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Clinical Trial Results:
Immunogenicity and Lot-to-Lot Consistency Study of a Quadrivalent Influenza Vaccine in Adult and Elderly Subjects

Summary
EudraCT number	2014-000785-21
Trial protocol	DE BE
Global end of trial date	23 Oct 2015

Results information
Results version number	v1(current)
This version publication date	27 Mar 2016
First version publication date	27 Mar 2016
Other versions

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

GQM11

ISRCTN number

US NCT number

WHO universal trial number (UTN)

U1111-1143-8801

Sponsor organisation name

Sanofi Pasteur SA

Sponsor organisation address

2, avenue Pont Pasteur, Lyon Cedex 07, France, F-69367

Public contact

Director, Clinical Development , Sanofi Pasteur SA, 33 4 37 37 5850, stephanie.pepin@sanofipasteur.com

Scientific contact

Director, Clinical Development , Sanofi Pasteur SA, 33 4 37 37 5850, stephanie.pepin@sanofipasteur.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?

Analysis stage

Final

Date of interim/final analysis

20 Jan 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

23 Oct 2015

Was the trial ended prematurely?

Main objective of the trial

• Immunogenicity: Lot Consistency To demonstrate equivalence of immune response induced by the 3 different industrial lots of Quadrivalent Influenza Vaccine (QIV) for each strain • Immunogenicity: Non-inferiority To demonstrate the non-inferiority of immune response induced by QIV compared with Trivalent Influenza Vaccine (TIV) for each strain

Protection of trial subjects

Only subjects that met all the study inclusion and none of the exclusion criteria were randomized and vaccinated in the study. Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment was also available on site in case of any immediate allergic reactions.

Background therapy

Not applicable

Evidence for comparator

Not applicable

Actual start date of recruitment

17 Sep 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 607

Country: Number of subjects enrolled

Belgium: 466

Country: Number of subjects enrolled

Germany: 587

Country: Number of subjects enrolled

France: 559

Worldwide total number of subjects

2219

EEA total number of subjects

2219

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)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1373

From 65 to 84 years

829

85 years and over

Subject disposition

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Recruitment details

The study subjects were enrolled from 17 September 2014 to 21 October 2014 at 3 clinic centers in Belgium, 3 in France, 4 in Germany, and 5 in Poland.

Screening details

A total of 2225 subjects who met all of the inclusion and none of the exclusion criteria were randomized; however, 3 subjects were not injected and 3 subjects had no post-vaccination blood sample resulting in a total of 2219 patients.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Assessor

Blinding implementation details

This was a double-blind study for subjects in the quadrivalent and trivalent influenza vaccine (TIV; Victoria) groups. The Investigator, the study staff, and the subject were blinded to study treatment. The study was a single-blind study up to Day 21 for all subjects included in the TIV (Yamagata) group. Immunogenicity was assessed in a blinded manner for all subjects. In the event of an emergency (i.e., serious adverse event), the code could be broken according to the code-breaking procedures.

Are arms mutually exclusive

Yes

QIV S4456

Arm description

Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 1 S4456.

Arm type

Experimental

Investigational medicinal product name

QIV (split-virion, inactivated)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular in the deltoid muscle or deep subcutaneous, 1 injection on Day 0.

QIV S4457

Arm description

Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 2 S4457.

Arm type

Experimental

Investigational medicinal product name

QIV (split-virion, inactivated)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular in the deltoid muscle or deep subcutaneous, 1 injection on Day 0.

QIV S4458

Arm description

Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 3 S4458.

Arm type

Experimental

Investigational medicinal product name

QIV (split-virion, inactivated)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular in the deltoid muscle or deep subcutaneous, 1 injection on Day 0.

TIV1

Arm description

Subjects received a single dose of trivalent influenza vaccine (TIV) 1 from the Victoria lineage.

Arm type

Active comparator

Investigational medicinal product name

TIV1 (split-virion, inactivated) Victoria lineage

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular in the deltoid muscle or deep subcutaneous, 1 injection on Day 0.

TIV2

Arm description

Subjects received a single dose of trivalent influenza vaccine (TIV) 2 from the Yamagata lineage.

Arm type

Active comparator

Investigational medicinal product name

TIV2 (split-virion, inactivated) Yamagata lineage

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular in the deltoid muscle or deep subcutaneous, 1 injection on Day 0.

Number of subjects in period 1	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Started	553	555	558	278	275
Completed	552	555	555	278	274
Not completed	1	0	3	0	1
Consent withdrawn by subject	-	-	2	-	-
Lost to follow-up	1	-	-	-	-
Protocol deviation	-	-	1	-	1

Baseline characteristics

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Reporting group title

QIV S4456

Reporting group description

Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 1 S4456.

Reporting group title

QIV S4457

Reporting group description

Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 2 S4457.

Reporting group title

QIV S4458

Reporting group description

Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 3 S4458.

Reporting group title

TIV1

Reporting group description

Subjects received a single dose of trivalent influenza vaccine (TIV) 1 from the Victoria lineage.

Reporting group title

TIV2

Reporting group description

Subjects received a single dose of trivalent influenza vaccine (TIV) 2 from the Yamagata lineage.

Reporting group values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2	Total
Number of subjects	553	555	558	278	275	2219
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0
Adults (18-64 years)	344	330	350	176	172	1372
From 65-84 years	204	221	204	101	100	830
85 years and over	5	4	4	1	3	17
Age continuous
Units: years
arithmetic mean (standard deviation)	54.5 ( 18.1 )	54.8 ( 18.2 )	54.5 ( 18.1 )	55.6 ( 16.9 )	53.7 ( 18.6 )	-
Gender categorical
Units: Subjects
Female	309	304	282	152	151	1198
Male	244	251	276	126	124	1021
History of influenza vaccination 2013/2014
Number of subjects with a history of influenza vaccination by year
Units: Subjects
Influenza vaccination 2013/2014; Yes	187	196	195	102	89	769
Influenza vaccination 2013/2014; No	366	355	362	175	186	1444
Influenza vaccination 2013/2014; Unknown	0	4	1	1	0	6
History of influenza vaccination 2012/2013
Units: Subjects
Influenza vaccination 2012/2013; Yes	177	199	199	105	97	777
Influenza vaccination 2012/2013; No	373	355	356	173	176	1433
Influenza vaccination 2012/2013; Unknown	3	1	3	0	2	9
History of influenza vaccination 2011/2012
Units: Subjects
Influenza vaccination 2011/2012; Yes	179	209	197	104	94	783
Influenza vaccination 2011/2012; No	369	344	356	170	179	1418
Influenza vaccination 2011/2012; Unknown	5	2	5	4	2	18

Subject analysis set title

Pooled QIV

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received a single dose of either quadrivalent influenza vaccine (QIV) Lot 1 S4456, Lot 2 S4457, or Lot 3 S4458.

Subject analysis set title

Pooled TIV

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received a single dose of either trivalent influenza vaccine (TIV) 1 from the Victoria lineage or TIV 2 from the Yamagata lineage.

Subject analysis sets values	Pooled QIV	Pooled TIV
Number of subjects	1666	553
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	1024	348
From 65-84 years	629	201
85 years and over	13	4
Age continuous
Units: years
arithmetic mean (standard deviation)	54.6 ( 18.1 )	54.7 ( 17.8 )
Gender categorical
Units: Subjects
Female	895	303
Male	771	250
History of influenza vaccination 2013/2014
Number of subjects with a history of influenza vaccination by year
Units: Subjects
Influenza vaccination 2013/2014; Yes	578	191
Influenza vaccination 2013/2014; No	1083	361
Influenza vaccination 2013/2014; Unknown	5	1
History of influenza vaccination 2012/2013
Units: Subjects
Influenza vaccination 2012/2013; Yes	575	202
Influenza vaccination 2012/2013; No	1084	349
Influenza vaccination 2012/2013; Unknown	7	2
History of influenza vaccination 2011/2012
Units: Subjects
Influenza vaccination 2011/2012; Yes	585	198
Influenza vaccination 2011/2012; No	1069	349
Influenza vaccination 2011/2012; Unknown	12	6

End points

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Reporting group title

QIV S4456

Reporting group description

Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 1 S4456.

Reporting group title

QIV S4457

Reporting group description

Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 2 S4457.

Reporting group title

QIV S4458

Reporting group description

Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 3 S4458.

Reporting group title

TIV1

Reporting group description

Subjects received a single dose of trivalent influenza vaccine (TIV) 1 from the Victoria lineage.

Reporting group title

TIV2

Reporting group description

Subjects received a single dose of trivalent influenza vaccine (TIV) 2 from the Yamagata lineage.

Subject analysis set title

Pooled QIV

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received a single dose of either quadrivalent influenza vaccine (QIV) Lot 1 S4456, Lot 2 S4457, or Lot 3 S4458.

Subject analysis set title

Pooled TIV

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received a single dose of either trivalent influenza vaccine (TIV) 1 from the Victoria lineage or TIV 2 from the Yamagata lineage.

Primary: Geometric Mean Titers (GMTs) of Influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in All Subjects

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End point title

Geometric Mean Titers (GMTs) of Influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in All Subjects

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.

End point type

Primary

End point timeframe

Day 21 post-vaccination

End point values	Pooled QIV	Pooled TIV
Number of subjects analysed	830	278
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
A/California/07/2009 (H1N1); 18 to 60 years	612 (567 to 661)	685 (587 to 800)
A/California/07/2009 (H1N1); >60 years	219 (198 to 241)	268 (228 to 314)
A/Texas/50/2012 (H3N2); 18 to 60 years	501 (461 to 544)	629 (543 to 728)
A/Texas/50/2012 (H3N2); >60 years	359 (329 to 391)	410 (352 to 476)
B/Brisbane/60/2008 (B Victoria); 18 to 60 years	708 (660 to 760)	735 (615 to 879)
B/Brisbane/60/2008 (B Victoria); >60 years	287 (265 to 312)	301 (244 to 372)
B/Massachusetts/02/2012 (B Yamagata); 18 to 60 yrs	1713 (1604 to 1829)	1735 (1490 to 2019)
B/Massachusetts/02/2012 (B Yamagata); >60 yrs	656 (612 to 703)	697 (593 to 820)

Non-inferiority (A/H1N1; GMT Ratio; Overall)

Statistical analysis description

Ratio of GMTs were assessed in the H1N1 strain between the pooled QIV and TIV groups to determine non-inferiority.

Comparison groups

Pooled QIV v Pooled TIV

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

Method

Parameter type

Ratio of GMTs

Point estimate

0.855

Confidence interval

level

95%

sides

2-sided

lower limit

0.757

upper limit

0.968

Notes
[1] - Non-inferiority was confirmed if the lower limit of the overall age-stratified two-sided 95% confidence interval of the ratio of geometric mean titers (GMTs) between groups (QIV/TIV) is >1/1.5 for each strain.

Non-inferiority (A/H3N2; GMT Ratio; Overall)

Statistical analysis description

Ratio of GMTs were assessed in the H3N2 strain between the pooled QIV and TIV groups to determine non-inferiority.

Comparison groups

Pooled QIV v Pooled TIV

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Parameter type

Ratio of GMTs

Point estimate

0.835

Confidence interval

level

95%

sides

2-sided

lower limit

0.741

upper limit

0.941

Notes
[2] - Non-inferiority was confirmed if the lower limit of the overall age-stratified two-sided 95% confidence interval of the ratio of geometric mean titers (GMTs) between groups (QIV/TIV) is >1/1.5 for each strain.

Non-inferiority (B/Brisbane; GMT Ratio; Overall)

Statistical analysis description

Ratio of GMTs were assessed in the H1N1 strain between the pooled QIV and TIV groups to determine non-inferiority.

Comparison groups

Pooled QIV v Pooled TIV

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Ratio of GMTs

Point estimate

0.959

Confidence interval

level

95%

sides

2-sided

lower limit

0.831

upper limit

1.11

Notes
[3] - Non-inferiority was confirmed if the lower limit of the overall age-stratified two-sided 95% confidence interval of the ratio of geometric mean titers (GMTs) between groups (QIV/TIV) is >1/1.5 for each strain.

Non-inferiority (B/Massachusett; GMTR; Overall)

Statistical analysis description

Ratio of GMTs were assessed in the H3N2 strain between the pooled QIV and TIV groups to determine non-inferiority.

Comparison groups

Pooled QIV v Pooled TIV

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

Parameter type

Ratio of GMTs

Point estimate

0.964

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.09

Notes
[4] - Non-inferiority was confirmed if the lower limit of the overall age-stratified two-sided 95% confidence interval of the ratio of geometric mean titers (GMTs) between groups (QIV/TIV) is >1/1.5 for each strain.

Primary: Geometric Mean Titers (GMTs) of Influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

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End point title

Geometric Mean Titers (GMTs) of Influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years ^[5]

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 post-vaccination

Notes
[5] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Number of subjects analysed	277	276	280	140	138
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
A/H1N1; Day 0	59.7 (49.2 to 72.5)	63.5 (52.3 to 77.1)	63.6 (52.1 to 77.7)	57.4 (43.7 to 75.4)	77.6 (58.9 to 102)
A/H1N1; Day 21	603 (525 to 694)	649 (567 to 743)	575 (507 to 653)	737 (586 to 926)	637 (515 to 787)
A/H3N2; Day 0	47.5 (39 to 57.9)	47.7 (38.9 to 58.6)	50.5 (41.6 to 61.2)	39.6 (30.3 to 51.8)	44.9 (34.1 to 59.1)
A/H3N2; Day 21	526 (454 to 609)	487 (422 to 562)	484 (421 to 556)	583 (468 to 725)	680 (558 to 829)
B/Brisbane; Day 0	62.3 (52.3 to 74.2)	61.8 (51.4 to 74.3)	59.8 (50.4 to 71)	64.5 (50.1 to 83)	67.1 (52.5 to 85.8)
B/Brisbane; Day 21	711 (631 to 801)	723 (640 to 818)	692 (612 to 783)	735 (615 to 879)	204 (170 to 243)
B/Massachusetts; Day 0	213 (178 to 255)	249 (206 to 300)	240 (202 to 283)	214 (166 to 276)	285 (222 to 365)
B/Massachusetts; Day 21	1739 (1556 to 1944)	1736 (1550 to 1945)	1670 (1489 to 1874)	689 (556 to 854)	1735 (1490 to 2019)

No statistical analyses for this end point

Primary: Geometric Mean Titers (GMTs) of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older

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End point title

Geometric Mean Titers (GMTs) of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older ^[6]

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 post-vaccination

Notes
[6] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Number of subjects analysed	276	277	279	138	137
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
A/H1N1; Day 0	42 (35.2 to 50)	48 (39.9 to 57.9)	43.3 (36 to 51.9)	53.5 (40.7 to 70.5)	36.7 (28.3 to 47.6)
A/H1N1; Day 21	222 (186 to 264)	216 (184 to 254)	219 (185 to 259)	328 (265 to 406)	218 (171 to 277)
A/H3N2; Day 0	59.3 (48.6 to 72.4)	70.3 (58 to 85.1)	63.2 (52.1 to 76.6)	79.8 (58.4 to 109)	62.6 (48.3 to 81.3)
A/H3N2; Day 21	362 (312 to 420)	395 (341 to 456)	324 (278 to 376)	492 (395 to 612)	340 (276 to 419)
B/Brisbane; Day 0	52.9 (44.3 to 63.1)	70.2 (58.5 to 84.4)	64.9 (54.8 to 76.9)	65.4 (51.1 to 83.7)	60.9 (47.9 to 77.4)
B/Brisbane; Day 21	272 (236 to 314)	314 (273 to 360)	277 (240 to 319)	301 (244 to 372)	121 (101 to 147)
B/Massachusetts; Day 0	140 (117 to 166)	156 (134 to 182)	186 (158 to 218)	172 (138 to 214)	170 (132 to 217)
B/Massachusetts; Day 21	595 (527 to 672)	661 (588 to 744)	712 (632 to 803)	351 (294 to 420)	697 (593 to 820)

No statistical analyses for this end point

Primary: Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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End point title

Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route ^[7]

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroprotection was defined as antibody titers ≥ 40 (1/dil).

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 post-vaccination

Notes
[7] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Number of subjects analysed	277	276	280	140	138
Units: Percentage of subjects
number (not applicable)
A/H1N1; Day 0	63.5	64.9	65.4	65.7	71
A/H1N1; Day 21	97.8	97.8	98.9	97.1	97.1
A/H3N2; Day 0	57.4	55.6	62.5	56.4	55.1
A/H3N2; Day 21	98.6	98.2	97.1	97.9	99.3
B/Brisbane; Day 0	62.5	61.5	61.8	67.9	65.2
B/Brisbane; Day 21	100	99.3	100	100	97.8
B/Massachusetts; Day 0	86.6	86.5	90.7	87.1	90.6
B/Massachusetts; Day 21	100	100	100	99.3	100

No statistical analyses for this end point

Primary: Percentage of Subjects Aged 60 Years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination with a Quadrivalent Influenza Vaccine Administered via the Intramuscular Route

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End point title

Percentage of Subjects Aged 60 Years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination with a Quadrivalent Influenza Vaccine Administered via the Intramuscular Route ^[8]

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroprotection was defined as antibody titers ≥ 40 (1/dil).

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 post-vaccination

Notes
[8] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Number of subjects analysed	276	277	279	138	137
Units: Percentage of subjects
number (not applicable)
A/H1N1; Day 0	57.6	58.1	57.3	64.5	54
A/H1N1; Day 21	89.1	91.7	91	97.8	91.2
A/H3N2; Day 0	64.5	67	65.9	65.9	69.9
A/H3N2; Day 21	96	97.8	94.6	98.6	97.1
B/Brisbane; Day 0	59.8	69	69.1	70.3	66.4
B/Brisbane; Day 21	96.4	97.1	96	95.7	85.4
B/Massachusetts; Day 0	81.9	88	88.9	85.5	86.9
B/Massachusetts; Day 21	100	100	100	98.6	100

No statistical analyses for this end point

Primary: Geometric Mean Titer Ratios (GMTRs) of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

Top of page

End point title

Geometric Mean Titer Ratios (GMTRs) of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years ^[9]

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.

End point type

Primary

End point timeframe

Day 21 post-vaccination/Day 0 (pre-vaccination)

Notes
[9] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Number of subjects analysed	277	276	280	140	138
Units: Titer ratios (1/dil)
geometric mean (confidence interval 95%)
A/H1N1	10.1 (8.28 to 12.3)	10.2 (8.32 to 12.6)	9.04 (7.37 to 11.1)	12.8 (9.36 to 17.6)	8.2 (6.27 to 10.7)
A/H3N2	11.1 (9.07 to 13.5)	10.2 (8.32 to 12.5)	9.58 (7.87 to 11.7)	14.7 (10.9 to 19.8)	15.1 (11.2 to 20.4)
B/Brisbane	11.4 (9.44 to 13.8)	11.7 (9.66 to 14.2)	11.6 (9.59 to 14)	11.4 (8.66 to 15)	3.03 (2.49 to 3.7)
B/Massachusetts	8.17 (6.87 to 9.72)	6.97 (5.84 to 8.33)	6.97 (5.91 to 8.23)	3.22 (2.67 to 3.9)	6.08 (4.79 to 7.72)

No statistical analyses for this end point

Primary: Geometric Mean Titer Ratios (GMTRs) of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older

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End point title

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.

End point type

Primary

End point timeframe

Day 21 post-vaccination/Day 0 (pre-vaccination)

Notes
[10] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Number of subjects analysed	276	277	279	138	137
Units: Titer ratios (1/dil)
geometric mean (confidence interval 95%)
A/H1N1	5.29 (4.4 to 6.35)	4.5 (3.81 to 5.33)	5.06 (4.21 to 6.08)	6.13 (4.51 to 8.33)	5.94 (4.56 to 7.72)
A/H3N2	6.1 (5.01 to 7.43)	5.61 (4.67 to 6.75)	5.12 (4.24 to 6.18)	6.16 (4.53 to 8.39)	5.43 (4.22 to 6.99)
B/Brisbane	5.15 (4.33 to 6.13)	4.47 (3.77 to 5.3)	4.26 (3.61 to 5.03)	4.6 (3.5 to 6.05)	1.99 (1.7 to 2.34)
B/Massachusetts	4.26 (3.57 to 5.1)	4.24 (3.62 to 4.97)	3.83 (3.26 to 4.52)	2.04 (1.71 to 2.43)	4.11 (3.19 to 5.3)

No statistical analyses for this end point

Primary: Percentage of Subjects Aged 18 to 60 Years Achieving Seroconversion or Significant increase Against Influenza Antigens after Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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End point title

Percentage of Subjects Aged 18 to 60 Years Achieving Seroconversion or Significant increase Against Influenza Antigens after Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route ^[11]

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroconversion was defined as the proportion of subjects with a pre-vaccination titer < 10 (1/dil) to a post-vaccination titer ≥ 40 (1/dil). Significant increase was defined as proportion of subjects with a pre-vaccination titer ≥ 10 (1/dil) and ≥ 4-fold increase of the titer.

End point type

Primary

End point timeframe

Day 21 post-vaccination/Day 0 (pre-vaccination)

Notes
[11] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Number of subjects analysed	277	276	280	140	138
Units: Percentage of subjects
number (not applicable)
A/H1N1	65	65.6	61.8	63.6	66.7
A/H3N2	70.8	66.5	61.4	72.9	73.9
B/Brisbane	71.5	70.5	70.7	70	38.4
B/Massachusetts	67.1	61.1	62.9	42.1	60.9

No statistical analyses for this end point

Primary: Percentage of Subjects Aged 60 Years or Older Achieving Seroconversion or Significant increase Against Influenza Antigens after Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route

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End point title

Percentage of Subjects Aged 60 Years or Older Achieving Seroconversion or Significant increase Against Influenza Antigens after Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route ^[12]

End point description

End point type

Primary

End point timeframe

Day 21 post-vaccination/Day 0 (pre-vaccination)

Notes
[12] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Number of subjects analysed	276	277	279	138	137
Units: Percentage of subjects
number (not applicable)
A/H1N1	49.3	43	44.4	48.6	51.8
A/H3N2	47.1	50.7	44.8	47.1	50
B/Brisbane	45.7	46.6	43.5	43.5	21.2
B/Massachusetts	42.8	45.3	40.1	28.3	38.7

No statistical analyses for this end point

Primary: Percentage of Subjects Aged 18 to 60 years Reporting Solicited Injection-site or Systemic Reaction After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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End point title

Percentage of Subjects Aged 18 to 60 years Reporting Solicited Injection-site or Systemic Reaction After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route ^[13]

End point description

Solicited injection site reactions: Pain, Erythema, Swelling, Induration, and Ecchymosis. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Shivering. Grade 3 Solicited injection site reactions: Pain, Significant; prevents daily activity; Erythema, Swelling, Induration, and Ecchymosis > 100 mm. Grade 3 Solicited systemic reactions: Fever, ≥ 39.0°C; Headache, Malaise, Myalgia, and Shivering, Significant; prevents daily activity.

End point type

Primary

End point timeframe

Day 0 up to Day 7 post-vaccination

Notes
[13] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Number of subjects analysed	277	276	280	140	138
Units: Percentage of subjects
number (not applicable)
Injection site Pain	53.1	57.2	53.9	48.6	61.6
Grade 3 Injection site Pain	0	0.7	0.4	0	0.7
Injection site Erythema	9	6.9	11.8	5	6.5
Grade 3 Injection site Erythema	0	0	0	0	0.7
Injection site Swelling	5.1	6.5	7.1	2.9	4.3
Grade 3 Injection site Swelling	0	0	0	0	0
Injection site Induration	4.3	6.9	8.2	4.3	6.5
Grade 3 Injection site Induration	0	0	0	0	0
Injection site Ecchymosis	0.7	0.7	0.7	0.7	0.7
Grade 3 Injection site Ecchymosis	0	0	0	0	0
Fever	0	0.7	1.4	0	0.7
Grade 3 Fever	0	0	0	0	0
Headache	26.4	27.2	26.4	23.6	30.4
Grade 3 Headache	0.7	3.3	1.1	0.7	1.4
Malaise	21.7	16.3	17.5	20.7	22.5
Grade 3 Malaise	1.1	2.5	0.7	0.7	0.7
Myalgia	24.5	25.7	28.6	17.9	23.9
Grade 3 Myalgia	0.4	0.4	0.7	1.4	0
Shivering	8.3	8.3	6.1	7.1	5.1
Grade 3 Shivering	0.7	0.4	0.7	0	0

No statistical analyses for this end point

Primary: Percentage of Subjects Aged 60 years and older Reporting Solicited Injection-site or Systemic Reaction After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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End point title

Percentage of Subjects Aged 60 years and older Reporting Solicited Injection-site or Systemic Reaction After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route ^[14]

End point description

End point type

Primary

End point timeframe

Day 0 up to Day 7 post-vaccination

Notes
[14] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Number of subjects analysed	276	278	279	139	137
Units: Percentage of subjects
number (not applicable)
Injection site Pain	20.3	25.3	23.3	25.2	14.6
Grade 3 Injection site Pain	0	0.4	0	0	0
Injection site Erythema	8	9.4	5.4	7.9	5.8
Grade 3 Injection site Erythema	0	0	0	0.7	0.7
Injection site Swelling	3.3	4.3	2.2	2.9	3.6
Grade 3 Injection site Swelling	0	0	0	0	0
Injection site Induration	2.5	2.9	2.5	2.9	3.6
Grade 3 Injection site Induration	0	0	0	0	0
Injection site Ecchymosis	1.1	0.4	0	0	0.7
Grade 3 Injection site Ecchymosis	0	0	0	0	0
Fever	1.8	0.7	0.7	0	0.7
Grade 3 Fever	0.4	0.4	0	0	0
Headache	17	12.2	16.5	12.2	11.7
Grade 3 Headache	0.7	0.4	0.4	0	0.7
Malaise	12.7	9.4	9.3	10.1	12.4
Grade 3 Malaise	0	1.1	0.7	0	1.5
Myalgia	12	12.6	14	10.1	13.1
Grade 3 Myalgia	0	0.7	1.1	0	0
Shivering	3.3	4.3	5.7	3.6	4.4
Grade 3 Shivering	0.4	0	0.7	0.7	0

No statistical analyses for this end point

Primary: Percentage of Subjects Aged 18 to 60 Years Reporting Solicited Reactions Listed in the EMA Note for Guidance within 3 Days After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route

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End point title

Percentage of Subjects Aged 18 to 60 Years Reporting Solicited Reactions Listed in the EMA Note for Guidance within 3 Days After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route ^[15]

End point description

Reactions listed in the European Medicines Agency (EMA) Note for Guidance: Injection site induration ≥ 5 cm for at least 4 consecutive days; Injection site ecchymosis (injection site bruising); Pyrexia (recorded temperature > 38.0°C) for at least 1 day; Malaise; Shivering (Rigors).

End point type

Primary

End point timeframe

Day 0 up to Day 3 post-vaccination

Notes
[15] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Number of subjects analysed	277	276	280	140	138
Units: Percentage of subjects
number (not applicable)
Reaction listed in the EMA recommendations	22.7	19.9	18.2	20	19.6
Injection site Induration ≥ 5 cm for 4 days	0	0	0	0	0
Injection site Ecchymosis	2.2	2.2	3.2	2.1	2.9
Pyrexia (> 38.0°C) for at least 1 day	0	0.4	1.1	0	0
Malaise	18.8	14.5	13.9	17.1	15.2
Shivering (Rigors)	7.2	7.2	5.7	6.4	3.6

No statistical analyses for this end point

Primary: Percentage of Subjects Aged 60 years and older Reporting Solicited Reactions Listed in the EMA Note for Guidance within 3 Days of Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route

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End point title

Percentage of Subjects Aged 60 years and older Reporting Solicited Reactions Listed in the EMA Note for Guidance within 3 Days of Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route ^[16]

End point description

End point type

Primary

End point timeframe

Day 0 up to Day 3 post-vaccination

Notes
[16] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Number of subjects analysed	276	278	279	139	137
Units: Percentage of subjects
number (not applicable)
Reaction listed in the EMA recommendations	13	10.4	11.5	7.9	11.7
Injection site Induration ≥ 5 cm for 4 days	0	0	0.4	0	0
Injection site Ecchymosis	2.5	4	1.1	1.4	2.9
Pyrexia (> 38.0°C) for at least 1 day	0.7	0.7	0.4	0	0
Malaise	10.5	6.8	7.5	7.2	8.8
Shivering (Rigors)	2.5	4	4.7	2.2	2.2

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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End point title

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroprotection was defined as antibody titers ≥ 40 (1/dil).

End point type

Other pre-specified

End point timeframe

Day 0 (pre-vaccination) and Day 21 post-vaccination

End point values	Pooled QIV	Pooled TIV
Number of subjects analysed	833	278
Units: Percentage
number (not applicable)
A/H1N1; Day 0	64.6	68.3
A/H1N1; Day 21	98.2	97.1
A/H3N2; Day 0	58.5	55.8
A/H3N2; Day 21	98	98.6
B/Brisbane; Day 0	61.9	67.9
B/Brisbane; Day 21	99.8	100
B/Massachusetts; Day 0	88	90.6
B/Massachusetts; Day 21	100	100

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Aged 60 years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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End point title

Percentage of Subjects Aged 60 years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroprotection was defined as antibody titers ≥ 40 (1/dil).

End point type

Other pre-specified

End point timeframe

Day 0 (pre-vaccination) and Day 21 post-vaccination

End point values	Pooled QIV	Pooled TIV
Number of subjects analysed	832	275
Units: Percentage
number (not applicable)
A/H1N1; Day 0	57.7	59.3
A/H1N1; Day 21	90.6	94.5
A/H3N2; Day 0	65.8	67.9
A/H3N2; Day 21	96.1	97.8
B/Brisbane; Day 0	65.9	70.3
B/Brisbane; Day 21	96.5	95.7
B/Massachusetts; Day 0	86.3	86.9
B/Massachusetts; Day 21	100	100

No statistical analyses for this end point

Other pre-specified: Geometric Mean Titers of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years.

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End point title

Geometric Mean Titers of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years.

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method

End point type

Other pre-specified

End point timeframe

Day 0 (pre-vaccination); Day 21; Day 180 and Day 365 post-vaccination

End point values	Pooled QIV	Pooled TIV
Number of subjects analysed	145	70
Units: Geometric Mean Titers
geometric mean (confidence interval 95%)
A/H1N1; Day 0	68.7 (52.2 to 90.5)	65.2 (45.9 to 92.6)
A/H1N1; Day 21	658 (565 to 767)	681 (501 to 925)
A/H1N1; Day 180	290 (244 to 345)	253 (189 to 339)
A/H1N1; Day 365	250 (208 to 301)	207 (151 to 285)
A/H3N2; Day 0	47.8 (36.8 to 62.1)	42 (29.5 to 59.7)
A/H3N2; Day 21	470 (386 to 571)	703 (517 to 955)
A/H3N2; Day 180	225 (185 to 274)	275 (206 to 366)
A/H3N2; Day 365	184 (150 to 226)	202 (149 to 273)
B/Brisbane; Day 0	58.7 (45.3 to 76.1)	57.2 (33.2 to 98.6)
B/Brisbane; Day 21	675 (575 to 793)	718 (462 to 1118)
B/Brisbane; Day 180	285 (235 to 346)	271 (179 to 409)
B/Brisbane; Day 365	248 (199 to 309)	217 (142 to 332)
B/Massachusetts; Day 0	197 (153 to 254)	256 (175 to 374)
B/Massachusetts; Day 21	1731 (1492 to 2009)	1759 (1341 to 2307)
B/Massachusetts; Day 180	830 (684 to 1007)	873 (637 to 1197)
B/Massachusetts; Day 365	685 (558 to 840)	764 (551 to 1059)

No statistical analyses for this end point

Other pre-specified: Geometric Mean Titers of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older.

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End point title

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method

End point type

Other pre-specified

End point timeframe

Day 0 (pre-vaccination); Day 21; Day 180 and Day 365 post-vaccination.

End point values	Pooled QIV	Pooled TIV
Number of subjects analysed	145	70
Units: Geometric Mean Titers
geometric mean (confidence interval 95%)
A/H1N1; Day 0	42.7 (33.4 to 54.4)	45.5 (30.7 to 67.4)
A/H1N1; Day 21	204 (162 to 257)	240 (176 to 327)
A/H1N1; Day 180	87.3 (68.8 to 111)	120 (86.4 to 167)
A/H1N1; Day 365	77.4 (60.8 to 98.7)	107 (75.5 to 153)
A/H3N2; Day 0	63.9 (48 to 85)	79.6 (52.8 to 120)
A/H3N2; Day 21	392 (317 to 484)	404 (293 to 557)
A/H3N2; Day 180	180 (144 to 225)	221 (155 to 314)
A/H3N2; Day 365	144 (113 to 182)	144 (101 to 205)
B/Brisbane; Day 0	64.5 (50.5 to 82.5)	55.7 (33.5 to 92.7)
B/Brisbane; Day 21	281 (233 to 340)	282 (161 to 493)
B/Brisbane; Day 180	132 (108 to 161)	147 (85.2 to 253)
B/Brisbane; Day 365	118 (93.9 to 147)	117 (73 to 188)
B/Massachusetts; Day 0	169 (135 to 212)	182 (117 to 284)
B/Massachusetts; Day 21	667 (563 to 789)	645 (497 to 836)
B/Massachusetts; Day 180	340 (284 to 407)	334 (247 to 451)
B/Massachusetts; Day 365	324 (272 to 387)	340 (249 to 463)

No statistical analyses for this end point

Other pre-specified: Geometric Mean Titer Ratios of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

Top of page

End point title

Geometric Mean Titer Ratios of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.

End point type

Other pre-specified

End point timeframe

Day 0 (pre-vaccination); Day 21; Day 180 and Day 365 post-vaccination

End point values	Pooled QIV	Pooled TIV
Number of subjects analysed	148	78
Units: Geometric Mean Titer Ratios
geometric mean (confidence interval 95%)
A/H1N1; Day 21/Day 0	9.58 (7.21 to 12.7)	10.4 (7.25 to 15)
A/H1N1; Day 180/Day 21	0.441 (0.388 to 0.5)	0.373 (0.324 to 0.43)
A/H1N1; Day 365/Day 21	0.361 (0.31 to 0.421)	0.324 (0.275 to 0.382)
A/H3N2; Day 21/Day 0	9.83 (7.62 to 12.7)	16.7 (11.4 to 24.6)
A/H3N2; Day 180/Day 21	0.479 (0.414 to 0.555)	0.377 (0.303 to 0.468)
A/H3N2; Day 365/Day 21	0.382 (0.328 to 0.446)	0.277 (0.218 to 0.353)
B/Brisbane; Day 21/Day 0	11.5 (8.88 to 14.9)	12.6 (6.81 to 23.1)
B/Brisbane; Day 180/Day 21	0.422 (0.38 to 0.47)	0.366 (0.28 to 0.48)
B/Brisbane; Day 365/Day 21	0.352 (0.308 to 0.402)	0.275 (0.201 to 0.377)
B/Massachusetts; Day 21/Day 0	8.79 (7.01 to 11)	6.87 (4.85 to 9.74)
Massachusetts; Day 180/Day 21	0.479 (0.432 to 0.532)	0.496 (0.415 to 0.594)
Massachusetts; Day 365/Day 21	0.407 (0.361 to 0.459)	0.454 (0.362 to 0.569)

No statistical analyses for this end point

Other pre-specified: Geometric Mean Titer Ratios of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older

Top of page

End point title

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.

End point type

Other pre-specified

End point timeframe

Day 0 (pre-vaccination); Day 21; Day 180 and Day 365 post-vaccination.

End point values	Pooled QIV	Pooled TIV
Number of subjects analysed	145	70
Units: Geometric Mean Titer Ratios
geometric mean (confidence interval 95%)
A/H1N1; Day 21/Day 0	4.77 (3.84 to 5.94)	5.28 (3.57 to 7.8)
A/H1N1; Day 180/Day 21	0.431 (0.376 to 0.494)	0.508 (0.403 to 0.64)
A/H1N1; Day 365/Day 21	0.358 (0.313 to 0.411)	0.422 (0.317 to 0.56)
A/H3N2; Day 21/Day 0	6.14 (4.64 to 8.11)	5.07 (3.48 to 7.39)
A/H3N2; Day 180/Day 21	0.46 (0.387 to 0.548)	0.554 (0.423 to 0.724)
A/H3N2; Day 365/Day 21	0.359 (0.298 to 0.434)	0.376 (0.288 to 0.493)
B/Brisbane; Day 21/Day 0	4.39 (3.55 to 5.44)	5.07 (2.37 to 10.8)
B/Brisbane; Day 180/Day 21	0.465 (0.417 to 0.518)	0.555 (0.388 to 0.793)
B/Brisbane; Day 365/Day 21	0.423 (0.373 to 0.481)	0.443 (0.303 to 0.648)
B/Massachusetts; Day 21/Day 0	3.94 (3.15 to 4.94)	3.54 (2.27 to 5.52)
B/Massachusetts; Day 180/Day 21	0.51 (0.454 to 0.573)	0.518 (0.424 to 0.634)
B/Massachusetts; Day 365/Day 21	0.475 (0.416 to 0.542)	0.53 (0.42 to 0.671)

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Top of page

End point title

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroprotection was defined as antibody titers ≥ 40 (1/dil).

End point type

Other pre-specified

End point timeframe

Day 0 (pre-vaccination); Day 21; Day 180 and Day 365 post-vaccination

End point values	Pooled QIV	Pooled TIV
Number of subjects analysed	148	78
Units: Percentage
number (not applicable)
A/H1N1; Day 0	67.6	70.5
A/H1N1; Day 21	98.6	97.4
A/H1N1; Day 180	96.6	90.9
A/H1N1; Day 365	94.5	89.7
A/H3N2; Day 0	60.8	60.3
A/H3N2; Day 21	97.3	98.7
A/H3N2; Day 180	92.6	93.5
A/H3N2; Day 365	91.4	92.5
B/Brisbane; Day 0	58.1	73.3
B/Brisbane; Day 21	100	100
B/Brisbane; Day 180	97.3	100
B/Brisbane; Day 365	95.3	100
B/Massachusetts; Day 0	85.1	91.7
B/Massachusetts; Day 21	100	100
B/Massachusetts; Day 180	100	100
B/Massachusetts; Day 365	99.2	100

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Aged 60 years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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End point title

End point description

Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroprotection was defined as antibody titers ≥ 40 (1/dil).

End point type

Other pre-specified

End point timeframe

Day 0 (pre-vaccination); Day 21; Day 180 and Day 365 post-vaccination

End point values	Pooled QIV	Pooled TIV
Number of subjects analysed	145	70
Units: Percentage
number (not applicable)
A/H1N1; Day 0	57.9	58.6
A/H1N1; Day 21	89.7	94.3
A/H1N1; Day 180	76.2	85.3
A/H1N1; Day 365	75	80.3
A/H3N2; Day 0	65.5	71.4
A/H3N2; Day 21	94.5	97.1
A/H3N2; Day 180	89.5	92.6
A/H3N2; Day 365	85.9	83.6
B/Brisbane; Day 0	66.9	72.7
B/Brisbane; Day 21	97.2	100
B/Brisbane; Day 180	89.5	95
B/Brisbane; Day 365	83.6	95
B/Massachusetts; Day 0	86.2	85.4
B/Massachusetts; Day 21	100	100
B/Massachusetts; Day 180	100	100
B/Massachusetts; Day 365	100	100

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse event data were collected from Day 0 up to 12 months post-vaccination.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

QIV S4456

Reporting group description

Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 1 S4456.

Reporting group title

QIV S4457

Reporting group description

Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 2 S4457.

Reporting group title

QIV S4458

Reporting group description

Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 3 S4458.

Reporting group title

TIV1

Reporting group description

Subjects received a single dose of trivalent influenza vaccine (TIV) 1 from the Victoria lineage.

Reporting group title

TIV2

Reporting group description

Subjects received a single dose of trivalent influenza vaccine (TIV) 2 from the Yamagata lineage.

Serious adverse events	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Total subjects affected by serious adverse events
subjects affected / exposed	19 / 554 (3.43%)	12 / 554 (2.17%)	14 / 560 (2.50%)	9 / 279 (3.23%)	6 / 275 (2.18%)
number of deaths (all causes)	1	1	1	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anaplastic astrocytoma
subjects affected / exposed	0 / 554 (0.00%)	1 / 554 (0.18%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic lymphocytic leukaemia
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endometrial cancer
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	1 / 275 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal carcinoma
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	0 / 560 (0.00%)	1 / 279 (0.36%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Metastatic neoplasm
subjects affected / exposed	0 / 554 (0.00%)	1 / 554 (0.18%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thyroid neoplasm
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Aneurysm
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Varicose vein
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Rotator cuff repair
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	0 / 560 (0.00%)	1 / 279 (0.36%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Hyperemesis gravidarum
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	0 / 560 (0.00%)	1 / 279 (0.36%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 554 (0.00%)	1 / 554 (0.18%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Completed suicide
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Confusional state
subjects affected / exposed	0 / 554 (0.00%)	1 / 554 (0.18%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Accident
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	0 / 560 (0.00%)	1 / 279 (0.36%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	1 / 560 (0.18%)	1 / 279 (0.36%)	1 / 275 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ligament sprain
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	1 / 275 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus lesion
subjects affected / exposed	0 / 554 (0.00%)	1 / 554 (0.18%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 554 (0.00%)	1 / 554 (0.18%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	0 / 554 (0.00%)	1 / 554 (0.18%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	1 / 279 (0.36%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiomyopathy
subjects affected / exposed	0 / 554 (0.00%)	1 / 554 (0.18%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sick sinus syndrome
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 554 (0.00%)	1 / 554 (0.18%)	0 / 560 (0.00%)	1 / 279 (0.36%)	0 / 275 (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	0 / 0	0 / 0	0 / 0	0 / 0
Convulsion
subjects affected / exposed	0 / 554 (0.00%)	1 / 554 (0.18%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	0 / 560 (0.00%)	1 / 279 (0.36%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Deafness neurosensory
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Maculopathy
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Intestinal obstruction
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal polyp
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis chronic
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	1 / 275 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	0 / 554 (0.00%)	1 / 554 (0.18%)	2 / 560 (0.36%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	2 / 554 (0.36%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Scleroderma
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Erysipelas
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	0 / 560 (0.00%)	1 / 279 (0.36%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Groin abscess
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	1 / 275 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 554 (0.00%)	1 / 554 (0.18%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pilonidal cyst
subjects affected / exposed	0 / 554 (0.00%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	1 / 275 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	1 / 560 (0.18%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	1 / 554 (0.18%)	0 / 554 (0.00%)	0 / 560 (0.00%)	0 / 279 (0.00%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	QIV S4456	QIV S4457	QIV S4458	TIV1	TIV2
Total subjects affected by non serious adverse events
subjects affected / exposed	147 / 554 (26.53%)	158 / 554 (28.52%)	151 / 560 (26.96%)	68 / 279 (24.37%)	85 / 275 (30.91%)
Nervous system disorders
Headache
alternative assessment type: Systematic
subjects affected / exposed ^[1]	73 / 277 (26.35%)	75 / 276 (27.17%)	74 / 280 (26.43%)	33 / 140 (23.57%)	42 / 138 (30.43%)
occurrences all number	73	75	74	33	42
General disorders and administration site conditions
Injection site Pain
alternative assessment type: Systematic
subjects affected / exposed ^[2]	147 / 277 (53.07%)	158 / 276 (57.25%)	151 / 280 (53.93%)	68 / 140 (48.57%)	85 / 138 (61.59%)
occurrences all number	147	158	151	68	85
Injection site Erythema
alternative assessment type: Systematic
subjects affected / exposed ^[3]	25 / 277 (9.03%)	26 / 278 (9.35%)	33 / 280 (11.79%)	11 / 139 (7.91%)	9 / 138 (6.52%)
occurrences all number	25	26	33	11	9
Injection site Swelling
alternative assessment type: Systematic
subjects affected / exposed ^[4]	14 / 277 (5.05%)	18 / 276 (6.52%)	20 / 280 (7.14%)	4 / 140 (2.86%)	6 / 138 (4.35%)
occurrences all number	14	18	20	4	6
Injection site Induration
alternative assessment type: Systematic
subjects affected / exposed ^[5]	12 / 277 (4.33%)	19 / 276 (6.88%)	23 / 280 (8.21%)	6 / 140 (4.29%)	9 / 138 (6.52%)
occurrences all number	12	19	23	6	9
Malaise
alternative assessment type: Systematic
subjects affected / exposed ^[6]	60 / 277 (21.66%)	45 / 276 (16.30%)	49 / 280 (17.50%)	29 / 140 (20.71%)	31 / 138 (22.46%)
occurrences all number	60	45	49	29	31
Shivering
alternative assessment type: Systematic
subjects affected / exposed ^[7]	23 / 277 (8.30%)	23 / 276 (8.33%)	17 / 280 (6.07%)	10 / 140 (7.14%)	7 / 138 (5.07%)
occurrences all number	23	23	17	10	7
Musculoskeletal and connective tissue disorders
Myalgia
alternative assessment type: Systematic
subjects affected / exposed ^[8]	68 / 277 (24.55%)	71 / 276 (25.72%)	80 / 280 (28.57%)	25 / 140 (17.86%)	33 / 138 (23.91%)
occurrences all number	68	71	80	25	33
Infections and infestations
Nasopharyngitis
subjects affected / exposed ^[9]	19 / 552 (3.44%)	19 / 554 (3.43%)	16 / 560 (2.86%)	11 / 279 (3.94%)	9 / 275 (3.27%)
occurrences all number	19	20	17	11	9

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was an unsolicited adverse event recorded in a diary card within 21 days after vaccination; the total number (N) reflects those subjects for which data were available for the event during the period.

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Were there any global substantial amendments to the protocol? Yes

21 Nov 2014

Included an additional blood sample collection to be used to test the persistence of the immune response and the informed consent form was updated to inform the subjects of the observational subset, addition of a 4th visit, and to obtain their consent to continue in the study.

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 reported

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Clinical trials

Clinical Trial Results: Immunogenicity and Lot-to-Lot Consistency Study of a Quadrivalent Influenza Vaccine in Adult and Elderly Subjects

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Geometric Mean Titers (GMTs) of Influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in All Subjects

Primary: Geometric Mean Titers (GMTs) of Influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in All Subjects

Primary: Geometric Mean Titers (GMTs) of Influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

Primary: Geometric Mean Titers (GMTs) of Influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

Primary: Geometric Mean Titers (GMTs) of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older

Primary: Geometric Mean Titers (GMTs) of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older

Primary: Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Primary: Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Primary: Percentage of Subjects Aged 60 Years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination with a Quadrivalent Influenza Vaccine Administered via the Intramuscular Route

Primary: Percentage of Subjects Aged 60 Years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination with a Quadrivalent Influenza Vaccine Administered via the Intramuscular Route

Primary: Geometric Mean Titer Ratios (GMTRs) of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

Primary: Geometric Mean Titer Ratios (GMTRs) of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

Primary: Geometric Mean Titer Ratios (GMTRs) of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older

Primary: Geometric Mean Titer Ratios (GMTRs) of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older

Primary: Percentage of Subjects Aged 18 to 60 Years Achieving Seroconversion or Significant increase Against Influenza Antigens after Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Primary: Percentage of Subjects Aged 18 to 60 Years Achieving Seroconversion or Significant increase Against Influenza Antigens after Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Primary: Percentage of Subjects Aged 60 Years or Older Achieving Seroconversion or Significant increase Against Influenza Antigens after Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route

Primary: Percentage of Subjects Aged 60 Years or Older Achieving Seroconversion or Significant increase Against Influenza Antigens after Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route

Primary: Percentage of Subjects Aged 18 to 60 years Reporting Solicited Injection-site or Systemic Reaction After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Primary: Percentage of Subjects Aged 18 to 60 years Reporting Solicited Injection-site or Systemic Reaction After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Primary: Percentage of Subjects Aged 60 years and older Reporting Solicited Injection-site or Systemic Reaction After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Primary: Percentage of Subjects Aged 60 years and older Reporting Solicited Injection-site or Systemic Reaction After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Primary: Percentage of Subjects Aged 18 to 60 Years Reporting Solicited Reactions Listed in the EMA Note for Guidance within 3 Days After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route

Primary: Percentage of Subjects Aged 18 to 60 Years Reporting Solicited Reactions Listed in the EMA Note for Guidance within 3 Days After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route

Primary: Percentage of Subjects Aged 60 years and older Reporting Solicited Reactions Listed in the EMA Note for Guidance within 3 Days of Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route

Primary: Percentage of Subjects Aged 60 years and older Reporting Solicited Reactions Listed in the EMA Note for Guidance within 3 Days of Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route

Other pre-specified: Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Other pre-specified: Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Other pre-specified: Percentage of Subjects Aged 60 years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Other pre-specified: Percentage of Subjects Aged 60 years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Other pre-specified: Geometric Mean Titers of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years.

Other pre-specified: Geometric Mean Titers of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years.

Other pre-specified: Geometric Mean Titers of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older.

Other pre-specified: Geometric Mean Titers of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older.

Other pre-specified: Geometric Mean Titer Ratios of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

Other pre-specified: Geometric Mean Titer Ratios of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

Other pre-specified: Geometric Mean Titer Ratios of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older

Other pre-specified: Geometric Mean Titer Ratios of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older

Other pre-specified: Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Other pre-specified: Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Other pre-specified: Percentage of Subjects Aged 60 years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Other pre-specified: Percentage of Subjects Aged 60 years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Immunogenicity and Lot-to-Lot Consistency Study of a Quadrivalent Influenza Vaccine in Adult and Elderly Subjects