Clinical Trial Results:
A Phase 1/2, randomized, observer-blind, controlled, multi-center, dose-escalation study to evaluate safety, reactogenicity and immunogenicity of GSK Biologicals’ respiratory syncytial virus (RSV) investigational vaccine based on the RSV viral proteins F, N and M2-1 encoded by chimpanzee-derived adenovector (ChAd155-RSV) (GSK3389245A), when administered intramuscularly according to a 0, 1-month schedule to RSV-seropositive infants aged 12 to 23 months.

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Subject disposition

Baseline characteristics

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Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Adverse events

Adverse events

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Primary: Number of subjects with any solicited local adverse events (AEs)

Primary: Number of subjects with any solicited general AEs

Primary: Number of subjects with any unsolicited AEs

Primary: Number of subjects with any serious adverse events (SAEs) from Day 1 up to Day 61

Primary: Number of subjects with episode of spontaneous or excessive bleeding (AE of specific interest)

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 2

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 8

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 31

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 32

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 38

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 61

Primary: Number of subjects with biochemical laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 31

Primary: Number of subjects with biochemical laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 61

Secondary: Number of subjects with any SAEs from Day 1 up to Day 366

Secondary: Number of subjects with lower respiratory tract infection associated with RSV infection (RSV-LRTI) (AE of specific interest) from Dose 1 administration (Day 1) up to Day 366

Secondary: Number of subjects with respiratory tract infection associated with RSV infection (RSV-RTI), RSV-LRTI, severe RSV-LRTI (according to standardized case definitions) from Dose 1 administration (Day 1) up to Day 366

Secondary: Number of subjects with any SAEs from Day 1 up to study conclusion at Day 731

Secondary: Number of subjects with RSV-LRTI (AE of specific interest) from Dose 1 administration (Day 1) up to study conclusion at Day 731

Secondary: Number of subjects with RSV-RTI, RSV-LRTI, severe RSV-LRTI (according to standardized case definitions) from Dose 1 administration (Day 1) up to study conclusion at Day 731

Secondary: Frequency of RSV-specific CD4+ T-cells expressing at least two markers upon stimulation with F, N and M2-1 peptide pools

Secondary: Anti-RSV-A neutralizing antibody titers

Secondary: Anti-RSV-F antibody concentrations

Secondary: Palivizumab-competing antibody concentrations

Primary: Number of subjects with any solicited local adverse events (AEs)

Primary: Number of subjects with any solicited local adverse events (AEs)

Primary: Number of subjects with any solicited general AEs

Primary: Number of subjects with any solicited general AEs

Primary: Number of subjects with any unsolicited AEs

Primary: Number of subjects with any unsolicited AEs

Primary: Number of subjects with any serious adverse events (SAEs) from Day 1 up to Day 61

Primary: Number of subjects with any serious adverse events (SAEs) from Day 1 up to Day 61

Primary: Number of subjects with episode of spontaneous or excessive bleeding (AE of specific interest)

Primary: Number of subjects with episode of spontaneous or excessive bleeding (AE of specific interest)

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 2

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 2

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 8

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 8

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 31

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 31

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 32

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 32

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 38

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 38

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 61

Primary: Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 61

Primary: Number of subjects with biochemical laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 31

Primary: Number of subjects with biochemical laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 31

Primary: Number of subjects with biochemical laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 61

Primary: Number of subjects with biochemical laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 61

Secondary: Number of subjects with any SAEs from Day 1 up to Day 366

Secondary: Number of subjects with any SAEs from Day 1 up to Day 366

Secondary: Number of subjects with lower respiratory tract infection associated with RSV infection (RSV-LRTI) (AE of specific interest) from Dose 1 administration (Day 1) up to Day 366

Secondary: Number of subjects with lower respiratory tract infection associated with RSV infection (RSV-LRTI) (AE of specific interest) from Dose 1 administration (Day 1) up to Day 366

Secondary: Number of subjects with respiratory tract infection associated with RSV infection (RSV-RTI), RSV-LRTI, severe RSV-LRTI (according to standardized case definitions) from Dose 1 administration (Day 1) up to Day 366

Secondary: Number of subjects with respiratory tract infection associated with RSV infection (RSV-RTI), RSV-LRTI, severe RSV-LRTI (according to standardized case definitions) from Dose 1 administration (Day 1) up to Day 366

Secondary: Number of subjects with any SAEs from Day 1 up to study conclusion at Day 731

Secondary: Number of subjects with any SAEs from Day 1 up to study conclusion at Day 731

Secondary: Number of subjects with RSV-LRTI (AE of specific interest) from Dose 1 administration (Day 1) up to study conclusion at Day 731

Secondary: Number of subjects with RSV-LRTI (AE of specific interest) from Dose 1 administration (Day 1) up to study conclusion at Day 731

Secondary: Number of subjects with RSV-RTI, RSV-LRTI, severe RSV-LRTI (according to standardized case definitions) from Dose 1 administration (Day 1) up to study conclusion at Day 731

Secondary: Number of subjects with RSV-RTI, RSV-LRTI, severe RSV-LRTI (according to standardized case definitions) from Dose 1 administration (Day 1) up to study conclusion at Day 731

Secondary: Frequency of RSV-specific CD4+ T-cells expressing at least two markers upon stimulation with F, N and M2-1 peptide pools

Secondary: Frequency of RSV-specific CD4+ T-cells expressing at least two markers upon stimulation with F, N and M2-1 peptide pools

Secondary: Anti-RSV-A neutralizing antibody titers

Secondary: Anti-RSV-A neutralizing antibody titers

Secondary: Anti-RSV-F antibody concentrations

Secondary: Anti-RSV-F antibody concentrations

Secondary: Palivizumab-competing antibody concentrations

Secondary: Palivizumab-competing antibody concentrations

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Summary
EudraCT number	2016-000117-76
Trial protocol	ES PL IT
Global end of trial date	31 Mar 2021

Results information
Results version number	v1(current)
This version publication date	14 Oct 2021
First version publication date	14 Oct 2021
Other versions

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

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Sponsor protocol code

204838

ISRCTN number

US NCT number

NCT02927873

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

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

Public contact

GSK Response Center, GlaxoSmithKline, 044 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 044 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

13 Aug 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

19 Feb 2019

Global end of trial reached?

Yes

Global end of trial date

31 Mar 2021

Was the trial ended prematurely?

Main objective of the trial

To evaluate the safety and reactogenicity of three dose levels of the RSV investigational vaccine when administered as two IM doses according to a 0, 1-month schedule, up to 30 days after Dose 2 (i.e. Day 61) in RSV-seropositive infants aged 12 to 23 months.

Protection of trial subjects

All subjects were supervised for at least 60 min after vaccination with appropriate medical treatment readily available. As requested by Italian health authorities, in addition to the 60 minutes supervision after vaccination, the first 8 infants have completed a period of observation of at least 48 hours following administration of dose 1 prior to continuing to immunize the rest of the subjects (i.e. from the ninth subject and beyond) with dose 1 in the step 1. The same process has been applied following the administration of dose 2 in step 1 and further applied in step 2 and step 3 of the trial. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines. Subjects were followed-up for 2 years after the last vaccination.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Jan 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 1

Country: Number of subjects enrolled

Italy: 7

Country: Number of subjects enrolled

Mexico: 4

Country: Number of subjects enrolled

Panama: 31

Country: Number of subjects enrolled

Poland: 1

Country: Number of subjects enrolled

Spain: 26

Country: Number of subjects enrolled

Taiwan: 12

Country: Number of subjects enrolled

United States: 25

Worldwide total number of subjects

107

EEA total number of subjects

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)

107

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

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Recruitment details

The study was conducted at 32 centers in 8 countries (Canada, Italy, Mexico, Panama, Poland, Spain, Taiwan and United States).

Screening details

Out of 107 participants enrolled in the study, 21 participants were not assigned to any study group and 4 participants did not receive any study treatment. 82 subjects were vaccinated and included in the Exposed Set.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

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

Blinding implementation details

Observer-blind

Are arms mutually exclusive

Yes

RSV LD Group

Arm description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of the RSV low dose (LD) vaccine, administered intramuscularly, one each at Day 1 and Day 31.

Arm type

Experimental

Investigational medicinal product name

RSV (GSK3389245A) low dose formulation vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses of 0.5 ml each of RSV (GSK3389245A) low dose formulation vaccine administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.

RSV MD Group

Arm description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.15 mL each) of the RSV middle dose (MD) vaccine, administered intramuscularly, one each at Day 1 and Day 31.

Arm type

Experimental

Investigational medicinal product name

RSV (GSK3389245A) middle dose formulation vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses of 0.15 ml each of RSV (GSK3389245A) middle dose formulation vaccine administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.

RSV HD Group

Arm description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of the RSV high dose (HD) vaccine, administered intramuscularly, one each at Day 1 and Day 31.

Arm type

Experimental

Investigational medicinal product name

RSV (GSK3389245A) high dose formulation vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses of 0.5 ml each of RSV (GSK3389245A) high dose formulation vaccine administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.

Placebo LD group

Arm description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses (0.5 mL each for Placebo LD and Placebo HD groups and 0.15 mL for Placebo MD group) of Placebo administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.

Placebo MD group

Arm description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.15 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses (0.5 mL each for Placebo LD and Placebo HD groups and 0.15 mL for Placebo MD group) of Placebo administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.

Placebo HD group

Arm description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses (0.5 mL each for Placebo LD and Placebo HD groups and 0.15 mL for Placebo MD group) of Placebo administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.

Number of subjects in period 1 ^[1]	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Started	11	14	18	11	11	17
Completed	9	11	18	11	11	16
Not completed	2	3	0	0	0	1
PARENTS REFUSED SAFETY FOLLOW-UP	1	-	-	-	-	-
PARENTS NOT ABLE TO COME TO SITE	-	1	-	-	-	-
WITHDRAWN, ACCEPTED CALLS FOR SAFETY SURVEILLANCE	1	-	-	-	-	-
MIGRATED / MOVED FROM THE STUDY AREA	-	-	-	-	-	1
Lost to follow-up	-	1	-	-	-	-
CONSENT WITHDRAWAL NOT DUE TO ADV. EVENT	-	1	-	-	-	-

Notes
[1] - 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: Out of 107 participants enrolled in the study, 21 participants were not assigned to any study group and 4 participants did not receive any study treatment. 82 subjects were vaccinated and included in the Exposed Set.

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Reporting group title

RSV LD Group

Reporting group description

Reporting group title

RSV MD Group

Reporting group description

Reporting group title

RSV HD Group

Reporting group description

Reporting group title

Placebo LD group

Reporting group description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31.

Reporting group title

Placebo MD group

Reporting group description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.15 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31.

Reporting group title

Placebo HD group

Reporting group description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31.

Reporting group values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group	Total
Number of subjects	11	14	18	11	11	17	82
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	11	14	18	11	11	17	82
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	0	0	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0
Age continuous
Units: months
arithmetic mean (standard deviation)	15.4 ( 1.6 )	15.6 ( 3.3 )	16.3 ( 4.0 )	15.0 ( 1.9 )	16.2 ( 2.7 )	17.4 ( 3.8 )	-
Sex: Female, Male
Units: Subjects
FEMALE	4	7	10	5	3	12	41
MALE	7	7	8	6	8	5	41
Race/Ethnicity, Customized
Units: Subjects
AFRICAN HERITAGE / AFRICAN AMERICAN	0	0	0	0	1	0	1
ASIAN - EAST ASIAN HERITAGE	0	0	3	0	1	3	7
ASIAN - SOUTH EAST ASIAN HERITAGE	0	0	1	0	1	0	2
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	0	1	0	0	0	0	1
OTHER, NOT SPECIFIED	0	7	12	2	4	9	34
WHITE - CAUCASIAN / EUROPEAN HERITAGE	11	6	2	9	4	5	37

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Reporting group title

RSV LD Group

Reporting group description

Reporting group title

RSV MD Group

Reporting group description

Reporting group title

RSV HD Group

Reporting group description

Reporting group title

Placebo LD group

Reporting group description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31.

Reporting group title

Placebo MD group

Reporting group description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.15 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31.

Reporting group title

Placebo HD group

Reporting group description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31.

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End point title

Number of subjects with any solicited local adverse events (AEs) ^[1]

End point description

Assessed solicited local symptoms are pain, redness and swelling at injection site. Any = occurrence of the symptom regardless of intensity grade. Any redness and swelling symptom = symptom reported with a surface diameter greater than 0 millimeters.

End point type

Primary

End point timeframe

During a 7-day follow-up period after each vaccination (vaccine/placebo administered at Day 1 and Day 31)

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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	11	13	18	11	11	17
Units: Subjects
DOSE 1, Any Pain (N=11,13,18,11,11,17)	1	2	0	2	0	2
DOSE 1, Any Redness (N=11,13,18,11,11,17)	2	1	3	3	0	3
DOSE 1, Any Swelling (N=11,13,18,11,11,17)	0	0	1	1	1	2
DOSE 2, Any Pain (N=10,12,17,11,11,17)	2	2	2	1	0	3
DOSE 2, Any Redness (N=10,12,17,11,11,17)	2	1	2	3	0	2
DOSE 2, Any Swelling (N=10,12,17,11,11,17)	0	0	0	1	0	2

No statistical analyses for this end point

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End point title

Number of subjects with any solicited general AEs ^[2]

End point description

Assessed solicited general symptoms are drowsiness, fever [defined as temperature equal to or above (≥) 37.5 degrees Celsius (°C)/99.5 degrees Fahrenheit (°F) for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal route, the preferred route for recording temperature in this study being axillary], irritability/fussiness and loss of appetite. Any = occurrence of the symptom regardless of intensity grade or relation to study vaccination.

End point type

Primary

End point timeframe

During a 7-day follow-up period after each vaccination (vaccine/placebo administered at Day 1 and Day 31)

Notes
[2] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	11	13	18	11	11	17
Units: Subjects
DOSE 1, Any Drowsiness (N=11,13,18,11,11,17)	4	2	4	5	3	4
DOSE 1, Any Irritability (N=11,13,18,11,11,17)	3	3	4	4	2	2
DOSE 1, Any Loss Of Appetite (N=11,13,18,11,11,17)	3	3	4	2	2	3
DOSE 1, Any Fever (N=11,13,18,11,11,17)	3	3	10	3	2	0
DOSE 2, Any Drowsiness (N=10, 12,17,11,11,17)	2	1	5	3	2	5
DOSE 2, Any Irritability (N=10,12,17,11,11,17)	3	1	5	3	1	6
DOSE 2, Any Loss Of Appetite (N=10,12,17,11,11,17)	3	0	6	3	2	5
DOSE 2, Any Fever (N=10,12,17,11,11,17)	2	2	5	1	2	1

No statistical analyses for this end point

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End point title

Number of subjects with any unsolicited AEs ^[3]

End point description

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Unsolicited AEs are reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to study vaccination.

End point type

Primary

End point timeframe

During a 30-day follow-up period after each vaccination (vaccine/placebo administered at Day 1 and Day 31)

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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	11	14	18	11	11	17
Units: Subjects	9	9	13	7	10	13

No statistical analyses for this end point

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End point title

Number of subjects with any serious adverse events (SAEs) from Day 1 up to Day 61 ^[4]

End point description

Assessed SAEs include any untoward medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. Any = occurrence of SAE regardless of intensity grade or relation to study vaccination.

End point type

Primary

End point timeframe

From Day 1 up to Day 61

Notes
[4] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	11	14	18	11	11	17
Units: Subjects	0	0	1	1	0	2

No statistical analyses for this end point

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End point title

Number of subjects with episode of spontaneous or excessive bleeding (AE of specific interest) ^[5]

End point description

Any episode of spontaneous or excessive bleeding if occurring after vaccination was to be fully investigated with a full range of hematological tests to identify the underlying cause and reported as an AE of specific interest.

End point type

Primary

End point timeframe

During a 30-day follow-up period after each vaccination (vaccine/placebo administered at Day 1 and Day 31)

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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	11	14	18	11	11	17
Units: Subjects	0	0	0	0	0	0

No statistical analyses for this end point

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End point title

Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 2 ^[6]

End point description

Assessed hematological laboratory parameters include hemoglobin level [HgL] white blood cells [WBC] and platelet count [PLC]. Hematological abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Unknown, Below, Within or Above. [e.g. HgL, Below, Below = HgL below normal ranges at baseline versus below normal ranges at Day 2].

End point type

Primary

End point timeframe

At Day 2

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	11	14	15	11	11	16
Units: Subjects
HgL, Below, Below (N = 3, 2, 1, 1, 0, 0)	3	2	1	1	0	0
HgL, Within, Unknown (N = 8, 12, 15, 10, 11, 16)	0	1	0	0	0	0
HgL, Within, Below (N = 8, 12, 15, 10, 11, 16)	0	2	0	0	2	2
HgL, Within, Within (N = 8, 12, 15, 10, 11, 16)	8	9	15	10	9	13
HgL, Within, Above (N = 8, 12, 15, 10, 11, 16)	0	0	0	0	0	1
HgL, Above, Within (N = 0, 0, 1, 0, 0, 1)	0	0	0	0	0	1
HgL, Above, Above (N = 0, 0, 1, 0, 0, 1)	0	0	1	0	0	0
WBC, Below, Below (N = 0, 0, 1, 0, 0, 1)	0	0	1	0	0	0
WBC, Below, Within (N = 0, 0, 1, 0, 0, 1)	0	0	0	0	0	1
WBC, Within, Unknown (N = 11, 14, 14, 11, 7, 16)	0	1	0	0	0	0
WBC, Within, Below (N = 11, 14, 14, 11, 7, 16)	0	2	1	0	0	2
WBC, Within, Within (N = 11, 14, 14, 11, 7, 16)	11	11	13	11	6	13
WBC, Within, Above (N = 11, 14, 14, 11, 7, 16)	0	0	0	0	1	1
WBC, Above, Within (N = 0, 0, 2, 0, 4, 0)	0	0	1	0	2	0
WBC, Above, Above (N = 0, 0, 2, 0, 4, 0)	0	0	1	0	2	0
PLC, Within, Unknown (N = 10, 12, 15, 9, 6, 15)	0	1	0	0	0	0
PLC, Within, Below (N = 10, 12, 15, 9, 6, 15)	0	0	1	0	0	0
PLC, Within, Within (N = 10, 12, 15, 9, 6, 15)	10	10	12	9	4	12
PLC, Within, Above (N = 10, 12, 15, 9, 6, 15)	0	1	2	0	2	3
PLC, Above, Within (N = 1, 1, 2, 2, 5, 2)	1	1	2	1	2	0
PLC, Above, Above (N = 1, 1, 2, 2, 5, 2)	0	0	0	1	3	2

No statistical analyses for this end point

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End point title

Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 8 ^[7]

End point description

Assessed hematological laboratory parameters include hemoglobin level [HgL] white blood cells [WBC] and platelet count [PLC]. Hematological abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Below, Within or Above. [e.g. HgL, Below, Below = HgL below normal ranges at baseline versus below normal ranges at Day 8].

End point type

Primary

End point timeframe

At Day 8

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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	9	3	2	8	5	3
Units: Subjects
HgL, Below, Below (N = 2, 1, 0, 1, 0,0)	2	1	0	1	0	0
HgL, Within, Within (N = 7, 2, 2, 7, 5, 2)	7	2	2	7	5	2
HgL, Above, Above (N = 0, 0, 0, 0, 0, 1)	0	0	0	0	0	1
WBC, Within, Within (N = 9, 3, 2, 8, 2, 3)	8	2	2	8	2	3
WBC, Within, Above (N = 9, 3, 2, 8, 2, 3)	1	1	0	0	0	0
WBC, Above, Within (N = 0, 0, 0, 0, 3, 0)	0	0	0	0	3	0
PLC, Within, Within (N = 8, 3, 2, 8, 3, 3)	7	3	1	8	0	3
PLC, Within, Above (N = 8, 3, 2, 8, 3, 3)	1	0	1	0	3	0
PLC, Above, Within (N = 1, 0 0, 0, 2, 0)	1	0	0	0	1	0
PLC, Above, Above (N = 1, 0 0, 0, 2, 0)	0	0	0	0	1	0

No statistical analyses for this end point

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End point title

Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 31 ^[8]

End point description

End point type

Primary

End point timeframe

At Day 31

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	10	12	16	10	9	16
Units: Subjects
HgL, Below, Below (N = 3, 2, 1, 1, 0, 0)	3	1	1	1	0	0
HgL, Below, Within (N = 3, 2, 1, 1, 0, 0)	0	1	0	0	0	0
HgL, Within, Unknown (N = 7, 10, 16, 9, 9, 16)	0	1	0	0	0	0
HgL, Within, Below (N = 7, 10, 16, 9, 9, 16)	0	0	0	0	1	2
HgL, Within, Within (N = 7, 10, 16, 9, 9, 16)	7	9	15	9	8	14
HgL, Within, Above (N = 7, 10, 16, 9, 9, 16)	0	0	1	0	0	0
HgL, Above, Within (N = 0, 0, 1, 0, 0, 1)	0	0	1	0	0	1
WBC, Below, Within (N = 0, 0, 1, 0, 0, 1)	0	0	1	0	0	1
WBC, Within, Unknown (N = 10, 12, 15, 10, 5, 16)	0	1	0	0	0	0
WBC, Within, Below (N = 10, 12, 15, 10, 5, 16)	0	0	0	0	0	1
WBC, Within, Within (N = 10, 12, 15, 10, 5, 16)	10	9	13	10	4	15
WBC, Within, Above (N = 10, 12, 15, 10, 5, 16)	0	2	2	0	1	0
WBC, Above, Within (N = 0, 0, 2, 0, 4, 0)	0	0	1	0	3	0
WBC, Above, Above (N = 0, 0, 2, 0, 4, 0)	0	0	1	0	1	0
PLC, Within, Unknown (N = 10, 11, 16, 8, 5, 15)	0	1	0	0	0	0
PLC, Within, Within (N = 10, 11, 16, 8, 5, 15)	9	8	15	8	4	13
PLC, Within, Above (N = 10, 11, 16, 8, 5, 15)	1	2	1	0	1	2
PLC, Above, Within (N = 0, 1, 2, 2, 4, 2)	0	1	2	2	2	1
PLC, Above, Above (N = 0, 1, 2, 2, 4, 2)	0	0	0	0	2	1

No statistical analyses for this end point

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End point title

Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 32 ^[9]

End point description

End point type

Primary

End point timeframe

At Day 32

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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	10	10	15	11	10	16
Units: Subjects
HgL, Below, Below (N = 3, 2, 1, 1, 0, 0)	2	2	1	1	0	0
HgL, Below, Within (N = 3, 2, 1, 1, 0, 0)	1	0	0	0	0	0
HgL, Within, Unknown (N = 7, 8, 15, 10, 10, 16)	0	0	0	1	0	0
HgL, Within, Below (N = 7, 8, 15, 10, 10, 16)	1	1	0	0	1	2
HgL, Within, Within (N = 7, 8, 15, 10, 10, 16)	6	7	14	9	8	14
HgL, Within, Above (N = 7, 8, 15, 10, 10, 16)	0	0	1	0	1	0
HgL, Above, Within (N = 0, 0, 1, 0, 0, 1)	0	0	0	0	0	1
HgL, Above, Above (N = 0, 0, 1, 0, 0, 1)	0	0	1	0	0	0
WBC, Below, Within (N = 0, 0, 1, 0, 0, 1)	0	0	1	0	0	1
WBC, Within, Unknown (N = 10, 10, 14, 11, 7, 16)	0	0	0	1	0	0
WBC, Within, Below (N = 10, 10, 14, 11, 7, 16)	1	2	3	0	1	2
WBC, Within, Within (N = 10, 10, 14, 11, 7, 16)	9	7	11	10	5	14
WBC, Within, Above (N = 10, 10, 14, 11, 7, 16)	0	1	0	0	1	0
WBC, Above, Within (N = 0, 0, 2, 0, 3, 0)	0	0	1	0	2	0
WBC, Above, Above (N = 0, 0, 2, 0, 3, 0)	0	0	1	0	1	0
PLC, Within, Unknown (N = 10, 9, 15, 9, 5, 15)	0	0	0	1	0	0
PLC, Within, Below (N = 10, 9, 15, 9, 5, 15)	0	1	0	0	0	0
PLC, Within, Within (N = 10, 9, 15, 9, 5, 15)	10	7	15	7	4	14
PLC, Within, Above (N = 10, 9, 15, 9, 5, 15)	0	1	0	1	1	1
PLC, Above, Within (N = 0, 1, 2, 2, 5, 2)	0	1	2	2	4	1
PLC, Above, Above (N = 0, 1, 2, 2, 5, 2)	0	0	0	0	1	1

No statistical analyses for this end point

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End point title

Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 38 ^[10]

End point description

Assessed hematological laboratory parameters include hemoglobin level [HgL] white blood cells [WBC] and platelet count [PLC]. Hematological abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Below, Within or Above. [e.g. HgL, Below, Below = HgL below normal ranges at baseline versus below normal ranges at Day 38]. Note: As per Protocol, hematology testing for RSV HD group on Day 38 was not performed since no platelet decrease (i.e., less than 150000 cells/cubic millimeter) was detected on Day 32.

End point type

Primary

End point timeframe

At Day 38

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	8	1	0 ^[11]	6	2	2
Units: Subjects
HgL, Below, Below (N = 2, 0, 0, 1, 0, 0)	2	0		1	0	0
HgL, Within, Within (N = 6, 1, 0, 5, 2, 1)	6	1		5	2	1
HgL, Above, Above (N = 0, 0, 0, 0, 0, 1)	0	0		0	0	1
WBC, Within, Within (N = 8, 1, 0, 6, 1, 2)	8	1		4	1	2
WBC, Within, Above (N = 8, 1, 0, 6, 1, 2)	0	0		2	0	0
WBC, Above, Above (N = 0, 0, 0, 0, 1, 0)	0	0		0	1	0
PLC, Within, Within (N = 8, 1, 0, 6, 1, 2)	7	1		5	0	1
PLC, Within, Above (N = 8, 1, 0, 6, 1, 2)	1	0		1	1	1
PLC, Above, Above (N = 0, 0, 0, 0, 1, 0,)	0	0		0	1	0

Notes
[11] - No data collected for this study group at this time point.

No statistical analyses for this end point

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End point title

Number of subjects with hematological laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 61 ^[12]

End point description

End point type

Primary

End point timeframe

At Day 61

Notes
[12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	10	12	16	9	11	15
Units: Subjects
HgL, Below, Below (N = 3, 1, 1, 0, 0, 0)	2	1	0	0	0	0
HgL, Below, Within (N = 3, 1, 1, 0, 0, 0)	1	0	1	0	0	0
HgL, Within, Unknown (N = 7, 11, 16, 9, 11, 15)	0	0	0	1	0	0
HgL, Within, Below (N = 7, 11, 16, 9, 11, 15)	0	1	0	0	0	2
HgL, Within, Within (N = 7, 11, 16, 9, 11, 15)	7	10	16	8	11	13
HgL, Above, Within (N = 0, 0, 1, 0, 0, 1)	0	0	0	0	0	1
HgL, Above, Above (N = 0, 0, 1, 0, 0, 1)	0	0	1	0	0	0
WBC, Below, Within (N = 0, 0, 1, 0, 0, 1)	0	0	1	0	0	1
WBC, Within, Unknown (N = 10, 12, 15, 9, 7, 15)	0	0	0	1	0	0
WBC, Within, Below (N = 10, 12, 15, 9, 7, 15)	1	0	0	0	0	3
WBC, Within, Within (N = 10, 12, 15, 9, 7, 15)	9	11	14	8	6	10
WBC, Within, Above (N = 10, 12, 15, 9, 7, 15)	0	1	1	0	1	2
WBC, Above, Within (N = 0, 0, 2, 0, 4, 0)	0	0	1	0	4	0
WBC, Above, Above (N = 0, 0, 2, 0, 4, 0)	0	0	1	0	0	0
PLC, Within, Unknown (N = 10, 11, 16, 6, 6, 14)	0	0	0	1	0	0
PLC, Within, Below (N = 10, 11, 16, 6, 6, 14)	0	0	0	0	0	1
PLC, Within, Within (N = 10, 11, 16, 6, 6, 14)	9	8	15	4	5	8
PLC, Within, Above (N = 10, 11, 16, 6, 6, 14)	1	3	1	1	1	5
PLC, Above, Within (N = 0, 1, 2, 2, 5, 2)	0	1	2	2	4	1
PLC, Above, Above (N = 0, 1, 2, 2, 5, 2)	0	0	0	0	1	1

No statistical analyses for this end point

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End point title

Number of subjects with biochemical laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 31 ^[13]

End point description

Assessed biochemical laboratory parameters include alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. Biochemical abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Unknown, Below, Within or Above. [e.g. ALT, Below, Below = ALT below normal ranges at baseline versus below normal ranges at Day 31].

End point type

Primary

End point timeframe

At Day 31

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	9	11	16	11	9	17
Units: Subjects
ALT, Below, Below (N = 2, 0, 0, 0, 0, 1)	1	0	0	0	0	0
ALT, Below, Within (N = 2, 0, 0, 0, 0, 1)	1	0	0	0	0	0
ALT, Below, Above (N = 2, 0, 0, 0, 0, 1)	0	0	0	0	0	1
ALT, Within, Unknown (N = 8, 11, 16, 11, 9, 13)	0	1	0	0	0	0
ALT, Within, Below (N = 8, 11, 16, 11, 9, 13)	1	0	0	0	0	0
ALT, Within, Within (N = 8, 11, 16, 11, 9, 13)	7	10	15	11	7	13
ALT, Within, Above (N = 8, 11, 16, 11, 9, 13)	0	0	1	0	2	0
ALT, Above, Within (N = 0, 1, 2, 0, 0, 3)	0	1	1	0	0	2
ALT, Above, Above (N = 0, 1, 2, 0, 0, 3)	0	0	1	0	0	1
AST, Within, Unknown (N = 9, 9, 15, 10, 8, 14)	0	1	0	0	0	0
AST, Within, Within (N = 9, 9, 15, 10, 8, 14)	9	7	13	9	7	14
AST, Within, Above (N = 9, 9, 15, 10, 8, 14)	0	1	2	1	1	0
AST, Above, Below (N = 1, 3, 3, 1, 1, 3)	0	0	0	0	0	1
AST, Above, Within (N = 1, 3, 3, 1, 1, 3)	1	1	1	1	0	0
AST, Above, Above (N = 1, 3, 3, 1, 1, 3)	0	2	2	0	1	2
CREA, Below, Unknown (N = 7, 4, 4, 8, 1, 0)	0	1	0	0	0	0
CREA, Below, Below (N = 7, 4, 4, 8, 1, 0)	4	3	1	7	1	0
CREA, Below, Within (N = 7, 4, 4, 8, 1, 0)	3	0	3	1	0	0
CREA, Within, Below (N = 3, 8, 14, 3, 7, 17)	3	1	4	0	0	4
CREA, Within, Within (N = 3, 8, 14, 3, 7, 17)	0	7	10	3	7	12
CREA, Within, Above(N = 3, 8, 14, 3, 7, 17)	0	0	0	0	0	1
CREA, Above, Within (N = 0, 0, 0, 0, 1, 0)	0	0	0	0	1	0

No statistical analyses for this end point

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End point title

Number of subjects with biochemical laboratory results change with respect to normal laboratory ranges and versus baseline, at Day 61 ^[14]

End point description

Assessed biochemical laboratory parameters include alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatinine [CREA]. Biochemical abnormalities refer to range indicator at timing, categorized as Below, Within or Above normal ranges, and compared to baseline range indicator of the same parameter, at Screening (Day-29 to Day 1) i.e. Below, Within or Above. [e.g. ALT, Below, Below = ALT below normal ranges at baseline versus below normal ranges at Day 61].

End point type

Primary

End point timeframe

At Day 61

Notes
[14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	9	11	16	11	10	16
Units: Subjects
ALT, Below, Below (N = 2, 0, 0, 0, 0, 1)	1	0	0	0	0	0
ALT, Below, Within (N = 2, 0, 0, 0, 0, 1)	1	0	0	0	0	1
ALT, Within, Within (N = 8, 11, 16, 11, 10, 12)	8	10	15	10	9	12
ALT, Within, Above (N = 8, 11, 16, 11, 10, 12)	0	1	1	1	1	0
ALT, Above, Within (N = 0, 1, 2, 0, 1, 2)	0	1	2	0	1	1
ALT, Above, Above (N = 0, 1, 2, 0, 1, 2)	0	0	0	0	0	1
AST, Within, Within (N = 9, 10, 15, 10, 9, 13)	9	9	15	10	8	13
AST, Within, Above (N = 9, 10, 15, 10, 9, 13)	0	1	0	0	1	0
AST, Above, Within (N = 1, 2, 3, 1, 2, 3)	1	1	1	0	0	1
AST, Above, Above (N = 1, 2, 3, 1, 2, 3)	0	1	2	1	2	2
CREA, Below, Below (N = 7, 3, 4, 8, 2, 0)	4	2	2	7	1	0
CREA, Below, Within (N = 7, 3, 4, 8, 2, 0)	3	1	2	1	1	0
CREA, Within, Below (N = 3, 9, 14, 3, 8, 16)	3	1	3	0	0	1
CREA, Within, Within (N = 3, 9, 14, 3, 8, 16)	0	8	10	3	8	15
CREA, Within, Above (N = 3, 9, 14, 3, 8, 16)	0	0	1	0	0	0
CREA, Above, Within (N = 0, 0, 0, 0, 1, 0)	0	0	0	0	1	0

No statistical analyses for this end point

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End point title

Number of subjects with any SAEs from Day 1 up to Day 366

End point description

End point type

Secondary

End point timeframe

From Day 1 up to Day 366

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	11	14	18	11	11	17
Units: Subjects	1	1	1	3	1	2

No statistical analyses for this end point

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End point title

Number of subjects with lower respiratory tract infection associated with RSV infection (RSV-LRTI) (AE of specific interest) from Dose 1 administration (Day 1) up to Day 366

End point description

Subjects experiencing an LRTI associated with RSV infection were reported as AE of specific interest. To identify RSV-LRTI for the purpose of AE of specific interest, the diagnosis was based on the investigators’ clinical judgment taking into account the clinical history, the examination, relevant medical investigations and locally-available diagnostic test for RSV.

End point type

Secondary

End point timeframe

From Dose 1 administration (Day 1) up to Day 366

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	11	14	18	11	11	17
Units: Subjects	0	1	0	3	0	0

No statistical analyses for this end point

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End point title

Number of subjects with respiratory tract infection associated with RSV infection (RSV-RTI), RSV-LRTI, severe RSV-LRTI (according to standardized case definitions) from Dose 1 administration (Day 1) up to Day 366

End point description

RSV-RTI refers to subject having runny nose OR blocked nose OR cough AND confirmed RSV infection [RSV infection confirmed on nasal swab positive for RSV A or B by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) performed at sponsor level]. RSV-LRTI refers to subject with history of cough OR difficulty breathing [based on history reported by parents/legally acceptable representatives (LARs) and includes difficulty breathing (e.g. showing signs of wheezing or stridor, tachypnoea, flaring of nostrils, chest in-drawing, apnoea) associated with nasal obstruction] AND Blood Oxygen Saturation (SpO2) lower than (<) 95 percent (%), OR respiratory rate (RR) increase [defined as ≥ 40/minute (12 months of age or above)] AND confirmed RSV infection. RSV-severe LRTI are cases meeting the case definition of RSV-LRTI AND SpO2 < 93%, OR lower chest wall in-drawing.

End point type

Secondary

End point timeframe

From Dose 1 administration (Day 1) up to Day 366

No statistical analyses for this end point

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End point title

Number of subjects with any SAEs from Day 1 up to study conclusion at Day 731

End point description

End point type

Secondary

End point timeframe

From Day 1 up to study conclusion at Day 731

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	11	14	18	11	11	17
Units: Subjects	1	1	2	3	1	2

No statistical analyses for this end point

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End point title

Number of subjects with RSV-LRTI (AE of specific interest) from Dose 1 administration (Day 1) up to study conclusion at Day 731

End point description

End point type

Secondary

End point timeframe

From Dose 1 administration (Day 1) up to study conclusion at Day 731

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	11	14	18	11	11	17
Units: Subjects	0	1	0	3	0	0

No statistical analyses for this end point

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End point title

Number of subjects with RSV-RTI, RSV-LRTI, severe RSV-LRTI (according to standardized case definitions) from Dose 1 administration (Day 1) up to study conclusion at Day 731

End point description

RSV-RTI refers to subject having runny nose OR blocked nose OR cough AND confirmed RSV infection (RSV infection confirmed on nasal swab positive for RSV A or B by qRT-PCR performed at sponsor level). RSV-LRTI refers to subject with history of cough OR difficulty breathing [based on history reported by parents/LARs and includes difficulty breathing (e.g. showing signs of wheezing or stridor, tachypnoea, flaring of nostrils, chest in-drawing, apnoea) associated with nasal obstruction] AND Sp02 < 95% OR respiratory rate (RR) increase [defined as ≥ 40/minute (12 months of age or above)] AND confirmed RSV infection. RSV-severe LRTI are cases meeting the case definition of RSV-LRTI AND SpO2 < 93%, OR lower chest wall in-drawing.

End point type

Secondary

End point timeframe

From Dose 1 administration (Day 1) up to study conclusion at Day 731

No statistical analyses for this end point

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End point title

Frequency of RSV-specific CD4+ T-cells expressing at least two markers upon stimulation with F, N and M2-1 peptide pools

End point description

Magnitude of cell mediated immunity (CMI) response to the investigational RSV vaccine was measured in terms of frequency of RSV-specific CD4+ T-cells expressing at least two markers upon stimulation with F, N and M2-1 peptide pools and expressed in RSV-specific CD4+ T-cells/million cells. Assessed markers were CD40-L, IL-2, TNF-α and IFN-ɣ.

End point type

Secondary

End point timeframe

At Pre-vaccination (Screening), Day 31, Day 61 and Day 366

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	9	3	1	10	2	1
Units: RSV-specific CD4+ T-cells/million cells
median (inter-quartile range (Q1-Q3))
RSV F pool 15/11 Ag, Screening (N=8,3,1,9,1,0)	169.5 (85 to 218)	123 (32 to 268)	1 (1 to 1)	176 (120 to 336)	1813 (1813 to 1813)	0 (0 to 0)
RSV F pool 15/11 Ag, Day 31 (N=9,2,1,7,2,0)	291 (231 to 469)	546 (484 to 608)	1086 (1086 to 1086)	234 (48 to 350)	1129.5 (379 to 1880)	0 (0 to 0)
RSV F pool 15/11 Ag, Day 61 (N =8,3,1,10,2,0)	214 (74.5 to 331.5)	451 (93 to 495)	394 (394 to 394)	105.5 (1 to 193)	759 (218 to 1300)	0 (0 to 0)
RSV F pool 15/11 Ag, Day 366 (N=4,2,1,4,2,1)	206 (71 to 288.5)	108.5 (1 to 216)	1164 (1164 to 1164)	252.5 (169.5 to 495)	664.5 (252 to 1077)	229 (229 to 229)
RSV N pool 15/11 Ag, Screening (N=8,3,1,8,1,0)	51 (1 to 121)	54 (1 to 369)	140 (140 to 140)	104 (27 to 174)	253 (253 to 253)	0 (0 to 0)
RSV N pool 15/11 Ag, Day 31 (N=8,2,1,9,2,0)	129.5 (23.5 to 226.5)	229 (1 to 457)	289 (289 to 289)	58 (1 to 102)	193 (180 to 206)	0 (0 to 0)
RSV N pool 15/11 Ag, Day 61 (N=7,3,1,10,2, 0)	70 (1 to 165)	144 (34 to 426)	1 (1 to 1)	71 (50 to 117)	64.5 (52 to 77)	0 (0 to 0)
RSV N pool 15/11 Ag, Day 366 (N=6,2,1,6,2,1)	56 (1 to 269)	41.5 (1 to 82)	82 (82 to 82)	89 (42 to 113)	78 (27 to 129)	91 (91 to 91)
RSV M2-1 pool 15/11 Ag, Screening (N=5,3,1,5,1,0)	1 (1 to 9)	1 (1 to 10)	56 (56 to 56)	1 (1 to 1)	214 (214 to 214)	0 (0 to 0)
RSV M2-1 pool 15/11 Ag, Day 31 (N=5,2,1,8,2,0)	1 (1 to 34)	21.5 (1 to 42)	229 (229 to 229)	1 (1 to 13)	145.5 (100 to 191)	0 (0 to 0)
RSV M2-1 pool 15/11 Ag, Day 61 (N=6,3,1,9,2,0)	8 (1 to 57)	2 (1 to 55)	46 (46 to 46)	30 (1 to 33)	1 (1 to 1)	0 (0 to 0)
RSV M2-1 pool 15/11 Ag, Day 366 (N=6,2,1,5,2,1)	7 (1 to 81)	2.5 (1 to 4)	13 (13 to 13)	23 (6 to 27)	48 (1 to 95)	56 (56 to 56)

No statistical analyses for this end point

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End point title

Anti-RSV-A neutralizing antibody titers

End point description

Humoral response to the investigational RSV vaccine was measured in terms of anti-RSV-A neutralizing antibody titers and expressed as geometric mean titers (GMTs) in Estimated Dilution 60 (ED60) titers.

End point type

Secondary

End point timeframe

At Pre-vaccination (Screening), Day 31, Day 61 and Day 366

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	10	13	18	11	11	17
Units: Titers
geometric mean (confidence interval 95%)
Screening (N = 10, 13, 17, 10, 11, 16)	127.4 (44 to 368.5)	179.4 (99.2 to 324.5)	495.7 (242.5 to 1013.1)	376.5 (89.3 to 1587.5)	214.6 (80.8 to 569.9)	332 (158.5 to 695.4)
Day 31 (N = 10, 12, 18, 10, 9, 17)	711.7 (229.7 to 2204.9)	1646 (815.8 to 3321)	2203.9 (1383.7 to 3510.3)	645.9 (266.3 to 1566.5)	703.9 (244.3 to 2028.4)	295 (149.6 to 581.8)
Day 61 (N = 10, 12, 17, 11, 11, 15)	1081.3 (648.3 to 1803.3)	1809 (1022.6 to 3200.2)	1974.9 (1356.9 to 2874.3)	421.5 (178.9 to 993.1)	316.4 (169 to 592.3)	307.1 (148.5 to 634.9)
Day 366 (N = 9, 11, 16, 11, 11, 16)	236.9 (105.7 to 531)	837 (546.6 to 1281.6)	1038 (629.3 to 1712.3)	398.5 (163.5 to 971.7)	545.4 (269.4 to 1104.3)	493.8 (216 to 1129.1)

No statistical analyses for this end point

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End point title

Anti-RSV-F antibody concentrations

End point description

Humoral response to the investigational RSV vaccine was measured as anti-RSV F antibody concentrations and expressed as geometric mean concentrations (GMCs) in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL).

End point type

Secondary

End point timeframe

At Pre-vaccination (Screening), Day 31, Day 61 and Day 366

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	10	13	17	11	11	17
Units: EU/mL
geometric mean (confidence interval 95%)
Screening (N = 9, 13, 17, 10, 9, 16)	2082 (864.3 to 5015.5)	2061.6 (1343.6 to 3163.4)	3686.4 (1964.5 to 6917.5)	3933.2 (1789.1 to 8646.7)	1216.3 (472.9 to 3128.7)	2988.6 (1420.9 to 6286)
Day 31 (N = 10, 11, 17, 9, 9, 17)	4807.2 (1738.5 to 13292.8)	10810.9 (4062.2 to 28771.1)	17419 (11639.6 to 26068.2)	6134.2 (2752 to 13673)	7911.6 (3187.7 to 19636)	2350.6 (1235.9 to 4470.7)
Day 61 (N = 9, 12, 15, 11, 11, 15)	6167.5 (3701.3 to 10277.1)	15577.4 (8012.9 to 30283.2)	15083.8 (10555 to 21555.7)	2983.3 (1612.8 to 5518.3)	3182 (1737.1 to 5828.8)	2101.3 (1038.3 to 4252.6)
Day 366 (N = 9, 11, 17, 11, 11, 16)	3988.5 (1789.4 to 8890.1)	6521.1 (3702.5 to 11485.4)	6490.7 (4509.7 to 9341.8)	3591.3 (1472.8 to 8756.9)	3047.5 (1577.7 to 5886.6)	4487.9 (1936.8 to 10398.8)

No statistical analyses for this end point

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End point title

Palivizumab-competing antibody concentrations

End point description

Humoral response to the investigational RSV vaccine was measured as Palivizumab-competing antibody concentrations and expressed as geometric mean concentrations (GMCs) in microgram/milliliter (µg/mL).

End point type

Secondary

End point timeframe

At Pre-vaccination (Screening), Day 31 and Day 61

End point values	RSV LD Group	RSV MD Group	RSV HD Group	Placebo LD group	Placebo MD group	Placebo HD group
Number of subjects analysed	10	13	17	11	11	17
Units: µg/mL
geometric mean (confidence interval 95%)
Screening (N = 9, 13, 17, 10, 9, 16)	5.2 (4.3 to 6.3)	4.8 (4.8 to 4.8)	6.6 (5 to 8.6)	6.2 (4.2 to 9.2)	4.8 (4.8 to 4.8)	7.2 (4.8 to 10.9)
Day 31 (N = 10, 11, 17, 9, 9, 17)	7.9 (5.3 to 11.7)	11.1 (6.2 to 19.8)	17.5 (13 to 23.6)	8 (4.4 to 14.5)	12.5 (6.2 to 25.5)	6.8 (4.8 to 9.6)
Day 61 (N = 9, 12, 15, 11, 11, 15)	6.3 (4.6 to 8.6)	15.2 (9.2 to 25.1)	14 (10.1 to 19.4)	6.1 (4.3 to 8.6)	7 (4.5 to 10.8)	6.6 (4.8 to 9)

No statistical analyses for this end point

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Timeframe for reporting adverse events

Solicited adverse events were collected during the 7-day follow-up period and unsolicited adverse events during the 30-day follow-up period after any vaccination. Serious adverse events were collected from Day 1 up to Day 731.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

RSV LD Group

Reporting group description

Reporting group title

RSV MD Group

Reporting group description

Reporting group title

Placebo MD group

Reporting group description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.15 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31.

Reporting group title

Placebo LD group

Reporting group description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31.

Reporting group title

Placebo HD group

Reporting group description

RSV-seropositive infants, aged 12 to 23 months at the time of first vaccination, received 2 doses (0.5 mL each) of placebo, administered intramuscularly, one each at Day 1 and Day 31.

Reporting group title

RSV HD Group

Reporting group description

Serious adverse events	RSV LD Group	RSV MD Group	Placebo MD group	Placebo LD group	Placebo HD group	RSV HD Group
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 11 (9.09%)	1 / 14 (7.14%)	1 / 11 (9.09%)	3 / 11 (27.27%)	2 / 17 (11.76%)	2 / 18 (11.11%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Nervous system disorders
Unresponsive to stimuli
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Febrile convulsion
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Infections and infestations
Respiratory syncytial virus infection
subjects affected / exposed	0 / 11 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	2 / 11 (18.18%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronavirus infection
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	1 / 11 (9.09%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	2 / 18 (11.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Enterovirus infection
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	1 / 11 (9.09%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Rhinovirus infection
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Tonsillitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Herpangina
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Pneumonia
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0

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

Non-serious adverse events	RSV LD Group	RSV MD Group	Placebo MD group	Placebo LD group	Placebo HD group	RSV HD Group
Total subjects affected by non serious adverse events
subjects affected / exposed	10 / 11 (90.91%)	11 / 14 (78.57%)	10 / 11 (90.91%)	11 / 11 (100.00%)	14 / 17 (82.35%)	17 / 18 (94.44%)
Injury, poisoning and procedural complications
Face injury
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0
Head injury
subjects affected / exposed	1 / 11 (9.09%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0
Procedural pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0
Arthropod bite
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	5 / 11 (45.45%)	5 / 14 (35.71%)	4 / 11 (36.36%)	5 / 11 (45.45%)	2 / 17 (11.76%)	11 / 18 (61.11%)
occurrences all number	7	5	6	5	2	15
Injection site erythema
subjects affected / exposed	2 / 11 (18.18%)	2 / 14 (14.29%)	0 / 11 (0.00%)	3 / 11 (27.27%)	4 / 17 (23.53%)	4 / 18 (22.22%)
occurrences all number	4	2	0	6	5	5
Injection site pain
subjects affected / exposed	3 / 11 (27.27%)	3 / 14 (21.43%)	0 / 11 (0.00%)	2 / 11 (18.18%)	4 / 17 (23.53%)	2 / 18 (11.11%)
occurrences all number	3	4	0	3	5	2
Injection site swelling
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	1 / 11 (9.09%)	3 / 17 (17.65%)	1 / 18 (5.56%)
occurrences all number	0	0	1	2	4	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0
Ear and labyrinth disorders
Tympanic membrane perforation
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0
Immune system disorders
Seasonal allergy
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	2 / 11 (18.18%)	2 / 14 (14.29%)	2 / 11 (18.18%)	2 / 11 (18.18%)	3 / 17 (17.65%)	0 / 18 (0.00%)
occurrences all number	2	3	3	3	3	0
Teething
subjects affected / exposed	1 / 11 (9.09%)	0 / 14 (0.00%)	1 / 11 (9.09%)	1 / 11 (9.09%)	1 / 17 (5.88%)	0 / 18 (0.00%)
occurrences all number	1	0	1	1	1	0
Vomiting
subjects affected / exposed	1 / 11 (9.09%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 17 (0.00%)	2 / 18 (11.11%)
occurrences all number	1	0	0	1	0	2
Constipation
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0
Gastrointestinal inflammation
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0
Stomatitis
subjects affected / exposed	0 / 11 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	2 / 11 (18.18%)	0 / 11 (0.00%)	1 / 17 (5.88%)	2 / 18 (11.11%)
occurrences all number	0	0	2	0	1	2
Rhinorrhoea
subjects affected / exposed	0 / 11 (0.00%)	1 / 14 (7.14%)	1 / 11 (9.09%)	0 / 11 (0.00%)	1 / 17 (5.88%)	1 / 18 (5.56%)
occurrences all number	0	1	1	0	1	2
Catarrh
subjects affected / exposed	0 / 11 (0.00%)	1 / 14 (7.14%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	1	1	0	0	0
Rhinitis allergic
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	1	0
Nasal congestion
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	0	0	1
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	1 / 11 (9.09%)	0 / 14 (0.00%)	1 / 11 (9.09%)	1 / 11 (9.09%)	1 / 17 (5.88%)	0 / 18 (0.00%)
occurrences all number	2	0	1	1	1	0
Eczema
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	1 / 17 (5.88%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	1	0
Dermatitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0
Dermatitis diaper
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0
Miliaria
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	0	1	0	0
Rash macular
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)
occurrences all number	0	0	0	0	1	0
Erythema
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	0	0	1
Psychiatric disorders
Irritability
subjects affected / exposed	1 / 11 (9.09%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)
occurrences all number	1	1	0	0	1	0
Infections and infestations
Nasopharyngitis
subjects affected / exposed	2 / 11 (18.18%)	6 / 14 (42.86%)	4 / 11 (36.36%)	0 / 11 (0.00%)	5 / 17 (29.41%)	7 / 18 (38.89%)
occurrences all number	2	10	5	0	7	8
Gastroenteritis
subjects affected / exposed	0 / 11 (0.00%)	1 / 14 (7.14%)	3 / 11 (27.27%)	0 / 11 (0.00%)	1 / 17 (5.88%)	3 / 18 (16.67%)
occurrences all number	0	1	3	0	1	3
Conjunctivitis
subjects affected / exposed	3 / 11 (27.27%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	3	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	1 / 11 (9.09%)	1 / 14 (7.14%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	2	1	0	0	0
Pharyngotonsillitis
subjects affected / exposed	1 / 11 (9.09%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 17 (5.88%)	1 / 18 (5.56%)
occurrences all number	1	0	0	0	1	1
Influenza
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	2 / 18 (11.11%)
occurrences all number	0	0	1	0	0	2
Tonsillitis streptococcal
subjects affected / exposed	1 / 11 (9.09%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	1	0	0
Otitis media
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 17 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	1	0	1
Varicella
subjects affected / exposed	0 / 11 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)
occurrences all number	0	1	0	0	1	0
Impetigo
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	2 / 18 (11.11%)
occurrences all number	0	0	0	0	0	2
Bronchiolitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0
Croup infectious
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0
Hand-foot-and-mouth disease
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0
Paronychia
subjects affected / exposed	1 / 11 (9.09%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0
Pharyngitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	0	0	1	0	0	0
Tonsillitis
subjects affected / exposed	1 / 11 (9.09%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)
occurrences all number	1	0	0	0	0	0
Acarodermatitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	0	0	1
Bronchitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	0	0	2
Pharyngitis streptococcal
subjects affected / exposed	0 / 11 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)
occurrences all number	0	0	0	0	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 11 (9.09%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	3 / 17 (17.65%)	2 / 18 (11.11%)
occurrences all number	1	0	0	0	3	2

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Were there any global substantial amendments to the protocol? Yes

16 Jan 2017

• The Spanish competent authorities requested the Sponsor to extend the long term medical follow-up for one additional year. The purpose of this amendment was to respond to this request by increasing the follow-up of the subjects from one year to two years. This included the collection of adverse events of specific interest [RSV-LRTI] and serious adverse events, the surveillance for respiratory tract infection, difficulty of breathing and wheezing. • The Italian competent authorities requested that, in addition to the 60 minutes observation planned per protocol between each infant receiving ChAd155-RSV vaccination, the Sponsor monitors potential hypersensitivity reactions for a longer period following both vaccine administrations in a sufficient number of infants before another one could be vaccinated with the same dose. The Sponsor agreed to put in place a 48-hour observation period after the first and second doses administered to the first eight infants enrolled in each step, before continuing vaccination of more infants with a minimum interval of 60 minutes. • Following the request from investigators, the screening period has been increased from 15 days (Day -14 to Day 0) to 30 days (Day -29 to Day 0) in order to improve recruitment of subjects. • Following the request from investigators, the following exclusion criteria have been clarified: History of wheezing; History of chronic cough. • The satisfactory outcome of the review by an Independent Data Monitoring Committee (IDMC) of safety data from study 201974 (RSV PED-001) in healthy adults has been added to the rationale for the choice of study population. • The holding rule for hospitalization due to any local or general solicited AE has been restricted to any local or general solicited AE that could not reasonably be attributed to a cause other than vaccination in order to exclude irrelevant cases. • In addition, possibility to assess RSV infection using WHO case definition, has been added to this protocol.

08 Jun 2017

• During initial implementation of this study, parents have given feedback that the number of visits and blood tests were challenging to accommodate with busy family schedules and were demanding for young children. This amendment reduced the burden on families whilst maintaining the intended close oversight of the potential risk of thrombocytopenia, by reducing the number and frequency of required blood tests and visits unless clinically required. • It has been clarified that blood samples for CMI and for humoral immunogenicity may be postponed until after the RSV serostatus was known and eligibility was confirmed up to or on Day 0 (but before vaccination). • The age range for enrolment has been expanded an additional 6 months, from 12 to 17 months initially, to 12 to 23 months. • The following inclusion criterion has been removed, to be able to include those infants who despite being mildly underweight or premature have had normal subsequent courses: “Born full-term (i.e. after a gestation period of 37 to less than 42 completed weeks) with a minimum birth weight of 2.5 kg”. Other criteria pertaining to current weight, health status of the child, and Synagis administration excluded infants who have experienced prematurity and its associated complications. • Because enrolment in the trial was slower than anticipated, the safety monitoring oversight plan of the IDMC was adapted to provide regular review of accumulating safety data every four weeks in addition to the currently planned review at end of each dose level. • To allow the extension of the recruitment network, some investigational sites without a laboratory in proximity capable to perform the whole blood stimulation (WBS) necessary for the CMI assay was allowed to participate. Therefore, blood sampling for the assessment of CMI was only performed for subjects recruited in sites with a WBS capable laboratory in proximity.

12 Sep 2017

• The Spanish competent authorities (Agencia Española de Medicamentos y Productos Sanitarios [AEMPS]) requested the Sponsor to add the inclusion criterion of being born full-term, which was removed for Protocol Amendment 2. This inclusion criterion was required for Spain. • The collection of birth weight and gestation at birth in weeks at the screening visit has been added to the list of study procedures. This procedure was applicable to all participating countries and permitted the identification of pre-term infants recruited in the study.

10 Dec 2017

• An Independent Data Monitoring Committee (IDMC) reviewed all accumulating unblinded safety and reactogenicity data on a monthly basis for this study to ensure that there was a timely identification of any safety signal. As safety data accumulated, it may have been that there was sufficient evidence of safety of the current dose level to allow progression to the next dose level. For instance, taking the a priori safety concern of thrombocytopenia, this amendment applied both Frequentist and Bayesian approaches to the existing data, to show the likelihood of observing more extreme values. The number of subjects evaluated by the IDMC for the two-step dose escalation to steps 2 and 3 after administration of two doses of study vaccine could continue to be 32 subjects at steps 1 and 2 as before. However, in the absence of a significant safety concern detected in the regular monitoring of all parameters of accumulating safety data, the IDMC agreed to recommend that dose escalation could potentially proceed on at least 16 subjects, without requiring the enrolment and evaluation of the full group size of 32 subjects.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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End point values

RSV LD Group

RSV MD Group

RSV HD Group

Placebo LD group

Placebo MD group

Placebo HD group

Number of subjects analysed

Units: Subjects

RSV-severe LRTI