Download PDF

Clinical Trial Results:
A Phase III, observer-blind, randomized, multi-country study to evaluate the lot-to-lot consistency of GSK’s investigational RSV maternal vaccine and the immune response, safety and reactogenicity of RSV maternal vaccine when co-administered with GSK’s quadrivalent influenza D-QIV vaccine in healthy non-pregnant women 18-49 years of age.

Summary
EudraCT number	2021-000357-26
Trial protocol	ES FI
Global end of trial date	06 Jun 2022

Results information
Results version number	v2(current)
This version publication date	14 Dec 2023
First version publication date	18 Jun 2023
Other versions	v1
Version creation reason	Correction of full data set Corrections made on Group definitions.

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

214709

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

Rue de l’Institut 89, Rixensart, Belgium, B-1330

Public contact

GSK Response Center, GlaxoSmithKline, 44 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 44 8664357343, GSKClinicalSupportHD@gsk.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

11 Nov 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

06 Jun 2022

Was the trial ended prematurely?

Main objective of the trial

To evaluate the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV vaccine up to study end. • To demonstrate the lot-to-lot consistency of 3 lots of the investigational RSV MAT vaccine based on Geometric mean concentration (GMC) of RSV MAT IgG ELISA at Day 31. • To demonstrate non-inferiority of Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone based on Geometric mean titer (GMT) of Flu D-QIV antibody titers against 3 influenza strains at Day 31 post administration.

Protection of trial subjects

Study participants were observed closely for at least 30 minutes after the administration of the study intervention(s). Appropriate medical treatment was readily available during the observation period.

Background therapy

Evidence for comparator

Actual start date of recruitment

15 Sep 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 451

Country: Number of subjects enrolled

Finland: 113

Country: Number of subjects enrolled

Korea, Republic of: 117

Country: Number of subjects enrolled

Spain: 584

Country: Number of subjects enrolled

United States: 321

Worldwide total number of subjects

1586

EEA total number of subjects

697

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)

1586

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Out of 1586 participants enrolled,47 participants did not receive vaccination as they did not meet the eligibility criteria or they were lost to follow up, therefore only 1539 participants were included in the Exposed Set and started the study.

Screening details

As pre-specified in statistical plan, data reported were presented for individual RSV lot groups, pooled RSV+Flu group and Flu+Placebo Group. As pre-specified in protocol, immunogenicity outcome measures presented data for the pooled groups, and individual RSV lot groups were used for lot-to-lot analyses.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Investigator ^[1]

Are arms mutually exclusive

Yes

RSV lot1 Group

Arm description

Participants randomized to the RSV lot1 Group received one dose of RSV MAT Lot 1 vaccine intramuscularly at Day 1. Participants were also provided with an option of receiving Flu D-QIV vaccine at Day 31 to allow the participants receive the standard of care.

Arm type

Experimental

Investigational medicinal product name

RSVPreF3(120 μg)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

A single dose of RSVPreF3(120 μg) combined with Sodium Chloride (NaCl) was administrated intramuscular (IM). There were used 3 different lots of RSVPreF3(120 μg), one for each individual group (RSV lot1 Group, RSV lot2 Group and RSV lot3 Group) considered under RSV pooled Group.

RSV lot2 Group

Arm description

Participants randomized to the RSV lot2 Group received one dose of RSV MAT Lot 2 vaccine intramuscularly at Day 1. Participants were also provided with an option of receiving Flu D-QIV vaccine at Day 31 to allow the participants receive the standard of care.

Arm type

Experimental

Investigational medicinal product name

RSVPreF3(120 μg)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

RSV lot3 Group

Arm description

Participants randomized to the RSV lot3 Group received one dose of RSV MAT Lot 3 vaccine intramuscularly at Day 1. Participants were also provided with an option of receiving Flu D-QIV vaccine at Day 31 to allow the participants receive the standard of care.

Arm type

Experimental

Investigational medicinal product name

RSVPreF3(120μg)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

A single dose of RSVPreF3(120μg) combined with Sodium Chloride (NaCl) was administrated intramuscular (IM). There were used 3 different lots of RSVPreF3(120μg), one for each individual group (RSV lot1 Group, RSVlot2 Group and RSV lot3 Group) considered under RSV pooled Group.

RSV+Flu pooled Group

Arm description

Participants randomized in this group received one dose of RSVPreF3 vaccine (RSV MAT vaccine) from one of the three lots used (Lot 1, Lot 2 or Lot 3 of same formulation of RSVPreF3 vaccine) and one dose of the Flu D-QIV vaccine on Day 1, and were followed up until the end of the study (Day 181). The participants in this group were considered for the immunogenicity and safety analyses of the RSV MAT and Flu D-QIV vaccines.

Arm type

Experimental

Investigational medicinal product name

RSVPreF3(120μg)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

A single dose of RSVPreF3 (120μg) combined with Sodium Chloride (NaCl) was administrated intramuscular (IM). There were used 3 different lots of RSVPreF3 (120μg), one for each individual group (RSV lot1 Group, RSVlot2 Group and RSV lot3 Group) considered under RSV pooled Group.

Investigational medicinal product name

Flu Quadrivalent influenza vaccine (15 μg HA)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

A single dose of Flu Quadrivalent influenza (15 μg HA) vaccine was administrated intramuscular (IM).

Flu+Placebo Group

Arm description

Participants randomized in this group received one dose of Flu D-QIV vaccine co-administered with one dose of placebo at Day 1, and were followed up until the end of the study (Day 181). This group was considered comparator for immunogenicity and safety analyses for RSV+ Flu Pooled group.

Arm type

Experimental

Investigational medicinal product name

Flu Quadrivalent influenza vaccine (15 μg HA)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

A single dose of Flu Quadrivalent influenza (15 μg HA) vaccine was administrated intramuscular (IM).

Notes
[1] - The roles blinded appear inconsistent with a simple blinded trial.
Justification: This study had the purpuse to evaluate the lot-to-lot consistency of RSVPreF3 vaccine and the immune response, reactogenicity and safety of the RSVPreF3 vaccine when coadministered with Flu D-QIV vaccine, thus the study is a single blinded trial.

Number of subjects in period 1 ^[2]	RSV lot1 Group	RSV lot2 Group	RSV lot3 Group	RSV+Flu pooled Group	Flu+Placebo Group
Started	220	223	218	438	440
Completed	217	220	214	433	427
Not completed	3	3	4	5	13
Consent withdrawn by subject	-	1	-	-	-
MIGRATED / MOVED FROM THE STUDY AREA	-	-	1	-	-
Lost to follow-up	3	2	3	5	13

Notes
[2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: In this study, only the eligible participants from the worldwide total received the study intervention and started the study, hence the difference between the worldwide number enrolled in the trial and the baseline period number of participants.

Baseline characteristics

Top of page

Reporting group title

RSV lot1 Group

Reporting group description

Reporting group title

RSV lot2 Group

Reporting group description

Reporting group title

RSV lot3 Group

Reporting group description

Reporting group title

RSV+Flu pooled Group

Reporting group description

Reporting group title

Flu+Placebo Group

Reporting group description

Reporting group values	RSV lot1 Group	RSV lot2 Group	RSV lot3 Group	RSV+Flu pooled Group	Flu+Placebo Group	Total
Number of subjects	220	223	218	438	440	1539
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)	220	223	218	438	440	1539
From 65-84 years	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0
Age continuous
Units: years
median (standard deviation)	32.0 ( 9.6 )	31.4 ( 9.4 )	31.9 ( 9.3 )	32.0 ( 8.9 )	32.1 ( 8.9 )	-
Sex: Female, Male
Units: Participants
Female	220	223	218	438	440	1539
Male	0	0	0	0	0	0
Race/Ethnicity, Customized
Units: Subjects
AMERICAN INDIAN OR ALASKA NATIVE	2	4	3	10	7	26
ASIAN	22	25	21	38	43	149
BLACK OR AFRICAN AMERICAN	12	3	6	17	17	55
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	0	0	0	1	0	1
OTHER	1	4	3	3	7	18
WHITE	183	187	185	369	366	1290

Subject analysis set title

RSV pooled Group

Subject analysis set type

Per protocol

Subject analysis set description

The RSV pooled Group consisted of participants pooled from RSV lot1, RSV lot2 and RSV lot3 groups. This pooled group was considered for the immunogenicity analysis of the RSV MAT vaccine.

Subject analysis sets values	RSV pooled Group
Number of subjects	661
Age categorical
Units: Subjects
In utero	0
Preterm newborn infants (gestational age < 37 wks)	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	661
From 65-84 years	0
85 years and over	0
Age continuous
Units: years
median (standard deviation)	( )
Sex: Female, Male
Units: Participants
Female	661
Male	0
Race/Ethnicity, Customized
Units: Subjects
AMERICAN INDIAN OR ALASKA NATIVE	9
ASIAN	68
BLACK OR AFRICAN AMERICAN	21
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	0
OTHER	8
WHITE	555

End points

Top of page

Reporting group title

RSV lot1 Group

Reporting group description

Reporting group title

RSV lot2 Group

Reporting group description

Reporting group title

RSV lot3 Group

Reporting group description

Reporting group title

RSV+Flu pooled Group

Reporting group description

Reporting group title

Flu+Placebo Group

Reporting group description

Subject analysis set title

RSV pooled Group

Subject analysis set type

Per protocol

Subject analysis set description

The RSV pooled Group consisted of participants pooled from RSV lot1, RSV lot2 and RSV lot3 groups. This pooled group was considered for the immunogenicity analysis of the RSV MAT vaccine.

Primary: Percentage of participants reporting solicited administration site events in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Top of page

End point title

Percentage of participants reporting solicited administration site events in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group ^[1] ^[2]

End point description

Assessed solicited administration site events include pain, erythema and swelling. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. Analysis was performed on the Solicited Safety Set (SSS), which includes all participants who received at least 1 dose of the study intervention (Exposed Set [ES]) and who have solicited safety data.

End point type

Primary

End point timeframe

From Day 1 to Day 7 (including Day 7)

Notes
[1] - 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: This endpoint was descriptive, hence no statistical analysis was presented.
[2] - 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: This endpoint was descriptive, hence no statistical analysis was presented.

End point values	RSV+Flu pooled Group	Flu+Placebo Group	RSV pooled Group
Number of subjects analysed	438	439	660
Units: Percentage of participants
number (confidence interval 95%)
Pain	51.1 (46.4 to 55.9)	34.4 (30 to 39)	53.6 (49.7 to 57.5)
Erythema	3.7 (2.1 to 5.9)	0.5 (0.1 to 1.6)	4.4 (3 to 6.2)
Swelling	4.6 (2.8 to 7)	0.9 (0.2 to 2.3)	4.5 (3.1 to 6.4)

No statistical analyses for this end point

Primary: Percentage of participants reporting solicited systemic events in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Top of page

End point title

Percentage of participants reporting solicited systemic events in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group ^[3] ^[4]

End point description

Assessed solicited systemic events include fatigue, headache, gastrointestinal (GI) symptoms (nausea, vomiting, diarrhea, abdominal pain) and fever. The preferred location for measuring temperature was the oral cavity. Fever was defined as temperature equal to or above (≥) 38.0 °C/ 100.4°F. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. Analysis was performed on the Solicited Safety Set (SSS), which includes all participants who received at least 1 dose of the study intervention (Exposed Set [ES]) and who have solicited safety data.

End point type

Primary

End point timeframe

From Day 1 to Day 7 (including Day 7)

Notes
[3] - 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: This endpoint was descriptive, hence no statistical analysis was presented.
[4] - 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: This endpoint was descriptive, hence no statistical analysis was presented.

End point values	RSV+Flu pooled Group	Flu+Placebo Group	RSV pooled Group
Number of subjects analysed	438	439	660
Units: Percentage of participants
number (confidence interval 95%)
Fatigue	59.8 (55.1 to 64.4)	51.9 (47.1 to 56.7)	52 (48.1 to 55.8)
Headache	51.4 (46.6 to 56.1)	43.1 (38.4 to 47.8)	47.6 (43.7 to 51.5)
Nausea	15.3 (12.1 to 19)	12.3 (9.4 to 15.7)	14.5 (11.9 to 17.5)
Vomiting	1.8 (0.8 to 3.6)	2.3 (1.1 to 4.1)	2.3 (1.3 to 3.7)
Diarrhea	13 (10 to 16.5)	17.1 (13.7 to 20.9)	12.1 (9.7 to 14.9)
Abdominal pain	13.5 (10.4 to 17)	14.1 (11 to 17.7)	12 (9.6 to 14.7)
Temperature	3 (1.6 to 5)	0.7 (0.1 to 2)	2.4 (1.4 to 3.9)

No statistical analyses for this end point

Primary: Percentage of participants reporting unsolicited adverse events (AEs) in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Top of page

End point title

Percentage of participants reporting unsolicited adverse events (AEs) in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group ^[5] ^[6]

End point description

An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any ‘solicited’ symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. Analysis was performed on the ES (Exposed Set), which includes all participants who received at least 1 dose of the study treatment.

End point type

Primary

End point timeframe

From Day 1 to Day 30 (including Day 30)

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: This endpoint was descriptive, hence no statistical analysis was presented.
[6] - 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: This endpoint was descriptive, hence no statistical analysis was presented.

End point values	RSV+Flu pooled Group	Flu+Placebo Group	RSV pooled Group
Number of subjects analysed	438	440	661
Units: Percentage of participants
number (confidence interval 95%)	30.1 (25.9 to 34.7)	25.7 (21.7 to 30)	26.6 (23.3 to 30.2)

No statistical analyses for this end point

Primary: Percentage of participants reporting serious adverse events (SAEs) in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Top of page

End point title

Percentage of participants reporting serious adverse events (SAEs) in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group ^[7] ^[8]

End point description

An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or results i+F2n abnormal pregnancy outcomes. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. Analysis was performed on the ES, which includes all participants who received at least 1 dose of the study treatment.

End point type

Primary

End point timeframe

From Day 1 to Day 30 (including Day 30)

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: This endpoint was descriptive, hence no statistical analysis was presented.
[8] - 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: This endpoint was descriptive, hence no statistical analysis was presented.

End point values	RSV+Flu pooled Group	Flu+Placebo Group	RSV pooled Group
Number of subjects analysed	438	440	661
Units: Percentage of participants
number (confidence interval 95%)	0 (0 to 0.8)	0.2 (0 to 1.3)	0.2 (0 to 0.8)

No statistical analyses for this end point

Primary: Percentage of participants reporting SAEs in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Top of page

End point title

Percentage of participants reporting SAEs in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group ^[9] ^[10]

End point description

An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or results in abnormal pregnancy outcomes. This objective analyzed the safety and reactogenicity of RSV MAT vaccine when given alone (pooled lots) or co-administered with Flu D-QIV. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. Analysis was performed on the ES, which includes all participants who received at least 1 dose of the study treatment.

End point type

Primary

End point timeframe

From first vaccination up to study end (Day 1 to Day 181)

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: This endpoint was descriptive, hence no statistical analysis was presented.
[10] - 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: This endpoint was descriptive, hence no statistical analysis was presented.

End point values	RSV+Flu pooled Group	Flu+Placebo Group	RSV pooled Group
Number of subjects analysed	438	440	661
Units: Percentage of participants
number (confidence interval 95%)	0.9 (0.2 to 2.3)	0.9 (0.2 to 2.3)	0.8 (0.2 to 1.8)

No statistical analyses for this end point

Primary: RSV MAT immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) concentrations for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 31

Top of page

End point title

RSV MAT immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) concentrations for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 31 ^[11]

End point description

Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. RSV MAT IgG concentrations were expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (EU/mL). As pre-specified in protocol, data reported in this outcome measure was presented only for individual RSV lot groups (RSV lot1, RSV lot2, RSV lot3), as the purpose was to analyze RSV MAT IgG ELISA concentrations, in order to demonstrate the lot-to-lot consistency of the vaccine lots. Analysis was performed on the Per Protocol Set (PPS), only on the participants who received only 1 dose of RSV MAT vaccine (from RSV MAT vaccine Lot 1, Lot 2 or Lot 3), and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.

End point type

Primary

End point timeframe

At Day 31

Notes
[11] - 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: This endpoind had the purpose to only analyse lot-to-lot RSV groups RSV lot 1, RSV lot 2, RSV lot 3).

End point values	RSV lot1 Group	RSV lot2 Group	RSV lot3 Group
Number of subjects analysed	201	204	207
Units: EU/mL
geometric mean (confidence interval 95%)	102811.0 (95243.6 to 110979.6)	100635.8 (92970.2 to 108933.4)	108709.3 (101913.7 to 115958.0)

RSV lot1 Group to RSV lot2 Group consistency

Statistical analysis description

To demonstrate lot-to-lot consistency of the immune responses of Lot 1 and Lot 2 of the RSV MAT vaccine, as measured by ELISA in terms of IgG GMCs at Day 31.

Comparison groups

RSV lot1 Group v RSV lot2 Group

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

other ^[12]

Method

GMC ratio

Parameter type

GMC Ratio

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.13

Notes
[12] - The lot-to-lot consistency is demonstrated only if two-sided 95% confidence intervals (CI) for the 3 pair-wise geometric mean ratios of RSV MAT IgG ELISA concentration falls within 0.67 and 1.5.

RSV lot1 Group to RSV lot3 Group consistency

Statistical analysis description

To demonstrate lot-to-lot consistency of the immune responses of Lot 1 and Lot 3 of the RSV MAT vaccine, as measured by ELISA in terms of IgG GMCs at Day 31.

Comparison groups

RSV lot1 Group v RSV lot3 Group

Number of subjects included in analysis

408

Analysis specification

Pre-specified

Analysis type

other ^[13]

Method

GMC ratio

Parameter type

GMC ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.05

Notes
[13] - The lot-to-lot consistency is demonstrated only if two-sided 95% confidence intervals (CI) for the 3 pair-wise geometric mean ratios of RSV MAT IgG ELISA concentration falls within 0.67 and 1.5.

RSV lot2 Group to RSV lot3 Group consistency

Statistical analysis description

To demonstrate lot-to-lot consistency of the immune responses of Lot 2 and Lot 3 of the RSV MAT vaccine, as measured by ELISA in terms of IgG GMCs at Day 31.

Comparison groups

RSV lot2 Group v RSV lot3 Group

Number of subjects included in analysis

411

Analysis specification

Pre-specified

Analysis type

other ^[14]

Method

GMC ratio

Parameter type

GMC ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.03

Notes
[14] - The lot-to-lot consistency is demonstrated only if two-sided 95% confidence intervals (CI) for the 3 pair-wise geometric mean ratios of RSV MAT IgG ELISA concentration falls within 0.67 and 1.5.

Primary: Flu D-QIV haemagglutinin inhibition (HI) antibody titers against 3 influenza strains for participants in Flu+Placebo Group and RSV+Flu pooled Group at Day 31

Top of page

End point title

Flu D-QIV haemagglutinin inhibition (HI) antibody titers against 3 influenza strains for participants in Flu+Placebo Group and RSV+Flu pooled Group at Day 31 ^[15]

End point description

Flu D-QIV HI antibody titers against 3 influenza strains (A/Tasmania/503/2020 (H3N2) IVR-221; B/Washington/02/2019; B/Phuket/3073/2013) were expressed as geometric mean titers (GMTs), as assessed by HI assay. This objective analyzed the humoral immune response to the Flu D-QIV vaccine when given alone and co-administered with RSV MAT vaccine in terms of antibody titers against 3 influenza strains. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV+Flu Group and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of Flu D-QIV vaccine and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.

End point type

Primary

End point timeframe

At Day 31

Notes
[15] - 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: This endpoint considered only participants who received Flu vaccination and optionally other study interventions, therefore only the Flu groups were considred for statistical analises.

End point values	RSV+Flu pooled Group	Flu+Placebo Group
Number of subjects analysed	398	404
Units: Titers
geometric mean (confidence interval 95%)
A/Tasmania/503/2020 (H3N2)	301.6 (274.0 to 331.9)	421.3 (383.4 to 463.0)
B/Washington/02/2019	30.7 (27.3 to 34.6)	33.0 (29.3 to 37.2)
B/Phuket/3073/2013	56.2 (50.7 to 62.3)	69.9 (62.6 to 77.9)

A/Tasmania/503/2020 (H3N2) IVR-221 strain

Statistical analysis description

To demonstrate the immunological non-inferiority of the Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone as measured by the ratio of HI GMTs of Flu D-QIV antibody titers against A/Tasmania/503/2020 (H3N2) IVR-221 strain at 30 days post administration (Day 31).

Comparison groups

RSV+Flu pooled Group v Flu+Placebo Group

Number of subjects included in analysis

802

Analysis specification

Pre-specified

Analysis type

other ^[16]

Method

GMC ratio

Parameter type

GMC ratio

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

0.82

Notes
[16] - The non-inferiority of Flu D-QIV vaccine is demonstrated for the A/Tasmania/503/2020 (H3N2) IVR-221 strain, if the lower limit (LL) of the 95% CI on the GMT ratio (RSV MAT + Flu D-QIV vaccine divided by Flu D-QIV vaccine) is greater than 0.67 at Day 31 post vaccination.

B/Phuket/3073/2013 strain

Statistical analysis description

To demonstrate the immunological non-inferiority of the Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone as measured by the ratio of HI GMTs of Flu D-QIV antibody titers against B/Phuket/3073/2013 strain at 30 days post administration (Day 31).

Comparison groups

RSV+Flu pooled Group v Flu+Placebo Group

Number of subjects included in analysis

802

Analysis specification

Pre-specified

Analysis type

other ^[17]

Method

GMC ratio

Parameter type

GMC ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

0.93

Notes
[17] - The non-inferiority of Flu D-QIV vaccine is demonstrated for B/Phuket/3073/2013 strain, if the lower limit (LL) of the 95% CI on the GMT ratio (RSV MAT + Flu D-QIV vaccine divided by Flu D-QIV vaccine) is greater than 0.67 at Day 31 post vaccination.

B/Washington/02/2019 strain

Statistical analysis description

To demonstrate the immunological non-inferiority of the Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone as measured by the ratio of HI GMTs of Flu D-QIV antibody titers against B/Washington/02/2019 strain at 30 days post administration (Day 31).

Comparison groups

RSV+Flu pooled Group v Flu+Placebo Group

Number of subjects included in analysis

802

Analysis specification

Pre-specified

Analysis type

other ^[18]

Method

GMC ratio

Parameter type

GMC ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.1

Notes
[18] - The non-inferiority of Flu D-QIV vaccine is demonstrated for B/Washington/02/2019 strain, if the lower limit (LL) of the 95% CI on the GMT ratio (RSV MAT + Flu D-QIV vaccine divided by Flu D-QIV vaccine) is greater than 0.67 at Day 31 post vaccination.

Secondary: RSV A neutralizing antibody titers for participants in RSV pooled Group and RSV+Flu pooled Group at Day 1 and Day 31

Top of page

End point title

RSV A neutralizing antibody titers for participants in RSV pooled Group and RSV+Flu pooled Group at Day 1 and Day 31 ^[19]

End point description

Serological assays for the determination of antibodies against RSV A were performed by neutralization assay. RSV A neutralizing antibody titers were expressed as geometric mean titers (GMTs), in serum dilution inducing 60% inhibition in plaque forming units (ED60). This objective analyzed the humoral immune response of RSV MAT vaccine when given alone and co-administered with Flu D-QIV in terms of RSV A neutralizing antibody. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled groups, since minimal differences were expected between participants who received different RSV lots of the vaccine. Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of RSV MAT vaccine and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.

End point type

Secondary

End point timeframe

At Day 1 and Day 31

Notes
[19] - 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: This endpoint considered only participants who received RSV vaccination and optionally other study interventions, therefore only the RSV groups were considred for statistical analises.

End point values	RSV+Flu pooled Group	RSV pooled Group
Number of subjects analysed	436	657
Units: Titers
geometric mean (confidence interval 95%)
Day 1 (N=657,436)	707.2 (653.4 to 765.5)	721.6 (676.5 to 769.7)
Day 31 (N=611,398)	7761.6 (7092.8 to 8493.6)	8900.9 (8272.1 to 9577.5)

RSV MAT compared with Flu D-QIV

Statistical analysis description

To demonstrate the immunological non-inferiority of the RSV MAT vaccine when co-administered with Flu D-QIV vaccine, compared to RSV MAT vaccine given alone as measured by the ratio of GMTs of RSV A neutralizing antibody titers at 30 days post administration (Day 31).

Comparison groups

RSV+Flu pooled Group v RSV pooled Group

Number of subjects included in analysis

1093

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

Method

GMC ratio

Parameter type

GMC ratio

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

0.97

Notes
[20] - The non-inferiority of RSV MAT vaccine is demonstrated for RSV A neutralizing antibody titers, if the LL of the 95% CI on the GMT ratio (RSV MAT + Flu D-QIV vaccine divided by RSV MAT vaccine) is greater than 0.67 at Day 31 post vaccination.

Secondary: Seroconversion rate (SCR) to Flu D-QIV HI antibody titers against 3 influenza strains for participants in Flu+Placebo group and RSV+Flu pooled group at Day 31

Top of page

End point title

Seroconversion rate (SCR) to Flu D-QIV HI antibody titers against 3 influenza strains for participants in Flu+Placebo group and RSV+Flu pooled group at Day 31 ^[21]

End point description

The SCR was defined as the percentage of participants with: a Day 1 (pre-vaccination) serum anti-HI titer <1:10 and a Day 31 (post-vaccination) serum anti-HI titer ≥1:40, or a Day 1 (pre-vaccination) serum anti-HI titer ≥ 1:10 and a fold increase (post/pre) ≥ 4 at Day 31. This objective analyzed the seroconversion rate to the Flu D-QIV vaccine when given alone and co-administered with RSV MAT vaccine. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled groups, since minimal differences were expected between participants who received different RSV lots of the vaccine. Analysis was performed on the PPS, only on the participants who received 1 dose of Flu D-QIV vaccine and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.

End point type

Secondary

End point timeframe

At Day 31

Notes
[21] - 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: This endpoint considered only participants who received Flu vaccination and optionally other study interventions, therefore only the Flu groups were considred for statistical analises.

End point values	RSV+Flu pooled Group	Flu+Placebo Group
Number of subjects analysed	398	403
Units: Percentage of participants
number (confidence interval 95%)
A/Tasmania/503/2020 (H3N2)	42.5 (37.6 to 47.5)	45.9 (41 to 50.9)
B/Washington/02/2019	25.4 (21.2 to 30)	29.5 (25.1 to 34.2)
B/Phuket/3073/2013	31.4 (26.9 to 36.2)	35.5 (30.8 to 40.4)

A/Tasmania/503/2020 (H3N2) IVR-221 strain

Statistical analysis description

To demonstrate the immunological non-inferiority of the Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone as measured by the difference of proportion of participants achieving seroconversion for HI antibody titers against A/Tasmania/503/2020 (H3N2) IVR-221 strain at 30 days post administration (Day 31).

Comparison groups

RSV+Flu pooled Group v Flu+Placebo Group

Number of subjects included in analysis

801

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

Method

Miettinen and Nurminen

Parameter type

Difference of Proportion

Point estimate

3.44

Confidence interval

level

95%

sides

2-sided

lower limit

-3.44

upper limit

10.29

Notes
[22] - The non-inferiority of Flu D-QIV vaccine is demonstrated with respect to the SCR difference for Flu D-QIV antibody titers against A/Tasmania/503/2020 (H3N2) IVR-221 strain, if the upper limit (UL) of the 95% CI on the SCR difference (Flu D-QIV vaccine minus RSV MAT + Flu D-QIV vaccine) is less than or equal to the pre-defined clinical limit of 10% at Day 31 post vaccination.

B/Phuket/3073/2013 strain

Statistical analysis description

To demonstrate the immunological non-inferiority of the Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone as measured by the difference of proportion of participants achieving seroconversion for HI antibody titers against B/Phuket/3073/2013 strain at 30 days post administration (Day 31).

Comparison groups

RSV+Flu pooled Group v Flu+Placebo Group

Number of subjects included in analysis

801

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

Method

Miettinen and Nurminen

Parameter type

Difference of Proportion

Point estimate

4.08

Confidence interval

level

95%

sides

2-sided

lower limit

-2.46

upper limit

10.58

Notes
[23] - The non-inferiority of Flu D-QIV vaccine is demonstrated with respect to the SCR difference for Flu D-QIV antibody titers against B/Phuket/3073/2013 strain, if the upper limit (UL) of the 95% CI on the SCR difference (Flu D-QIV vaccine minus RSV MAT + Flu D-QIV vaccine) is less than or equal to the pre-defined clinical limit of 10% at Day 31 post vaccination.

B/Washington/02/2019 strain

Statistical analysis description

To demonstrate the immunological non-inferiority of the Flu D-QIV vaccine when co-administered with RSV MAT vaccine compared to Flu D-QIV vaccine given alone as measured by the difference of proportion of participants achieving seroconversion for HI antibody titers against B/Washington/02/2019 strain at 30 days post administration (Day 31).

Comparison groups

RSV+Flu pooled Group v Flu+Placebo Group

Number of subjects included in analysis

801

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[24]

Method

Miettinen and Nurminen

Parameter type

Difference of Proportion

Point estimate

4.15

Confidence interval

level

95%

sides

2-sided

lower limit

-2.04

upper limit

10.32

Notes
[24] - The non-inferiority of Flu D-QIV vaccine is demonstrated with respect to the SCR difference for Flu D-QIV antibody titers against B/Washington/02/2019 strain, if the upper limit (UL) of the 95% CI on the SCR difference (Flu D-QIV vaccine minus RSV MAT + Flu D-QIV vaccine) is less than or equal to the pre-defined clinical limit of 10% at Day 31 post vaccination.

Secondary: RSV B neutralizing antibody titers for participants in RSV pooled Group and RSV+Flu pooled Group at Day 1 and Day 31

Top of page

End point title

RSV B neutralizing antibody titers for participants in RSV pooled Group and RSV+Flu pooled Group at Day 1 and Day 31 ^[25]

End point description

Serological assays for the determination of antibodies against RSV B were performed by neutralization assay. RSV B neutralizing antibody titers were expressed as GMTs, in ED60. This objective analyzed the humoral immune response of RSV MAT vaccine when given alone and co-administered with Flu D-QIV in terms of RSV B neutralizing antibody. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups, since minimal differences were expected between participants who received different RSV lots of the vaccine. Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of RSV MAT vaccine (from one of the 3 lots used) and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.

End point type

Secondary

End point timeframe

At Day 1 and Day 31

Notes
[25] - 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: This endpoint considered only participants who received RSV vaccination and optionally other study interventions, therefore only the RSV groups were considred for statistical analises.

End point values	RSV+Flu pooled Group	RSV pooled Group
Number of subjects analysed	436	656
Units: Titers
geometric mean (confidence interval 95%)
Day 1 (N=656,436)	940.1 (871 to 1014.6)	967.4 (909.5 to 1028.9)
Day 31 (N=610,398)	9162.3 (8483.3 to 9895.8)	11030.5 (10344.5 to 11762)

No statistical analyses for this end point

Secondary: RSV MAT IgG concentrations for participants in RSV pooled Group and RSV+Flu pooled Group at Day 1 and Day 31

Top of page

End point title

RSV MAT IgG concentrations for participants in RSV pooled Group and RSV+Flu pooled Group at Day 1 and Day 31 ^[26]

End point description

Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. RSV MAT IgG concentrations were expressed as GMCs, in EU/mL. This objective analyzed the humoral immune response of RSV MAT vaccine when given alone and co-administered with Flu D-QIV in terms of RSV MAT IgG concentrations. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV and RSV+Flu groups, since minimal differences were expected between participants who received different RSV lots of the vaccine. Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of RSV MAT vaccine (from one of the 3 lots used) and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.

End point type

Secondary

End point timeframe

At Day 1 and Day 31

Notes
[26] - 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: This endpoint considered only participants who received RSV vaccination and optionally other study interventions, therefore only the RSV groups were considred for statistical analises.

End point values	RSV+Flu pooled Group	RSV pooled Group
Number of subjects analysed	436	657
Units: EU/mL
geometric mean (confidence interval 95%)
Day 1 (N=657,436)	5772 (5455.8 to 6106.4)	5522.7 (5285.7 to 5770.4)
Day 31 (N=612,398)	83937 (79640.9 to 88464.9)	104025.1 (99714.5 to 108522.2)

No statistical analyses for this end point

Secondary: Flu D-QIV HI antibody titers against 3 influenza strains for participants in Flu+Placebo Group and RSV+Flu pooled Group at Day 1 and Day 31

Top of page

End point title

Flu D-QIV HI antibody titers against 3 influenza strains for participants in Flu+Placebo Group and RSV+Flu pooled Group at Day 1 and Day 31 ^[27]

End point description

Flu D-QIV HI antibody titers against 3 influenza strains (A/Tasmania/503/2020 (H3N2) IVR-221;B/Washington/02/2019; B/Phuket/3073/2013) were expressed as geometric mean titers (GMTs), as assessed by HI assay. This objective analyzed the humoral immune response to the Flu D-QIV vaccine when given alone and co-administered with RSV MAT vaccine in terms of antibody titers against 3 influenza strains. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV+Flu Group and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of Flu D-QIV vaccine and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.

End point type

Secondary

End point timeframe

At Day 1 and Day 31

Notes
[27] - 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: This endpoint considered only participants who received Fly vaccination and optionally other study interventions, therefore only the Flu groups were considred for statistical analises.

End point values	RSV+Flu pooled Group	Flu+Placebo Group
Number of subjects analysed	436	437
Units: Titers
geometric mean (confidence interval 95%)
A/Tasmania/503/2020 (H3N2) , Day 1 (N=436,437)	92.2 (81.2 to 104.8)	110.3 (97.2 to 125.1)
A/Tasmania/503/2020 (H3N2) , Day 31 (N=398,404)	301.6 (274 to 331.9)	421.3 (383.4 to 463)
B/Washington/02/2019 , Day 1 (N=436,437)	11.7 (10.6 to 13)	10.3 (9.4 to 11.3)
B/Washington/02/2019 , Day 31 (N=398,404)	30.7 (27.3 to 34.6)	33 (29.3 to 37.2)
B/Phuket/3073/2013 , Day 1 (N=436,437)	21.2 (19 to 23.7)	21.9 (19.6 to 24.5)
B/Phuket/3073/2013 , Day 31 (N=398,404)	56.2 (50.7 to 62.3)	69.9 (62.6 to 77.9)

No statistical analyses for this end point

Secondary: Seroprotection rate (SPR) to Flu D-QIV HI antibody titers for participants in Flu+Placebo Group and RSV+Flu pooled Group at Day 1 and Day 31

Top of page

End point title

Seroprotection rate (SPR) to Flu D-QIV HI antibody titers for participants in Flu+Placebo Group and RSV+Flu pooled Group at Day 1 and Day 31 ^[28]

End point description

SPR was measured by the percentage of participants achieving an HI antibody titer ≥1:40. This objective analyzed the seroprotection rate to the Flu D-QIV vaccine when given alone and co-administered with RSV MAT vaccine. As pre-specified in protocol, data reported in this outcome measure was presented for the pooled RSV+Flu Group and Flu+Placebo Group, since minimal differences were expected between participants who received different RSV lots of the vaccine. Analysis was performed on the Per Protocol Set (PPS), only on the participants who received 1 dose of Flu D-QIV vaccine and optionally other study treatment, and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.

End point type

Secondary

End point timeframe

At Day 1 and Day 31

Notes
[28] - 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: This endpoint considered only participants who received Flu vaccination and optionally other study interventions, therefore only the Flu groups were considred for statistical analises.

End point values	RSV+Flu pooled Group	Flu+Placebo Group
Number of subjects analysed	436	437
Units: Percentage of participants
number (confidence interval 95%)
A/Tasmania/503/2020 (H3N2) , Day 1 (N=436,437)	78.7 (74.5 to 82.4)	82.8 (79 to 86.3)
A/Tasmania/503/2020 (H3N2) , Day 31 (N=398,404)	98 (96.1 to 99.1)	98.5 (96.8 to 99.5)
B/Washington/02/2019 , Day 1 (N=436,437)	19.7 (16.1 to 23.8)	16.9 (13.5 to 20.8)
B/Washington/02/2019 , Day 31 (N=398,404)	48 (43 to 53)	48.8 (43.8 to 53.8)
B/Phuket/3073/2013 , Day 1 (N=436,437)	36.7 (32.2 to 41.4)	39.8 (35.2 to 44.6)
B/Phuket/3073/2013 , Day 31 (N=398,404)	74.4 (69.8 to 78.6)	77.2 (72.8 to 81.2)

No statistical analyses for this end point

Secondary: RSV A neutralizing antibody titers for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 1 and Day 31

Top of page

End point title

RSV A neutralizing antibody titers for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 1 and Day 31 ^[29]

End point description

Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. RSV A neutralizing antibody titers were expressed as GMTs, in ED60. As pre-specified in protocol, data reported in this outcome measure was presented only for individual RSV lot groups (RSV lot1, RSV lot2, RSV lot3), as the purpose was to analyze the humoral immune response of RSV A neutralizing antibody titers, in order to demonstrate the lot-to-lot consistency of the vaccine lots. Analysis was performed on the Per Protocol Set (PPS), only on the participants who received only 1 dose of RSV MAT vaccine (from RSV MAT vaccine Lot 1, Lot 2 or Lot 3), and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.

End point type

Secondary

End point timeframe

At Day 1 and Day 31

Notes
[29] - 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: This endpoind had the purpose to only analyse lot-to-lot RSV groups RSV lot 1, RSV lot 2, RSV lot 3).

End point values	RSV lot1 Group	RSV lot2 Group	RSV lot3 Group
Number of subjects analysed	217	223	217
Units: TIters
geometric mean (confidence interval 95%)
Day 1 (N=217, 223, 217)	727.5 (652 to 811.6)	758.4 (676.7 to 849.9)	680.2 (607.4 to 761.7)
Day 31 (N=201, 204, 206)	8545.5 (7464.4 to 9783.2)	8760.3 (7716.2 to 9945.8)	9409.2 (8343.5 to 10611)

No statistical analyses for this end point

Secondary: RSV B neutralizing antibody titers for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 1 and Day 31

Top of page

End point title

RSV B neutralizing antibody titers for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 1 and Day 31 ^[30]

End point description

Serological assays for the determination of antibodies against RSV B were performed by neutralization assay. RSV B neutralizing antibody titers were expressed as GMTs, in ED60. As pre-specified in protocol, data reported in this outcome measure was presented only for individual RSV lot groups (RSV lot1, RSV lot2, RSV lot3), as the purpose was to analyze the humoral immune response of RSV B neutralizing antibody titers, in order to demonstrate the lot-to-lot consistency of the vaccine lots. Analysis was performed on the Per Protocol Set (PPS), only on the participants who received only 1 dose of RSV MAT vaccine (from RSV MAT vaccine Lot 1, Lot 2 or Lot 3), and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.

End point type

Secondary

End point timeframe

At Day 1 and Day 31

Notes
[30] - 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: This endpoind had the purpose to only analyse lot-to-lot RSV groups RSV lot 1, RSV lot 2, RSV lot 3).

End point values	RSV lot1 Group	RSV lot2 Group	RSV lot3 Group
Number of subjects analysed	216	223	217
Units: Titers
geometric mean (confidence interval 95%)
Day 1 (N=216, 223, 217)	895 (810.6 to 988.2)	1030.3 (929.3 to 1142.3)	979.7 (870.6 to 1102.4)
Day 31 (N=201, 204, 205)	10457 (9258.5 to 11810.6)	11107.2 (9984.4 to 12356.4)	11543.3 (10377.6 to 12840.1)

No statistical analyses for this end point

Secondary: RSV MAT IgG concentrations for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 1 and Day 31

Top of page

End point title

RSV MAT IgG concentrations for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 1 and Day 31 ^[31]

End point description

Serological assays for the determination of IgG antibodies against RSV MAT were performed by ELISA. RSV MAT IgG concentrations were expressed as GMCs, in EU/mL. As pre-specified in protocol, data reported in this outcome measure was presented only for individual RSV lot groups (RSV lot1, RSV lot2, RSV lot3), as the purpose was to analyze the RSV MAT IgG concentration, in order to demonstrate the lot-to-lot consistency of the vaccine lots. Analysis was performed on the Per Protocol Set (PPS), only on the participants who received only 1 dose of RSV MAT vaccine (from RSV MAT vaccine Lot 1, Lot 2 or Lot 3), and have post-vaccination data, from which are excluded participants with protocol deviations and for whom immunogenicity results were available for the specified assay and time point.

End point type

Secondary

End point timeframe

At Day 1 and Day 31

Notes
[31] - 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: This endpoind had the purpose to only analyse lot-to-lot RSV groups RSV lot 1, RSV lot 2, RSV lot 3).

End point values	RSV lot1 Group	RSV lot2 Group	RSV lot3 Group
Number of subjects analysed	217	223	217
Units: EU/mL
geometric mean (confidence interval 95%)
Day 1 (N=217, 223, 217)	5691.9 (5276.8 to 6139.7)	5613 (5197.8 to 6061.3)	5270.1 (4883.6 to 5687.1)
Day 31 (N=201, 204, 207)	102811 (95243.6 to 110979.6)	100635.8 (92970.2 to 108933.4)	108709.3 (101913.7 to 115958)

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Serious Adverse Events (SAEs) were collected through the entire period of the study (from Day 1 up to study end [Day 181]). Solicited AEs were collected from Day 1 to Day 7 included and unsolicited AEs were collected from Day 1 to Day 30 included.

Adverse event reporting additional description

As pre-specified in protocol, adverse events were presented for individual RSV lot groups, RSV+Flu pooled Group and Flu+Placebo group. Participants that received the Flu vaccine only as standard of care (group RSV pooled) were not included for safety analyses after receiving the Flu vaccine, as this was not a study objective.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.0

Reporting group title

RSV lot1 Group

Reporting group description

Reporting group title

RSV lot2 Group

Reporting group description

Reporting group title

RSV lot3 Group

Reporting group description

Reporting group title

RSV+Flu pooled Group

Reporting group description

Reporting group title

Flu+Placebo Group

Reporting group description

Participants randomized in this group received one dose of Flu D-QIV vaccine co-administered with one dose of placebo at Day 1, and were followed up until the end of the study (Day 181).This group was considered comparator for immunogenicity and safety analyses for RSV+ Flu Pooled group.

Serious adverse events	RSV lot1 Group	RSV lot2 Group	RSV lot3 Group	RSV+Flu pooled Group	Flu+Placebo Group
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 220 (0.91%)	1 / 223 (0.45%)	2 / 218 (0.92%)	4 / 438 (0.91%)	4 / 440 (0.91%)
number of deaths (all causes)	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Injury, poisoning and procedural complications
Fibula fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (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
Overdose
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (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
Ligament rupture
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
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
Multiple fractures
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
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
Eye disorders
Optic neuropathy
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
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
Reproductive system and breast disorders
Cervical dysplasia
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (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
Cholelithiasis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
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
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (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
Suicide attempt
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (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
Musculoskeletal and connective tissue disorders
Joint ankylosis
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (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
Back pain
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (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
Greater trochanteric pain syndrome
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (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
Intervertebral disc protrusion
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (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
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (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
COVID-19 pneumonia
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (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

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	RSV lot1 Group	RSV lot2 Group	RSV lot3 Group	RSV+Flu pooled Group	Flu+Placebo Group
Total subjects affected by non serious adverse events
subjects affected / exposed	182 / 220 (82.73%)	193 / 223 (86.55%)	194 / 218 (88.99%)	409 / 438 (93.38%)	396 / 440 (90.00%)
Vascular disorders
Hot flush
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	1	0	1	0
Hypertension
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
General disorders and administration site conditions
Administration site erythema
subjects affected / exposed	10 / 220 (4.55%)	9 / 223 (4.04%)	10 / 218 (4.59%)	18 / 438 (4.11%)	7 / 440 (1.59%)
occurrences all number	10	9	10	19	7
Administration site swelling
subjects affected / exposed	9 / 220 (4.09%)	11 / 223 (4.93%)	10 / 218 (4.59%)	32 / 438 (7.31%)	14 / 440 (3.18%)
occurrences all number	9	11	10	35	14
Fatigue
subjects affected / exposed	110 / 220 (50.00%)	113 / 223 (50.67%)	121 / 218 (55.50%)	263 / 438 (60.05%)	230 / 440 (52.27%)
occurrences all number	112	113	123	268	233
Administration site pain
subjects affected / exposed	108 / 220 (49.09%)	131 / 223 (58.74%)	115 / 218 (52.75%)	360 / 438 (82.19%)	327 / 440 (74.32%)
occurrences all number	108	131	115	440	346
Pyrexia
subjects affected / exposed	6 / 220 (2.73%)	3 / 223 (1.35%)	8 / 218 (3.67%)	14 / 438 (3.20%)	3 / 440 (0.68%)
occurrences all number	6	3	8	14	3
Pain
subjects affected / exposed	1 / 220 (0.45%)	2 / 223 (0.90%)	1 / 218 (0.46%)	2 / 438 (0.46%)	0 / 440 (0.00%)
occurrences all number	1	2	1	2	0
Chills
subjects affected / exposed	0 / 220 (0.00%)	2 / 223 (0.90%)	0 / 218 (0.00%)	6 / 438 (1.37%)	1 / 440 (0.23%)
occurrences all number	0	2	0	6	1
Chest pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Injection site pruritus
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	1 / 218 (0.46%)	2 / 438 (0.46%)	0 / 440 (0.00%)
occurrences all number	0	1	1	2	0
Injection site haematoma
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	1 / 438 (0.23%)	2 / 440 (0.45%)
occurrences all number	0	1	0	1	2
Injection site swelling
subjects affected / exposed	1 / 220 (0.45%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	1	1	0	0	0
Asthenia
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	1	0	0	1
Influenza like illness
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	2 / 440 (0.45%)
occurrences all number	0	0	0	1	2
Administration site warmth
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	0	1	0	0
Injection site discomfort
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	1	0	0	0	0
Injection site extravasation
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Vaccination site haematoma
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Vaccination site rash
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Chest discomfort
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Discomfort
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	2 / 218 (0.92%)	4 / 438 (0.91%)	3 / 440 (0.68%)
occurrences all number	1	0	4	5	3
Injection site lymphadenopathy
subjects affected / exposed	0 / 220 (0.00%)	3 / 223 (1.35%)	2 / 218 (0.92%)	0 / 438 (0.00%)	2 / 440 (0.45%)
occurrences all number	0	3	2	0	3
Injection site pain
subjects affected / exposed	4 / 220 (1.82%)	1 / 223 (0.45%)	0 / 218 (0.00%)	1 / 438 (0.23%)	5 / 440 (1.14%)
occurrences all number	4	1	0	1	5
Swelling
subjects affected / exposed	5 / 220 (2.27%)	1 / 223 (0.45%)	1 / 218 (0.46%)	3 / 438 (0.68%)	1 / 440 (0.23%)
occurrences all number	5	1	1	3	1
Axillary pain
subjects affected / exposed	4 / 220 (1.82%)	5 / 223 (2.24%)	4 / 218 (1.83%)	6 / 438 (1.37%)	2 / 440 (0.45%)
occurrences all number	4	5	4	6	3
Malaise
subjects affected / exposed	0 / 220 (0.00%)	2 / 223 (0.90%)	0 / 218 (0.00%)	3 / 438 (0.68%)	1 / 440 (0.23%)
occurrences all number	0	2	0	4	1
Feeling hot
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Injection site erythema
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Temperature regulation disorder
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Vaccination site pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Immune system disorders
Food allergy
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Immunisation reaction
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Social circumstances
High risk sexual behaviour
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	2 / 440 (0.45%)
occurrences all number	0	1	0	0	2
Menstrual disorder
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	0	1	0	0
Heavy menstrual bleeding
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Intermenstrual bleeding
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Menstruation irregular
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Menopausal symptoms
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	4
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	3 / 220 (1.36%)	3 / 223 (1.35%)	5 / 218 (2.29%)	6 / 438 (1.37%)	6 / 440 (1.36%)
occurrences all number	3	3	5	6	6
Rhinorrhoea
subjects affected / exposed	1 / 220 (0.45%)	2 / 223 (0.90%)	4 / 218 (1.83%)	3 / 438 (0.68%)	5 / 440 (1.14%)
occurrences all number	1	2	4	3	5
Nasal congestion
subjects affected / exposed	0 / 220 (0.00%)	3 / 223 (1.35%)	2 / 218 (0.92%)	6 / 438 (1.37%)	4 / 440 (0.91%)
occurrences all number	0	4	2	6	4
Productive cough
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	1	0	0	1
Dyspnoea
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	2 / 440 (0.45%)
occurrences all number	0	0	0	1	3
Catarrh
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	3 / 440 (0.68%)
occurrences all number	0	0	0	0	3
Sinus congestion
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	0	1	0	0
Cough
subjects affected / exposed	2 / 220 (0.91%)	2 / 223 (0.90%)	1 / 218 (0.46%)	8 / 438 (1.83%)	6 / 440 (1.36%)
occurrences all number	2	2	1	8	6
Sneezing
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	0	1	0	0
Paranasal sinus discomfort
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	2	0	0	0
Rhinitis allergic
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
Asthma
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Throat irritation
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Pulmonary calcification
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Aphonia
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
Bipolar disorder
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Irritability
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Investigations
Smear cervix abnormal
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Body temperature increased
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	1	0	0	0	0
Blood pressure decreased
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Injury, poisoning and procedural complications
Fascial rupture
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Limb injury
subjects affected / exposed	0 / 220 (0.00%)	2 / 223 (0.90%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	2	0	0	0
Fall
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	1	0	0	0	0
Lip injury
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
Concussion
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Patella fracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Thermal burn
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Animal bite
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Arthropod bite
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Muscle strain
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Congenital, familial and genetic disorders
Supernumerary teeth
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Nervous system disorders
Headache
subjects affected / exposed	110 / 220 (50.00%)	108 / 223 (48.43%)	108 / 218 (49.54%)	227 / 438 (51.83%)	196 / 440 (44.55%)
occurrences all number	122	115	111	247	209
Migraine
subjects affected / exposed	1 / 220 (0.45%)	1 / 223 (0.45%)	1 / 218 (0.46%)	2 / 438 (0.46%)	3 / 440 (0.68%)
occurrences all number	1	1	1	2	3
Dizziness
subjects affected / exposed	0 / 220 (0.00%)	2 / 223 (0.90%)	1 / 218 (0.46%)	2 / 438 (0.46%)	1 / 440 (0.23%)
occurrences all number	0	2	1	2	1
Hypoaesthesia
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	1	0	1
Paraesthesia
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	1	0	1
Idiopathic intracranial hypertension
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	0	1	0	0
Syncope
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	0	1	0	0
Dizziness exertional
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	6 / 220 (2.73%)	7 / 223 (3.14%)	5 / 218 (2.29%)	6 / 438 (1.37%)	4 / 440 (0.91%)
occurrences all number	6	8	5	6	4
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 220 (0.45%)	1 / 223 (0.45%)	0 / 218 (0.00%)	2 / 438 (0.46%)	1 / 440 (0.23%)
occurrences all number	1	1	0	2	1
Vertigo positional
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	0	1	0	0
Excessive cerumen production
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	1	0	0	0	0
Ear pain
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
Eustachian tube disorder
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
External ear inflammation
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	0	1	0	0
Eye disorders
Eye symptom
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
Blepharitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Vision blurred
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Eczema eyelids
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Gastrointestinal disorders
Nausea
subjects affected / exposed	34 / 220 (15.45%)	31 / 223 (13.90%)	32 / 218 (14.68%)	68 / 438 (15.53%)	54 / 440 (12.27%)
occurrences all number	35	32	33	72	56
Diarrhoea
subjects affected / exposed	29 / 220 (13.18%)	25 / 223 (11.21%)	28 / 218 (12.84%)	59 / 438 (13.47%)	77 / 440 (17.50%)
occurrences all number	29	27	28	64	77
Abdominal pain
subjects affected / exposed	25 / 220 (11.36%)	33 / 223 (14.80%)	25 / 218 (11.47%)	61 / 438 (13.93%)	63 / 440 (14.32%)
occurrences all number	25	33	25	61	64
Vomiting
subjects affected / exposed	7 / 220 (3.18%)	5 / 223 (2.24%)	3 / 218 (1.38%)	9 / 438 (2.05%)	11 / 440 (2.50%)
occurrences all number	7	5	3	9	11
Flatulence
subjects affected / exposed	0 / 220 (0.00%)	2 / 223 (0.90%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	2	0	0	0
Abdominal pain upper
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	1 / 438 (0.23%)	1 / 440 (0.23%)
occurrences all number	0	1	0	1	1
Gastritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	1	1	0
Constipation
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	1	0	1	0
Dyspepsia
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Odynophagia
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Diarrhoea haemorrhagic
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Frequent bowel movements
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Paraesthesia oral
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Volvulus
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Haemorrhoids thrombosed
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	3 / 438 (0.68%)	1 / 440 (0.23%)
occurrences all number	0	0	1	3	1
Rash
subjects affected / exposed	2 / 220 (0.91%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	2	0	0	0	0
Pruritus
subjects affected / exposed	0 / 220 (0.00%)	2 / 223 (0.90%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	2	0	0	0
Erythema
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
Dermatitis atopic
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Dermatitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Rash macular
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Rash pruritic
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Renal and urinary disorders
Bladder pain
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	1	0	0	0	0
Tubulointerstitial nephritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Dysuria
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	2 / 220 (0.91%)	4 / 223 (1.79%)	1 / 218 (0.46%)	4 / 438 (0.91%)	5 / 440 (1.14%)
occurrences all number	2	4	1	4	5
Arthralgia
subjects affected / exposed	3 / 220 (1.36%)	0 / 223 (0.00%)	1 / 218 (0.46%)	3 / 438 (0.68%)	3 / 440 (0.68%)
occurrences all number	3	0	1	3	3
Pain in extremity
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	1 / 218 (0.46%)	4 / 438 (0.91%)	2 / 440 (0.45%)
occurrences all number	1	0	1	4	3
Neck pain
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	1 / 218 (0.46%)	2 / 438 (0.46%)	1 / 440 (0.23%)
occurrences all number	1	0	1	2	1
Synovial cyst
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	1 / 218 (0.46%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	1	1	0	1
Back pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	3 / 438 (0.68%)	1 / 440 (0.23%)
occurrences all number	0	0	0	3	1
Muscle contracture
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	2 / 440 (0.45%)
occurrences all number	0	0	0	1	2
Torticollis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	0	1	0	0
Groin pain
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
Musculoskeletal stiffness
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	1 / 440 (0.23%)
occurrences all number	0	0	0	1	1
Axillary mass
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Bone pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Muscular weakness
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Arthritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Musculoskeletal chest pain
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Pain in jaw
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Tendonitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Infections and infestations
Pharyngitis
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
Nasopharyngitis
subjects affected / exposed	4 / 220 (1.82%)	4 / 223 (1.79%)	2 / 218 (0.92%)	13 / 438 (2.97%)	15 / 440 (3.41%)
occurrences all number	4	4	2	13	15
Upper respiratory tract infection
subjects affected / exposed	4 / 220 (1.82%)	0 / 223 (0.00%)	3 / 218 (1.38%)	8 / 438 (1.83%)	2 / 440 (0.45%)
occurrences all number	4	0	3	8	3
COVID-19
subjects affected / exposed	0 / 220 (0.00%)	2 / 223 (0.90%)	4 / 218 (1.83%)	7 / 438 (1.60%)	2 / 440 (0.45%)
occurrences all number	0	2	4	7	2
Urinary tract infection
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	2 / 218 (0.92%)	3 / 438 (0.68%)	3 / 440 (0.68%)
occurrences all number	0	1	2	3	3
Sinusitis
subjects affected / exposed	1 / 220 (0.45%)	1 / 223 (0.45%)	2 / 218 (0.92%)	1 / 438 (0.23%)	2 / 440 (0.45%)
occurrences all number	1	1	2	1	2
Influenza
subjects affected / exposed	3 / 220 (1.36%)	0 / 223 (0.00%)	1 / 218 (0.46%)	2 / 438 (0.46%)	0 / 440 (0.00%)
occurrences all number	3	0	1	2	0
Bronchitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	3 / 218 (1.38%)	1 / 438 (0.23%)	3 / 440 (0.68%)
occurrences all number	0	0	3	1	3
Pharyngotonsillitis
subjects affected / exposed	1 / 220 (0.45%)	2 / 223 (0.90%)	0 / 218 (0.00%)	0 / 438 (0.00%)	2 / 440 (0.45%)
occurrences all number	1	2	0	0	2
Gastroenteritis viral
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	1	0	1	0	0
Respiratory tract infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	1 / 438 (0.23%)	1 / 440 (0.23%)
occurrences all number	0	0	1	1	1
Tonsillitis
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	1 / 438 (0.23%)	1 / 440 (0.23%)
occurrences all number	0	1	0	1	1
Nasal herpes
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	1 / 218 (0.46%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	0	1	0	0
Cystitis
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	1	0	0	0	0
Eczema impetiginous
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	1	0	0	0	0
Laryngitis
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	1	0	0	0	0
Upper respiratory tract infection bacterial
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	1	0	0	0	0
Vulvovaginitis
subjects affected / exposed	1 / 220 (0.45%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	1	0	0	0	0
Ear infection
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
Oral herpes
subjects affected / exposed	0 / 220 (0.00%)	1 / 223 (0.45%)	0 / 218 (0.00%)	0 / 438 (0.00%)	0 / 440 (0.00%)
occurrences all number	0	1	0	0	0
Viral infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Pharyngitis streptococcal
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	2 / 438 (0.46%)	0 / 440 (0.00%)
occurrences all number	0	0	0	2	0
Conjunctivitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	1 / 440 (0.23%)
occurrences all number	0	0	0	1	1
Gastroenteritis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	1 / 440 (0.23%)
occurrences all number	0	0	0	1	1
Viral upper respiratory tract infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	1 / 440 (0.23%)
occurrences all number	0	0	0	1	1
Bacterial vulvovaginitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Fungal infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Gingivitis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Otitis media acute
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Respiratory tract infection bacterial
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Suspected COVID-19
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0
Bacterial vaginosis
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Otitis externa
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	10	0	1
Pneumonia
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Respiratory tract infection viral
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Streptococcal infection
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	0 / 438 (0.00%)	1 / 440 (0.23%)
occurrences all number	0	0	0	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 220 (0.00%)	0 / 223 (0.00%)	0 / 218 (0.00%)	1 / 438 (0.23%)	0 / 440 (0.00%)
occurrences all number	0	0	0	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

26 May 2022

This protocol has been amended to reflect the following: • Primary and secondary objectives were modified to evaluate only 3 influenza strains (A/Tasmania/503/2020 (H3N2), B/Washington/02/2019, B/Phuket/3073/2013). The A/Victoria/2570/2019 (H1N1) was evaluated as part of the tertiary objectives. • The secondary safety objective and its corresponding endpoint related to assessment of safety of RSV maternal vaccine when given alone and co-administered with Flu D-QIV from vaccination up to study end was recategorized as a primary objective. • The interim analysis was removed following GSK’s decision to stop enrollment and vaccination for active enrollment in all RSV MAT studies.

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants reporting solicited administration site events in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Primary: Percentage of participants reporting solicited administration site events in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Primary: Percentage of participants reporting solicited systemic events in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Primary: Percentage of participants reporting solicited systemic events in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Primary: Percentage of participants reporting unsolicited adverse events (AEs) in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Primary: Percentage of participants reporting unsolicited adverse events (AEs) in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Primary: Percentage of participants reporting serious adverse events (SAEs) in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Primary: Percentage of participants reporting serious adverse events (SAEs) in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Primary: Percentage of participants reporting SAEs in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Primary: Percentage of participants reporting SAEs in RSV pooled Group, RSV+Flu pooled Group and Flu+Placebo Group

Primary: RSV MAT immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) concentrations for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 31

Primary: RSV MAT immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) concentrations for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 31

Primary: Flu D-QIV haemagglutinin inhibition (HI) antibody titers against 3 influenza strains for participants in Flu+Placebo Group and RSV+Flu pooled Group at Day 31

Primary: Flu D-QIV haemagglutinin inhibition (HI) antibody titers against 3 influenza strains for participants in Flu+Placebo Group and RSV+Flu pooled Group at Day 31

Secondary: RSV A neutralizing antibody titers for participants in RSV pooled Group and RSV+Flu pooled Group at Day 1 and Day 31

Secondary: RSV A neutralizing antibody titers for participants in RSV pooled Group and RSV+Flu pooled Group at Day 1 and Day 31

Secondary: Seroconversion rate (SCR) to Flu D-QIV HI antibody titers against 3 influenza strains for participants in Flu+Placebo group and RSV+Flu pooled group at Day 31

Secondary: Seroconversion rate (SCR) to Flu D-QIV HI antibody titers against 3 influenza strains for participants in Flu+Placebo group and RSV+Flu pooled group at Day 31

Secondary: RSV B neutralizing antibody titers for participants in RSV pooled Group and RSV+Flu pooled Group at Day 1 and Day 31

Secondary: RSV B neutralizing antibody titers for participants in RSV pooled Group and RSV+Flu pooled Group at Day 1 and Day 31

Secondary: RSV MAT IgG concentrations for participants in RSV pooled Group and RSV+Flu pooled Group at Day 1 and Day 31

Secondary: RSV MAT IgG concentrations for participants in RSV pooled Group and RSV+Flu pooled Group at Day 1 and Day 31

Secondary: Flu D-QIV HI antibody titers against 3 influenza strains for participants in Flu+Placebo Group and RSV+Flu pooled Group at Day 1 and Day 31

Secondary: Flu D-QIV HI antibody titers against 3 influenza strains for participants in Flu+Placebo Group and RSV+Flu pooled Group at Day 1 and Day 31

Secondary: Seroprotection rate (SPR) to Flu D-QIV HI antibody titers for participants in Flu+Placebo Group and RSV+Flu pooled Group at Day 1 and Day 31

Secondary: Seroprotection rate (SPR) to Flu D-QIV HI antibody titers for participants in Flu+Placebo Group and RSV+Flu pooled Group at Day 1 and Day 31

Secondary: RSV A neutralizing antibody titers for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 1 and Day 31

Secondary: RSV A neutralizing antibody titers for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 1 and Day 31

Secondary: RSV B neutralizing antibody titers for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 1 and Day 31

Secondary: RSV B neutralizing antibody titers for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 1 and Day 31

Secondary: RSV MAT IgG concentrations for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 1 and Day 31

Secondary: RSV MAT IgG concentrations for participants in RSV lot1, RSV lot2 and RSV lot3 groups at Day 1 and Day 31

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information