59)

Comparison groups

F_7.5aQIV+⅛MF59 v Q_7.5cTIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[214]

P-value

= 0.04

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

1.07

Notes
[214] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-MY: Day 1 (GH:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[215]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.03

Notes
[215] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (I:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for Day 1. (I_7.5aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[216]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[216] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (J:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (J_15aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[217]

P-value

= 0.056

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.07

Notes
[217] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-MY: Day 1 (KL:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (K_7.5TIV+½MF59 + L_15TIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[218]

P-value

= 0.17

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

1.05

Notes
[218] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (M:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (M_7.5aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[219]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[219] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (N:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (N_15 aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[220]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.04

Notes
[220] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (AB:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (A_7.5TIV+0MF59 + B_15TIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[221]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.24

Notes
[221] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (C:Q)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v Q_7.5cTIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[222]

P-value

= 0.035

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.28

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

1.66

Notes
[222] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY:Day 29 (D:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[223]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.28

Notes
[223] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY:Day 29 (E:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v E_7.5aTIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[224]

P-value

= 0.047

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.24

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.61

Notes
[224] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (F:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the three strains A/H1N1, A/H3N2/B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (F_7.5QIV+⅛MF59 : Q_7.5cTIV+0MF59)

Comparison groups

F_7.5aQIV+⅛MF59 v Q_7.5cTIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[225]

P-value

= 0.073

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.57

Notes
[225] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (GH:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[226]

P-value

= 0.23

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.37

Notes
[226] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (I:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (I_7.5aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[227]

P-value

= 0.12

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

1.51

Notes
[227] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (J:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (J_15aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[228]

P-value

= 0.021

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.31

Confidence interval

level

95%

sides

2-sided

lower limit

1.01

upper limit

1.7

Notes
[228] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-MY: Day 29 (KL:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[229]

P-value

= 0.095

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.44

Notes
[229] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (M:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (M_7.5QIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[230]

P-value

= 0.047

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.24

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.61

Notes
[230] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29 (N:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29. (N_15 aQIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[231]

P-value

= 0.002

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

1.12

upper limit

1.85

Notes
[231] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY:Day 50 (AB:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (A_7.5TIV+0MF59 + B_15TIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[232]

P-value

= 0.38

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.66

Notes
[232] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (C:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (C_7.5 QIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

C_7.5QIV+0MF59 v Q_7.5cTIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[233]

P-value

= 0.005

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.01

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

3.41

Notes
[233] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (D:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (D_15aQIV+0MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[234]

P-value

= 0.012

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

2.99

Notes
[234] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (E:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (E_7.5aTIV+⅛MF59 : Q_7.5cTIV+0MF59)

Comparison groups

E_7.5aTIV+⅛MF59 v Q_7.5cTIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[235]

P-value

= 0.007

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.93

Confidence interval

level

95%

sides

2-sided

lower limit

1.14

upper limit

3.28

Notes
[235] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (F:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (F_7.5QIV+⅛MF59 : Q_7.5cTIV+0MF59)

Comparison groups

F_7.5aQIV+⅛MF59 v Q_7.5cTIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[236]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

7.88

Confidence interval

level

95%

sides

2-sided

lower limit

4.65

upper limit

Notes
[236] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-MY: Day 50 (GH:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[237]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.12

Confidence interval

level

95%

sides

2-sided

lower limit

1.34

upper limit

3.35

Notes
[237] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (I:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (I_7.5aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[238]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

6.97

upper limit

Notes
[238] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (J:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (J_15aQIV+¼MF59 : Q_7.5cTIV+0MF59)

Comparison groups

J_15aQIV+¼MF59 v Q_7.5cTIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[239]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

6.81

upper limit

Notes
[239] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-MY: Day 50 (KL:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (K_7.5TIV+½MF59 + L_15TIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[240]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.63

Confidence interval

level

95%

sides

2-sided

lower limit

1.68

upper limit

4.12

Notes
[240] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (M:Q)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 50. (M_7.5QIV+½MF59 : Q_7.5cTIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[241]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

7.79

upper limit

Notes
[241] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 50 (N:Q)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[242]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

7.86

upper limit

Notes
[242] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

Primary: 7. Non-inferiority of the antibody responses (GMTs) to the study vaccines (combining TIV/QIV/aTIV/aQIV of identical antigen and adjuvant dose) to that of the marketed pediatric trivalent influenza vaccine Vaxigrip (7.5μg cTIV+0MF59).

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End point title

7. Non-inferiority of the antibody responses (GMTs) to the study vaccines (combining TIV/QIV/aTIV/aQIV of identical antigen and adjuvant dose) to that of the marketed pediatric trivalent influenza vaccine Vaxigrip (7.5μg cTIV+0MF59). ^[243]

End point description

To evaluate the non-inferiority of the antibody responses (GMTs) to the study vaccines (combining TIV/QIV/aTIV/aQIV of identical antigen and adjuvant dose) to that of the marketed pediatric trivalent influenza vaccine Vaxigrip (7.5μg cTIV+0MF59) for A/H1N1, A/H3N2 and first B-strain. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1, Day 29 and Day 50

Notes
[243] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

End point values	Q_7.5cTIV+0MF59	A_7.5TIV+0MF59 + C_7.5QIV+0MF59	B_15TIV+0MF59 + D_15QIV+0MF59	E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59	H_15aTIV+¼MF59 + J_15aQIV+¼MF59	K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59	L_15aTIV+½MF59 + N_15aQIV+½MF59	O_15aTIV+fullMF59 + P_15aQIV+fullMF59
Number of subjects analysed	26	49	49	44	44	44	49	45	45
Units: Titers
geometric mean (confidence interval 95%)
A/H1N1 (Day 1)	9.74 (6.39 to 15)	6.4 (4.71 to 8.71)	6.54 (4.81 to 8.89)	8.15 (5.89 to 11)	8.41 (6.08 to 12)	7.83 (5.67 to 11)	7.7 (5.66 to 10)	7.58 (5.5 to 10)	7.4 (5.37 to 10)
A/H1N1 (Day 29/50) (N= 23,37,43,37,35,33,40,37,36)	42 (21 to 85)	14 (7.83 to 24)	12 (7.26 to 21)	109 (62 to 191)	118 (66 to 210)	149 (82 to 270)	529 (308 to 909)	220 (125 to 386)	196 (111 to 346)
A/H3N2 (Day 1)	5 (3.14 to 7.97)	7.38 (5.25 to 10)	7.22 (5.14 to 10)	7.96 (5.56 to 11)	9.54 (6.67 to 14)	6.8 (4.75 to 9.73)	8.44 (6.01 to 12)	6.6 (4.63 to 9.4)	6.7 (4.7 to 9.55)
A/H3N2 (Day 29/50) (N= 23,37,43,37,35,33,40,37,36)	22 (12 to 38)	19 (12 to 29)	12 (7.68 to 17)	91 (59 to 142)	114 (73 to 180)	112 (70 to 179)	608 (397 to 929)	163 (105 to 254)	165 (105 to 258)
B_FL (Day 1)	5.87 (5.03 to 6.84)	5.37 (4.8 to 6)	5.29 (4.73 to 5.92)	6.23 (5.54 to 7.01)	6.33 (5.63 to 7.13)	5.16 (4.59 to 5.81)	5.8 (5.19 to 6.49)	5.48 (4.88 to 6.16)	5.57 (4.96 to 6.26)
B_FL (Day 29/50) (N= 23,37,43,37,35,33,40,37,36)	11 (6.49 to 18)	8.45 (5.67 to 13)	6.74 (4.65 to 9.76)	9.37 (6.28 to 14)	13 (8.33 to 19)	8.45 (5.54 to 13)	81 (55 to 119)	18 (12 to 27)	15 (9.71 to 22)

A/H1N1: Day 1 (AC:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[244]

P-value

= 0.16

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.28

Notes
[244] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 1 (BD:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[245]

P-value

= 0.14

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

1.31

Notes
[245] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 1 (EF:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1 . (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[246]

P-value

= 0.022

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.65

Notes
[246] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 1 (GI:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[247]

P-value

= 0.016

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.71

Notes
[247] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 1 (HJ:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[248]

P-value

= 0.033

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.59

Notes
[248] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 1 (LN:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (L_15aTIV+½MF59 + N_15 aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[249]

P-value

= 0.044

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.53

Notes
[249] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 1 (OP:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (O_15aTIV+fullMF59 + P_15aQIV+fullMF59 : K_7.5aTIV+½MF59+M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v O_15aTIV+fullMF59 + P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[250]

P-value

= 0.055

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

1.5

Notes
[250] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 1 (Q:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (Q_7.5cTIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[251]

P-value

= 0.009

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

2.13

Notes
[251] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 29/Day 50 (AC:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[252]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.026

Confidence interval

level

95%

sides

2-sided

lower limit

0.012

upper limit

0.057

Notes
[252] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 29/Day 50 (BD:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[253]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.023

Confidence interval

level

95%

sides

2-sided

lower limit

0.011

upper limit

0.049

Notes
[253] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 29/Day 50 (EF:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (E_7.5 aTIV+⅛MF59 + F_7.5 aQIV+⅛ MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[254]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.094

upper limit

0.45

Notes
[254] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 29/Day 50 (GI:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[255]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.22

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.49

Notes
[255] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 29/Day 50 (HJ:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50 . (H_15 aTIV+¼MF59 + J_15 aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[256]

P-value

= 0.98

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.28

Confidence interval

level

95%

sides

2-sided

lower limit

0.13

upper limit

0.63

Notes
[256] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 29/Day 50 (LN:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2/B strain (Florida), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for Day 29/Day 50 . (L_15aTIV+½MF59 + N_15 aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[257]

P-value

= 0.88

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.42

Confidence interval

level

95%

sides

2-sided

lower limit

0.19

upper limit

0.91

Notes
[257] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 29/Day 50 (OP:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (O_15aTIV+fullMF59 + P_15 aQIV+fullMF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v O_15aTIV+fullMF59 + P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[258]

P-value

= 0.93

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.37

Confidence interval

level

95%

sides

2-sided

lower limit

0.17

upper limit

0.81

Notes
[258] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 29/Day 50 (Q:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (Q_7.5 cTIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[259]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.079

Confidence interval

level

95%

sides

2-sided

lower limit

0.032

upper limit

0.19

Notes
[259] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (AC:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[260]

P-value

= 0.14

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.41

Notes
[260] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (BD:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (B_15 TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[261]

P-value

= 0.16

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.38

Notes
[261] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (EF:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (E_7.5 aTIV+⅛MF59 + F_7.5 aQIV+⅛ MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[262]

P-value

= 0.087

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

1.54

Notes
[262] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (GI:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[263]

P-value

= 0.019

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.85

Notes
[263] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (HJ:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[264]

P-value

= 0.23

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

1.32

Notes
[264] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (LN:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (L_15aTIV+½MF59 + N_15 aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

H_15aTIV+¼MF59 + J_15aQIV+¼MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[265]

P-value

= 0.27

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

1.28

Notes
[265] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (OP:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (O_15aTIV+fullMF59 + P_15 aQIV+fullMF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v O_15aTIV+fullMF59 + P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[266]

P-value

= 0.25

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

1.3

Notes
[266] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (Q:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (Q_7.5cTIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[267]

P-value

= 0.66

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.59

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

1.05

Notes
[267] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29/Day 50 (AC:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[268]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.031

Confidence interval

level

95%

sides

2-sided

lower limit

0.017

upper limit

0.056

Notes
[268] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29/Day 50 (BD:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the non adjuvanted 7.5μg cTIV for Day 29/Day 50 . (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[269]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.019

Confidence interval

level

95%

sides

2-sided

lower limit

0.011

upper limit

0.034

Notes
[269] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29/Day 50 (EF:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛ MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[270]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.081

upper limit

0.28

Notes
[270] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29/Day 50 (GI:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[271]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.19

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.35

Notes
[271] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29/Day 50 (HJ:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (H_15 aTIV + ¼MF59 + J_15 aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[272]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.098

upper limit

0.35

Notes
[272] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29/Day 50 (LN:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[273]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.15

upper limit

0.5

Notes
[273] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29/Day 50 (OP:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (O_15aTIV+fullMF59 + P_15aQIV+fullMF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v O_15aTIV+fullMF59 + P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[274]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.15

upper limit

0.5

Notes
[274] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29/Day 50 (Q:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (Q_7.5cTIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[275]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.035

Confidence interval

level

95%

sides

2-sided

lower limit

0.018

upper limit

0.072

Notes
[275] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (AC:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[276]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.08

Notes
[276] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (BD:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (B_15 TIV+ 0MF59 + D_15QIV+0MF59:K_7.5aTIV+½MF59+M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[277]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.07

Notes
[277] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (EF:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛ MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[278]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

1.26

Notes
[278] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (GI:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[279]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.28

Notes
[279] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (HJ:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (H_15 aTIV + ¼MF59+J_15 aQIV +¼MF59:K_7.5aTIV+½MF59+M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[280]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.05

Notes
[280] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (LN:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[281]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.11

Notes
[281] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (OP:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (O_15aTIV+fullMF59 + P_15aQIV+fullMF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v O_15aTIV+fullMF59 + P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[282]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.13

Notes
[282] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (Q:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 1. (Q_7.5cTIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[283]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.22

Notes
[283] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29/Day 50 (AC:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (A_7.5TIV+0MF59 + C_7.5QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[284]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

0.18

Notes
[284] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29/Day 50 (BD:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (B_15TIV+0MF59 + D_15QIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v B_15TIV+0MF59 + D_15QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[285]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.083

Confidence interval

level

95%

sides

2-sided

lower limit

0.049

upper limit

0.14

Notes
[285] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29/Day 50 (EF:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛ MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[286]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.066

upper limit

0.2

Notes
[286] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29/Day 50 (GI:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[287]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.15

Confidence interval

level

95%

sides

2-sided

lower limit

0.088

upper limit

0.27

Notes
[287] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29/Day 50 (HJ:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[288]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.059

upper limit

0.18

Notes
[288] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29/Day 50 (LN:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[289]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.22

Confidence interval

level

95%

sides

2-sided

lower limit

0.13

upper limit

0.38

Notes
[289] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29/Day 50 (OP:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (O_15aTIV+fullMF59 + P_15aQIV+fullMF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 v O_15aTIV+fullMF59 + P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[290]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.31

Notes
[290] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29/Day 50 (Q:KM)

Statistical analysis description

To evaluate the non-inferiority of GMTs against the three strains A/H1N1, A/H3N2, B strain (Florida), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content was pooled and compared with the non adjuvanted 7.5μg cTIV for day 29/day 50. (Q_7.5cTIV+0MF59 : K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59)

Comparison groups

Q_7.5cTIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[291]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.07

upper limit

0.25

Notes
[291] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

Primary: 8. Non-inferiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined TIV/QIV + ½MF59 group.

Top of page

End point title

8. Non-inferiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined TIV/QIV + ½MF59 group. ^[292]

End point description

To evaluate the non-inferiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined TIV/QIV + ½MF59 group. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1, Day 29 and Day 50

Notes
[292] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

C_7.5QIV+0MF59

D_15QIV+0MF59

Q_7.5cTIV+0MF59

E_7.5aTIV+⅛MF59

F_7.5aQIV+⅛MF59

I_7.5aQIV+¼MF59

J_15aQIV+¼MF59

M_7.5aQIV+½MF59

N_15aQIV+½MF59

O_15aTIV+fullMF59

P_15aQIV+fullMF59

A_7.5TIV+0MF59 + B_15TIV+0MF59

G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects analysed

Units: Titers

geometric mean (confidence interval 95%)

B_MY (Day 1)

5 (4.86 to 5.14)

5 (4.87 to 5.13)

5 (4.87 to 5.14)

5 (4.86 to 5.14)

5.17 (5.02 to 5.32)

5 (4.86 to 5.15)

5.15 (5 to 5.29)

5 (4.86 to 5.15)

5 (4.87 to 5.14)

5 (4.86 to 5.14)

5.17 (5.02 to 5.32)

5 (4.9 to 5.1)

5 (4.9 to 5.11)

5.07 (4.97 to 5.18)

B_MY (Day 29/50)

6.39 (4.81 to 8.47)

5 (3.9 to 6.41)

5 (3.92 to 6.38)

6.22 (4.76 to 8.13)

6.06 (4.61 to 7.98)

5.83 (4.43 to 7.68)

6.55 (4.97 to 8.62)

70 (54 to 92)

7.19 (5.57 to 9.27)

5.4 (4.1 to 7.11)

11 (8.36 to 14)

5 (4.16 to 6.01)

5.45 (4.44 to 6.7)

5.79 (4.79 to 6.99)

B_MY: Day 1 (AB:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 1. (A_7.5TIV+0MF59 + B_15TIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[293]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.04

Notes
[293] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (C:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 1. (C_7.5QIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

C_7.5QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[294]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[294] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (D:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 1. (D_15QIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

D_15QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[295]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[295] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (E:M)

Statistical analysis description

Comparison groups

M_7.5aQIV+½MF59 v E_7.5aTIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[296]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[296] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (F:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 1. (F_7.5aQIV+⅛ MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[297]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.08

Notes
[297] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (GH:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 1. (G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[298]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[298] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (I:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 1. (I_7.5aQIV+¼MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[299]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[299] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (J:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 1. (J_15aQIV+¼MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[300]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.07

Notes
[300] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (KL:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 1. (K_7.5aTIV+½MF59 + L_15aTIV+½MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[301]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

1.05

Notes
[301] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (N:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 1. (N_15aQIV+½MF59 : M_7.5aQIV+½MF59)

Comparison groups

N_15aQIV+½MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[302]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[302] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (O:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 1. (O_15aTIV+fullMF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v O_15aTIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[303]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[303] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (P:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 1. (P_15aQIV+fullMF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[304]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.08

Notes
[304] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (Q:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 1. (Q_7.5cTIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v Q_7.5cTIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[305]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[305] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day50 (AB:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 29/Day50. (A_7.5TIV+0MF59 + B_15TIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[306]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.071

Confidence interval

level

95%

sides

2-sided

lower limit

0.051

upper limit

0.098

Notes
[306] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (C:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 29/Day 50. (C_7.5QIV+0MF59 : M_7.5 aQIV+½MF59)

Comparison groups

C_7.5QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[307]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.091

Confidence interval

level

95%

sides

2-sided

lower limit

0.061

upper limit

0.13

Notes
[307] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (D:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 29/Day 50. (D_15QIV+0MF59 : M_7.5aQIV+½MF59)

Comparison groups

D_15QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[308]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.071

Confidence interval

level

95%

sides

2-sided

lower limit

0.049

upper limit

0.1

Notes
[308] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (E:M)

Statistical analysis description

Comparison groups

M_7.5aQIV+½MF59 v E_7.5aTIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[309]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.088

Confidence interval

level

95%

sides

2-sided

lower limit

0.061

upper limit

0.13

Notes
[309] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (F:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 29/Day 50. (F_7.5aQIV+⅛ MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[310]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.086

Confidence interval

level

95%

sides

2-sided

lower limit

0.059

upper limit

0.13

Notes
[310] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (GH:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 29/Day 50. (G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[311]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.077

Confidence interval

level

95%

sides

2-sided

lower limit

0.055

upper limit

0.11

Notes
[311] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (I:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 29/Day 50. (I_7.5aQIV+¼MF59 : M_7.5aQIV+½MF59)

Comparison groups

M_7.5aQIV+½MF59 v I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[312]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.083

Confidence interval

level

95%

sides

2-sided

lower limit

0.056

upper limit

0.12

Notes
[312] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (J:M)

Statistical analysis description

Comparison groups

M_7.5aQIV+½MF59 v J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[313]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.093

Confidence interval

level

95%

sides

2-sided

lower limit

0.063

upper limit

0.14

Notes
[313] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (KL:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 29/Day 50. (K_7.5 aTIV+½MF59 + L_15 aTIV+ ½MF59:M_7.5 aQIV+ ½MF59)

Comparison groups

M_7.5aQIV+½MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[314]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.082

Confidence interval

level

95%

sides

2-sided

lower limit

0.059

upper limit

0.11

Notes
[314] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (N:M)

Statistical analysis description

Comparison groups

N_15aQIV+½MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[315]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.071

upper limit

0.15

Notes
[315] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (O:M)

Statistical analysis description

Comparison groups

M_7.5aQIV+½MF59 v O_15aTIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[316]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.077

Confidence interval

level

95%

sides

2-sided

lower limit

0.052

upper limit

0.11

Notes
[316] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (P:M)

Statistical analysis description

To evaluate the Non-inferiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content were pooled and compared with the half adjuvanted 7.5μg aQIV for Day 29/Day 50. (P_15 aQIV+ fullMF59:M_7.5 aQIV+ ½MF59)

Comparison groups

M_7.5aQIV+½MF59 v P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[317]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.11

upper limit

0.23

Notes
[317] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (Q:M)

Statistical analysis description

Comparison groups

M_7.5aQIV+½MF59 v Q_7.5cTIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[318]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.071

Confidence interval

level

95%

sides

2-sided

lower limit

0.049

upper limit

0.1

Notes
[318] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

Primary: 9. Assessing Geometric Mean Titer (GMTs) to Compare the nonadjuvanted pediatric vaccine (7.5 TIV/QIV+0MF59) non adjuvanted vaccine.

Top of page

End point title

9. Assessing Geometric Mean Titer (GMTs) to Compare the nonadjuvanted pediatric vaccine (7.5 TIV/QIV+0MF59) non adjuvanted vaccine. ^[319]

End point description

To evaluate immunogenicity in terms of GMT if any of the vaccine groups could induce antibody titers after one vaccination that were non-inferior to the antibody titers after two 7.5μg TIV/QIV+0MF59 vaccinations, the GMTs at day 29 of the vaccine group combinations were compared with those at day 50 in the 7.5μg TIV/QIV+ 0MF59 group for three strains. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1 and Day 29/50

Notes
[319] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

End point values	Q_7.5cTIV+0MF59	A_7.5TIV+0MF59 + C_7.5QIV+0MF59	B_15TIV+0MF59 + D_15QIV+0MF59	E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59	H_15aTIV+¼MF59 + J_15aQIV+¼MF59	K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59	L_15aTIV+½MF59 + N_15aQIV+½MF59	O_15aTIV+fullMF59 + P_15aQIV+fullMF59
Number of subjects analysed	26	49	49	44	44	44	49	44	45
Units: Titers
geometric mean (confidence interval 95%)
A/H1N1 (Day 1)	9.74 (6.39 to 15)	6.4 (4.71 to 8.71)	6.54 (4.81 to 8.89)	8.15 (5.89 to 11)	8.41 (6.08 to 12)	7.83 (5.67 to 11)	7.7 (5.66 to 10)	7.58 (5.5 to 10)	7.4 (5.37 to 10)
A/H1N1 (Day29/Day50)(N=23,37,43,37,35,33,41,37,36)	42 (21 to 85)	14 (7.38 to 24)	12 (7.2 to 21)	109 (62 to 193)	118 (65 to 212)	149 (81 to 272)	118 (69 to 203)	220 (124 to 389)	196 (110 to 349)
A/H3N2 (Day 1)	5 (3.14 to 7.97)	7.38 (5.25 to 10)	7.22 (5.14 to 10)	7.96 (5.56 to 11)	9.54 (6.67 to 14)	6.8 (4.75 to 9.73)	8.44 (6.01 to 12)	6.6 (4.63 to 9.4)	6.7 (4.7 to 9.55)
A/H3N2 (Day29/Day50)(N=23,37,43,37,35,33,41,37,36)	22 (12 to 39)	19 (12 to 29)	12 (7.56 to 18)	91 (58 to 144)	114 (71 to 183)	112 (69 to 182)	150 (97 to 231)	163 (103 to 258)	165 (104 to 262)
B_FL (Day 1)	5.87 (5.03 to 6.84)	5.37 (4.8 to 6)	6.74 (4.6 to 9.87)	6.23 (5.54 to 7.01)	6.33 (5.63 to 7.13)	5.16 (4.59 to 5.81)	5.8 (5.19 to 6.49)	5.48 (4.88 to 6.16)	5.57 (4.96 to 6.26)
B_FL (Day29/Day50) (N=23,37,43,37,35,33,41,37,36)	11 (6.49 to 18)	8.45 (5.67 to 13)	5.29 (4.73 to 5.92)	9.37 (6.2 to 14)	13 (8.22 to 19)	8.45 (5.47 to 13)	9.59 (6.48 to 14)	18 (12 to 27)	15 (9.59 to 22)

A/H1N1:Day 1 (BD:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen and 15μg/antigen adjuvanted aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+ QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (B_15TIV+0MF59 + D_15QIV+0MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[320]

P-value

= 0.028

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

1.58

Notes
[320] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1:Day 1 (EF:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[321]

P-value

= 0.002

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.99

Notes
[321] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1:Day 1 (GI:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[322]

P-value

= 0.002

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.31

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

2.05

Notes
[322] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 1 (HJ:AC)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[323]

P-value

= 0.004

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.22

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.91

Notes
[323] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 1 (KM:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[324]

P-value

= 0.004

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.86

Notes
[324] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1:Day 1 (LN:AC)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (L_15aTIV+½MF59 + N_15 aQIV+½MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[325]

P-value

= 0.006

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.84

Notes
[325] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1:Day 1 (OP:AC)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (O_15aTIV+fullMF59 + P_15aQIV+fullMF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

O_15aTIV+fullMF59 + P_15aQIV+fullMF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[326]

P-value

= 0.008

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.8

Notes
[326] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1:Day 1 (Q:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted cTIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (Q_7.5cTIV+0MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[327]

P-value

= 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.52

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

2.56

Notes
[327] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1:Day 29/Day 50 (BD:AC)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen adjuvanted TIV+QIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (B_15TIV+0MF59 + D_15QIV+0MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[328]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.22

Confidence interval

level

95%

sides

2-sided

lower limit

0.099

upper limit

0.47

Notes
[328] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1:Day 29/Day 50 (EF:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted TIV+QIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[329]

P-value

= 0.005

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

4.32

Notes
[329] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1: Day 29/Day 50 (GI:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : A_7.5TIV+0MF59+C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[330]

P-value

= 0.003

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

4.72

Notes
[330] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1:Day 29/Day 50 (HJ:AC)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : A_7.5TIV+0MF59+C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[331]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.63

Confidence interval

level

95%

sides

2-sided

lower limit

1.14

upper limit

6.03

Notes
[331] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1:Day 29/Day 50 (KM:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[332]

P-value

= 0.002

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

4.59

Notes
[332] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1:Day 29/Day 50 (LN:AC)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[333]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

3.89

Confidence interval

level

95%

sides

2-sided

lower limit

1.74

upper limit

8.72

Notes
[333] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1:Day 29/Day 50 (OP:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7μg/antigen and 15μg/antigen adjuvanted aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+ QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on Day 29/Day 50. (O_15 aTIV+fullMF59 + P_15 aQIV+fullMF59:A_7.5 TIV+0MF59 + C_7.5 QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v O_15aTIV+fullMF59 + P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[334]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

3.46

Confidence interval

level

95%

sides

2-sided

lower limit

1.54

upper limit

7.8

Notes
[334] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H1N1:Day 29/Day 50 (Q:AC)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen adjuvanted cTIV to that of 2 doses of nonadjuvanted 7.5μg/antigen TIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (Q_7.5cTIV+0MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[335]

P-value

= 0.42

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

1.86

Notes
[335] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2 : Day 1 (BD:AC)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen adjuvanted TIV+QIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (B_15TIV+0MF59 + D_15QIV+0MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[336]

P-value

= 0.061

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

1.58

Notes
[336] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (EF:AC)

Statistical analysis description

Comparison groups

E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[337]

P-value

= 0.029

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

1.77

Notes
[337] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (GI:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[338]

P-value

= 0.005

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

2.12

Notes
[338] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2:Day 1 (HJ:AC)

Statistical analysis description

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[339]

P-value

= 0.1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

1.51

Notes
[339] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2:Day 1 (KM:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[340]

P-value

= 0.015

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.85

Notes
[340] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (LN:AC)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[341]

P-value

= 0.12

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

1.46

Notes
[341] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 1 (OP:AC)

Statistical analysis description

Non-inferiority of study vaccine of 15μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (O_15aTIV+fullMF59 + P_15aQIV+fullMF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v O_15aTIV+fullMF59 + P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[342]

P-value

= 0.11

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

1.48

Notes
[342] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2:Day 1 (Q:AC)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[343]

P-value

= 0.48

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.68

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

1.21

Notes
[343] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2: Day 29/Day 50 (BD:AC)

Statistical analysis description

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[344]

P-value

= 1

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.085

upper limit

0.3

Notes
[344] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2:Day 29/Day 50 (EF:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/50. (E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[345]

P-value

= 0.029

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.25

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

2.39

Notes
[345] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2:Day 29/Day 50 (GI:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/50. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[346]

P-value

= 0.006

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.57

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

3.03

Notes
[346] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2:Day 29/Day 50 (HJ:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[347]

P-value

< 0.007

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.54

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

2.99

Notes
[347] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2:Day 29/Day 50 (KM:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[348]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.05

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

3.86

Notes
[348] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2:Day 29/Day 50 (LN:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[349]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.24

Confidence interval

level

95%

sides

2-sided

lower limit

1.17

upper limit

4.28

Notes
[349] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2:Day 29/Day 50 (OP:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (O_15aTIV+fullMF59 + P_15aQIV+fullMF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v O_15aTIV+fullMF59 + P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[350]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.26

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

4.34

Notes
[350] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

A/H3N2:Day 29/Day 50 (Q:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (Q_7.5cTIV+0MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[351]

P-value

= 0.98

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.14

upper limit

0.62

Notes
[351] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL:Day 1 (BD:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (B_15TIV+0MF59 + D_15QIV+0MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[352]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.15

Notes
[352] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL:Day 1 (EF:AC)

Statistical analysis description

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[353]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.37

Notes
[353] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL:Day 1 (GI:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[354]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.18

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

1.39

Notes
[354] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL:Day 1 (HJ:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[355]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.13

Notes
[355] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (KM:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[356]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.27

Notes
[356] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (LN:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 1. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[357]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.2

Notes
[357] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL:Day 1 (OP:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7μg/antigen and 15μg/antigen adjuvanted aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+ QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on Day 1. (O_15 aTIV+fullMF59 + P_15 aQIV+fullMF59:A_7.5 TIV+0MF59 + C_7.5 QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v O_15aTIV+fullMF59 + P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[358]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.22

Notes
[358] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 1 (Q:AC)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[359]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

1.32

Notes
[359] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29/Day 50 (BD:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (B_15TIV+0MF59 + D_15QIV+MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

B_15TIV+0MF59 + D_15QIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[360]

P-value

= 0.82

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.51

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

0.9

Notes
[360] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL:Day 29/Day 50 (EF:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7μg/antigen and 15μg/antigen adjuvanted aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+ QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on Day 29/Day 50. (E_7.5 aTIV+⅛MF59 + F_7.5 aQIV+⅛MF59:A_7.5 TIV + 0MF59 + C_7.5 QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[361]

P-value

= 0.42

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.28

Notes
[361] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL:Day 29/Day 50 (GI:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[362]

P-value

= 0.12

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.73

Notes
[362] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL:Day 29/Day 50 (HJ:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (H_15aTIV+¼MF59 + J_15aQIV+¼MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v H_15aTIV+¼MF59 + J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[363]

P-value

= 0.55

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.35

upper limit

1.17

Notes
[363] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL:Day 29/Day 50 (KM:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[364]

P-value

= 0.38

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

1.29

Notes
[364] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29/Day 50 (LN:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (L_15aTIV+½MF59 + N_15aQIV+½MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v L_15aTIV+½MF59 + N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[365]

P-value

= 0.009

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.36

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

2.44

Notes
[365] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL:Day 29/Day 50 (OP:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (O_15aTIV+fullMF59 + P_15aQIV+fullMF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

A_7.5TIV+0MF59 + C_7.5QIV+0MF59 v O_15aTIV+fullMF59 + P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[366]

P-value

= 0.046

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

1.99

Notes
[366] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_FL: Day 29/Day 50 (Q:AC)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen adjuvanted aTIV+aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigenTIV+QIV, for the three strains A/H1N1,A/H3N2 and B/Florida (B_FL) on day 29/day 50. (Q_7.5cTIV+0MF59 : A_7.5TIV+0MF59 + C_7.5QIV+0MF59)

Comparison groups

Q_7.5cTIV+0MF59 v A_7.5TIV+0MF59 + C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[367]

P-value

= 0.27

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

1.6

Notes
[367] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

Primary: 10. Assessing Geometric Mean Titers (GMTs) to evaluate non-inferior antibody responses to the second influenza B strain when compared with two 7.5μg QIV+0MF59 vaccinations.

Top of page

End point title

10. Assessing Geometric Mean Titers (GMTs) to evaluate non-inferior antibody responses to the second influenza B strain when compared with two 7.5μg QIV+0MF59 vaccinations. ^[368]

End point description

To assess immunogenicity in terms of GMT in order to evaluate non-inferior antibody responses to the second influenza B strain when compared with two 7.5μg QIV+0MF59 vaccinations, GMTs at day 29 from the other groups were compared with those at day 50 from 7.5μg QIV+0MF59 strains. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1 and Day 29/50

Notes
[368] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

C_7.5QIV+0MF59

D_15QIV+0MF59

Q_7.5cTIV+0MF59

E_7.5aTIV+⅛MF59

F_7.5aQIV+⅛MF59

I_7.5aQIV+¼MF59

J_15aQIV+¼MF59

M_7.5aQIV+½MF59

N_15aQIV+½MF59

O_15aTIV+fullMF59

P_15aQIV+fullMF59

A_7.5TIV+0MF59 + B_15TIV+0MF59

G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects analysed

Units: Titers

geometric mean (confidence interval 95%)

5 (4.86 to 5.14)

5 (4.87 to 5.13)

5 (4.87 to 5.14)

5 (4.86 to 5.14)

5.17 (5.02 to 5.32)

5 (4.86 to 5.15)

5.15 (5 to 5.29)

5 (4.86 to 5.15)

5 (4.87 to 5.14)

5 (4.86 to 5.14)

5.17 (5.02 to 5.32)

5 (4.9 to 5.11)

5.07 (4.97 to 5.18)

D29/50(N=18,22,23,19,18,18,18,19,21,18,18,40,32,38

11 (8.26 to 14)

5 (3.92 to 6.37)

5 (3.95 to 6.34)

6.22 (4.8 to 8.08)

6.06 (4.64 to 7.92)

5.83 (4.46 to 7.62)

6.55 (5.01 to 8.56)

6.22 (4.8 to 8.08)

7.19 (5.61 to 9.21)

5.4 (4.13 to 7.06)

11 (8.42 to 14)

5.74 (4.32 to 7.64)

5.45 (4.46 to 6.67)

5.79 (4.81 to 6.96)

B_MY: Day 1 (AB:C)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen and 15μg/antigen adjuvanted aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigen QIV, for strains B_Malaysia (B_MY) on Day 1. (A_7.5TIV+0MF59 + B_15TIV+0MF59 : C_7.5QIV+0MF59)

Comparison groups

C_7.5QIV+0MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[369]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.04

Notes
[369] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (D:C)

Statistical analysis description

Non-inferiority of study vaccine of 7.5μg/antigen and 15μg/antigen adjuvanted aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigen QIV, for strains B_Malaysia (B_MY) on day 1. (D_15QIV+0MF59 : C_7.5QIV+0MF59)

Comparison groups

D_15QIV+0MF59 v C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[370]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[370] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (E:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v E_7.5aTIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[371]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[371] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (F:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[372]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.08

Notes
[372] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (GH:C)

Statistical analysis description

Non-inferiority of study vaccine of 7μg/antigen and 15μg/antigen adjuvanted aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigen QIV, for strains B_Malaysia (B_MY) on day 1. (G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59 : C_7.5QIV+0MF59)

Comparison groups

C_7.5QIV+0MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[373]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.04

Notes
[373] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (I:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[374]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[374] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (J:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[375]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.07

Notes
[375] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (KL:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[376]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

1.05

Notes
[376] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (M:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[377]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[377] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (N:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[378]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[378] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (O:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v O_15aTIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[379]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[379] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (P:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[380]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.08

Notes
[380] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 1 (Q:C)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[381]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[381] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (AB:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[382]

P-value

= 0.99

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

0.64

Notes
[382] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (D:C)

Statistical analysis description

Comparison groups

D_15QIV+0MF59 v C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[383]

P-value

= 0.98

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

0.66

Notes
[383] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (E:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v E_7.5aTIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[384]

P-value

= 0.79

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.58

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

0.84

Notes
[384] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (F:C)

Statistical analysis description

Non-inferiority of study vaccine of 7μg/antigen and 15μg/antigen adjuvanted aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigen QIV, for strains B_Malaysia (B_MY) on Day 29/Day 50. (F_7.5 aQIV+⅛MF59:C_7.5 QIV + 0MF59)

Comparison groups

F_7.5aQIV+⅛MF59 v C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[385]

P-value

= 0.82

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

0.82

Notes
[385] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (GH:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[386]

P-value

= 0.95

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

0.71

Notes
[386] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (I:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v I_7.5aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[387]

P-value

= 0.87

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.54

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

0.79

Notes
[387] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (J:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v J_15aQIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[388]

P-value

= 0.7

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

0.89

Notes
[388] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (KL:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[389]

P-value

= 0.91

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.54

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

0.74

Notes
[389] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (M:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v M_7.5aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[390]

P-value

= 0.79

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.58

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

0.84

Notes
[390] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (N:C)

Statistical analysis description

NoNon-inferiority of study vaccine of 7.5μg/antigen and 15μg/antigen adjuvanted aQIV to that of 2 doses of nonadjuvanted 7.5μg/antigen QIV, for strains B_Malaysia (B_MY) on day 29/day 50. (N_15aQIV+½MF59 : C_7.5QIV+0MF59)

Comparison groups

C_7.5QIV+0MF59 v N_15aQIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[391]

P-value

= 0.51

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

0.96

Notes
[391] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (O:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v O_15aTIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[392]

P-value

= 0.94

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

0.73

Notes
[392] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (P:C)

Statistical analysis description

Comparison groups

C_7.5QIV+0MF59 v P_15aQIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[393]

P-value

= 0.015

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.49

Notes
[393] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

B_MY: Day 29/Day 50 (Q:C)

Statistical analysis description

Comparison groups

Q_7.5cTIV+0MF59 v C_7.5QIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[394]

P-value

= 0.98

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

0.66

Notes
[394] - Non-inferiority was to be shown if the lower margin of the 95% confidence interval (CI) was >0.67.

Primary: 11. Assessing Geometric Mean Titer (GMTs) to evaluate whether the addition of a second influenza B strain (Malaysia) to a TIV (QIV) increases the antibody responses to this influenza B strain.

Top of page

End point title

11. Assessing Geometric Mean Titer (GMTs) to evaluate whether the addition of a second influenza B strain (Malaysia) to a TIV (QIV) increases the antibody responses to this influenza B strain. ^[395]

End point description

To assess immunogenicity in terms of GMT in order to evaluate if the second influenza B strain (Malaysia) is immunogenic in QIV, antibody responses to B/Malaysia induced by QIV were assessed for superiority to those of TIV at day 29 (for groups that only received one vaccination [i.e., formulated with full MF59]) or at day 50 (for groups that received two vaccinations). The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1, Day 29/Day 50

Notes
[395] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

C_7.5QIV+0MF59

D_15QIV+0MF59

E_7.5aTIV+⅛MF59

F_7.5aQIV+⅛MF59

I_7.5aQIV+¼MF59

J_15aQIV+¼MF59

M_7.5aQIV+½MF59

N_15aQIV+½MF59

O_15aTIV+fullMF59

P_15aQIV+fullMF59

A_7.5TIV+0MF59 + B_15TIV+0MF59

G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects analysed

Units: Titers

geometric mean (confidence interval 95%)

B_MY (Day 1)

5 (4.86 to 5.15)

5 (4.87 to 5.14)

5 (4.85 to 5.15)

5.17 (5.01 to 5.33)

5 (4.85 to 5.15)

5.15 (5 to 5.3)

5 (4.85 to 5.15)

5 (4.86 to 5.14)

5 (4.86 to 5.15)

5.17 (5.01 to 5.33)

5 (4.9 to 5.11)

5 (4.89 to 5.11)

5.07 (4.97 to 5.18)

B_MY (Day 29/50) (N=18,21,18,18,18,17,19,21,22,18)

11 (7.06 to 17)

9.68 (6.53 to 14)

10 (6.8 to 16)

42 (28 to 65)

63 (42 to 97)

63 (40 to 97)

70 (47 to 106)

70 (47 to 104)

5.33 (3.63 to 7.82)

11 (7.2 to 17)

5.74 (4.32 to 7.64)

11 (8.28 to 16)

14 (10 to 19)

B_MY: Day 1 (C:AB)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 1. (C_7.5QIV+0MF59:A_7.5TIV +0MF59 + B_15TIV+0MF59)

Comparison groups

C_7.5QIV+0MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[396]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[396] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (D:AB)

Statistical analysis description

Comparison groups

D_15QIV+0MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[397]

P-value

= 0.5

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.03

Notes
[397] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (F:E)

Statistical analysis description

Comparison groups

E_7.5aTIV+⅛MF59 v F_7.5aQIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[398]

P-value

= 0.065

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.08

Notes
[398] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (I:GH)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day1. (I_7.5 aQIV+ ¼MF59:G_7.5 aTIV+ ¼MF59 + H_15 aTIV + ¼MF59)

Comparison groups

I_7.5aQIV+¼MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[399]

P-value

= 0.065

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.04

Notes
[399] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (J:GH)

Statistical analysis description

Comparison groups

J_15aQIV+¼MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[400]

P-value

= 0.059

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.07

Notes
[400] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (M:KL)

Statistical analysis description

Comparison groups

M_7.5aQIV+½MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[401]

P-value

= 0.79

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

1.02

Notes
[401] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (N:KL)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15μg TIV for Day 1. (N_15 aQIV + ½MF59:K_7.5 aTIV+ ½MF59 + L_15 aTIV+ ½MF59)

Comparison groups

N_15aQIV+½MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[402]

P-value

= 0.8

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

1.02

Notes
[402] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 1 (P:O)

Statistical analysis description

Comparison groups

P_15aQIV+fullMF59 v O_15aTIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[403]

P-value

= 0.063

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

1.08

Notes
[403] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29/Day 50 (C:AB)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 29/Day 50 . (C_7.5QIV+0MF59:A_7.5TIV +0MF59 + B_15TIV+0MF59)

Comparison groups

C_7.5QIV+0MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[404]

P-value

= 0.008

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.88

Confidence interval

level

95%

sides

2-sided

lower limit

1.13

upper limit

3.14

Notes
[404] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29/Day 50 (D:AB)

Statistical analysis description

Comparison groups

D_15QIV+0MF59 v A_7.5TIV+0MF59 + B_15TIV+0MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[405]

P-value

= 0.018

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.68

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

2.74

Notes
[405] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29/Day 50 (F:E)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 29/Day 50. (F_7.5 aQIV+ ⅛MF59:E_7.5 aTIV+ ⅛MF59)

Comparison groups

F_7.5aQIV+⅛MF59 v E_7.5aTIV+⅛MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[406]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

4.08

Confidence interval

level

95%

sides

2-sided

lower limit

2.23

upper limit

7.43

Notes
[406] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29/Day 50 (I:GH)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 29/Day 50. (I_7.5 aQIV+ ¼MF59:G_7.5 aTIV+ ¼MF59 + H_15 aTIV + ¼MF59)

Comparison groups

I_7.5aQIV+¼MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[407]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

5.58

Confidence interval

level

95%

sides

2-sided

lower limit

3.28

upper limit

9.48

Notes
[407] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29/Day 50 (J:GH)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 29/Day 50 . (J_15 aQIV + ¼MF59:G_7.5 aTIV+ ¼MF59 + H_15 aTIV + ¼MF59)

Comparison groups

J_15aQIV+¼MF59 v G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[408]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

5.5

Confidence interval

level

95%

sides

2-sided

lower limit

3.2

upper limit

9.45

Notes
[408] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29/Day 50 (M:KL)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 29/Day 50. (M_7.5 aQIV+ ½MF59:K_7.5 aTIV+ ½MF59 + L_15 aTIV+ ½MF59)

Comparison groups

M_7.5aQIV+½MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[409]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

4.98

Confidence interval

level

95%

sides

2-sided

lower limit

2.99

upper limit

8.3

Notes
[409] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29/Day 50 (N:KL)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15μg TIV for Day 29/Day 50. (N_15 aQIV + ½MF59:K_7.5 aTIV+ ½MF59 + L_15 aTIV+ ½MF59)

Comparison groups

N_15aQIV+½MF59 v K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[410]

P-value

< 0.001

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

4.96

Confidence interval

level

95%

sides

2-sided

lower limit

3.02

upper limit

8.13

Notes
[410] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_MY: Day 29/Day 50 (P:O)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 29/Day 50. (P_15 aQIV+fullMF59:O_15 aTIV + fullMF59)

Comparison groups

P_15aQIV+fullMF59 v O_15aTIV+fullMF59

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[411]

P-value

= 0.007

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.07

Confidence interval

level

95%

sides

2-sided

lower limit

1.17

upper limit

3.67

Notes
[411] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

Primary: 12. Assessing Geometric Mean Titer (GMTs) to evaluate whether the addition of a second influenza B strain (Malaysia) to a TIV (QIV) increases cross-reactive antibody responses to A/H3N2, A/H1N1 and the first influenza B strain (Florida).

Top of page

End point title

12. Assessing Geometric Mean Titer (GMTs) to evaluate whether the addition of a second influenza B strain (Malaysia) to a TIV (QIV) increases cross-reactive antibody responses to A/H3N2, A/H1N1 and the first influenza B strain (Florida).

End point description

To assess immunogenicity in terms of GMTs against strains A/H1N1, A/H3N2 and B/Florida 06 for the combined pediatric QIV group (i.e., all study vaccine groups with 7.5μg TIV formulated with a second B strain, B/Malaysia 04), were compared with GMTs against the same strains for the combined pediatric TIV group (i.e. all study vaccine groups with 7.5μg TIV formulated without the second B strain) and GMTs for the combined non-pediatric (15μg) QIV groups were compared with those from the corresponding TIV groups. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1, Day 29 and Day 50

End point values	AEGK	BHL	CFIM	DJN
Number of subjects analysed	97	61	89	77
Units: Titers
geometric mean (confidence interval 95%)
A/H1N1 (Day 1)	7.81 (6.31 to 9.67)	7.27 (5.56 to 9.52)	7.35 (5.88 to 9.19)	7.26 (5.72 to 9.23)
A/H1N1 (Day 29) (N=77,52,73,61)	72 (45 to 114)	59 (34 to 104)	64 (40 to 103)	71 (42 to 119)
A/H1N1 (Day 50) (N=74,52,73,59)	287 (198 to 416)	255 (164 to 397)	304 (209 to 441)	298 (197 to 451)
A/H3N2 (Day 1)	9.65 (7.49 to 12)	6.64 (4.83 to 9.14)	6.99 (5.37 to 9.1)	7.07 (5.32 to 9.39)
A/H3N2 (Day 29) (N=77,52,73,61)	102 (68 to 151)	65 (41 to 106)	53 (36 to 80)	45 (29 to 70)
A/H3N2 (Day 50) (N=74,52,73,59)	418 (297 to 589)	293 (195 to 442)	255 (180 to 360)	191 (130 to 280)
B_FL (Day 1)	5.77 (5.33 to 6.24)	5.23 (4.74 to 5.78)	6.05 (5.58 to 6.57)	5.37 (4.92 to 5.87)
B_FL (Day 29) (N=77,52,73,61)	11 (7.96 to 14)	9.54 (6.77 to 13)	9.14 (6.84 to 12)	10 (7.45 to 14)
B_FL (Day 50) (N=74,52,73,59)	49 (36 to 66)	37 (26 to 53)	41 (30 to 55)	40 (29 to 56)

A/H1N1:Day 1 (CFIM: AEGK)

Statistical analysis description

Comparison groups

CFIM v AEGK

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority ^[412]

P-value

= 0.7

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.28

Notes
[412] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1:Day 1 (DJN:BHL)

Statistical analysis description

Comparison groups

BHL v DJN

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority ^[413]

P-value

= 0.99

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.43

Notes
[413] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (CFIM: AEGK)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for day 1. (C_7.5QIV+0MF59 + F_7.5aQIV+⅛MF59 + I_7.5aQIV+¼MF59 + M_7.5aQIV+½MF59 : A_7.5TIV+0MF59+ E_7.5aTIV+⅛MF59 + G_7.5aTIV+¼MF59 + K_7.5aTIV+½MF59)

Comparison groups

CFIM v AEGK

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority ^[414]

P-value

= 0.084

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.04

Notes
[414] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2: Day 1 (DJN:BHL)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15μg TIV for day 1. (D_15aQIV+0MF59 + J_15aQIV+¼MF59 + N_15aQIV+½MF59 : B_15TIV+0MF59 + H_15aTIV+¼MF59 + L_15aTIV+½MF59)

Comparison groups

BHL v DJN

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority ^[415]

P-value

= 0.77

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.63

Notes
[415] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL:Day 1 (CFIM: AEGK)

Statistical analysis description

Comparison groups

CFIM v AEGK

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority ^[416]

P-value

= 0.41

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

1.17

Notes
[416] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL:Day 1 (DJN:BHL)

Statistical analysis description

Comparison groups

BHL v DJN

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority ^[417]

P-value

= 0.69

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

1.17

Notes
[417] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1:Day 29 (CFIM: AEGK)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 29. (C_7.5 QIV+0MF59 + F_7.5 aQIV+⅛MF59 + I_7.5 aQIV+¼MF59 + M_7.5 aQIV+½MF59 : A_7.5 TIV+0MF59+ E_7.5 aTIV+⅛MF59 + G_7.5 aTIV+¼MF59 + K_7.5 aTIV+½MF59)

Comparison groups

CFIM v AEGK

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority ^[418]

P-value

= 0.74

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

1.74

Notes
[418] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1:Day 29 (DJN:BHL)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 29. (D_15 aQIV + 0MF59 + J_15 aQIV + ¼MF59 + N_15 aQIV + ½MF59 : B_15 TIV + 0MF59 + H_15 aTIV + ¼MF59 + L_15 aTIV+ ½MF59)

Comparison groups

BHL v DJN

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority ^[419]

P-value

= 0.64

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

2.58

Notes
[419] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2:Day 29 (CFIM: AEGK)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 29. (C_7.5 QIV+0MF59 + F_7.5 aQIV+⅛MF59 + I_7.5 aQIV+¼MF59 + M_7.5 aQIV+½MF59 : A_7.5 TIV+0MF59+ E_7.5 aTIV+⅛MF59 + G_7.5 aTIV+¼MF59 + K_7.5 aTIV+½MF59)

Comparison groups

CFIM v AEGK

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority ^[420]

P-value

= 0.026

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

0.93

Notes
[420] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2:Day 29 (DJN:BHL)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 29. (D_15 aQIV + 0MF59 + J_15 aQIV + ¼MF59 + N_15 aQIV + ½MF59 : B_15 TIV + 0MF59 + H_15 aTIV + ¼MF59 + L_15 aTIV+ ½MF59)

Comparison groups

BHL v DJN

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority ^[421]

P-value

= 0.25

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.68

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

1.32

Notes
[421] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL:Day 29 (CFIM: AEGK)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 29. (C_7.5 QIV+0MF59 + F_7.5 aQIV+⅛MF59 + I_7.5 aQIV+¼MF59 + M_7.5 aQIV+½MF59 : A_7.5 TIV+0MF59+ E_7.5 aTIV+⅛MF59 + G_7.5 aTIV+¼MF59 + K_7.5 aTIV+½MF59)

Comparison groups

CFIM v AEGK

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority ^[422]

P-value

= 0.48

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

1.3

Notes
[422] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL: Day 29 (DJN:BHL)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg/15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 29. (D_15QIV+0MF59 + J_15aQIV+¼MF59 + N_15aQIV+½MF59 : B_15TIV+0MF59 + H_15aTIV+¼MF59 + L_15aTIV+½MF59)

Comparison groups

BHL v DJN

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority ^[423]

P-value

= 0.77

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.71

Notes
[423] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1:Day 50 (CFIM: AEGK)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 50. (C_7.5 QIV+0MF59 + F_7.5 aQIV+⅛MF59 + I_7.5 aQIV+¼MF59 + M_7.5 aQIV+½MF59 : A_7.5 TIV+0MF59+ E_7.5 aTIV+⅛MF59 + G_7.5 aTIV+¼MF59 + K_7.5 aTIV+½MF59)

Comparison groups

CFIM v AEGK

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority ^[424]

P-value

= 0.84

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.79

Notes
[424] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H1N1:Day 50 (DJN:BHL)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 50. (D_15 aQIV + 0MF59 + J_15 aQIV + ¼MF59 + N_15 aQIV + ½MF59 : B_15 TIV + 0MF59 + H_15 aTIV + ¼MF59 + L_15 aTIV+ ½MF59)

Comparison groups

DJN v BHL

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority ^[425]

P-value

= 0.61

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

2.14

Notes
[425] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2:Day 50 (CFIM: AEGK)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 50. (C_7.5 QIV+0MF59 + F_7.5 aQIV+⅛MF59 + I_7.5 aQIV+¼MF59 + M_7.5 aQIV+½MF59 : A_7.5 TIV+0MF59+ E_7.5 aTIV+⅛MF59 + G_7.5 aTIV+¼MF59 + K_7.5 aTIV+½MF59)

Comparison groups

CFIM v AEGK

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority ^[426]

P-value

= 0.046

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

0.99

Notes
[426] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

A/H3N2:Day 50 (DJN:BHL)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 50. (D_15 aQIV + 0MF59 + J_15 aQIV + ¼MF59 + N_15 aQIV + ½MF59 : B_15 TIV + 0MF59 + H_15 aTIV + ¼MF59 + L_15 aTIV+ ½MF59)

Comparison groups

BHL v DJN

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority ^[427]

P-value

= 0.13

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

1.14

Notes
[427] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B-FL:Day 50 (CFIM: AEGK)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 50. (C_7.5 QIV+0MF59 + F_7.5 aQIV+⅛MF59 + I_7.5 aQIV+¼MF59 + M_7.5 aQIV+½MF59 : A_7.5 TIV+0MF59+ E_7.5 aTIV+⅛MF59 + G_7.5 aTIV+¼MF59 + K_7.5 aTIV+½MF59)

Comparison groups

CFIM v AEGK

Number of subjects included in analysis

186

Analysis specification

Pre-specified

Analysis type

superiority ^[428]

P-value

= 0.42

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

1.28

Notes
[428] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

B_FL:Day 50 (DJN:BHL)

Statistical analysis description

To evaluate the superiority of GMTs against the B strain (Malaysia), the 7.5μg / 15μg TIV/QIV/aTIV/aQIV groups of identical MF59 content pooled and compared with the non adjuvanted 7.5μg and 15 μg TIV for Day 50. (D_15 aQIV + 0MF59 + J_15 aQIV + ¼MF59 + N_15 aQIV + ½MF59 : B_15 TIV + 0MF59 + H_15 aTIV + ¼MF59 + L_15 aTIV+ ½MF59)

Comparison groups

BHL v DJN

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority ^[429]

P-value

= 0.71

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.78

Notes
[429] - Superiority was to be shown if the lower margin of the 95% confidence interval (CI) was >1.

Primary: 13. Assessing Geometric Mean Titer (GMTs) to evaluate whether increases in antigen dose in TIV increases cross-reactive antibody responses to the second influenza B strain.

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End point title

13. Assessing Geometric Mean Titer (GMTs) to evaluate whether increases in antigen dose in TIV increases cross-reactive antibody responses to the second influenza B strain.

End point description

To assess immunogenicity in terms of GMTs to test for cross-reactivity of 7.5μg and 15μg TIV to the second B strain, the GMT against the second B-strain (B/Malaysia04Ba) in the groups receiving 7.5μg TIV formulated with ½, ¼, and 0 MF59 were combined and compared with GMTs for the combined 15μg TIV formulated with ½, ¼, and 0 MF59. The 7.5μg TIV+⅛ MF59 and the 15μg TIV+full MF59 groups were excluded from this analysis as the corresponding antigen-adjuvant combinations (i.e.,7.5μgTIV + full MF59 and 15μg TIV + ⅛ MF59) were not used in this study. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1 and Day 50

End point values	BHL	AGK
Number of subjects analysed	61	74
Units: Titers
geometric mean (confidence interval 95%)
B_MY (Day 1)	5 (4.92 to 5.08)	5.05 (4.98 to 5.12)
B_MY (Day 50) (N=52,56)	9.87 (7.82 to 12)	9.17 (7.33 to 11)

Ratio of GMTs BHL / AGK

Statistical analysis description

Assessing the crossreactivity of the 7.5μg and 15μg TIV to the second B strain.(B_15 TIV + 0MF59 +H_15 aTIV + ¼MF59 + L_15 aTIV+ ½MF59 : A_7.5 TIV + 0MF59 + G_7.5 aTIV+ ¼MF59 + K_7.5 aTIV+ ½MF59)

Comparison groups

BHL v AGK

Number of subjects included in analysis

135

Analysis specification

Pre-specified

Analysis type

other ^[430]

P-value

= 0.37

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.01

Notes
[430] - Evaluating whether increase in antigen dose in TIV increases crossreactive antibody responses to the second influenza B strain.

Primary: 14. GMTs to assess the immunogenicity of the study vaccine formulations according to the EMEA recommendations (CPMP/BWP/214/96).

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End point title

14. GMTs to assess the immunogenicity of the study vaccine formulations according to the EMEA recommendations (CPMP/BWP/214/96). ^[431] ^[432]

End point description

To assess the immunogenicity of study vaccine formulations in terms of GMTs for various vaccine group for Homologous A/H1N1,A/H3N2, and First Influenza B strains After Each Vaccination according to the EMEA recommendations (CPMP/BWP/214/96). The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 1, Day 29 and Day 50

Notes
[431] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point.
[432] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

End point values	Q_7.5cTIV+0MF59	A_7.5TIV+0MF59 + C_7.5QIV+0MF59	B_15TIV+0MF59 + D_15QIV+0MF59	E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59	H_15aTIV+¼MF59 + J_15aQIV+¼MF59	K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59	L_15aTIV+½MF59 + N_15aQIV+½MF59	O_15aTIV+fullMF59 + P_15aQIV+fullMF59
Number of subjects analysed	26	49	49	44	44	44	49	45	45
Units: Titers
geometric mean (confidence interval 95%)
A/H1N1 (Day 1)	9.74 (6.39 to 15)	6.4 (4.71 to 8.71)	6.54 (4.81 to 8.89)	8.15 (5.89 to 11)	8.41 (6.08 to 12)	7.83 (5.67 to 11)	7.7 (5.66 to 10)	7.58 (5.5 to 10)	7.4 (5.37 to 10)
A/H1N1 (Day 29) (N=23,37,43,37,35,33,41,37,36)	42 (20 to 87)	14 (7.74 to 24)	12 (7.18 to 21)	109 (61 to 194)	118 (65 to 213)	149 (81 to 273)	118 (68 to 204)	220 (124 to 391)	196 (109 to 351)
A/H1N1 (Day 50) (N=24,37,42,36,34,33,40,36,0)	261 (157 to 437)	57 (37 to 85)	69 (47 to 102)	533 (351 to 810)	481 (313 to 740)	576 (372 to 892)	529 (356 to 787)	718 (473 to 1092)	0 (0 to 0)
A/H3N2 (Day 1)	5 (3.14 to 7.97)	7.38 (5.25 to 10)	7.22 (5.14 to 10)	7.96 (5.56 to 11)	9.54 (6.67 to 14)	6.8 (4.75 to 9.73)	8.44 (6.01 to 12)	6.6 (4.63 to 9.4)	6.7 (4.7 to 9.55)
A/H3N2 (Day 29) (N=23,37,43,37,35,33,41,37,36)	22 (12 to 38)	19 (12 to 29)	12 (7.58 to 18)	91 (58 to 144)	114 (72 to 182)	112 (69 to 181)	150 (97 to 230)	163 (104 to 257)	165 (104 to 261)
A/H3N2 (Day 50) (N=24,37,42,36,34,33,40,36,0)	133 (83 to 211)	73 (50 to 106)	60 (42 to 86)	518 (354 to 758)	496 (335 to 734)	503 (338 to 748)	608 (423 to 872)	559 (382 to 819)	0 (0 to 0)
B_FL (Day 1)	5.87 (5.03 to 6.84)	5.37 (4.8 to 6)	5.29 (4.73 to 5.92)	6.23 (5.54 to 7.01)	6.33 (5.63 to 7.13)	5.16 (4.59 to 5.81)	5.8 (5.19 to 6.49)	5.48 (4.88 to 6.16)	5.57 (4.96 to 6.26)
B_FL (Day 29) (N=23,37,43,37,35,33,41,37,36)	11 (6.41 to 18)	8.45 (5.61 to 13)	6.74 (4.61 to 9.85)	9.37 (6.22 to 14)	13 (8.24 to 19)	8.45 (5.48 to 13)	9.59 (6.5 to 14)	18 (12 to 27)	15 (9.61 to 22)
B_FL (Day 50) (N=24,37,42,36,34,33,40,36,0)	24 (16 to 36)	13 (9.45 to 18)	11 (7.98 to 15)	61 (43 to 84)	61 (43 to 86)	69 (49 to 98)	81 (59 to 112)	101 (72 to 141)	0 (0 to 0)

No statistical analyses for this end point

Primary: 15. Geometric Mean Ratios (GMRs) to assess the immunogenicity of the study vaccine formulations according to the EMEA recommendations (CPMP/BWP/214/96).

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End point title

15. Geometric Mean Ratios (GMRs) to assess the immunogenicity of the study vaccine formulations according to the EMEA recommendations (CPMP/BWP/214/96). ^[433] ^[434]

End point description

To assess the immunogenicity of study vaccine formulations in terms of GMRs for various vaccine group for Homologous A/H1N1,A/H3N2, and First Influenza B strains After Each Vaccination according to the EMEA recommendations (CPMP/BWP/214/96). The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day29/ Day1 and Day50/ Day1

Notes
[433] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point.
[434] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

End point values	Q_7.5cTIV+0MF59	A_7.5TIV+0MF59 + C_7.5QIV+0MF59	B_15TIV+0MF59 + D_15QIV+0MF59	E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59	H_15aTIV+¼MF59 + J_15aQIV+¼MF59	K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59	L_15aTIV+½MF59 + N_15aQIV+½MF59	O_15aTIV+fullMF59 + P_15aQIV+fullMF59
Number of subjects analysed	24	37	43	36	34	33	41	36	36
Units: Titers
geometric mean (confidence interval 95%)
A/H1N1 (Day29/Day1) (N=23,37,43,36,34,33,41,36,36)	4.44 (2.82 to 7)	1.98 (1.39 to 2.83)	1.83 (1.31 to 2.55)	14 (9.82 to 20)	14 (9.45 to 20)	19 (13 to 27)	16 (11 to 23)	25 (18 to 37)	24 (17 to 34)
A/H1N1 (Day50/Day1) (N=24,37,42,35,33,33,40,35,0)	25 (17 to 39)	8.15 (5.79 to 11)	10 (7.43 to 14)	72 (51 to 103)	61 (43 to 88)	65 (45 to 93)	78 (56 to 109)	84 (59 to 120)	0 (0 to 0)
A/H3N2 (Day29/Day1) (N=23,37,43,36,34,33,41,36,36)	4.31 (2.87 to 6.49)	2.22 (1.61 to 3.06)	1.91 (1.41 to 2.57)	10 (7.48 to 14)	13 (9.52 to 19)	17 (12 to 24)	18 (13 to 24)	21 (15 to 30)	23 (16 to 32)
A/H3N2 (Day50/Day1) (N=24,37,42,35,33,33,40,35,0)	27 (16 to 43)	8.7 (5.9 to 13)	9.91 (6.88 to 14)	61 (41 to 91)	57 (38 to 86)	77 (51 to 117)	72 (50 to 105)	76 (51 to 114)	0 (0 to 0)
B_FL (Day29/Day1) (N=23,37,43,36,34,33,41,36,36)	1.8 (1.19 to 2.73)	1.54 (1.11 to 2.14)	1.28 (0.95 to 1.74)	1.73 (1.24 to 2.41)	2.06 (1.46 to 2.9)	1.62 (1.15 to 2.29)	1.67 (1.23 to 2.29)	3.3 (2.37 to 4.6)	2.54 (1.82 to 3.55)
B_FL (Day50/Day1) (N=24,37,42,35,33,33,40,35,0)	4.06 (2.8 to 5.89)	2.39 (1.77 to 3.22)	2.07 (1.56 to 2.74)	11 (8.15 to 15)	10 (7.42 to 14)	13 (9.64 to 18)	14 (11 to 19)	18 (13 to 25)	0 (0 to 0)

No statistical analyses for this end point

Primary: 16. Percentage of Subjects With HI Titers >= 1:40 for Homologous A/H1N1, A/H3N2, and First Influenza B Homologous Strains After Each Vaccination

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End point title

16. Percentage of Subjects With HI Titers >= 1:40 for Homologous A/H1N1, A/H3N2, and First Influenza B Homologous Strains After Each Vaccination ^[435] ^[436]

End point description

To assess the immunogenicity in terms of Percentage of subjects with HI Titers >= 1:40 increase for various vaccine group for Homologous A/H1N1,A/H3N2, and First Influenza B strains After Each Vaccination according to the EMEA recommendations (CPMP/BWP/214/96). Seroconversion is defined as negative pre-vaccination serum (i.e., HI titer <10) and post-vaccination HI titer ≥ 40; Significant increase is defined at least a 4-fold increase from non-negative (≥ 10) pre-vaccination HI titer. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 29 and Day 50

Notes
[435] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point.
[436] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

End point values	Q_7.5cTIV+0MF59	A_7.5TIV+0MF59 + C_7.5QIV+0MF59	B_15TIV+0MF59 + D_15QIV+0MF59	E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59	H_15aTIV+¼MF59 + J_15aQIV+¼MF59	K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59	L_15aTIV+½MF59 + N_15aQIV+½MF59	O_15aTIV+fullMF59 + P_15aQIV+fullMF59
Number of subjects analysed	24	37	43	37	35	33	41	37	36
Units: Percentage of Subjects
number (confidence interval 95%)
A/H1N1 (Day 29) (N=23,37,43,37,35,33,41,37,36)	43 (23 to 66)	16 (6 to 32)	21 (10 to 36)	81 (65 to 92)	77 (60 to 90)	85 (68 to 95)	88 (74 to 96)	95 (82 to 99)	94 (81 to 99)
A/H1N1 (Day 50) (N=24,37,42,36,34,33,40,36,0)	96 (79 to 100)	65 (47 to 80)	79 (63 to 90)	97 (85 to 100)	100 (90 to 100)	100 (89 to 100)	100 (91 to 100)	100 (90 to 100)	0 (0 to 0)
A/H3N2 (Day 29) (N=23,37,43,37,35,33,41,37,36)	35 (16 to 57)	30 (16 to 47)	12 (4 to 25)	84 (68 to 94)	89 (73 to 97)	88 (72 to 97)	98 (87 to 100)	92 (78 to 98)	97 (85 to 100)
A/H3N2 (Day 50) (N=24,37,42,36,34,33,40,36,0)	92 (73 to 99)	70 (53 to 84)	71 (55 to 84)	100 (90 to 100)	100 (90 to 100)	100 (89 to 100)	100 (91 to 100)	100 (90 to 100)	0 (0 to 0)
B_FL (Day 29) (N=23,37,43,37,35,33,41,37,36)	22 (7 to 44)	14 (5 to 29)	7 (1 to 19)	11 (3 to 25)	14 (5 to 30)	9 (2 to 24)	12 (4 to 26)	22 (10 to 38)	17 (6 to 33)
B_FL (Day 50) (N=24,37,42,36,34,33,40,36,0)	42 (22 to 63)	19 (8 to 35)	12 (4 to 26)	83 (67 to 94)	88 (73 to 94)	85 (68 to 95)	90 (76 to 97)	97 (85 to 100)	0 (0 to 0)

No statistical analyses for this end point

Primary: 17. Percentage of subjects with Seroconversion and significant increase for Homologous A/H1N1, A/H3N2, and First Influenza B Homologous Strains After Each Vaccination

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End point title

17. Percentage of subjects with Seroconversion and significant increase for Homologous A/H1N1, A/H3N2, and First Influenza B Homologous Strains After Each Vaccination ^[437] ^[438]

End point description

To assess the immunogenicity in terms of Percentage of subjects with Seroconversion and significant increase for various vaccine group for Homologous A/H1N1,A/H3N2, and First Influenza B strains After Each Vaccination according to the EMEA recommendations (CPMP/BWP/214/96). Seroconversion is defined as negative pre-vaccination serum (i.e., HI titer <10) and post-vaccination HI titer ≥ 40; Significant increase is defined at least a 4-fold increase from non-negative (≥ 10) pre-vaccination HI titer. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 29 and Day 50

Notes
[437] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point.
[438] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

End point values	Q_7.5cTIV+0MF59	A_7.5TIV+0MF59 + C_7.5QIV+0MF59	B_15TIV+0MF59 + D_15QIV+0MF59	E_7.5aTIV+⅛MF59 + F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59 + I_7.5aQIV+¼MF59	H_15aTIV+¼MF59 + J_15aQIV+¼MF59	K_7.5aTIV+½MF59 + M_7.5aQIV+½MF59	L_15aTIV+½MF59 + N_15aQIV+½MF59	O_15aTIV+fullMF59 + P_15aQIV+fullMF59
Number of subjects analysed	24	37	43	36	34	33	41	36	36
Units: Percentage of subjects
geometric mean (confidence interval 95%)
A/H1N1 (Day 29) (N= 23,37,43,36,34,33,41,36,36)	39 (20 to 61)	14 (5 to 29)	21 (10 to 36)	81 (64 to 95)	79 (62 to 91)	85 (68 to 95)	88 (74 to 96)	94 (81 to 99)	94 (81 to 99)
A/H1N1 (Day 50) (N= 24,37,42,35,33,33,40,35,0)	96 (79 to 100)	62 (45 to 78)	79 (63 to 90)	97 (85 to 100)	100 (89 to 100)	100 (89 to 100)	100 (91 to 100)	100 (90 to 100)	0 (0 to 0)
A/H3N2 (Day 29) (N= 23,37,43,36,34,33,41,36,36)	35 (16 to 57)	22 (10 to 38)	9 (3 to 22)	81 (64 to 92)	85 (69 to 95)	88 (72 to 97)	98 (87 to 100)	92 (78 to 98)	94 (81 to 99)
A/H3N2 (Day 50) (N= 24,37,42,35,33,33,40,35,0)	92 (73 to 99)	62 (45 to 78)	71 (55 to 84)	97 (85 to 100)	94 (80 to 99)	100 (89 to 100)	100 (91 to 100)	100 (90 to 100)	0 (0 to 0)
B_FL (Day 29) (N= 23,37,43,36,34,33,41,36,36)	22 (7 to 44)	14 (5 to 29)	7 (1 to 19)	11 (3 to 26)	15 (5 to 31)	9 (2 to 24)	12 (4 to 26)	22 (10 to 39)	17 (6 to 33)
B_FL (Day 50) (N= 24,37,42,35,33,33,40,35,0)	42 (22 to 63)	19 (8 to 35)	12 (4 to 26)	83 (66 to 93)	88 (72 to 97)	85 (68 to 95)	90 (76 to 97)	97 (85 to 100)	0 (0 to 0)

No statistical analyses for this end point

Primary: 18. Assessing Immunogenicity in terms of GMTs of the Study Vaccine Formulations for Homologous second B strain after Each QIV Vaccination

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End point title

18. Assessing Immunogenicity in terms of GMTs of the Study Vaccine Formulations for Homologous second B strain after Each QIV Vaccination ^[439] ^[440]

End point description

To assess the immunogenicity in terms of GMTs for various vaccine group for Homologous second B strain After Each QIV Vaccination according to the EMEA recommendations (CPMP/BWP/214/96). The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 29/Day 1 and Day 50/Day 1

Notes
[439] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point.
[440] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

C_7.5QIV+0MF59

D_15QIV+0MF59

Q_7.5cTIV+0MF59

E_7.5aTIV+⅛MF59

F_7.5aQIV+⅛MF59

I_7.5aQIV+¼MF59

J_15aQIV+¼MF59

M_7.5aQIV+½MF59

N_15aQIV+½MF59

O_15aTIV+fullMF59

P_15aQIV+fullMF59

A_7.5TIV+0MF59 + B_15TIV+0MF59

G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects analysed

Units: Titers

geometric mean (confidence interval 95%)

Day29(N=17,22,23,19,18,18,18,19,21,18,18,40,32,38)

6.39 (4.94 to 8.25)

5 (3.99 to 6.26)

5 (4.01 to 6.23)

6.22 (4.89 to 7.93)

6.06 (4.73 to 7.77)

5.83 (4.55 to 7.48)

6.55 (5.11 to 8.4)

6.22 (4.89 to 7.93)

7.19 (5.71 to 9.05)

5.4 (4.21 to 6.93)

11 (8.59 to 14)

5 (4.23 to 5.91)

5.45 (4.52 to 6.57)

5.79 (4.88 to 6.87)

Day50 (N=18,21,24,18,18,18,17,19,21,0,0,40,32,36)

11 (7.24 to 16)

9.68 (6.68 to 14)

5.37 (3.8 to 7.59)

10 (6.97 to 15)

42 (28 to 63)

63 (43 to 95)

63 (42 to 94)

70 (48 to 104)

70 (48 to 101)

0 (0 to 0)

5.74 (4.39 to 7.51)

11 (8.44 to 15)

14 (11 to 19)

No statistical analyses for this end point

Primary: 19. Assessing Immunogenicity in terms of GMRs of the Study Vaccine Formulations for Homologous second B strain after Each QIV Vaccination

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End point title

19. Assessing Immunogenicity in terms of GMRs of the Study Vaccine Formulations for Homologous second B strain after Each QIV Vaccination ^[441] ^[442]

End point description

To assess the immunogenicity in terms of GMRs for various vaccine group for Homologous second B strain After Each QIV Vaccination according to the EMEA recommendations (CPMP/BWP/214/96).

End point type

Primary

End point timeframe

Day 29/Day 1 and Day 50/Day 1

Notes
[441] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point.
[442] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

C_7.5QIV+0MF59

D_15QIV+0MF59

Q_7.5cTIV+0MF59

E_7.5aTIV+⅛MF59

F_7.5aQIV+⅛MF59

I_7.5aQIV+¼MF59

J_15aQIV+¼MF59

M_7.5aQIV+½MF59

N_15aQIV+½MF59

O_15aTIV+fullMF59

P_15aQIV+fullMF59

A_7.5TIV+0MF59 + B_15TIV+0MF59

G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects analysed

Units: Ratios

geometric mean (confidence interval 95%)

Day29(N=17,22,23,19,17,17,18,19,21,18,18,40,32,37)

1.28 (0.99 to 1.64)

1 (0.8 to 1.25)

1 (0.81 to 1.24)

1.24 (0.98 to 1.58)

1.18 (0.92 to 1.51)

1.26 (0.99 to 1.61)

1.24 (0.98 to 1.58)

1.44 (1.15 to 1.8)

1.08 (0.85 to 1.38)

2.12 (1.66 to 2.7)

1 (0.85 to 1.18)

1.09 (0.91 to 1.31)

1.14 (0.96 to 1.35)

Day50 (N= 18,21,24,18,17,17,17,19,21,0,0,40,32,35)

2.16 (1.45 to 3.22)

1.94 (1.34 to 2.8)

1.07 (0.76 to 1.52)

2.08 (1.39 to 3.1)

8.85 (5.86 to 13)

13 (8.3 to 19)

12 (7.97 to 18)

14 (9.54 to 21)

14 (9.68 to 20)

0 (0 to 0)

1.15 (0.88 to 1.5)

2.28 (1.69 to 3.07)

2.86 (2.14 to 3.81)

No statistical analyses for this end point

Primary: 20. Assessment of Immunogenicity of the Study Vaccine Formulations in terms of Percentage of Subjects with HI titers >=1:40 for Homologous second B strain After Each QIV Vaccination.

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End point title

20. Assessment of Immunogenicity of the Study Vaccine Formulations in terms of Percentage of Subjects with HI titers >=1:40 for Homologous second B strain After Each QIV Vaccination. ^[443] ^[444]

End point description

To assess the immunogenicity in terms of Percentage of Subjects with HI titers >=1:40 for various vaccine group for Homologous second B strain After Each QIV Vaccination according to the EMEA recommendations (CPMP/BWP/214/96). The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 29 and Day 50

Notes
[443] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point.
[444] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

C_7.5QIV+0MF59

D_15QIV+0MF59

Q_7.5cTIV+0MF59

E_7.5aTIV+⅛MF59

F_7.5aQIV+⅛MF59

I_7.5aQIV+¼MF59

J_15aQIV+¼MF59

M_7.5aQIV+½MF59

N_15aQIV+½MF59

O_15aTIV+fullMF59

P_15aQIV+fullMF59

A_7.5TIV+0MF59 + B_15TIV+0MF59

G_7.5aTIV+¼MF59 + H_15aTIV+¼MF59

K_7.5aTIV+½MF59 + L_15aTIV+½MF59

Number of subjects analysed

Units: Percentage of Subjects

number (confidence interval 95%)

Day29(N=18,22,23,19,18,18,18,19,21,18,18,40,32,38)

6 (0 to 27)

0 (0 to 15)

5 (0 to 26)

0 (0 to 19)

6 (0 to 27)

0 (0 to 18)

5 (0 to 24)

0 (0 to 19)

17 (4 to 41)

0 (0 to 9)

0 (0 to 11)

0 (0 to 9)

Day50 (N=18,21,24,18,18,18,17,19,21,0,0,40,32,36)

17 (4 to 41)

14 (3 to 36)

0 (0 to 14)

11 (1 to 35)

72 (47 to 90)

83 (59 to 96)

76 (50 to 93)

79 (54 to 94)

95 (76 to 100)

0 (0 to 0)

3 (0.063 to 13)

9 (2 to 25)

25 (12 to 42)

No statistical analyses for this end point

Primary: 21. Assessment of Immunogenicity of the Study Vaccine Formulations in terms of Percentage of Subjects with Seroconversion and significant increase for Homologous second B strain After Each QIV Vaccination.

Top of page

End point title

21. Assessment of Immunogenicity of the Study Vaccine Formulations in terms of Percentage of Subjects with Seroconversion and significant increase for Homologous second B strain After Each QIV Vaccination. ^[445] ^[446]

End point description

To assess the immunogenicity in terms of Percentage of Subjects with Seroconversion and significant increase for various vaccine group for Homologous second B strain After Each QIV Vaccination according to the EMEA recommendations (CPMP/BWP/214/96). The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 29 and Day 50

Notes
[445] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point.
[446] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses for this end point.

End point values	C_7.5QIV+0MF59	D_15QIV+0MF59	F_7.5aQIV+⅛MF59	I_7.5aQIV+¼MF59	J_15aQIV+¼MF59	M_7.5aQIV+½MF59	N_15aQIV+½MF59	P_15aQIV+fullMF59
Number of subjects analysed	18	22	17	17	18	19	21	18
Units: Percentage of Subjects
number (confidence interval 95%)
B_MY (Day 29) (N= 17,22,17,17,18,19,21,18)	6 (0 to 29)	0 (0 to 15)	0 (0 to 20)	0 (0 to 20)	6 (0 to 27)	0 (0 to 18)	5 (0 to 24)	17 (4 to 41)
B_MY (Day 50) (N= 18,21,17,17,17,19,21,0)	17 (4 to 41)	14 (3 to 36)	76 (50 to 93)	82 (57 to 96)	76 (50 to 93)	79 (54 to 94)	95 (76 to 100)	0 (0 to 0)

No statistical analyses for this end point

Primary: 22. To assess if there is a dose-response trend in immunogenicity responses across all doses of MF59.

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End point title

22. To assess if there is a dose-response trend in immunogenicity responses across all doses of MF59. ^[447]

End point description

To analyse the dose-response relationship for MF59 using a linear regression analysis with dose and day 50 antibody titers as dependent variables for the three strains and two doses 7.5μg and 15μg/antigen. The analysis was done on per protocol set.

End point type

Primary

End point timeframe

Day 50

Notes
[447] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point.

End point values	Slope (log10) inc. 95% CI	Slope incl. 95% CI
Number of subjects analysed	395	395
Units: Dose-response
number (confidence interval 95%)
A/H1N1 (7.5μg)	1.52 (0.97 to 2.07)	33.1 (9.3 to 117.5)
A/H1N1 (15μg)	2.07 (1.58 to 2.56)	117.5 (38 to 363.1)
A/H3N2 (7.5μg)	1.48 (0.97 to 1.99)	30.2 (9.3 to 97.7)
A/H3N2 (15μg)	1.97 (1.51 to 2.43)	93.3 (32.4 to 269.2)
B_FL (7.5μg)	1.31 (0.91 to 1.72)	20.4 (8.1 to 52.5)
B_FL (15μg)	1.96 (1.57 to 2.36)	91.2 (37 to 229.1)
B_MY (0μg)	0.74 (0.44 to 1.05)	5.5 (2.8 to 11.2)
B_MY (7.5μg)	1.43 (0.83 to 2.03)	26.9 (6.8 to 114.8)
B_MY (15μg)	1.72 (1.17 to 2.27)	52.5 (14.8 to 186.2)

No statistical analyses for this end point

Primary: 23. Number of subjects with local and systemic solicited adverse events after vaccination with one/two Injections of Trivalent Inactivated Influenza Vaccine (TIV).

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End point title

23. Number of subjects with local and systemic solicited adverse events after vaccination with one/two Injections of Trivalent Inactivated Influenza Vaccine (TIV). ^[448]

End point description

Assessment of safety on the basis of number of subjects with local and systemic solicited adverse events formulated with non-adjuvant, Eight Dose or Quarted Dose of Adjuvant, Half Dose or Full Dose of Adjuvant. The analysis was done on safety set.

End point type

Primary

End point timeframe

Throughout the study

Notes
[448] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point.

End point values	A_7.5TIV+0MF59	B_15TIV+0MF59	C_7.5QIV+0MF59	D_15QIV+0MF59	Q_7.5cTIV+0MF59	E_7.5aTIV+⅛MF59	F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59	H_15aTIV+¼MF59	I_7.5aQIV+¼MF59	J_15aQIV+¼MF59	K_7.5aTIV+½MF59	L_15aTIV+½MF59	M_7.5aQIV+½MF59	N_15aQIV+½MF59	O_15aTIV+fullMF59	P_15aQIV+fullMF59
Number of subjects analysed	25	22	25	28	26	24	23	23	21	24	24	27	23	22	25	26	22
Units: Number of subjects
Any Local	13	15	8	13	15	11	16	13	12	11	14	15	14	10	18	13	8
Injection site Ecchymosis	7	5	5	3	4	4	4	2	2	3	3	6	7	2	2	1	2
Injection site Erythema	8	7	6	9	10	8	12	11	8	6	11	9	10	7	13	8	3
Injection site Induration	3	2	1	5	4	4	6	4	5	6	3	6	7	3	6	6	2
Injection site Swelling	1	2	0	1	0	2	4	2	4	3	5	3	4	0	6	0	2
Tenderness	5	8	3	6	8	7	7	5	6	8	7	12	7	5	9	7	4
Any Systemic	17	14	17	20	16	17	16	11	15	14	18	19	19	18	19	14	12
Sleepiness	6	5	5	6	9	7	10	2	7	3	6	7	5	7	7	6	4
Diarrhoea	5	6	5	7	5	7	10	3	9	3	6	6	5	7	8	6	5
Vomiting	2	3	5	4	3	5	5	0	1	3	1	6	4	2	5	2	1
Irritability	8	8	8	11	8	11	10	6	8	7	11	9	12	10	9	6	5
Shivering	2	1	2	1	2	2	2	3	2	2	3	1	2	2	1	0	1
Change eating habits	9	8	5	8	3	7	9	2	7	5	5	10	9	7	6	0	5
Unusual Crying	8	7	3	9	4	9	4	5	4	4	10	8	11	10	7	4	6
Fever (>=38.5 C)	5	4	6	5	3	7	6	3	4	8	5	3	4	6	3	2	3
Body Temp (>40.0 C)	0	1	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0
Analg Antipy Medic.	4	9	8	11	5	12	8	4	11	9	10	10	12	13	9	7	6

No statistical analyses for this end point

Primary: 24. Number of subjects with unsolicited adverse events after vaccination with one/two Injections of Trivalent Inactivated Influenza Vaccine (TIV).

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End point title

24. Number of subjects with unsolicited adverse events after vaccination with one/two Injections of Trivalent Inactivated Influenza Vaccine (TIV). ^[449]

End point description

Assessment of safety on the basis of number of subjects unsolicited adverse events formulated with non-adjuvant, Eight Dose or Quarter Dose of Adjuvant, Half Dose or Full Dose of Adjuvant. The analysis was done on safety set.

End point type

Primary

End point timeframe

Throughout the study

Notes
[449] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for this end point.

End point values	A_7.5TIV+0MF59	B_15TIV+0MF59	C_7.5QIV+0MF59	D_15QIV+0MF59	Q_7.5cTIV+0MF59	E_7.5aTIV+⅛MF59	F_7.5aQIV+⅛MF59	G_7.5aTIV+¼MF59	H_15aTIV+¼MF59	I_7.5aQIV+¼MF59	J_15aQIV+¼MF59	K_7.5aTIV+½MF59	L_15aTIV+½MF59	M_7.5aQIV+½MF59	N_15aQIV+½MF59	O_15aTIV+fullMF59	P_15aQIV+fullMF59
Number of subjects analysed	25	22	25	28	26	24	23	23	21	24	24	27	23	22	25	26	22
Units: Number of subjects
Any AEs	21	18	23	20	19	23	15	19	17	18	19	24	20	19	22	15	20
At least possibly related AEs	5	8	1	5	5	5	5	6	4	2	7	3	3	7	5	3	7
Serious AEs	0	0	1	1	1	1	0	0	0	0	1	0	2	1	1	0	0
At least possibly related SAEs	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
AEs leading to discontinuation	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Throughout the study.

Adverse event reporting additional description

Number and percentage of children with at least one adverse event or at least one serious adverse event or one adverse event leading to medical visit/consultation or to withdrawal from the study throughout the study (day 50 for groups A through N and group Q; day 29 for groups O and P).

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

11.1

Reporting group title

A_7.5 TIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted trivalent influenza vaccine (TIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

B_15 TIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted trivalent influenza vaccine (TIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

C_7.5 QIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted quadravalent influenza vaccine (QIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

D_15 QIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted quadravalent influenza vaccine (QIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

Q_7.5 cTIV+0MF59

Reporting group description

Subjects who received 2 doses of non adjuvanted trivalent influenza vaccine (cTIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

E_7.5 aTIV+ ⅛MF59

Reporting group description

Subjects who received 2 doses of ⅛ MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

F_7.5 aQIV+ ⅛MF59

Reporting group description

Subjects who received 2 doses of ⅛MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

G_7.5 aTIV+ ¼MF59

Reporting group description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

H_15 aTIV+¼MF59

Reporting group description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

I_7.5 aQIV+¼MF59

Reporting group description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV – 7.5μg per antigen) on day 1 and day 29.

Reporting group title

J_15 aQIV+¼MF59

Reporting group description

Subjects who received 2 doses of ¼MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

K_7.5 aTIV+½MF59

Reporting group description

Subjects who received 2 doses of ½MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

L_15 aTIV+½MF59

Reporting group description

Subjects who received 2 doses of ½MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

M_7.5 aQIV+½MF59

Reporting group description

Subjects who received 2 doses of ½ MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 7.5μg per antigen) on day 1 and day 29.

Reporting group title

N_15 aQIV+½MF59

Reporting group description

Subjects who received 2 doses of ½ MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 15μg per antigen) on day 1 and day 29.

Reporting group title

O_15 aTIV+fullMF59

Reporting group description

Subjects who received one dose of full MF59 Dose adjuvanted trivalent influenza vaccine (aTIV - 15μg per antigen) on day 1.

Reporting group title

P_15 aQIV+fullMF59

Reporting group description

Subjects who received one dose of full MF59 Dose adjuvanted quadravalent influenza vaccine (aQIV - 15μg per antigen) on day 1.

A_7.5 TIV+0MF59

B_15 TIV+0MF59

C_7.5 QIV+0MF59

D_15 QIV+0MF59

Q_7.5 cTIV+0MF59

E_7.5 aTIV+ ⅛MF59

F_7.5 aQIV+ ⅛MF59

G_7.5 aTIV+ ¼MF59

H_15 aTIV+¼MF59

I_7.5 aQIV+¼MF59

J_15 aQIV+¼MF59

K_7.5 aTIV+½MF59

L_15 aTIV+½MF59

M_7.5 aQIV+½MF59

N_15 aQIV+½MF59

O_15 aTIV+fullMF59

P_15 aQIV+fullMF59

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 25 (0.00%)

0 / 22 (0.00%)

1 / 25 (4.00%)

1 / 28 (3.57%)

1 / 26 (3.85%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 21 (0.00%)

0 / 24 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

2 / 23 (8.70%)

1 / 22 (4.55%)

1 / 25 (4.00%)

0 / 26 (0.00%)

0 / 22 (0.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Infections and infestations

Gastroenteritis

alternative dictionary used: MedDRA 17.1

subjects affected / exposed

0 / 25 (0.00%)

0 / 22 (0.00%)

0 / 25 (0.00%)

1 / 28 (3.57%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 21 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

1 / 23 (4.35%)

1 / 22 (4.55%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 22 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis rotavirus

alternative dictionary used: MedDRA 17.1

subjects affected / exposed

0 / 25 (0.00%)

0 / 22 (0.00%)

0 / 25 (0.00%)

0 / 28 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 21 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

1 / 25 (4.00%)

0 / 26 (0.00%)

0 / 22 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Laryngitis

alternative dictionary used: MedDRA 17.1

subjects affected / exposed

0 / 25 (0.00%)

0 / 22 (0.00%)

0 / 25 (0.00%)

0 / 28 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 21 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

1 / 23 (4.35%)

0 / 22 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 22 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lymphadenitis bacterial

alternative dictionary used: MedDRA 17.1

subjects affected / exposed

0 / 25 (0.00%)

0 / 22 (0.00%)

1 / 25 (4.00%)

0 / 28 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 21 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 22 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

alternative dictionary used: MedDRA 17.1

subjects affected / exposed

0 / 25 (0.00%)

0 / 22 (0.00%)

0 / 25 (0.00%)

0 / 28 (0.00%)

0 / 26 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 21 (0.00%)

0 / 24 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 22 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis

alternative dictionary used: MedDRA 17.1

subjects affected / exposed

0 / 25 (0.00%)

0 / 22 (0.00%)

0 / 25 (0.00%)

0 / 28 (0.00%)

0 / 26 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 21 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 23 (0.00%)

0 / 22 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 22 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	A_7.5 TIV+0MF59	B_15 TIV+0MF59	C_7.5 QIV+0MF59	D_15 QIV+0MF59	Q_7.5 cTIV+0MF59	E_7.5 aTIV+ ⅛MF59	F_7.5 aQIV+ ⅛MF59	G_7.5 aTIV+ ¼MF59	H_15 aTIV+¼MF59	I_7.5 aQIV+¼MF59	J_15 aQIV+¼MF59	K_7.5 aTIV+½MF59	L_15 aTIV+½MF59	M_7.5 aQIV+½MF59	N_15 aQIV+½MF59	O_15 aTIV+fullMF59	P_15 aQIV+fullMF59
Total subjects affected by non serious adverse events
subjects affected / exposed	23 / 25 (92.00%)	20 / 22 (90.91%)	25 / 25 (100.00%)	26 / 28 (92.86%)	22 / 26 (84.62%)	23 / 24 (95.83%)	20 / 23 (86.96%)	22 / 23 (95.65%)	19 / 21 (90.48%)	20 / 24 (83.33%)	24 / 24 (100.00%)	26 / 27 (96.30%)	21 / 23 (91.30%)	21 / 22 (95.45%)	24 / 25 (96.00%)	21 / 26 (80.77%)	21 / 22 (95.45%)
Nervous system disorders
Somnolence
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	6 / 25 (24.00%)	6 / 22 (27.27%)	8 / 25 (32.00%)	6 / 28 (21.43%)	11 / 26 (42.31%)	10 / 24 (41.67%)	10 / 23 (43.48%)	3 / 23 (13.04%)	7 / 21 (33.33%)	3 / 24 (12.50%)	8 / 24 (33.33%)	9 / 27 (33.33%)	6 / 23 (26.09%)	7 / 22 (31.82%)	8 / 25 (32.00%)	7 / 26 (26.92%)	5 / 22 (22.73%)
occurrences all number	14	14	14	8	13	13	19	5	12	8	12	13	9	11	14	7	5
General disorders and administration site conditions
Chills
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	2 / 25 (8.00%)	2 / 22 (9.09%)	2 / 25 (8.00%)	1 / 28 (3.57%)	2 / 26 (7.69%)	4 / 24 (16.67%)	2 / 23 (8.70%)	4 / 23 (17.39%)	3 / 21 (14.29%)	2 / 24 (8.33%)	4 / 24 (16.67%)	2 / 27 (7.41%)	3 / 23 (13.04%)	2 / 22 (9.09%)	1 / 25 (4.00%)	0 / 26 (0.00%)	1 / 22 (4.55%)
occurrences all number	6	2	2	4	2	7	3	4	4	2	6	2	4	4	1	0	1
Crying
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	10 / 25 (40.00%)	10 / 22 (45.45%)	5 / 25 (20.00%)	11 / 28 (39.29%)	8 / 26 (30.77%)	10 / 24 (41.67%)	6 / 23 (26.09%)	7 / 23 (30.43%)	5 / 21 (23.81%)	5 / 24 (20.83%)	11 / 24 (45.83%)	11 / 27 (40.74%)	13 / 23 (56.52%)	11 / 22 (50.00%)	8 / 25 (32.00%)	5 / 26 (19.23%)	6 / 22 (27.27%)
occurrences all number	15	25	6	23	9	20	9	10	7	8	22	20	28	15	16	5	7
Injection site erythema
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	8 / 25 (32.00%)	8 / 22 (36.36%)	6 / 25 (24.00%)	9 / 28 (32.14%)	10 / 26 (38.46%)	8 / 24 (33.33%)	12 / 23 (52.17%)	11 / 23 (47.83%)	8 / 21 (38.10%)	6 / 24 (25.00%)	11 / 24 (45.83%)	9 / 27 (33.33%)	10 / 23 (43.48%)	7 / 22 (31.82%)	13 / 25 (52.00%)	8 / 26 (30.77%)	3 / 22 (13.64%)
occurrences all number	11	10	9	13	13	12	15	14	10	7	15	16	13	11	21	8	4
Injection site haemorrhage
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	7 / 25 (28.00%)	5 / 22 (22.73%)	5 / 25 (20.00%)	3 / 28 (10.71%)	4 / 26 (15.38%)	4 / 24 (16.67%)	4 / 23 (17.39%)	2 / 23 (8.70%)	2 / 21 (9.52%)	3 / 24 (12.50%)	3 / 24 (12.50%)	6 / 27 (22.22%)	7 / 23 (30.43%)	2 / 22 (9.09%)	2 / 25 (8.00%)	1 / 26 (3.85%)	2 / 22 (9.09%)
occurrences all number	10	8	5	4	5	4	4	2	2	3	3	7	8	3	2	1	2
Injection site induration
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	3 / 25 (12.00%)	2 / 22 (9.09%)	1 / 25 (4.00%)	5 / 28 (17.86%)	4 / 26 (15.38%)	4 / 24 (16.67%)	6 / 23 (26.09%)	4 / 23 (17.39%)	5 / 21 (23.81%)	6 / 24 (25.00%)	4 / 24 (16.67%)	6 / 27 (22.22%)	8 / 23 (34.78%)	3 / 22 (13.64%)	6 / 25 (24.00%)	6 / 26 (23.08%)	2 / 22 (9.09%)
occurrences all number	3	2	1	6	6	5	6	4	6	7	4	7	9	3	10	6	3
Injection site pain
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	5 / 25 (20.00%)	8 / 22 (36.36%)	3 / 25 (12.00%)	6 / 28 (21.43%)	8 / 26 (30.77%)	7 / 24 (29.17%)	7 / 23 (30.43%)	5 / 23 (21.74%)	6 / 21 (28.57%)	8 / 24 (33.33%)	7 / 24 (29.17%)	12 / 27 (44.44%)	7 / 23 (30.43%)	5 / 22 (22.73%)	9 / 25 (36.00%)	7 / 26 (26.92%)	4 / 22 (18.18%)
occurrences all number	8	8	3	10	9	8	10	6	8	10	9	18	9	6	13	7	4
Injection site swelling
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	1 / 25 (4.00%)	2 / 22 (9.09%)	0 / 25 (0.00%)	1 / 28 (3.57%)	0 / 26 (0.00%)	2 / 24 (8.33%)	4 / 23 (17.39%)	2 / 23 (8.70%)	4 / 21 (19.05%)	3 / 24 (12.50%)	5 / 24 (20.83%)	3 / 27 (11.11%)	4 / 23 (17.39%)	0 / 22 (0.00%)	6 / 25 (24.00%)	0 / 26 (0.00%)	2 / 22 (9.09%)
occurrences all number	1	2	0	2	0	2	4	2	4	3	5	4	6	0	9	0	2
Irritability postvaccinal
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 25 (0.00%)	0 / 22 (0.00%)	0 / 25 (0.00%)	0 / 28 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 23 (0.00%)	0 / 21 (0.00%)	2 / 24 (8.33%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	2	0	0	0	0	0	0	0
Pyrexia
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	7 / 25 (28.00%)	7 / 22 (31.82%)	9 / 25 (36.00%)	9 / 28 (32.14%)	7 / 26 (26.92%)	11 / 24 (45.83%)	6 / 23 (26.09%)	6 / 23 (26.09%)	4 / 21 (19.05%)	12 / 24 (50.00%)	9 / 24 (37.50%)	9 / 27 (33.33%)	7 / 23 (30.43%)	10 / 22 (45.45%)	5 / 25 (20.00%)	6 / 26 (23.08%)	5 / 22 (22.73%)
occurrences all number	10	10	12	9	9	16	10	7	5	12	12	12	13	13	12	6	8
Gastrointestinal disorders
Constipation
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	1 / 25 (4.00%)	1 / 22 (4.55%)	1 / 25 (4.00%)	0 / 28 (0.00%)	0 / 26 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 21 (0.00%)	0 / 24 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	2 / 25 (8.00%)	0 / 26 (0.00%)	1 / 22 (4.55%)
occurrences all number	1	1	1	0	0	0	0	0	0	0	0	0	0	0	2	0	1
Diarrhoea
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	10 / 25 (40.00%)	8 / 22 (36.36%)	10 / 25 (40.00%)	10 / 28 (35.71%)	9 / 26 (34.62%)	11 / 24 (45.83%)	10 / 23 (43.48%)	6 / 23 (26.09%)	10 / 21 (47.62%)	4 / 24 (16.67%)	7 / 24 (29.17%)	8 / 27 (29.63%)	8 / 23 (34.78%)	10 / 22 (45.45%)	11 / 25 (44.00%)	9 / 26 (34.62%)	6 / 22 (27.27%)
occurrences all number	13	15	15	19	11	17	19	6	19	6	13	15	12	14	14	14	7
Gastrooesophageal reflux disease
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 25 (0.00%)	0 / 22 (0.00%)	0 / 25 (0.00%)	0 / 28 (0.00%)	0 / 26 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 21 (0.00%)	0 / 24 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	2
Teething
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	1 / 25 (4.00%)	1 / 22 (4.55%)	1 / 25 (4.00%)	3 / 28 (10.71%)	0 / 26 (0.00%)	3 / 24 (12.50%)	2 / 23 (8.70%)	1 / 23 (4.35%)	4 / 21 (19.05%)	0 / 24 (0.00%)	2 / 24 (8.33%)	1 / 27 (3.70%)	1 / 23 (4.35%)	2 / 22 (9.09%)	2 / 25 (8.00%)	1 / 26 (3.85%)	1 / 22 (4.55%)
occurrences all number	1	1	2	4	0	3	3	1	5	0	3	1	1	2	3	1	1
Respiratory, thoracic and mediastinal disorders
Cough
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	5 / 25 (20.00%)	5 / 22 (22.73%)	5 / 25 (20.00%)	4 / 28 (14.29%)	8 / 26 (30.77%)	6 / 24 (25.00%)	2 / 23 (8.70%)	6 / 23 (26.09%)	4 / 21 (19.05%)	3 / 24 (12.50%)	3 / 24 (12.50%)	7 / 27 (25.93%)	6 / 23 (26.09%)	4 / 22 (18.18%)	5 / 25 (20.00%)	1 / 26 (3.85%)	5 / 22 (22.73%)
occurrences all number	8	5	5	6	9	6	4	6	5	3	4	9	6	5	6	1	5
Nasal congestion
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 25 (0.00%)	0 / 22 (0.00%)	0 / 25 (0.00%)	0 / 28 (0.00%)	1 / 26 (3.85%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 21 (4.76%)	0 / 24 (0.00%)	1 / 24 (4.17%)	1 / 27 (3.70%)	0 / 23 (0.00%)	2 / 22 (9.09%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	1	1	0	2	0	0	0
Rhinorrhoea
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 25 (0.00%)	1 / 22 (4.55%)	1 / 25 (4.00%)	0 / 28 (0.00%)	0 / 26 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 21 (0.00%)	2 / 24 (8.33%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 22 (4.55%)
occurrences all number	0	1	1	0	0	1	0	0	0	3	0	0	0	0	0	0	2
Psychiatric disorders
Eating disorder
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	10 / 25 (40.00%)	9 / 22 (40.91%)	7 / 25 (28.00%)	10 / 28 (35.71%)	5 / 26 (19.23%)	7 / 24 (29.17%)	10 / 23 (43.48%)	3 / 23 (13.04%)	8 / 21 (38.10%)	5 / 24 (20.83%)	7 / 24 (29.17%)	11 / 27 (40.74%)	11 / 23 (47.83%)	8 / 22 (36.36%)	8 / 25 (32.00%)	3 / 26 (11.54%)	5 / 22 (22.73%)
occurrences all number	14	20	14	21	6	18	19	5	11	10	9	13	20	12	15	4	8
Insomnia
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 25 (0.00%)	0 / 22 (0.00%)	0 / 25 (0.00%)	0 / 28 (0.00%)	2 / 26 (7.69%)	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 23 (4.35%)	0 / 21 (0.00%)	0 / 24 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	0	2	0	0	1	0	0	0	0	0	0	0	0	0
Irritability
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	9 / 25 (36.00%)	9 / 22 (40.91%)	10 / 25 (40.00%)	12 / 28 (42.86%)	10 / 26 (38.46%)	12 / 24 (50.00%)	10 / 23 (43.48%)	7 / 23 (30.43%)	9 / 21 (42.86%)	7 / 24 (29.17%)	11 / 24 (45.83%)	11 / 27 (40.74%)	13 / 23 (56.52%)	10 / 22 (45.45%)	12 / 25 (48.00%)	7 / 26 (26.92%)	6 / 22 (27.27%)
occurrences all number	16	24	16	24	11	29	20	10	17	19	29	19	36	19	21	8	6
Infections and infestations
Bronchitis
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	1 / 25 (4.00%)	0 / 22 (0.00%)	1 / 25 (4.00%)	2 / 28 (7.14%)	1 / 26 (3.85%)	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 23 (4.35%)	2 / 21 (9.52%)	0 / 24 (0.00%)	1 / 24 (4.17%)	2 / 27 (7.41%)	2 / 23 (8.70%)	3 / 22 (13.64%)	1 / 25 (4.00%)	0 / 26 (0.00%)	2 / 22 (9.09%)
occurrences all number	1	0	1	2	1	1	0	1	2	0	1	2	2	3	1	0	2
Conjunctivitis
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 25 (0.00%)	0 / 22 (0.00%)	2 / 25 (8.00%)	1 / 28 (3.57%)	1 / 26 (3.85%)	3 / 24 (12.50%)	0 / 23 (0.00%)	0 / 23 (0.00%)	2 / 21 (9.52%)	0 / 24 (0.00%)	1 / 24 (4.17%)	2 / 27 (7.41%)	0 / 23 (0.00%)	0 / 22 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	0	2	1	1	3	0	0	3	0	1	2	0	0	0	0	2
Ear infection
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 25 (0.00%)	3 / 22 (13.64%)	2 / 25 (8.00%)	2 / 28 (7.14%)	1 / 26 (3.85%)	2 / 24 (8.33%)	1 / 23 (4.35%)	5 / 23 (21.74%)	1 / 21 (4.76%)	2 / 24 (8.33%)	5 / 24 (20.83%)	3 / 27 (11.11%)	3 / 23 (13.04%)	0 / 22 (0.00%)	1 / 25 (4.00%)	3 / 26 (11.54%)	1 / 22 (4.55%)
occurrences all number	0	3	4	3	1	2	1	5	1	2	5	4	5	0	1	4	2
Gastroenteritis
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	1 / 25 (4.00%)	0 / 22 (0.00%)	1 / 25 (4.00%)	2 / 28 (7.14%)	0 / 26 (0.00%)	4 / 24 (16.67%)	3 / 23 (13.04%)	1 / 23 (4.35%)	1 / 21 (4.76%)	2 / 24 (8.33%)	1 / 24 (4.17%)	3 / 27 (11.11%)	1 / 23 (4.35%)	1 / 22 (4.55%)	2 / 25 (8.00%)	1 / 26 (3.85%)	1 / 22 (4.55%)
occurrences all number	1	0	1	2	0	4	3	1	1	2	1	3	1	1	2	1	1
Laryngitis
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 25 (0.00%)	1 / 22 (4.55%)	2 / 25 (8.00%)	0 / 28 (0.00%)	0 / 26 (0.00%)	2 / 24 (8.33%)	0 / 23 (0.00%)	1 / 23 (4.35%)	1 / 21 (4.76%)	0 / 24 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	1 / 23 (4.35%)	0 / 22 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	2	0	0	2	0	1	1	0	0	2	1	0	0	0	0
Nasopharyngitis
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	4 / 25 (16.00%)	5 / 22 (22.73%)	5 / 25 (20.00%)	3 / 28 (10.71%)	3 / 26 (11.54%)	5 / 24 (20.83%)	1 / 23 (4.35%)	1 / 23 (4.35%)	4 / 21 (19.05%)	4 / 24 (16.67%)	5 / 24 (20.83%)	3 / 27 (11.11%)	1 / 23 (4.35%)	8 / 22 (36.36%)	4 / 25 (16.00%)	2 / 26 (7.69%)	3 / 22 (13.64%)
occurrences all number	4	7	5	3	4	5	1	1	4	5	6	4	1	8	4	2	4
Otitis media
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	1 / 25 (4.00%)	2 / 22 (9.09%)	2 / 25 (8.00%)	2 / 28 (7.14%)	2 / 26 (7.69%)	2 / 24 (8.33%)	2 / 23 (8.70%)	1 / 23 (4.35%)	1 / 21 (4.76%)	3 / 24 (12.50%)	2 / 24 (8.33%)	2 / 27 (7.41%)	1 / 23 (4.35%)	1 / 22 (4.55%)	3 / 25 (12.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)
occurrences all number	1	2	2	2	2	2	2	1	1	4	3	2	1	2	4	0	0
Rhinitis
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	4 / 25 (16.00%)	4 / 22 (18.18%)	4 / 25 (16.00%)	4 / 28 (14.29%)	4 / 26 (15.38%)	2 / 24 (8.33%)	3 / 23 (13.04%)	3 / 23 (13.04%)	3 / 21 (14.29%)	1 / 24 (4.17%)	4 / 24 (16.67%)	6 / 27 (22.22%)	3 / 23 (13.04%)	3 / 22 (13.64%)	6 / 25 (24.00%)	4 / 26 (15.38%)	4 / 22 (18.18%)
occurrences all number	6	4	4	5	4	2	3	3	3	1	5	6	3	3	7	5	4
Tonsillitis
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 25 (0.00%)	1 / 22 (4.55%)	1 / 25 (4.00%)	0 / 28 (0.00%)	0 / 26 (0.00%)	2 / 24 (8.33%)	0 / 23 (0.00%)	1 / 23 (4.35%)	0 / 21 (0.00%)	0 / 24 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 23 (0.00%)	0 / 22 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	1	1	0	0	2	0	1	0	0	0	0	0	0	1	0	0
Upper respiratory tract infection
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	4 / 25 (16.00%)	4 / 22 (18.18%)	4 / 25 (16.00%)	5 / 28 (17.86%)	3 / 26 (11.54%)	5 / 24 (20.83%)	6 / 23 (26.09%)	3 / 23 (13.04%)	7 / 21 (33.33%)	5 / 24 (20.83%)	4 / 24 (16.67%)	6 / 27 (22.22%)	5 / 23 (21.74%)	4 / 22 (18.18%)	8 / 25 (32.00%)	8 / 26 (30.77%)	1 / 22 (4.55%)
occurrences all number	5	5	4	7	5	5	7	3	7	5	4	7	7	4	9	8	1
Varicella
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 25 (0.00%)	0 / 22 (0.00%)	1 / 25 (4.00%)	0 / 28 (0.00%)	0 / 26 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	2 / 23 (8.70%)	0 / 21 (0.00%)	2 / 24 (8.33%)	0 / 24 (0.00%)	1 / 27 (3.70%)	1 / 23 (4.35%)	0 / 22 (0.00%)	2 / 25 (8.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	1	0	0	1	0	2	0	2	0	1	1	0	2	0	0
Metabolism and nutrition disorders
Decreased appetite
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 25 (0.00%)	0 / 22 (0.00%)	0 / 25 (0.00%)	1 / 28 (3.57%)	2 / 26 (7.69%)	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 23 (4.35%)	0 / 21 (0.00%)	0 / 24 (0.00%)	1 / 24 (4.17%)	1 / 27 (3.70%)	0 / 23 (0.00%)	0 / 22 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)
occurrences all number	0	0	0	1	4	0	0	1	0	0	1	1	0	0	1	0	0

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 1. To assess non-inferiority of study vaccine formulations to the pediatric trivalent influenza vaccine (TIV - 7.5μg per antigen) formulated with MF59 at half the dose of the marketed adult adjuvanted vaccine.

Primary: 1. To assess non-inferiority of study vaccine formulations to the pediatric trivalent influenza vaccine (TIV - 7.5μg per antigen) formulated with MF59 at half the dose of the marketed adult adjuvanted vaccine.

Primary: 2. To assess non-inferiority of 7.5 μg QIV formulated with half MF59 to 7.5μg and 15μg TIV and QIV groups.

Primary: 2. To assess non-inferiority of 7.5 μg QIV formulated with half MF59 to 7.5μg and 15μg TIV and QIV groups.

Primary: 3. To evaluate superiority of any of the study vaccine formulations to the pediatric trivalent influenza vaccine (TIV - 7.5μg per antigen) formulated with MF59 at half the dose of the marketed adult adjuvanted vaccine, Fluad.

Primary: 3. To evaluate superiority of any of the study vaccine formulations to the pediatric trivalent influenza vaccine (TIV - 7.5μg per antigen) formulated with MF59 at half the dose of the marketed adult adjuvanted vaccine, Fluad.

Primary: 4. To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV + ½MF59 group.

Primary: 4. To evaluate the superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined aTIV/aQIV + ½MF59 group.

Primary: 5. Evaluating the superiority of the antibody responses in terms of GMTs to the study vaccines (combining TIV/QIV/ aTIV/aQIV of identical antigen and adjuvant dose) to that of the marketed pediatric trivalent influenza vaccine Vaxigrip (7.5μg cTIV+0MF59).

Primary: 5. Evaluating the superiority of the antibody responses in terms of GMTs to the study vaccines (combining TIV/QIV/ aTIV/aQIV of identical antigen and adjuvant dose) to that of the marketed pediatric trivalent influenza vaccine Vaxigrip (7.5μg cTIV+0MF59).

Primary: 6. Superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined TIV/QIV+½MF59 group.

Primary: 6. Superiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined TIV/QIV+½MF59 group.

Primary: 7. Non-inferiority of the antibody responses (GMTs) to the study vaccines (combining TIV/QIV/aTIV/aQIV of identical antigen and adjuvant dose) to that of the marketed pediatric trivalent influenza vaccine Vaxigrip (7.5μg cTIV+0MF59).

Primary: 7. Non-inferiority of the antibody responses (GMTs) to the study vaccines (combining TIV/QIV/aTIV/aQIV of identical antigen and adjuvant dose) to that of the marketed pediatric trivalent influenza vaccine Vaxigrip (7.5μg cTIV+0MF59).

Primary: 8. Non-inferiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined TIV/QIV + ½MF59 group.

Primary: 8. Non-inferiority of GMTs against the second B strain (Malaysia), the 7.5μg and 15μg TIV groups of identical MF59 content were pooled and compared with the 7.5μg combined TIV/QIV + ½MF59 group.

Primary: 9. Assessing Geometric Mean Titer (GMTs) to Compare the nonadjuvanted pediatric vaccine (7.5 TIV/QIV+0MF59) non adjuvanted vaccine.

Primary: 9. Assessing Geometric Mean Titer (GMTs) to Compare the nonadjuvanted pediatric vaccine (7.5 TIV/QIV+0MF59) non adjuvanted vaccine.

Primary: 10. Assessing Geometric Mean Titers (GMTs) to evaluate non-inferior antibody responses to the second influenza B strain when compared with two 7.5μg QIV+0MF59 vaccinations.

Primary: 10. Assessing Geometric Mean Titers (GMTs) to evaluate non-inferior antibody responses to the second influenza B strain when compared with two 7.5μg QIV+0MF59 vaccinations.

Primary: 11. Assessing Geometric Mean Titer (GMTs) to evaluate whether the addition of a second influenza B strain (Malaysia) to a TIV (QIV) increases the antibody responses to this influenza B strain.

Primary: 11. Assessing Geometric Mean Titer (GMTs) to evaluate whether the addition of a second influenza B strain (Malaysia) to a TIV (QIV) increases the antibody responses to this influenza B strain.

Primary: 12. Assessing Geometric Mean Titer (GMTs) to evaluate whether the addition of a second influenza B strain (Malaysia) to a TIV (QIV) increases cross-reactive antibody responses to A/H3N2, A/H1N1 and the first influenza B strain (Florida).

Primary: 12. Assessing Geometric Mean Titer (GMTs) to evaluate whether the addition of a second influenza B strain (Malaysia) to a TIV (QIV) increases cross-reactive antibody responses to A/H3N2, A/H1N1 and the first influenza B strain (Florida).

Primary: 13. Assessing Geometric Mean Titer (GMTs) to evaluate whether increases in antigen dose in TIV increases cross-reactive antibody responses to the second influenza B strain.

Primary: 13. Assessing Geometric Mean Titer (GMTs) to evaluate whether increases in antigen dose in TIV increases cross-reactive antibody responses to the second influenza B strain.

Primary: 14. GMTs to assess the immunogenicity of the study vaccine formulations according to the EMEA recommendations (CPMP/BWP/214/96).

Primary: 14. GMTs to assess the immunogenicity of the study vaccine formulations according to the EMEA recommendations (CPMP/BWP/214/96).

Primary: 15. Geometric Mean Ratios (GMRs) to assess the immunogenicity of the study vaccine formulations according to the EMEA recommendations (CPMP/BWP/214/96).

Primary: 15. Geometric Mean Ratios (GMRs) to assess the immunogenicity of the study vaccine formulations according to the EMEA recommendations (CPMP/BWP/214/96).

Primary: 16. Percentage of Subjects With HI Titers >= 1:40 for Homologous A/H1N1, A/H3N2, and First Influenza B Homologous Strains After Each Vaccination

Primary: 16. Percentage of Subjects With HI Titers >= 1:40 for Homologous A/H1N1, A/H3N2, and First Influenza B Homologous Strains After Each Vaccination

Primary: 17. Percentage of subjects with Seroconversion and significant increase for Homologous A/H1N1, A/H3N2, and First Influenza B Homologous Strains After Each Vaccination

Primary: 17. Percentage of subjects with Seroconversion and significant increase for Homologous A/H1N1, A/H3N2, and First Influenza B Homologous Strains After Each Vaccination

Primary: 18. Assessing Immunogenicity in terms of GMTs of the Study Vaccine Formulations for Homologous second B strain after Each QIV Vaccination

Primary: 18. Assessing Immunogenicity in terms of GMTs of the Study Vaccine Formulations for Homologous second B strain after Each QIV Vaccination

Primary: 19. Assessing Immunogenicity in terms of GMRs of the Study Vaccine Formulations for Homologous second B strain after Each QIV Vaccination

Primary: 19. Assessing Immunogenicity in terms of GMRs of the Study Vaccine Formulations for Homologous second B strain after Each QIV Vaccination

Primary: 20. Assessment of Immunogenicity of the Study Vaccine Formulations in terms of Percentage of Subjects with HI titers >=1:40 for Homologous second B strain After Each QIV Vaccination.

Primary: 20. Assessment of Immunogenicity of the Study Vaccine Formulations in terms of Percentage of Subjects with HI titers >=1:40 for Homologous second B strain After Each QIV Vaccination.

Primary: 21. Assessment of Immunogenicity of the Study Vaccine Formulations in terms of Percentage of Subjects with Seroconversion and significant increase for Homologous second B strain After Each QIV Vaccination.

Primary: 21. Assessment of Immunogenicity of the Study Vaccine Formulations in terms of Percentage of Subjects with Seroconversion and significant increase for Homologous second B strain After Each QIV Vaccination.

Primary: 22. To assess if there is a dose-response trend in immunogenicity responses across all doses of MF59.

Primary: 22. To assess if there is a dose-response trend in immunogenicity responses across all doses of MF59.

Primary: 23. Number of subjects with local and systemic solicited adverse events after vaccination with one/two Injections of Trivalent Inactivated Influenza Vaccine (TIV).

Primary: 23. Number of subjects with local and systemic solicited adverse events after vaccination with one/two Injections of Trivalent Inactivated Influenza Vaccine (TIV).

Primary: 24. Number of subjects with unsolicited adverse events after vaccination with one/two Injections of Trivalent Inactivated Influenza Vaccine (TIV).

Primary: 24. Number of subjects with unsolicited adverse events after vaccination with one/two Injections of Trivalent Inactivated Influenza Vaccine (TIV).

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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