Conditions: Respiratory Syncytial Virus Infections
Keywords: Safety Respiratory syncytial virus (RSV) Immunogenicity Reactogenicity Infants Vaccine
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 107
Healthy volunteers: yes

Brief summary:
The purpose of this study is to evaluate the safety, reactogenicity and immunogenicity of the respiratory syncytial virus (RSV) candidate vaccine when first administered via intramuscular (IM) injection according to a 0, 1-month schedule to RSV-seropositive infants aged 12 to 23 months.

Detailed description:
The RSV PED-002 study, designed to evaluate the safety, reactogenicity and immunogenicity of the RSV candidate vaccine when administered in 3 sequential doses to seropositive infants aged 12 to 23 months, will be conducted in an observer-blind manner in Epoch 1 and single-blinded in Epoch 2.

Arms:
arm 1: 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 2: 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 3: 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 4: 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 5: 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 6: 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.

Interventions: intervention 1: RSV (GSK3389245A) low dose formulation vaccine intervention 2: RSV (GSK3389245A) middle dose formulation vaccine intervention 3: RSV (GSK3389245A) high dose formulation vaccine intervention 4: Placebo
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: 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. intervention 4: 2 doses (0.5 mL each for Placebo LD and Placebo HD groups and 0.15 mL each for Placebo MD group) of Placebo administered intramuscularly in the left anterolateral thigh or deltoid, at Day 1 and Day 31.

Protocol document:
Prot_000.pdf: 
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Clinical Study Protocol
Sponsor:
GlaxoSmithKline Biologicals
Rue de l’Institut, 89
1330 Rixensart, Belgium
Primary Study vaccine and 
number

GlaxoSmithKline (GSK) Biologicals’ respiratory 
syncytial virus (RSV) vaccine based on the RSV 
viral proteins F, N and M2-1 encoded by 
chimpanzee-derived adenovector (ChAd155-
RSV) (GSK3389245A)
Other Study vaccine

Placebo (Formulation buffer S9b)
eTrack study number and 
Abbreviated Title
204838 (RSV PED-002)
Investigational New Drug 
(IND) number
16999
EudraCT number
2016-000117-76
Date of protocol
Final Version 1: 26 April 2016
Date of administrative 
change
Administrative change 1 Final: 06 July 2016
Administrative change 2 Final: 13 September 2016
Date of protocol 
amendment
Amendment 1 Final: 16 January 2017
Amendment 2 Final: 08 June 2017
Amendment 3 Final: 12 September 2017
Amendment 4 Final: 10 December 2017
Title
A study to evaluate safety, reactogenicity and 
immunogenicity of GSK Biologicals’ RSV 
investigational vaccine based on viral proteins encoded 
by chimpanzee-derived adenovector (ChAd155-RSV) 
(GSK3389245A) in RSV-seropositive infants.
Detailed Title
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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eTrack study number and 
Abbreviated Title
204838 (RSV PED-002)
Investigational New Drug 
(IND) number
16999
EudraCT number
2016-000117-76
Detailed Title
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.
Co-ordinating authors
!
 (Expert Scientific Writer)
!
 (Scientific Writer, Keyrus 
Biopharma contractor for GSK Biologicals)
!
, Scientific Writer
Contributing authors
(Amended 10 December
2017)
!
 (Clinical Research and 
Development Lead [CRDL])
!
 (Clinical and Epidemiology 
Research & Development Project Lead)
!
 (Lead Statistician)
!
 (Lead Statistician)
!
 (Lead Statistician)
!
(Project Statistician)
!
(Project Statistician)
!
 (Project Statistician)
!
 (Study Delivery Lead)
!
 (Study Delivery Lead)
!
 (Study Delivery Manager, 
Synteract HCR contractor for GSK Biologicals)
!
 (Vaccine Supply 
Coordinator, CVO-Europe contractor for GSK 
Biologicals)
!
 (Vaccine Supply Coordinator)

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eTrack study number and 
Abbreviated Title
204838 (RSV PED-002)
Investigational New Drug 
(IND) number
16999
EudraCT number
2016-000117-76
Detailed Title
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.
Contributing authors 
(continued) (Amended 10 
December 2017)
!
, (Clinical Trial Supply Manager)
!
 (Clinical Trial Supply Manager, 
Aixial contractor for GSK Biologicals)
!
 (Clinical Read-out Team Leader)
!
 (Clinical Laboratory Sciences 
[CLS] Study Manager, Business & Decision Life 
Sciences contractor for GSK Biologicals)
!
 (Central Safety Physician)
!
 (Safety Scientist)
!
 (Central Safety Physician)
!
 (Project Data Manager)
!
 (Portfolio Data Manager)
!
 (Oversight Data Manager)
!
(Oversight Data Manager, Keyrus 
Biopharma contractor for GSK Biologicals)
!
 (Global Regulatory 
Representative)
!
 (Global Regulatory 
Representative)
!
 (Global Regulatory 
Representative)
!
 (Global Patent Representative)
GSK Biologicals’ Protocol DS v 14.1.1
© 2016-2017 the GSK group of companies or its licensor. Unauthorized copying or use of this 
information is prohibited.

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Protocol Amendment 4 Sponsor Signatory Approval
eTrack study number and 
Abbreviated Title
204838 (RSV PED-002)
IND number
16999
EudraCT number
2016-000117-76
Date of protocol amendment
Amendment 4 Final: 10 December 2017
Detailed Title 
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.
Sponsor signatory
Amanda Leach,
Clinical and Epidemiology Research & Development 
Project Lead
Signature
Date
 
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Protocol Amendment 4 Rationale
Amendment number:
Amendment 4
Rationale/background for changes: 

An Independent Data Monitoring Committee (IDMC) is reviewing all 
accumulating unblinded safety and reactogenicity data on a monthly basis for this 
study to ensure that there is a timely identification of any safety signal. As safety 
data accumulates, it may be that there is 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 will apply both 
Frequentist and Bayesian approaches to the existing data, as described in Section 
11.4 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 may 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. These amendment changes were implemented in the 
Synopsis and Synopsis Table 1, as well as Sections 1.2.4.1, 1.2.4.2, 1.3, Figure 1 
in Section 3, Table 1 in Section 3, Sections 5.1, 6.2.2.2.1, Table 7 in 6.7.2, Table 
11 in Section 6.7.3, Table 12 and Table 13 in Section 6.7.4.1, and in Sections 
9.10.4 and 11.4.

A footnote was added to indicate the requirement to record the white blood cell 
differential including absolute neutrophil and lymphocyte counts in the eCRF to
Table 11 in Section 6.7.3 and the toxicity grading scales for the absolute neutrophil 
and lymphocyte counts were indicated in Table 25 of Appendix C.

In addition, some typographical errors have been corrected throughout the
protocol.
 
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Protocol Amendment 4 Investigator Agreement
I agree:

To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GlaxoSmithKline (GSK) Biologicals.

To assume responsibility for the proper conduct of the study at this site.

That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all
applicable regulatory requirements. 

To ensure that all persons assisting me with the study are adequately informed about 
the GSK Biologicals’ investigational vaccine(s) and other study-related duties and 
functions as described in the protocol.

To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual.

To ensure that no clinical samples (including serum samples) are retained onsite or 
elsewhere without the approval of GSK Biologicals and the express written informed 
consent of the subject and/or the subject’s legally acceptable representative. 

To perform no other biological assays on the clinical samples except those described 
in the protocol or its amendment(s). 

To co-operate with a representative of GSK Biologicals in the monitoring process of 
the study and in resolution of queries about the data.

That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational vaccine(s), and more generally about his/her 
financial ties with the sponsor. GSK Biologicals will use and disclose the 
information solely for the purpose of complying with regulatory requirements.
Hence I:

Agree to supply GSK Biologicals with any necessary information regarding 
ownership interest and financial ties (including those of my spouse and dependent 
children).

Agree to promptly update this information if any relevant changes occur during the 
course of the study and for one year following completion of the study. 

Agree that GSK Biologicals may disclose any information it has about such 
ownership interests and financial ties to regulatory authorities.

Agree to provide GSK Biologicals with an updated Curriculum Vitae and other 
documents required by regulatory agencies for this study.
 
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eTrack study number and 
Abbreviated Title
204838 (RSV PED-002)
IND number
16999
EudraCT number
2016-000117-76
Date of protocol amendment
Amendment 4 Final: 10 December 2017
Detailed Title
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.
Investigator name
Signature
Date
 
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Sponsor Information
1.
Sponsor
GlaxoSmithKline Biologicals
Rue de l’Institut, 89
1330 Rixensart, Belgium
2.
Sponsor Medical Expert for the Study
Refer to the local study contact information document.
3.
Sponsor Study Monitor
Refer to the local study contact information document.
4.
Sponsor Study Contact for Reporting of a Serious Adverse Event
GSK Biologicals Central Back-up Study Contact for Reporting SAEs: refer to protocol 
Section 9.4.2.
5.
GSK Biologicals’ Central Safety Physician On-Call Contact information for 
Emergency Unblinding
GSK Biologicals Central Safety Physician and Back-up Phone contact: refer to
protocol Section 9.8.
 
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SYNOPSIS
Detailed Title
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.
Indication
Active immunization of infants for the prevention of any lower 
respiratory tract infections (LRTI; bronchiolitis and 
[broncho]pneumonia) associated with respiratory syncytial 
virus (RSV [subtypes A and B]).
Rationale for the 
study and study 
design
Rationale for the study
GlaxoSmithKline (GSK) Biologicals is developing a new 
investigational RSV vaccine to protect infants from RSV 
diseases. The candidate vaccine is based on the RSV viral 
proteins F, N and M2-1 encoded by chimpanzee-derived 
adenovector (ChAd155-RSV).
The purpose of this trial is to evaluate the safety, reactogenicity 
and immunogenicity of this RSV candidate vaccine when first 
administered via intramuscular (IM) injection according to a 0, 
1-month schedule to RSV-seropositive infants aged 12 to 23 
months.
Rationale for the study design

Study population: The immunogenicity, safety and 
reactogenicity of the pediatric candidate RSV vaccine 
(ChAd155-RSV vaccine) has been evaluated in healthy 
adult subjects aged 18 to 45 years (study 201974 [RSV 
PED-001]). The ChAd155-RSV vaccine is being developed 
for the active immunization of infants as from 6 weeks of 
age. To allow age de-escalation from the adult population 
to the targeted population and to not enroll and administer 
the ChAd155-RSV vaccine to older children who are 
beyond the age of severe RSV disease and would not 
benefit from this vaccine, the present study will be 
performed on RSV-seropositive infants aged 12 to 23 
months, after the safety profile of the ChAd155-RSV 
vaccine in adults (study 201974 [RSV PED-001; 
NCT02491463]) was evaluated as satisfactory by an 
Independent Data Monitoring Committee (IDMC). The 
present study will provide critical information on the safety 
and immunogenicity profile of the ChAd155-RSV vaccine 
before a subsequent trial in seronegative infants.
 
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
Control: A placebo group is included as a control for the 
reactogenicity, the safety and the immunogenicity 
assessments.

Study blinding: Given the different storage conditions of 
the investigational RSV vaccine and placebo, double 
blinding is not possible and the study will be conducted in 
an observer-blind manner (Amended 10 December 2017).
When all data up to Day 60 are available, a statistical 
analysis will be performed. This analysis may lead to the 
unblinding of some subjects. As a consequence, after Day 
60, the study cannot be considered as observer-blind, but 
will be conducted in a single-blind manner, with subjects’ 
parent(s)/ legally acceptable representative (LAR[s]) 
remaining blinded up to study end (Day 730). The 
investigators will not have access to the treatment 
allocation up to study end (Day 730).

Regimen, dose and route of administration: A vaccination 
regimen based on two IM injections (in the deltoid [if the 
muscle size is adequate; otherwise injections might be done 
in the anterolateral thigh]) of 5 x 109, 1.5 x 1010, or 5 x 1010
viral particles (vp) of the ChAd155-RSV vaccine 
administered according to a 0, 1-month schedule (4-week 
interval between vaccinations) will be evaluated in this 
study.
The 4-week interval regimen has been tested in pre-clinical 
models and results from a bovine RSV challenge model in 
which seronegative, colostrum-restricted newborn calves 
were vaccinated with two doses of 5 x 1010 vp ChAd155-
RSV, four weeks apart showed that dose regimen was 
immunogenic and protected calves from bovine RSV 
disease and infection and was not associated to pulmonary 
pathology.
A Phase I clinical trial evaluated a simian adenoviral 
vector-based RSV vaccine with the same insert (PanAd3-
RSV) [RSV001 Interim Study Report, 2014]. Data from 
this trial, with 42 subjects, showed that a vaccination 
regimen based on two IM injections, separated by four 
weeks, was safe and immunogenic.
Similar to the Phase I adult study (201974 [RSV PED-
001]), the current study is designed in a staggered manner 
to allow dose escalation from 5 x 109 vp (1-log lower dose) 
to 5 x 1010 vp dose. A third intermediate dose of 1.5 x 1010
vp will be tested in this first time in pediatric population 
study to allow a more progressive escalation of the dose-
related risk in this vulnerable population.
 
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
Staggered design with 3 steps: The investigational 
ChAd155-RSV vaccine will be administered for the first 
time in a pediatric population therefore a three-step 
staggered design will be used to allow dose escalation of 
three dose levels and ensure maximum safety of the 
participating infants.
The investigational ChAd155-RSV vaccine will be 
administered to up to 48 subjects in total. As a control, up 
to 48 subjects will be vaccinated with placebo across the 
three steps (Amended 10 December 2017).
Vaccination will be limited to a maximum of 10 infants per 
day. In the same investigational center, infants will be 
vaccinated sequentially, separated by a minimum interval 
of 60 minutes to allow monitoring of any acute events (e.g. 
hypersensitivity reaction). In addition, to monitor delayed 
potential reactions following vaccination, there will be a 
48-hour observation period following Dose 1 and Dose 2 
administration to the first eight infants (corresponding to 
three to five ChAd155-RSV vaccine recipients) in each 
Step (1, 2, and 3) before continuing vaccination of more 
infants (i.e. from the ninth infant). From the ninth infant, 
infants will be vaccinated sequentially, separated by a 
minimum interval of 60 minutes. Refer to the study 
procedures manual (SPM) for more details about the 48-
hour observation period after the first eight subjects 
vaccinated in each Step.

In Step 1, between a maximum of 32 to a minimum of 
16 RSV-seropositive infants will receive two doses of 
either low dose ChAd155-RSV vaccine (5 x 109 vp 
[RSV-Ld]; 0.5 mL) or placebo (0.5 mL), according to 
their random assignment (Amended 10 December
2017).

In Step 2, between a maximum of 32 to a minimum of 
16 RSV-seropositive infants will receive two doses of 
either middle dose ChAd155-RSV vaccine (1.5 x 1010
vp [RSV-Md]; 0.15 mL) or placebo (0.15 mL), 
according to their random assignment (Amended 10
December 2017).

In Step 3, 32 RSV-seropositive infants will receive two 
doses of either high dose ChAd155-RSV vaccine (5 x 
1010 vp [RSV-Hd]; 0.5 mL) or placebo (0.5 mL), 
according to their random assignment.
An internal Safety Review Committee (iSRC) will review 
all accumulating safety data three weeks after the start of 
vaccination and then about every three weeks until the 
IDMC has reviewed all safety data up to 30 days after 
 
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administration of Dose 2 in Step 3 (i.e. Day 60).
The IDMC will review accumulating reactogenicity and 
safety data monthly throughout the period of vaccination 
(up to 30 days after administration of Dose 2 in Step 3, i.e. 
Day 60). The IDMC will also review incidence of all 
serious adverse events (SAEs) and incidence of RSV-
respiratory tract infections (RTI), RSV-LRTI, RSV-severe 
LRTI and RSV-RTI leading to hospitalization monthly
after the start of vaccination and from beginning of the first 
RSV season to the end of the study.
Both iSRC and IDMC will receive critical safety data (i.e. 
SAEs and adverse events of specific interest) within 48 
hours upon GSK becoming aware of it.
The iSRC and IDMC will determine whether any of the 
predefined study holding rules are met. If this is the case, 
vaccination in the study will be immediately put on hold. 
At any time, the IDMC may recommend to the sponsor to 
suspend the enrolment to the study and/or vaccination 
based on the safety data regularly arising in this study.
Dose escalation will proceed after administration of the 
vaccine to all subjects in the previous step if no significant 
safety concern is detected by the IDMC in their regular 
review of accumulating safety data. The IDMC may 
recommend for dose escalation to proceed in the absence 
of a concern based on safety data review on a minimum 
of 16 subjects completing dose 2. The IDMC may 
recommend that based on the evolving safety profile, 
sufficient information has been accumulated to allow 
safe progression to the next sequential dose level. Thus,
the number of subjects enrolled to the low and mid dose is 
between 16 and 32 subjects but the number of subjects 
enrolled to the high dose remains fixed at 32 subjects.
(Amended 10 December 2017)
Additionally, the IDMC will perform a review when all 
safety data up to 30 days after administration of Dose 2 in 
Step 3 (i.e. Day 60) are available.
 
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Objectives
Primary

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 60) in RSV-
seropositive infants aged 12 to 23 months.
Secondary

To evaluate the safety of two IM doses of three dose levels 
of the RSV investigational vaccine when administered 
according to a 0, 1-month schedule from study start (Day 
0) up to study conclusion (Day 730) in RSV-seropositive 
infants aged 12 to 23 months.

To evaluate the occurrence of RSV respiratory tract 
infections in RSV-seropositive infants from Visit 1 (Day 0, 
after Dose 1) up to study conclusion (Day 730).

To evaluate the magnitude of the CMI induced by two IM 
doses of three dose levels of the RSV investigational 
vaccine when administered according to a 0, 1-month 
schedule, up to Day 365 in RSV-seropositive infants aged 
12 to 23 months.

To evaluate the humoral immunogenicity induced by two 
IM doses of three dose levels of the RSV investigational 
vaccine when administered according to a 0, 1-month 
schedule, up to Day 365 in RSV-seropositive infants aged 
12 to 23 months.
Tertiary

To further evaluate the CMI profile induced by two IM 
doses of three dose levels of the RSV investigational 
vaccine when administered according to a 0, 1-month 
schedule, up to Day 365 in RSV-seropositive infants aged 
12 to 23 months.

If deemed necessary, to further characterize the immune 
response of the RSV investigational vaccine when two IM 
doses are administered according to a 0, 1-month schedule 
in RSV-seropositive infants.
Study design

Experimental design: Phase I/II, observer-blind, 
randomized, placebo-controlled, multi-centric, study with 
two parallel groups per step in a 3-step staggered design.

Duration of the study: approximately 24 months:

Epoch 001: primary starting at the Screening visit and 
ending at Visit 9 (Day 60).
 
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
Epoch 002: follow-up starting at Visit 10 (Day 365) 
and ending at Visit 11 (Day 730).
Any safety, immunogenicity and disease surveillance data 
collected beyond Visit 9 (Day 60) will be collected in 
Epoch 002.

Primary completion Date: Visit 9 (Day 60).
End of Study: Last testing results released of samples 
collected at Visit 11 (Day 730).*
* Up to Visit 11 (Day 730), there will be monthly nasal 
swab to detect asymptomatic RSV infections during the 
RSV season and if following active or a passive 
surveillance contacts, a subject presents symptoms of RTI, 
a nasal swab will be collected.

Study groups: throughout the three steps, infants will be 
randomized in two groups to receive either ChAd155-RSV 
vaccine or placebo (Synopsis Table 1).
Synopsis Table 1
Study groups and epochs foreseen in the study
Step
Study groups
Number of 
subjects*
Age (Min/Max)
Epochs
Epoch 001
Epoch 002
1
RSV-Ld
16
12 months - 23 months
x
x
Placebo-Ld
16
12 months - 23 months
x
x
2
RSV-Md
16
12 months - 23 months
x
x
Placebo-Md
16
12 months - 23 months
x
x
3
RSV-Hd
16
12 months - 23 months
x
x
Placebo-Hd
16
12 months - 23 months
x
x
RSV-Ld: low dose ChAd155-RSV vaccine (5 x 109 vp); RSV-Md: middle dose ChAd155-RSV vaccine (1.5 x 1010 vp); 
RSV-Hd: high dose ChAd155-RSV vaccine (5 x 1010 vp).
*The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the time of first 
vaccination (unless the dose escalation IDMC decision can be made based on the evaluation of accumulating 
safety data on fewer subjects) to ensure that at least 64 infants receive two doses of study vaccine (ChAd155-
RSV or Placebo). Then the number of subjects at each step will be at least 16 (approximately 8 subjects per 
group) at steps 1 and 2 and 32 (approximately 16 subjects per group) at step 3 (Amended 10 December 2017)
 
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Synopsis Table 2
Study groups and treatment foreseen in the study
Treatment name
Volume 
administered
Vaccine/Product 
name
Study Groups
Step 1
Step 2
Step 3
RSV-
Ld
Placebo-
Ld
RSV-
Md
Placebo-
Md
RSV-
Hd
Placebo-
Hd
ChAd155 5x109 vp
0.5 ml
ChAd155-RSV
X
ChAd155 1.5x1010 vp
0.15 ml
ChAd155-RSV
X
ChAd155 5x1010 vp
0.5 ml
ChAd155-RSV
X
Placebo 0.5
0.5 ml
Formulation 
buffer S9b
X
X
Placebo 0.15
0.15 ml
Formulation 
buffer S9b
X
RSV-Ld: low dose ChAd155-RSV vaccine (5 x 109 vp); RSV-Md: middle dose ChAd155-RSV vaccine (1.5 x 1010 vp); 
RSV-Hd: high dose ChAd155-RSV vaccine (5 x 1010 vp).

Control: placebo control (Formulation buffer S9b).

Vaccination schedule(s): two IM vaccine doses 
administered according to a 0, 1-month schedule (i.e. at 
Day 0 and Day 30).

Treatment allocation: infants will be randomized using a 
randomization system on internet (SBIR) at first 
vaccination.

Blinding: observer-blind in Epoch 001 and single-blind
in Epoch 002 .
Synopsis Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001
observer-blind
Epoch 002
single-blind

Sampling schedule:

Blood samples for biochemistry will be taken from all 
infants at Screening (29 days before first vaccination to 
Day 0) and on Day 30, and Day 60. Blood samples for 
hematology will be taken from all infants at Screening 
(29 days before first vaccination to Day 0) and on Day 
1, Day 30, Day 31, and Day 60. Day 7 hematology 
testing will be performed if any ≥ Grade 1 for platelet 
decrease is detected on Day 1 after vaccination, to 
ensure its resolution. Similarly, hematology testing on 
Day 37 will be performed if any ≥ Grade 1 for platelet 
decrease is detected on Day 31. A clinical examination 
with special attention given to detection of spontaneous 
bleeding or easy bruising and evidence of bruising or 
petechiae will be performed by the investigator/study 
staff on Day 1, Day 3 and Day 7 after each vaccination 
(i.e. Day 1, Day 3, Day 7, Day 31, Day 33, and Day 37).
 
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The visits on Day 3 and Day 33 may be replaced by a 
phone call by the investigator/study staff to inquire of 
the infants' general health and to solicit reports of a rash, 
spontaneous bleeding or easy bruising. On Day 1, and 
Day 31, special attention will also be given to the 
detection of petechiae or evidence of petechiae induced 
by the tourniquet. This special attention to detection of 
petechiae or evidence of petechiae induced by the 
tourniquet will also be given on Day 7 and/or Day 37 in 
case hematology testing will be performed on that day. 
Further testing may be required to investigate a finding 
or guide subject management based on the investigator’s 
clinical judgment. Subjects’ parent(s)/LAR(s) will be 
instructed to contact the investigator/study staff if their 
child presents symptoms of spontaneous bleeding or 
easy bruising or if their child develops a rash in the 
month following vaccination, in order to detect any 
thrombocytopenic petechiae or purpura. The investigator 
will, based on his/her medical judgement, appropriately 
investigate infants with clinical suspicion of low 
platelets.

Blood sample for RSV serostatus will be taken from all 
infants at Screening.

Blood samples for CMI are limited to those in 
investigational sites with a laboratory in proximity 
capable to perform WBS necessary for the CMI assay. 
In those sites, samples will be taken from all subjects at 
Screening and on Day 30, Day 60, and Day 365.

Blood samples for humoral immunogenicity will be 
taken from all subjects at Screening and on Day 30, Day 
60, and Day 365.

Blood sample for assessment of mechanism of illness 
(potential enhanced RSV disease [ERD]) will be taken 
from subjects hospitalized for LRTI (only for RSV-
positive subjects using a locally available RSV test).

Nasal swab: there will be monthly nasal swab to detect 
asymptomatic RSV infections during the RSV season 
and if following active or a passive surveillance 
contacts, a subject presents symptoms of respiratory 
tract infections (RTI), a nasal swab will be collected.

Study visits: Visit 1 (Day 0), Visit 5 (Day 30), Visit 9 (Day 
60) and Visit 10 (Day 365) must be performed at the 
investigators clinical facility. Visit 2 (Day 1), Visit 4 (Day 
7), Visit 6 (Day 31), Visit 8 (Day 37) and Visit 11 (Day 730) 
(no blood sampling for immune response and no vaccine 
 
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administration) may take place in the subject’s home or at 
the investigators clinical facility as appropriate to the 
circumstances in the judgment of the investigator. Visit 3 
(Day 3) and Visit 7 (Day 33) may take place at the 
investigators clinical facility or the investigator/clinical staff
may call the subjects’ parent(s)/LAR(s), as appropriate to the 
circumstances in the judgment of the investigator.

Type of study: e.g. self-contained

Data collection: Electronic Case Report Form (eCRF).

Safety monitoring: iSRC and IDMC.

Surveillance for RSV-RTI, difficulty in breathing and 
wheezing episodes.
Surveillance period will be carried out from Visit 1 (after 
Dose 1) until Visit 11 (Day 730). In order to detect 
asymptomatic RSV-RTI, monthly nasal swabs for analysis at 
sponsor laboratory will be performed for all subjects during 
the RSV season. In order to timely detect RSV-RTI and to 
ensure cases are timely captured by the study sites, both 
active and passive surveillance will be conducted:

Passive surveillance: Parent(s)/LAR(s) are instructed to 
contact the investigator/study staff as soon as the subject 
experiences new RTI symptoms (cough, runny nose or 
blocked nose) or worsening of RTI symptoms, or in case 
of difficulty in breathing or wheezing.

Active surveillance: parent(s)/LAR(s) of all the subjects 
will be contacted by the investigator/study staff on a 
regular basis (weekly during the RSV season and every 
month outside the RSV season) to identify any potential 
RSV-RTI and to remind the parent(s)/LAR(s) of the 
subjects to report any new occurrence of RTI symptoms 
(cough, runny nose, blocked nose) or worsening of RTI 
symptoms, or in case of difficulty in breathing or 
wheezing as soon as possible.
Case definition
During the analysis of the study, all cases identified during the 
surveillance of RSV-RTI will be definitively classified as either 
RTI, LRTI, severe LRTI or very severe LRTI according to the 
standardized case definitions (see Synopsis Table 4) based on 
the available World Health Organization (WHO) case 
definitions. 
 
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Synopsis Table 4
Case definitions for data analysis
RSV-RTI
Runny nose OR blocked nose OR cough
AND 
Confirmed RSV infection 4
RSV-LRTI
History of cough OR difficulty breathing 1
AND 
SpO2 < 95% 2, OR RR increase 3
AND 
Confirmed RSV infection 4
RSV-severe LRTI
Meeting the case definition of RSV-LRTI
AND
SpO2 < 93% 2, OR lower chest wall in-drawing
RSV-very severe LRTI
Meeting the case definition of RSV-LRTI 
AND 
SpO2 < 90% 2, OR inability to feed, OR failure to respond / unconscious
RSV hospitalization
Confirmed RSV infection 5
AND
Hospitalized for acute medical condition 6
All-cause LRTI
History of cough OR difficulty breathing 1 
AND 
SpO2 < 95% 2, OR RR increase 3
Definitions based on [Modjarrad, 2016]
LRTI = lower respiratory tract infections; RR = respiratory rate; RTI = respiratory tract infections; SpO2 = blood oxygen 
saturation.
1 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.
2 For blood oxygen saturation (SpO2), the lowest value monitored will be used.
3 RR increase defined as 40/minute (12 months of age or above).
4 RSV infection confirmed on nasal swab positive for RSV A or B by quantitative Reverse Transcription Polymerase 
Chain Reaction (qRT-PCR).
5 RSV sampling and testing is based on medical judgment of medical practitioner or driven by algorithm.
6 Hospitalization is defined as a medical decision that the infant requires admission for observation or treatment.
Number of subjects
The target will be to enroll up to 96 RSV-seropositive infants
aged 12 to 23 months at the time of first vaccination (unless the 
dose escalation IDMC decision can be made based on the 
evaluation of accumulating safety data on fewer subjects) to 
ensure that at least 64 infants receive two doses of study vaccine
(ChAd155-RSV or Placebo) (Amended 10 December 2017).
 
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Endpoints
Primary

Occurrence of AEs from first vaccination (Day 0) up to Day 
60.

Occurrence of each solicited local and general AE, 
during a 7-day follow-up period after each vaccination 
(i.e. the day of vaccination and 6 subsequent days).

Occurrence of any unsolicited AE, during a 30-day 
follow-up period after each vaccination (i.e. the day of 
vaccination and 29 subsequent days).

Occurrence of any SAE from Day 0 up to Day 60.

Occurrence of episode of spontaneous or excessive 
bleeding (AE of specific interest), during a 30-day 
follow-up period after each vaccination.

Occurrence of any hematological (hemoglobin level, 
white blood cells and platelets) laboratory abnormalities 
at Screening, Day 1, Day 7, Day 30, Day 31, Day 37, 
and Day 60.

Occurrence of any biochemical (alanine 
aminotransferase, aspartate aminotransferase and 
creatinine) laboratory abnormalities at Screening, Day 
30, and Day 60.
Secondary

Occurrence of SAEs from study start (Day 0) up to study 
conclusion (Day 730).

Occurrence of RSV-LRTI (AE of specific interest) as from 
Dose 1 administration up to study conclusion (Day 730).

Occurrence of RSV-RTI, RSV-LRTI, severe RSV-LRTI 
(according to standardized case definitions) as from Dose 1 
administration up to study conclusion (Day 730).

Magnitude of the CMI response to the investigational RSV 
vaccine, pre-vaccination (Screening), post-Dose 1 (Day 30) 
and post-Dose 2 (Day 60 and Day 365).

CD3+/CD4+ T-cells expressing at least two markers 
among CD40L, IL-2, TNF-α, and IFN-γ upon 
stimulation with F, N and M2-1 peptide pools.

Humoral response to the investigational RSV vaccine, pre-
vaccination (Screening), post-Dose 1 (Day 30) and post-
Dose 2 (Day 60 and Day 365):

Neutralizing antibody titers against RSV-A.

RSV F antibody concentrations.
 
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
Humoral response to the investigational RSV vaccine, pre-
vaccination (Screening), post-Dose 1 (Day 30) and post-
Dose 2 (Day 60):

Palivizumab-competing antibody concentrations.
Tertiary

CMI response profile (Th1, Th2, Th17) to the investigational 
RSV vaccine, pre-vaccination (Screening), post-Dose 1 (Day 
30) and post-Dose 2 (Day 60 and Day 365).

CD3+/CD4+ and/or CD3+/CD8+ T-cells expressing at 
least one or any combination of immune marker(s) 
among CD40L, 41BB, IL-2, TNF-α, IFN-γ, IL-13 and 
IL-17 upon stimulation with F, N and M2-1 peptide 
pools.

Any further exploratory immunology to detect disease-
related or vaccine-related immune responses, such as but not 
limited to:

Anti-vector immunity: neutralization.
 
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TABLE OF CONTENTS
PAGE
SPONSOR INFORMATION ............................................................................................8
SYNOPSIS......................................................................................................................9
LIST OF ABBREVIATIONS...........................................................................................30
GLOSSARY OF TERMS ...............................................................................................33
TRADEMARKS .............................................................................................................37
1.
INTRODUCTION....................................................................................................38
1.1.
Background ................................................................................................38
1.1.1.
RSV disease burden....................................................................38
1.1.2.
Current management of RSV disease in infants...........................38
1.1.3.
History of enhanced RSV disease with formalin-
inactivated RSV vaccines ............................................................39
1.1.4.
Rationale for a viral vector-based RSV vaccine ...........................39
1.1.5.
Antigens selected for the vaccine ................................................40
1.1.6.
Pre-clinical and clinical experience ..............................................41
1.2.
Rationale for the study and study design ....................................................41
1.2.1.
Rationale for the study.................................................................41
1.2.2.
Rationale for the choice of study population.................................42
1.2.2.1.
Study population.........................................................42
1.2.2.2.
RSV serostatus using IBL International kit and 
choice of study population ..........................................42
1.2.3.
Rationale for regimen, dose and route of administration ..............43
1.2.4.
Rationale for safety monitoring plan.............................................44
1.2.4.1.
Rationale for earlier dose escalation decision 
making........................................................................44
1.2.4.2.
Staggered design with 3 steps....................................44
1.2.4.3.
Rationale for monitoring of hematology 
parameters.................................................................46
1.2.4.4.
Rationale for RSV disease surveillance......................47
1.2.5.
Rationale for study blinding..........................................................47
1.2.6.
Rationale for the use of placebo ..................................................48
1.3.
Benefit : Risk Assessment ..........................................................................48
1.3.1.
Risk Assessment .........................................................................48
1.3.2.
Benefit Assessment.....................................................................49
1.3.3.
Overall Benefit:Risk Conclusion...................................................50
2.
OBJECTIVES.........................................................................................................50
2.1.
Primary objective ........................................................................................50
2.2.
Secondary objectives..................................................................................50
2.3.
Tertiary objectives.......................................................................................50
3.
STUDY DESIGN OVERVIEW ................................................................................51
 
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4.
CASE DEFINITION OF RESPIRATORY TRACT INFECTION 
ASSOCIATED WITH RSV INFECTION..................................................................56
4.1.
RTI case definitions ....................................................................................56
4.2.
RTI episode ................................................................................................58
4.2.1.
Start date of the RTI episode .......................................................58
4.2.2.
End date of the RTI episode ........................................................58
5.
STUDY COHORT...................................................................................................58
5.1.
Number of subjects.....................................................................................58
5.2.
Inclusion criteria for enrolment....................................................................58
5.3.
Exclusion criteria for enrolment...................................................................59
6.
CONDUCT OF THE STUDY ..................................................................................61
6.1.
Regulatory and ethical considerations, including the informed 
consent process..........................................................................................61
6.2.
Subject identification and randomization of treatment .................................62
6.2.1.
Subject identification....................................................................62
6.2.2.
Randomization of treatment.........................................................62
6.2.2.1.
Randomization of supplies..........................................62
6.2.2.2.
Treatment allocation to the subject.............................62
6.2.2.2.1.
Study group and treatment 
number allocation ...................................63
6.2.2.2.2.
Treatment number allocation for 
subsequent doses ..................................63
6.3.
Method of blinding ......................................................................................64
6.4.
General study aspects ................................................................................64
6.5.
Outline of study procedures ........................................................................65
6.6.
Detailed description of study procedures ....................................................70
6.6.1.
Informed consent.........................................................................70
6.6.2.
Check inclusion and exclusion criteria .........................................70
6.6.3.
Collect demographic data ............................................................70
6.6.4.
Medical history.............................................................................70
6.6.5.
Physical examination ...................................................................71
6.6.6.
Growth monitoring .......................................................................71
6.6.7.
Check contraindications, warnings and precautions to 
vaccination...................................................................................71
6.6.8.
Assess pre-vaccination body temperature ...................................71
6.6.9.
Randomization.............................................................................71
6.6.10.
Study Vaccines administration.....................................................71
6.6.11.
Sampling......................................................................................72
6.6.11.1.
Blood sampling for RSV serostatus, humoral 
immunity, and cell-mediated immunity........................72
6.6.11.2.
Blood sampling for hematology and 
biochemistry ...............................................................73
6.6.11.3.
Nasal swab and other specimen for local assay .........75
6.6.12.
Detection of spontaneous bleeding or easy bruising and 
evidence of bruising or petechiae ................................................75
6.6.13.
Detection of petechiae or evidence of petechiae induced 
by the tourniquet..........................................................................76
6.6.14.
Surveillance for RSV-RTI and wheezing ......................................76
6.6.15.
Check and record concomitant medication/vaccination................76
6.6.16.
Recording of AEs, AEs of specific interest and SAEs ..................76
 
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6.6.17.
Screening conclusion...................................................................77
6.6.18.
Signing of investigator signature form by investigator ..................77
6.6.19.
Study conclusion..........................................................................77
6.7.
Biological sample handling and analysis.....................................................78
6.7.1.
Use of specified study materials ..................................................78
6.7.2.
Biological samples.......................................................................79
6.7.3.
Laboratory assays .......................................................................80
6.7.4.
Biological samples evaluation......................................................84
6.7.4.1.
Immunological read-outs ............................................84
6.7.5.
Immunological correlates of protection.........................................86
7.
STUDY VACCINES AND ADMINISTRATION ........................................................86
7.1.
Description of study vaccines......................................................................86
7.2.
Storage and handling of study vaccines......................................................87
7.3.
Dosage and administration of study vaccines .............................................88
7.4.
Replacement of unusable vaccine doses....................................................88
7.5.
Contraindications to subsequent vaccination ..............................................89
7.6.
Concomitant medications/products and concomitant vaccinations..............89
7.6.1.
Recording of concomitant medications/products and 
concomitant vaccinations.............................................................90
7.6.2.
Concomitant medications/products/vaccines that may lead 
to the elimination of a subject from ATP analyses........................90
8.
HEALTH ECONOMICS ..........................................................................................91
9.
SAFETY.................................................................................................................91
9.1.
Safety definitions ........................................................................................91
9.1.1.
Definition of an adverse event......................................................91
9.1.2.
Definition of a serious adverse event ...........................................92
9.1.3.
Solicited adverse events..............................................................93
9.1.3.1.
Solicited local (injection-site) adverse events..............93
9.1.3.2.
Solicited general adverse events................................93
9.1.4.
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events ............................................................................94
9.1.5.
Adverse events of specific interest...............................................94
9.1.5.1.
Spontaneous or excessive bleeding ...........................94
9.1.5.2.
RSV-LRTI...................................................................94
9.2.
Surveillance for RSV-RTI, difficulty in breathing and wheezing 
episodes .....................................................................................................95
9.2.1.
Passive surveillance ....................................................................97
9.2.2.
Surveillance for asymptomatic RSV-RTI ......................................97
9.2.3.
Active surveillance .......................................................................97
9.2.4.
Assessment visit..........................................................................98
9.2.5.
Subject hospitalized for LRTI .......................................................99
9.3.
Detecting and recording adverse events, adverse events of specific 
interest and serious adverse events............................................................99
9.3.1.
Time period for detecting and recording adverse events, 
adverse events of specific interest and serious adverse 
events..........................................................................................99
9.3.2.
Post-Study adverse events and serious adverse events............103
9.3.3.
Evaluation of adverse events and serious adverse events.........103
 
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9.3.3.1.
Active questioning to detect adverse events 
and serious adverse events......................................103
9.3.3.2.
Assessment of adverse events.................................104
9.3.3.2.1.
Assessment of intensity........................104
9.3.3.2.2.
Assessment of causality .......................105
9.3.3.3.
Assessment of outcomes..........................................106
9.3.3.4.
Medically attended visits...........................................107
9.4.
Reporting of serious adverse events and adverse events of specific 
interest......................................................................................................107
9.4.1.
Prompt reporting of serious adverse events and adverse 
events of specific interest to GSK Biologicals ............................107
9.4.2.
Contact information for reporting serious adverse events 
and adverse events of specific interest ......................................108
9.4.3.
Reporting of adverse events of specific interest (RSV-
LRTI and spontaneous or excessive bleeding) to GSK 
Biologicals .................................................................................108
9.4.4.
Completion and transmission of SAE reports to GSK 
Biologicals .................................................................................108
9.4.4.1.
Back-up system in case the electronic 
reporting system does not work................................109
9.4.5.
Updating of serious adverse event and adverse event of 
specific interest information after removal of write access 
to the subject’s eCRF.................................................................109
9.4.6.
Regulatory reporting requirements for serious adverse 
events........................................................................................109
9.5.
Follow-up of adverse events, serious adverse events and adverse 
events of specific interest..........................................................................110
9.5.1.
Follow-up during the study.........................................................110
9.5.2.
Follow-up after the subject is discharged from the study............110
9.6.
Treatment of adverse events ....................................................................110
9.7.
Unblinding.................................................................................................111
9.8.
Emergency unblinding ..............................................................................111
9.9.
Subject card..............................................................................................112
9.10.
Holding rules and safety monitoring..........................................................113
9.10.1.
Limited vaccination ....................................................................113
9.10.2.
Internal safety review committee (iSRC) oversight.....................113
9.10.3.
Independent Data Monitoring Committee (IDMC) oversight.......114
9.10.4.
Dose-escalation and safety evaluations by iSRC and 
IDMC .........................................................................................115
9.10.5.
Holding rules..............................................................................116
9.10.6.
Procedure if the trial is put on hold.............................................118
10. SUBJECT COMPLETION AND WITHDRAWAL...................................................119
10.1.
Subject completion ...................................................................................119
10.2.
Subject withdrawal....................................................................................119
10.2.1.
Subject withdrawal from the study .............................................119
10.2.2.
Subject withdrawal from investigational vaccine.........................120
10.3.
Extension study ........................................................................................120
10.4.
Screen and baseline failures.....................................................................120
11. STATISTICAL METHODS....................................................................................121
11.1.
Primary endpoint.......................................................................................121
 
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11.2.
Secondary endpoints ................................................................................121
11.3.
Tertiary endpoints.....................................................................................122
11.4.
Determination of sample size....................................................................122
11.5.
Cohorts for Analyses ................................................................................124
11.5.1.
Total vaccinated cohort..............................................................124
11.5.2.
According-to-protocol cohort for analysis of 
immunogenicity..........................................................................124
11.6.
Derived and transformed data...................................................................125
11.6.1.
Demography..............................................................................125
11.6.2.
Safety ........................................................................................125
11.6.3.
Immunogenicity..........................................................................125
11.6.4.
RTI and LRTI.............................................................................126
11.7.
Analysis of demographics.........................................................................126
11.8.
Analysis of safety......................................................................................127
11.8.1.
Within groups assessment.........................................................127
11.8.2.
Between groups assessment.....................................................128
11.9.
Analysis of immunogenicity.......................................................................128
11.9.1.
Within groups assessment.........................................................128
11.9.1.1.
Analysis of secondary objectives..............................128
11.9.1.2.
Analysis of tertiary objectives ...................................129
11.10. Analysis of RTI and LRTI..........................................................................129
11.11. Interpretation of analyses..........................................................................130
11.12. Conduct of analyses .................................................................................130
11.12.1. Sequence of analyses................................................................130
11.12.2. Statistical considerations for interim analyses............................130
12. ADMINISTRATIVE MATTERS .............................................................................131
12.1.
electronic Case Report Form instructions .................................................131
12.2.
Study Monitoring by GSK Biologicals........................................................131
12.3.
Record retention .......................................................................................132
12.4.
Quality assurance.....................................................................................132
12.5.
Posting of information on publicly available clinical trial registers and 
publication policy ......................................................................................133
12.6.
Provision of study results to investigators .................................................133
13. COUNTRY SPECIFIC REQUIREMENTS.............................................................133
14. REFERENCES.....................................................................................................134
 
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LIST OF TABLES
PAGE
Table 1
Study groups and epochs foreseen in the study (Amended 10 
December 2017) ....................................................................................53
Table 2
Study groups and treatment foreseen in the study .................................54
Table 3
Blinding of study epochs ........................................................................54
Table 4
Case definitions for data analysis...........................................................57
Table 5
List of study procedures .........................................................................65
Table 6
Intervals between study visits.................................................................70
Table 7
Biological samples (Amended 10 December 2017)................................79
Table 8
Cell-Mediated Immunity (CMI)................................................................81
Table 9
Humoral Immunity (Antibody determination)...........................................81
Table 10
Molecular Biology (PCR tests)................................................................82
Table 11
Hematology and biochemistry tests (Amended 10 December 
2017)......................................................................................................83
Table 12
Immunological read-outs (Amended 10 December 2017).......................84
Table 13
Molecular biology for nasal swab and specimen analysis 
(Amended 10 December 2017) ..............................................................85
Table 14
Study vaccines.......................................................................................87
Table 15
Dosage and administration.....................................................................88
Table 16
Solicited local adverse events ................................................................93
Table 17
Solicited general adverse events............................................................93
Table 18
Reporting periods for collecting safety information ...............................101
Table 19
Intensity scales for solicited symptoms in infants..................................104
Table 20
Timeframes for submitting serious adverse event and adverse 
events of specific interest reports to GSK Biologicals...........................107
Table 21
Holding rules assessed by the investigator...........................................117
Table 22
Holding rules during the planned iSRC and IDMC evaluation...............117
 
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Table 23
GSK Biologicals’ laboratories ...............................................................142
Table 24
Outsourced laboratories.......................................................................142
Table 25
Toxicity grading scales for hematology and biochemistry 
parameters applicable for this study (Amended 10 December 
2017)....................................................................................................143
 
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LIST OF FIGURES
PAGE
Figure 1
Study design ..........................................................................................51
Figure 2
Schematic overview of required additional hematology and 
biochemistry testing during the study .....................................................74
Figure 3
Decision tree for passive and active surveillance contacts .....................96
Figure 4
Evaluations based on 16 subjects - Risk assessment curve for 
one formulation based on the proposed safety holding rules................118
Figure 5
Exact 95% confidence interval on the percentage of subjects with 
adverse events following vaccination for 16 subjects per group ...........123
 
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LIST OF APPENDICES
PAGE
APPENDIX A LABORATORY ASSAYS .....................................................................139
APPENDIX B CLINICAL LABORATORIES ................................................................142
APPENDIX C TOXICITY GRADING FOR HEMATOLOGY AND 
BIOCHEMISTRY PARAMETERS ........................................................143
APPENDIX D AMENDMENTS AND ADMINISTRATIVE CHANGES TO THE 
PROTOCOL.........................................................................................144
 
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LIST OF ABBREVIATIONS
AE:
Adverse event
ATP:
According-to-protocol
CD (CD4, CD8):
Cluster of differentiation (4, 8)
CD40L:
Cluster of differentiation 40 ligand
ChAd155:
Chimpanzee adenovirus Type 155
ChAd155-RSV:
Investigational recombinant chimpanzee adenovirus Type 
155-vectored RSV vaccine
CI:
Confidence interval
CLS:
Clinical laboratory sciences
CMI:
Cell-mediated immunity
CRDL:
Clinical research & development lead
eCRF:
electronic case report form
ELISA:
Enzyme-linked immunosorbent assay
ERD:
Enhanced RSV disease
eTDF:
Electronic temperature excursion decision form
F:
RSV fusion protein
FI-RSV:
Formalin-inactivated whole virus RSV vaccine
GCP:
Good clinical practice
GMC:
Geometric mean concentration
GMT:
Geometric mean titer
GSK:
GlaxoSmithKline
HIV:
Human immunodeficiency virus
HR:
Heart rate
IB:
Investigator brochure
ICF:
Informed consent form
 
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ICH:
International conference on harmonization
ICS:
Intracellular staining
IDMC:
Independent data monitoring committee
IEC:
Independent ethics committee
IFN-:
Interferon gamma
IgG :
Immunoglobulin G
IL (IL-2, IL-13, IL-17):
Interleukin (2, 13, 17)
IM:
Intramuscular
IMP:
Investigational medicinal product
IND:
Investigational New Drug
IRB:
Institutional review board
iSRC:
Internal safety review committee
LAR:
Legally acceptable representative
LRTI:
Lower respiratory tract infection
M2-1:
RSV matrix protein
MedDRA:
Medical dictionary for regulatory activities
mm³
cubic millimeter (Amended 10 December 2017)
N:
RSV nucleocapsid protein
PCR:
Polymerase chain reaction
RNA:
Ribonucleic acid
RR:
Respiratory rate
RSV:
Respiratory syncytial virus
RSV-Hd:
High dose ChAd155-RSV vaccine (5 x 1010 vp)
RSV-Ld:
Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md:
Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
 
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RSV-RTI:
Respiratory tract infection associated with RSV infection
RTI:
Respiratory tract infection
RVP:
Respiratory viral panel
SAE:
Serious adverse event
SBIR:
Randomization system on internet
SPM:
Study procedures manual
SpO2:
Blood oxygen saturation by pulse oximetry
TNF-:
Tumor necrosis factor alpha
TVC:
Total vaccinated cohort
ULN:
Upper limit of normal
vp:
Viral particles
VSMB:
Vaccine safety monitoring board
WBS:
Whole blood stimulation
WHO:
World health organization
 
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GLOSSARY OF TERMS
Adverse event:
Any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use 
of a medicinal product, whether or not considered related 
to the medicinal product. 
An adverse event (AE) can therefore be any unfavorable
and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal product. 
For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), 
abuse or misuse.
Blinding:
A procedure in which one or more parties to the trial are 
kept unaware of the treatment assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the trial, 
and only when the data are cleaned to an acceptable level 
of quality will appropriate personnel be unblinded or 
when required in case of a serious adverse event. In a 
single-blind study, the investigator and/or his staff are 
aware of the treatment assignment but the subject is not. 
In an observer-blind study, the subject and the site and 
sponsor personnel involved in the clinical evaluation of 
the subjects are blinded while other study personnel may 
be aware of the treatment assignment (see Section 6.3 for 
details on observer-blinded studies).
Child in care:
A child who has been placed under the control or 
protection of an agency, organization, institution or entity 
by the courts, the government or a government body, 
acting in accordance with powers conferred on them by 
law or regulation. The definition of a child in care can 
include a child cared for by foster parents or living in a 
care home or institution, provided that the arrangement 
falls within the definition above. The definition of a child 
in care does not include a child who is adopted or has an 
appointed legal guardian.
Eligible:
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria.
 
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End of Study 
(Synonym of End of 
Trial)
For studies without collection of human biologicals 
samples or imaging data end of study is the Last Subject 
Last Visit (LSLV).
For studies with collection of Human Biologicals 
Samples or imaging data, end of study is defined as the 
date of the last testing/reading released of the Human 
Biological Samples or imaging data, related to primary 
and secondary endpoints. End of study must be achieved 
no later than 8 months after LSLV
Epoch:
An epoch is a self-contained set of consecutive 
timepoints or a single timepoint from a single protocol. 
Self-contained means that data collected for all subjects 
at all timepoints within that epoch allows to draw a 
complete conclusion to define or precise the targeted 
label of the product. Typical examples of epochs are 
primary vaccinations, boosters, yearly immunogenicity 
follow-ups, and surveillance periods for efficacy or 
safety.
eTrack:
GSK’s tracking tool for clinical trials.
Evaluable:
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the according-to-protocol (ATP) analysis (see 
Sections 7.6.2 and 11.5 for details on criteria for 
evaluability).
Grade 1 abnormality 
with potential clinical 
relevance
Grade 1 laboratory parameters which cannot be explained 
or which is judged by the investigator to be potentially 
clinically relevant (refer to Appendix C).
Grade 1 abnormality 
without clinical relevance
Grade 1 laboratory parameters which can be explained by 
a condition which is not related to vaccination and does 
not increase the risk for an adverse outcome of 
vaccination (refer to Appendix C).
Immunological correlate 
of protection:
The defined immune response above which there is a high 
likelihood of protection in the absence of any host factors 
that might increase susceptibility to the infectious agent.
Infant:
As per [US Food and Drug Administration]’s definition 
an infant is aged one month to two years. 
 
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Investigational vaccine:
(Synonym of 
Investigational Medicinal 
Product)
A pharmaceutical form of an active ingredient or placebo 
being tested or used as a reference in a clinical trial, 
including a product with a marketing authorization when 
used in a way different from the approved form, or when 
used for an unapproved indication, or when used to gain 
further information about an approved use. 
Legally acceptable 
representative
(The terms legal 
representative or legally 
authorized 
representative are used 
in some settings.)
An individual or juridical or other body authorized under 
applicable law to consent, on behalf of a prospective 
subject, to the subject's participation in the clinical trial.
Primary completion 
date:
The date that the final subject was examined or received 
an intervention for the purpose of final collection of data 
for the primary outcome, whether the clinical trial 
concluded according to the pre-specified protocol or was 
terminated.
Protocol amendment:
The International Conference on Harmonization (ICH) 
defines a protocol amendment as: ‘A written description 
of a change(s) to or formal clarification of a protocol.’ 
GSK Biologicals further details this to include a change 
to an approved protocol that affects the safety of subjects, 
scope of the investigation, study design, or scientific 
integrity of the study.
Protocol administrative 
change:
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study.
Randomization:
Process of random attribution of treatment to subjects in 
order to reduce bias of selection.
Self-contained study:
Study with objectives not linked to the data of another 
study.
Site Monitor:
An individual assigned by the sponsor who is responsible 
for assuring proper conduct of clinical studies at one or 
more investigational sites.
Solicited AE:
AEs to be recorded as endpoints in the clinical study. The 
presence/occurrence/intensity of these events is actively 
solicited from the subject or an observer during a 
specified post-vaccination follow-up period.
 
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Subject:
Term used throughout the protocol to denote an 
individual who has been contacted in order to participate 
or participates in the clinical study, either as a recipient of 
the vaccine(s) or as a control.
Subject number:
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study.
Treatment:
Term used throughout the clinical study to denote a set of 
investigational product(s) or marketed product(s) or 
placebo intended to be administered to a subject, 
identified by a unique number, according to the study 
randomization or treatment allocation.
Treatment number:
A number identifying a treatment to a subject, according 
to the study randomization or treatment allocation.
Unsolicited AE:
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 will be reported as an unsolicited AE.
 
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TRADEMARKS
The following trademarks are used in the present protocol.
Note: In the body of the protocol (including the synopsis), the names of the products will 
be written without the superscript symbol ™ or ® and in italics.
Trademarks of the GSK group of 
companies
Generic description
Bexsero
Meningococcal group B vaccine 
(recombinant, adsorbed)
Trademarks not owned by the GSK
group of companies
Generic description
Synagis (MedImmune)
Recombinant humanized monoclonal anti-
RSV antibodies
Allplex (Seegene)
Respiratory panel assay
 
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1.
INTRODUCTION
1.1.
Background
1.1.1.
RSV disease burden
Respiratory syncytial virus (RSV) is a ribonucleic acid virus of which two antigenically 
distinct subgroups exist, referred to as RSV-A and RSV-B [Borchers, 2013]. RSV is a 
highly contagious human pathogen that causes respiratory tract infections (RTI) in people 
of all ages.
During the first year of life, 50-70% of infants are infected with RSV and essentially all 
children have had an RSV infection by their second birthday. The risk for severe 
RSV-associated lower respiratory tract infections (LRTI) is highest in infants below 
6 months of age and is a leading cause for hospitalization. It is estimated that on average 
31 per 1000 children below 6 months of age are hospitalized for RSV-associated severe 
LRTI Boyce, 2000; Deshpande, 2003; Hall, 2009; Holman, 2004; Iwane, 2004; 
Paramore, 2004; Vicente, 2003. 50-70% of these hospitalized children do not have 
additional risk factors like preterm birth or cardiopulmonary disease Boyce, 2000; 
García, 2010; Hall, 2009; Rietveld, 2004. For human immunodeficiency virus (HIV)-
infected children, the incidence rate of hospitalization for RSV-associated LRTI was 
reported to be 2.5- to 5-fold greater than in HIV-uninfected children Cohen, 2015; 
Madhi, 2006. Although RSV hospitalization rates substantially decrease after 6 months 
of age, a considerable number of RSV infections in children of 6-15 months of age, still 
lead to bronchiolitis or (broncho)pneumonia requiring medical attention [Fisher, 1997].
Previous infection with RSV does not prevent subsequent infections. Therefore, re-
infection with RSV occurs throughout an individual’s lifetime and is common in all age 
groups [Simoes, 1999; Krilov, 2011]. These re-infections generally go undiagnosed 
because they usually present as common acute upper respiratory tract infections. In more 
vulnerable persons (e.g. immunocompromized subjects or elderly), re-infections can 
however also lead to severe disease [Graham, 2011].
1.1.2.
Current management of RSV disease in infants
To date, no vaccine is available against RSV and treatment of RSV disease is largely 
symptomatic and supportive care [Murray, 2014].
The antiviral drug ribavirin is currently the only approved antiviral therapy for RSV 
treatment, but its use is restricted to severe hospitalized cases due to uncertainties 
regarding its efficacy, difficulty in administration (aerosol) and high cost American 
Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis, 
2006.
 
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RSV-specific monoclonal antibodies (palivizumab, Synagis) are indicated for use in 
infants at highest risk for severe RSV disease. Synagis is only effective as prophylaxis 
and is not indicated or recommended in the general, healthy infant population.
1.1.3.
History of enhanced RSV disease with formalin-inactivated RSV 
vaccines
In the late sixties, a formalin-inactivated whole virus RSV vaccine (FI-RSV) tested in 
clinical trials led to more severe clinical symptoms upon subsequent natural infection 
with RSV in children under the age of two years. Thirty-seven out of 140 (26%) of 
children receiving the FI-RSV were hospitalized with severe RSV lower respiratory tract 
disease and there were two deaths [Polack, 2007]. The risk was greater in those children 
that were RSV-seronegative prior to immunization and did not occur in those that were 
RSV-seropositive.
This so-called ‘vaccine-induced enhanced RSV disease’ (ERD) is believed to have been 
due to the formalin inactivation step during vaccine production, leading to the induction 
of low-quality, non-neutralizing antibodies in RSV naïve infants Delgado, 2004. These 
antibodies did not neutralize RSV infectivity and contributed to the formation of immune 
complexes that may have contributed to the severe clinical symptoms and potentially 
immunopathology of FI-RSV ERD [Polack, 2002]. In addition, it is hypothesized that 
ERD may have been linked to the induction of a Th2-skewed cluster of differentiation 4
(CD4) T-cell immune response in previous naïve subjects [Castilow, 2008].
Since that time, several investigational vaccines have been explored but, despite half a 
century of intense RSV vaccine development, there is not a single licensed vaccine for 
the prevention of severe RSV disease [Anderson, 2013; Rudraraju, 2013; Murray, 2014].
1.1.4.
Rationale for a viral vector-based RSV vaccine
Immunity induced by natural RSV infection is not able to fully prevent RSV re-infection, 
allowing re-infections to occur commonly throughout life. Both arms of the immune 
system are involved in protection from severe disease.
The humoral immune response is capable of neutralizing the virus and inhibiting viral 
replication, thereby playing a major role in protection against lower RSV infection and 
severe disease [Piedra, 2003]. Indeed, passive immunization with RSV-specific 
monoclonal antibodies (Synagis), when given prophylactically, has been shown to reduce 
RSV disease in premature infants and newborns with bronchopulmonary dysplasia or 
underlying cardiopulmonary disease [Cardenas, 2005].
T-cells are also involved in the control of RSV disease. Lethal RSV infections have been 
described in patients with low CD8 T-cell counts as in the case of severe combined 
immunodeficiency, bone marrow and lung transplant recipients [Hertz, 1989]. The 
histopathology of fatal cases of RSV infection of newborns shows that there is a relative 
paucity of CD8 T-cells in the lung infiltrate [Welliver, 2007]. Moreover, the presence of 
CD8 T-cells producing interferon gamma (IFN-) has been associated with diminished 
both Th2 responses and eosinophilia in animal models of RSV [Castilow, 2008; Stevens, 
2009].
 
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A vaccine based on recombinant viral vectors carrying relevant RSV antigens, mobilizing 
both humoral and cellular arms of the immune response, is considered as an adequate 
solution to induce a balanced and more effective immune response against the RSV virus 
in a naïve population. Adenoviral vector-based vaccines have been shown to be potent 
inducers of CD8 T-cells producing IFN-and antibodies against expressed antigens 
[Liniger, 2007; Barnes, 2012].
Potent immunogenicity and lack of prolonged transgene expression have made 
replication incompetent adenoviruses attractive viral vectors for vaccine development. 
They possess a stable virion, allowing inserts of foreign genes not to be deleted and they 
can infect many different cell types; the transferred information remains epichromosomal 
thus avoiding the risk of insertional mutagenesis.
Chimpanzee-derived adenoviruses exhibit sequence homology to human adenoviruses 
within the hexon protein in particular, which is a major capsid protein used for subgroup 
classification of adenoviruses [Roy, 2011; Colloca, 2012]. They are not known to cause 
pathological illness in humans and antibodies against chimpanzee adenoviruses have low 
or no seroprevalence ranging from 0-4% in Europe and in the United States, up to 20% in 
the developing countries, which is far less than the most common human adenovirus 
serotype 5 (Ad5), with seroprevalence rates of 40–45% in the United States and up to 
90% in sub-Saharan Africa [Capone, 2013].
In conclusion, the chimpanzee-derived adenovectors have the following important 
features:

Weak neutralization by human sera.

Potent immunogenicity, mainly Th1-directed.

Track record of good tolerability in human clinical trials.
1.1.5.
Antigens selected for the vaccine
The investigational vaccine is a recombinant viral vector manufactured using a synthetic 
deoxyribonucleic acid fragment that encodes three RSV proteins:

The fusion (F) protein deleted from the transmembrane and cytoplasmic regions
(F0TM). The F protein is a major surface antigen of the RSV virus that is well 
conserved among RSV-A and RSV-B subgroups. In addition, it is the main target of 
the neutralizing antibody response to RSV, which is considered essential for 
protection against RSV-associated severe disease [Magro, 2012].

The nucleocapsid (N) protein is an internal (non-exposed) antigen, highly conserved 
between RSV strains and known to be a source of many T-cell epitopes [Anderson, 
2010; Townsend, 1984]. The N protein is essential for the replication and 
transcription of the RSV genome. Its primary function is to encapsidate the virus 
genome protecting it from ribonucleases.

The matrix (M2-1) protein is a transcription anti-termination factor that is important 
for the efficient synthesis of full-length messenger ribonucleic acid (RNA) as well as 
for the synthesis of polycistronic readthrough messenger RNA, which are 
 
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characteristic of non-segmented negative-strand RNA viruses. M2-1 is an internal 
(non-exposed) antigen, highly conserved between RSV strains and known to be a 
source of many T-cell epitopes [Anderson, 2010; Townsend, 1984].
The N and M2-1 antigens were therefore included in the vaccine construct as source of T-
cell epitopes for the induction of cell-mediated immunity (CMI).
Please refer to the current Investigator Brochure (IB) for additional information.
1.1.6.
Pre-clinical and clinical experience
The candidate vaccine is based on the RSV viral proteins F, N and M2-1 encoded by a 
chimpanzee-derived adenovector (ChAd155-RSV). A number of pre-clinical studies were 
conducted and have demonstrated immunogenicity, efficacy and safety of intramuscular 
(IM) injection of the ChAd155-RSV vaccine. Several animal models have been selected 
for such studies: mice, cotton rats and newborn calves. Importantly, vaccination has not 
induced hallmarks of enhanced pathology in these models. 
The immunogenicity, safety and reactogenicity of the pediatric candidate RSV vaccine 
(ChAd155-RSV vaccine) have been evaluated in healthy adults aged 18 to 45 years 
(study 201974 [RSV PED-001; NCT02491463]) There were no significant safety 
concerns identified up to Day 60 in study RSV PED-001. Overall, the ChAd155-RSV 
vaccine high dose (Hd) (5 x 1010 vp) seems to be more reactogenic (local and general) 
than the ChAd155-RSV vaccine low dose (Ld) (5 x 109 vp), however, the reactogenicity 
profile was less than that observed in the Bexsero group. No safety signal from the 
assessed hematology parameters (hemoglobin, platelet count, prothrombin time and 
APTT) was observed in subjects receiving the ChAd155-RSV vaccine. No significant 
reductions in platelet count or clinically significant changes in coagulation parameters 
were observed up to 30 days post Dose 2. An approximately 2.4-fold increase in RSV-A 
neutralizing antibody titers (geometric mean titer [GMT] from baseline) was observed in 
both RSV-Ld and RSV-Hd after Dose 1. No booster effect was evident after Dose 2. An 
anti-F IgA and IgG antibody secreting B-cells response and an RSV F, N and M2-1 
specific IFN-γ secreting T-cells response in RSV-Hd group after the first dose were 
observed with ELISpot. There was no booster response after the second vaccination. 
There was no specific vaccine-induced CD4 T-cellular response observed with 
intracellular staining (ICS). For CD8 T-cells only a weak CD8 IFN-γ response to N was 
shown with ICS for some subjects.
Please refer to the current IB for information regarding the pre-clinical and clinical
studies of GlaxoSmithKline (GSK) Biologicals’ investigational ChAd155-RSV vaccine.
1.2.
Rationale for the study and study design
1.2.1.
Rationale for the study
GSK Biologicals is developing the pediatric candidate RSV vaccine (ChAd155-RSV 
vaccine) to protect infants from RSV diseases.
 
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The purpose of this trial is to evaluate the safety, reactogenicity and immunogenicity of 
the ChAd155-RSV vaccine when first administered via IM injection according to a 0, 1-
month schedule to RSV-seropositive infants aged 12 to 23 months.
1.2.2.
Rationale for the choice of study population
1.2.2.1.
Study population
The immunogenicity, safety and reactogenicity of the pediatric candidate RSV vaccine 
(ChAd155-RSV vaccine) has been evaluated in healthy adults aged 18 to 45 years (study 
201974 [RSV PED-001; NCT02491463]). The ChAd155-RSV vaccine is being 
developed for the active immunization of infants as from 6 weeks of age. To allow age 
de-escalation from the adult population to the targeted population and to not enroll and 
administer the ChAd155-RSV vaccine to older children who are beyond the age of severe 
RSV disease and would not benefit from this vaccine, the present study will be performed
on RSV-seropositive infants aged 12 to 23 months, after the safety profile of the 
ChAd155-RSV vaccine in adults (study 201974 [RSV PED-001; NCT02491463]) was 
evaluated as satisfactory by an Independent Data Monitoring Committee (IDMC). The 
present study will provide critical information on the safety and immunogenicity profile 
of the ChAd155-RSV vaccine before a subsequent trial in seronegative infants.
1.2.2.2.
RSV serostatus using IBL International kit and choice of study 
population
To decrease the risk of ERD (refer to Section 1.1.3) in the present study, RSV-
seropositive infants aged 12 to 23 months will be enrolled.
RSV-seropositive infants will be screened using an enzyme-linked immunosorbent assay 
(ELISA) method (IBL International kit), detecting immunoglobulin G (IgG) antibody 
against RSV F or G protein. The objective of the screening for RSV-seropositive infants
is to limit the evaluation of the ChAd155-RSV vaccine to infants previously primed by 
RSV and therefore considered at low risk for ERD. However this assay does not 
discriminate between maternal antibodies and those naturally acquired by exposure to 
RSV. For this reason, although the ChAd155-RSV vaccine is not a FI-RSV vaccine, risk 
of ERD might still exist while vaccinating seropositive infants that have never been 
naturally exposed to RSV (RSV-naïve seropositive infants). However, GSK considers the 
risk of enrolling RSV-seronegative (i.e. false RSV-seropositive) infants in the present 
study as extremely low, for the two following reasons:

Beyond 12 months of age the number of RSV-naïve seropositive infants is expected 
to be very low. Indeed, published data suggest that the RSV seropositivity of infants 
aged 12 to 23 months is rather due to natural exposure to RSV than to maternal 
antibodies. In a randomized clinical trial performed in Bangladesh in which infants’ 
serum samples were collected at birth, 6, 10, 16, 20, 24, and 72 weeks of age the 
RSV-neutralizing antibody half-life in infants was 38 days and decreased below a 
protective titer by a median of 17 weeks. This corresponds to the clinical observation 
that infants are most vulnerable to developing severe RSV disease between 6 weeks 
and 6 months of age, a period when maternal antibodies are waning and the infant 
immune response may be incapable of generating a robust neutralizing antibody 
 
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response to infection [Chu, 2014]. In another study, a birth-cohort study performed 
in Kenya, the maternal-RSV antibodies in serum measured by ELISA declined 
rapidly following birth (half-life: 79 days; [Ochola, 2009]). Another birth-cohort 
study performed in Kenya, showed also a rapid decay in RSV-neutralizing 
antibodies, with an half-life of 36 days [Nyiro, 2015].

Despite the assay characterization performed by the manufacturer, a potential lack of 
sensitivity of the IBL International kit compared to a RSV neutralization assay has 
been reported [Malkin, 2013]. GSK considers that the specificity and sensitivity 
characteristics of the assay indicate a reduced risk of enrolling RSV-seronegative 
infants identified RSV-seropositive in the assay (i.e. false positive results).
Given these facts and data it is unlikely that infants aged 12 months or above reported 
RSV-seropositive by the IBL International kit will be RSV-seronegative and it was 
decided to perform this study in infants aged 12 to 23 months.
1.2.3.
Rationale for regimen, dose and route of administration
A vaccination regimen based on two IM injections (in the deltoid [if the muscle size is 
adequate; otherwise injections might be done in the anterolateral thigh]) of 5 x 109, 
1.5 x 1010, or 5 x 1010 viral particles (vp) of the ChAd155-RSV vaccine administered 
according to a 0, 1-month schedule (4-week interval between vaccinations) will be 
evaluated in this study.
The 4-week interval regimen has been tested in pre-clinical models and results from a 
bovine RSV challenge model in which seronegative, colostrum-restricted newborn calves 
were vaccinated with two doses of 5 x 1010 vp ChAd155-RSV, four weeks apart showed 
that dose regimen was immunogenic and protected calves from bovine RSV disease and 
infection and was not associated to pulmonary pathology.
Using a different adenovector, PanAd3, the 5 x 1010 vp dose regimen was shown to be 
safe in toxicology studies in mice. Pre-clinical data in different species (mice, cotton rats, 
non-human primates, and seronegative newborn calves) have shown that this regimen 
induces both anti-RSV F neutralizing antibodies and systemic T-cell responses [Taylor, 
2015; Pierantoni, 2015].
A Phase I clinical trial evaluated a simian adenoviral vector-based RSV vaccine with the 
same insert (PanAd3-RSV) [RSV001 Interim Study Report, 2014]. Data from this trial, 
with 42 subjects, showed that a vaccination regimen based on two IM injections, 
separated by four weeks, was safe and immunogenic.
Similar to the Phase I adult study (201974 [RSV PED-001]), the current study is designed 
in a staggered manner to allow dose escalation from 5 x 109 vp (1-log lower dose) to 5 x 
1010 vp dose. A third intermediate dose of 1.5 x 1010 vp will be tested in this first time in 
pediatric population study to allow a more progressive escalation of the dose-related risk 
in this vulnerable population.
Please refer to the current IB for information regarding the pre-clinical, clinical and 
toxicology studies of GSK Biologicals’ investigational ChAd155-RSV vaccine.
 
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1.2.4.
Rationale for safety monitoring plan
1.2.4.1.
Rationale for earlier dose escalation decision making
Under Amendment 4 of the protocol, the IDMC may on reviewing of the accumulating 
safety data recommend that dose escalation can safely proceed based on the experience 
of a minimum of 16 subjects.
Taking the a priori safety concern of thrombocytopenia, both Frequentist and 
Bayesian approaches are applied to provide complementary assurance on the 
possibility to exclude a signal based on the accumulated safety data. The Frequentist 
approach examines the statistical power to rule out a significant decrease in platelet 
counts due to vaccination that would suggest a four-fold or greater increase in the risk 
of a Grade 3 or higher thrombocytopenia with 16 subjects per dose cohort. The 
Bayesian approach calculates the posterior predictive probability of not observing any 
subject with a Grade 3 or higher thrombocytopenia among the future 16 subjects by 
basing it on what we have observed in the first 16 subjects (see Section 11.4).
(Amended 10 December 2017)
1.2.4.2.
Staggered design with 3 steps
The investigational ChAd155-RSV vaccine will be administered for the first time in a 
pediatric population therefore a three-step staggered design will be used to allow dose 
escalation of three dose levels and ensure maximum safety of the participating infants.
The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at 
the time of first vaccination (unless the dose escalation IDMC decision can be made 
based on the evaluation of accumulating safety data on fewer subjects) to ensure that at 
least 64 infants receive two doses of study vaccine (ChAd155-RSV or Placebo). 
(Amended 10 December 2017).
Vaccination will be limited to a maximum of 10 infants per day. In the same 
investigational center, infants will be vaccinated sequentially, separated by a minimum 
interval of 60 minutes to allow monitoring of any acute events (e.g. hypersensitivity 
reaction). In addition, to monitor delayed potential reactions following vaccination, there 
will be a 48-hour observation period following Dose 1 and Dose 2 administration to the 
first eight infants (corresponding to three to five ChAd155-RSV vaccine recipients) in 
each Step (1, 2, and 3) before continuing vaccination of more infants (i.e. from the ninth 
infant). From the ninth infant, infants will be vaccinated sequentially, separated by a 
minimum interval of 60 minutes. Refer to the study procedures manual (SPM) for more 
details about the 48-hour observation period after the first eight subjects vaccinated in 
each Step.

In Step 1, between a maximum of 32 to a minimum of 16 RSV-seropositive infants 
will receive two doses of either low dose ChAd155-RSV vaccine (5 x 109 vp [RSV-
Ld]; 0.5 mL) or placebo (0.5 mL), according to their random assignment (Amended 
10 December 2017).
 
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
In Step 2, between a maximum of 32 to a minimum of 16 RSV-seropositive infants 
will receive two doses of either middle dose ChAd155-RSV vaccine (1.5 x 1010 vp 
[RSV-Md]; 0.15 mL) or placebo (0.15 mL), according to their random assignment
(Amended 10 December 2017.

In Step 3, 32 RSV-seropositive infants will receive two doses of either high dose 
ChAd155-RSV vaccine (5 x 1010 vp [RSV-Hd]; 0.5 mL) or placebo (0.5 mL), 
according to their random assignment.
An internal Safety Review Committee (iSRC) will review all accumulating safety data 
three weeks after the start of vaccination and then about every three weeks until the 
IDMC has reviewed all safety data up to 30 days after administration of Dose 2 in Step 3 
(i.e. Day 60). Ad-hoc iSRC meetings may be held should safety concerns warrant a safety 
review. Refer to Section 9.10.2 for more information about iSRC.
The IDMC will review accumulating reactogenicity and safety data monthly throughout 
the period of vaccination (up to 30 days after administration of Dose 2 in Step 3, i.e. Day 
60). The IDMC will also review incidence of all serious adverse events (SAEs) and 
incidence of RSV-respiratory tract infections (RTI), RSV-LRTI, RSV-severe LRTI and 
RSV-RTI leading to hospitalization monthly after the start of vaccination and from 
beginning of the first RSV season to the end of the study.
Both iSRC and IDMC will receive critical safety data (i.e. SAEs and adverse events of 
specific interest) within 48 hours upon GSK becoming aware of it.
The iSRC and IDMC will determine whether any of the predefined study holding rules 
are met. If this is the case, vaccination in the study will be immediately put on hold. At 
any time, the IDMC may recommend to the sponsor to suspend the enrolment to the 
study and/or vaccination based on the safety data regularly arising in this study.
Dose escalation will proceed after administration of two doses of the vaccine to 32 
subjects. However, in the absence of a significant safety concern detected in the regular 
monitoring of accumulating safety data on at least 16 subjects, the IDMC may allow for 
dose escalation to proceed without the requirement of enrolling and evaluating the full 
group size of 32 subjects. A subsequent dose escalation will proceed after 
administration of two doses of the vaccine to between a maximum of 32 to a minimum 
of 16 subjects in in the absence of a significant safety concern detected by the IDMC in 
the regular monitoring of accumulating safety data. Thus, upon review of the 
accumulating safety data on a minimum of 16 subjects after administration of two 
doses of the vaccine, the IDMC may decide that based on the evolving safety profile, 
sufficient information has been accumulated to allow safe progression to the next 
sequential dose level (Amended 10 December 2017). It will be ensured that, as a 
minimum the IDMC will have reviewed safety data of at least 16 subjects for two doses 
and given their formal approval prior to enrolling subjects to the next dose level.
Additionally, the IDMC will perform a review when all safety data up to 30 days after 
administration of Dose 2 in Step 3 (i.e. Day 60) are available.
Refer to Section 9.10.3 for more information about IDMC.
 
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1.2.4.3.
Rationale for monitoring of hematology parameters
Emphasis on “minimal risk” is imperative for the protection of the pediatric population 
participating to research studies where blood sample volume limits is a critical parameter. 
To stay within blood sampling limits that are consistent with physiological “minimal 
risk” in this young and vulnerable population, but also to minimize any development of 
needle aversion, blood draws for the determination of hematological parameters are 
scheduled at Day 1 and Day 31 (corresponding to the first day after administration of the 
vaccine). Additional specimens will be drawn if any ≥ Grade 1 for platelet decrease is 
detected at Day 1 or Day 31 to investigate clinical symptoms suggestive of low platelets. 
Blood samples collected within the screening window will serve as baseline for the 
immunological analysis and for the hematology and biochemistry check-up before 
vaccination. Consequently, the maximum blood draw volumes collected per protocol 
have been restricted to 9.0 mL within 24 hours and 26.2 mL over eight weeks (refer to 
Table 5 and Table 7). For investigational sites without a laboratory in proximity capable
to perform whole blood stimulation [WBS] necessary for the CMI assay the volumes will 
be less. Of note, it is considered that blood sample volumes ranging from 1 to 5% of total 
blood volume within 24 hours and up to 10% of total blood volume over 8 weeks are 
consistent with the limited evidence available on the minimal physiological risk for 
healthy children [Howie; 2011]. The total blood volume of a child is around 75 to 80 
mL/kg (85 to 105 mL/kg in the neonatal period). Considering a girl of 12 months of age 
with a low weight of 7.3 kg (5th percentile [WHO; 2006]), the minimal individual total 
blood volume in the study population would be 547.5 mL and therefore the safer limits of 
blood draw volumes would range from 5.5 to 27.4 mL within 24 hours and be limited to 
54.7 mL over 8 weeks. To minimize any development of needle aversion, pain relief by 
means of a topical local anesthetic may be offered to infants prior to any blood sampling 
requested by the protocol at the discretion of the investigator.
During a study carried out in adult subjects (RSV001), a mild non-clinically significant 
drop in hemoglobin was noted following vaccination with another adenoviral vector 
(PanAd3-RSV) without clinical signs and with a reversal towards baseline values over 
time [RSV001 Interim Study Report, 2014]. In the repeat dose toxicology study in rabbits 
using the ChAd155-RSV vaccine, a transient non-clinically significant drop in platelets 
was noted post IM vaccination (maximal drop of platelet observed 24 hours after 
vaccination; refer to the current IB for further details). In light of these data, a clinical 
examination with special attention given to the detection of spontaneous bleeding or easy 
bruising and evidence of bruising or petechiae will be performed by the 
investigator/study staff on Day 1, Day 3, Day 7, Day 31, Day 33 and Day 37. The visits 
on Day 3 and Day 33 may be replaced by a phone call by the investigator/study staff to 
inquire of the infants' general health and to solicit reports of a rash, spontaneous bleeding 
or easy bruising. On Day 1 after each vaccination, special attention will also be given to 
the detection of petechiae or evidence of petechiae induced by the tourniquet. This 
special attention to detection of petechiae or evidence of petechiae induced by the 
tourniquet will also be given on Day 7 and Day 37 in case hematology testing will be 
performed on that day. Subjects’ parent(s)/ legally acceptable representative(s) (LAR[s]) 
will be instructed to contact the investigator/study staff if their child presents symptoms 
of spontaneous bleeding or easy bruising or if their child develops a rash in the month 
following vaccination, in order to detect any thrombocytopenic petechiae or purpura. The 
 
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investigator will, based on his/her medical judgement, appropriately investigate infants 
with clinical suspicion of low platelets.
Note that a broad safety hematology and biochemistry evaluation was performed at each 
study visit in adults during study RSV PED-001 (201974; NCT02491463). In this study, 
blood samples for hematology/biochemistry were taken from all subjects at all study 
visits, i.e. at Screening, on the day of vaccination (Day 0 and Day 30), 1 day post 
vaccination (Day 1 and Day 31), 3 days post vaccination (Day 3 and 33), 7 days post 
vaccination (Day 7 and 37), 30 days post Dose 2 (Day 60), on Day 180 and on Day 360. 
The safety profile of the ChAd155-RSV vaccine was found to be satisfactory by an 
IDMC. No safety signal from the assessed hematology parameters (hemoglobin, platelet 
count, prothrombin time and APTT) was observed in subjects receiving the ChAd155-
RSV vaccine. No significant reductions in platelet count or clinically significant changes 
in coagulation parameters were observed up to 30 days post Dose 2 (refer to Section 1.1.6
and current IB).
1.2.4.4.
Rationale for RSV disease surveillance
Although the risk of ERD is thought to be very low with an adenovirus-based vaccine 
(refer to Section 1.3.1), all children will be closely monitored by active and passive 
surveillance involving a clinical visit within 24 hours based on any suspicion of difficulty 
in breathing, wheezing or parental concern associated with symptoms of an RTI (refer to 
Section 9.2). This will ensure prompt assessment of need for medical care. Furthermore, 
a limited number of subjects will be enrolled in this study. All of them will be under 
surveillance allowing description of RSV associated LRTI and severe LRTI incidence in 
the ChAd155-RSV vaccine groups and the Placebo groups. All subjects experiencing 
LRTI associated with RSV will be considered as adverse events (AEs) of specific interest 
(refer to Section 9.1.5.2) and will have to be reported within 24 hours. In order to support 
this timely reporting, the investigator will make the diagnosis according to his/her 
medical judgment and locally-available diagnostic tests of RSV infections. Final analysis 
of RSV-LRTI will be performed according to standardized case definitions for clinical 
symptomatology and diagnostic test at sponsor laboratory (refer to Table 4) ensuring 
consistency across sites.
1.2.5.
Rationale for study blinding
Given the different storage conditions of the investigational RSV vaccine and placebo, 
double blinding is not possible and the study will be conducted in an observer-blind 
manner Amended 10 December 2017).
When all data up to Day 60 are available, a statistical analysis will be performed. This 
analysis may lead to the unblinding of some subjects. As a consequence, after Day 60, the 
study cannot be considered as observer-blind, but will be conducted in a single-blind 
manner, with subjects’ parent(s)/ LAR(s) remaining blinded up to study end (Day 730).
The investigators will not have access to the treatment allocation up to study end (Day 
730).
Please refer to the glossary of terms for the definition of observer-blind and single-blind.
 
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1.2.6.
Rationale for the use of placebo
The placebo group is included as a control for the reactogenicity, the safety and the 
immunogenicity assessments.
1.3.
Benefit : Risk Assessment
Approximately half of the infants (between 32 and 48) in this study will be exposed to 
the ChAd155-RSV vaccine, whereas the other infants will receive a placebo (Amended 
10 December 2017).
Please refer to the current IB for the summary of potential risks and benefits of
ChAd155-RSV vaccine.
The following section outlines the risk assessment and mitigation strategy for this study 
protocol:
1.3.1.
Risk Assessment
As with all injectable vaccines, immediate systemic allergic reactions to vaccination can 
occur. In order to be able to treat infants with an immediate systemic allergic reaction to 
vaccination, all infants across all steps will need to remain under observation (visual 
follow-up as well as measurement of vital signs) at the study site for at least 60 minutes 
after vaccination.
Syncope (fainting) can occur following or even before any vaccination as a psychogenic 
response to the needle injection. Therefore, it is important that procedures are in place to 
avoid injury from fainting.
Risks linked to the investigational RSV vaccine
This study is conducted in RSV-seropositive infants who are assumed to have been 
previously infected with RSV and therefore not at risk for ERD. The detection of 
antibody does not discriminate between maternally acquired antibodies and those 
naturally acquired by exposure to RSV. However, the risk of misclassification is believed 
to be low in infants from 6 months of age since in published data the estimated half-life
of maternally acquired RSV antibody ranged from 31 to 79 days [Chu, 2014; Ochola, 
2009; Nyiro, 2015].
IM vaccination commonly precipitates a transient and self-limiting local inflammatory 
reaction. This may typically include redness, swelling and tenderness.
Most systemic symptoms observed in a clinical trial with a similar product carried out in 
healthy adults (chimpanzee adenovirus-based vaccine with ChAd3 as vector for 
vaccination against hepatitis C) at doses to be used in this trial did not exceed mild 
severity [HCV001 Clinical Study Report, 2011]. Fatigue, headache and malaise were the 
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In a Phase I clinical trial with a similar simian adenoviral vector-based RSV vaccine with 
the same insert (PanAd3-RSV) carried out in healthy adults, the most commonly reported 
AEs concerned injection site reactions. However, a mild non-clinically significant drop in 
hemoglobin was noted following vaccination without clinical signs and with a reversal 
towards baseline values over time [RSV001 Interim Study Report, 2014].
A transient non-clinically significant drop in platelets was noted post IM vaccination in a 
preclinical study with the ChAd155-vector (refer to the current IB for further details). 
Furthermore, in Ebola Phase I studies in adults investigating a similar adenoviral 
vectored vaccine (ChAd3-EBO-Z), transient decreases in thrombocyte counts were also 
observed. These decreases occurred mostly on Day 1 after vaccination and generally 
returned to baseline by Day 7. Although most of these decreases remained within the 
normal range, the per protocol criteria for thrombocytopenia (i.e. thrombocyte count of < 
150 x 103/μL) were met for 2.6% (7 out of 270) of the vaccinated subjects. None of the 
decreases in thrombocyte counts or the cases of thrombocytopenia were clinically 
significant (i.e. no clinical signs or symptoms suggestive of increased tendency to 
bleeding were reported in any of the subjects; refer to the current IB of recombinant 
chimpanzee adenovirus Type 3-vectored Ebola Zaire vaccine for further details). 
Although the mechanism underlying these decreases currently remains unclear, it is well 
described in literature that, post intravenous administration, adenovirus activates platelets 
and induces platelet-leukocyte aggregate formation, causing an associated increase in 
platelet and leukocyte-derived microparticles [Othman, 2007; Stone, 2007].
No significant safety concerns were identified up to 30 days post Dose 2 in study RSV 
PED-001 with the ChAd155-RSV vaccine in healthy adults aged 18 to 45 years (refer to 
Section 1.1.6 and to the current IB). 
All available safety information from clinical and pre-clinical studies was evaluated by 
GSK’s Safety Review Team. It was concluded that the available information did not pose 
an immediate safety concern, since the decreases seen were transient and not clinically 
significant. Nevertheless, since this is the first time the ChAd155-RSV vaccine is 
administered to infants and to ensure a maximum safety follow-up, a safety monitoring 
plan has been put in place (refer to Section 1.2.4).
1.3.2.
Benefit Assessment
The infants receiving the investigational ChAd155-RSV vaccine may not directly benefit 
from vaccination since the efficacy of the investigational ChAd155-RSV vaccine has not 
been assessed yet and it is hence not known whether it is effective in protecting against 
RSV infection.
Subjects’ parent(s)/ LAR(s) could gain medical advices about their infant’s general health 
status through the medical evaluations/assessments associated with this study (i.e. 
physical examination, blood testing [hematology and biochemistry data], surveillance for 
RTI and LRTI).
 
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1.3.3.
Overall Benefit:Risk Conclusion
The investigational ChAd155-RSV vaccine is currently in a very early stage of clinical 
development and no vaccine efficacy has been demonstrated. Taking into account the 
measures taken to minimize the risk to infants participating in this study, the potential 
risks to the subjects are justified by the potential benefits linked to the development of 
this pediatric RSV vaccine.
2.
OBJECTIVES
2.1.
Primary objective

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 60) in RSV-seropositive infants
aged 12 to 23 months.
Refer to Section 11.1 for the definition of the primary endpoints.
2.2.
Secondary objectives

To evaluate the safety of two IM doses of three dose levels of the RSV 
investigational vaccine when administered according to a 0, 1-month schedule from 
study start (Day 0) up to study conclusion (Day 730) in RSV-seropositive infants 
aged 12 to 23 months.

To evaluate the occurrence of RSV respiratory tract infections in RSV-seropositive 
infants from Visit 1 (Day 0, after Dose 1) up to study conclusion (Day 730).

To evaluate the magnitude of the CMI induced by two IM doses of three dose levels 
of the RSV investigational vaccine when administered according to a 0, 1-month 
schedule, up to Day 365 in RSV-seropositive infants aged 12 to 23 months.

To evaluate the humoral immunogenicity induced by two IM doses of three dose 
levels of the RSV investigational vaccine when administered according to a 0, 1-
month schedule, up to Day 365 in RSV-seropositive infants aged 12 to 23 months.
Refer to Section 11.2 for the definition of the secondary endpoints.
2.3.
Tertiary objectives

To further evaluate the CMI profile induced by two IM doses of three dose levels of 
the RSV investigational vaccine when administered according to a 0, 1-month 
schedule, up to Day 365 in RSV-seropositive infants aged 12 to 23 months.

If deemed necessary, to further characterize the immune response of the RSV 
investigational vaccine when two IM doses are administered according to a 0, 1-
month schedule in RSV-seropositive infants
Refer to Section 11.3 for the definition of the tertiary endpoints.
 
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3.
STUDY DESIGN OVERVIEW
Figure 1
Study design
Step 1 (N = 32) Ld (5x109 vp) 
ChAd155-RSV = 16
Placebo = 16
Step 2 (N = 32) Md (1.5x1010 vp)
ChAd155-RSV = 16
Placebo = 16
Step 3 (N = 32) Hd (5x1010 vp) 
ChAd155-RSV = 16
Placebo = 16
D0
D1
D7
D30
D31
D37
Dose 1
SE up to D6
Dose 2
SE up to D36
D60
D365
BSS
BSS
V1
V2 c
V4 c
V5
V6 c
V8 c
V9
V10
Visit
Day
= Blood sample for safety
BSS
Epoch 001
Epoch 002
Dose 1
SE up to D6
Dose 2
SE up to D36
Dose 1
SE up to D6
Dose 2
SE up to D36
BSS
SCR
D-29 to D0
Surveillance period for RSV RTI a
BSH
BSH
BSH
BSH
BSC
BSC
BSC
BSC
BSR
= Blood sample for humoral immunogenicity
BSH
= Blood sample for CMI
BSC
= Blood sample for RSV serostatus
BSR
iSRC/IDMC review of all accumulating reactogenicity and safetyb
Nasal swab, as applicable g
D730
V11 c
BSS
BSS
BSS
IDMC 
review
BSS
d
d
e
f
f
e
D3
V3¥
D33
V7¥
h
IDMC review of SAEb
i
i
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Hd: High dose; IDMC: Independent Data Monitoring Committee; iSRC: Internal Safety Review Committee; Ld: low dose; Md: middle dose; RSV: respiratory syncytial virus; SCR: 
Screening; SE: solicited events; vp: viral particles.
¥ On Day 3 and Day 33, a visit may take place at the investigators clinical facility or the investigator/clinical staff may call the subjects’ parent(s)/LAR(s), as appropriate to the 
circumstances in the judgment of the investigator.
a Surveillance for RSV-RTI comprises monthly nasal swab collected to detect asymptomatic RSV infections during RSV season and active and passive surveillance contacts for RSV 
symptomatic RTI (see Section 9.2). Data about RSV–RTI incidence will be reviewed monthly by an IDMC.
b Within each step, an iSRC will review all accumulating safety data three weeks after the start of vaccination and then about every three weeks (until the IDMC has reviewed all safety 
data up to 30 days after administration of Dose 2 in Step 3 i.e. Day 60). The IDMC will review all accumulating reactogenicity and safety data monthly throughout the period of 
vaccination (up to 30 days after administration of Dose 2 in Step 3, i.e. Day 60) and accumulating SAEs until Day 730. Refer to Sections 9.10.2 and 9.10.3.
c Visit 2 (Day 1), Visit 4 (Day 7), Visit 6 (Day 31), Visit 8 (Day 37) and Visit 11 (Day 730) may take place in the subject’s home or at the investigators clinical facility as appropriate to the 
circumstances in the judgment of the investigator.
d Dose escalation will proceed after administration of two doses of the vaccine to 32 subjects in Step 1. However, in the absence of a significant safety concern detected in the 
regular monitoring of accumulating safety data on at least 16 subjects, the IDMC may allow for dose escalation to proceed without the requirement of enrolling and 
evaluating the full group size of 32 subjects. A subsequent dose escalation (from Step 2 to Step 3) will proceed after administration of two doses of the vaccine to 
between a maximum of 32 to a minimum of 16 subjects in the absence of a significant safety concern detected by the IDMC in the regular monitoring of accumulating 
safety data. Thus, upon review of the accumulating safety data on a minimum of 16 subjects after administration of two doses of the vaccine, the IDMC may decide that 
based on the evolving safety profile, sufficient information has been accumulated to allow safe progression to the next sequential dose level. (Amended 10 December
2017) It will be ensured that, as a minimum the IDMC will have reviewed safety data of at least 16 subjects for two doses and given their formal approval prior to enrolling subjects to 
the next dose level.
e Only for hematology.
f Day 7 hematology testing will be performed if any ≥ Grade 1 for platelet decrease is detected on Day 1 after vaccination; to ensure its resolution. Similarly, hematology testing on Day 
37 will be performed if any ≥ Grade 1 for platelet decrease is detected on Day 31.
g Refer to Section 6.6.11.3.
h The IDMC will perform a review when all safety data up to 30 days after administration of Dose 2 in Step 3 (i.e. Day 60) are available.
i Blood samples for CMI and for humoral immunogenicity may be postponed until after the RSV serostatus is known and eligibility is confirmed up to or on Day 0 (but before 
vaccination).
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Protocol waivers or exemptions are not allowed with the exception of immediate safety 
concerns. Therefore, adherence to the study design requirements, including those 
specified in the outline of study procedures (Section 6.5), are essential and required for 
study conduct.

Experimental design: Phase I/II, observer-blind, randomized, placebo-controlled, 
multi-centric, study with two parallel groups per step in a 3-step staggered design.

Duration of the study: approximately 24 months:

Epoch 001: primary starting at the Screening visit and ending at Visit 9 (Day 60).

Epoch 002: follow-up starting at Visit 10 (Day 365) and ending at Visit 11 (Day 
730).
Any safety, immunogenicity and disease surveillance data collected beyond Visit 9
(Day 60) will be collected in Epoch 002.

Primary completion Date: Visit 9 (Day 60).
Refer to glossary of terms for the definition of primary completion date.

End of Study: Last testing results released of samples collected at Visit 11 (Day 
730).*
* Up to Visit 11 (Day 730), there will be monthly nasal swab to detect asymptomatic 
RSV infections during the RSV season and if following active or a passive 
surveillance contacts, a subject presents symptoms of RTI, a nasal swab will be 
collected.
Refer to glossary of terms for the definition of end of study.

Study groups: throughout the three steps, infants will be randomized in two groups to 
receive either ChAd155-RSV vaccine or placebo (Table 1).
Table 1
Study groups and epochs foreseen in the study (Amended 10 
December 2017)
Step
Study groups
Number of 
subjects*
Age (Min/Max)
Epochs
Epoch 001
Epoch 002
1
RSV-Ld
16
12 months - 23 months
x
x
Placebo-Ld
16
12 months - 23 months
x
x
2
RSV-Md
16
12 months - 23 months
x
x
Placebo-Md
16
12 months - 23 months
x
x
3
RSV-Hd
16
12 months - 23 months
x
x
Placebo-Hd
16
12 months - 23 months
x
x
RSV-Ld: low dose ChAd155-RSV vaccine (5 x 109 vp); RSV-Md: middle dose ChAd155-RSV vaccine (1.5 x 1010 vp); 
RSV-Hd: high dose ChAd155-RSV vaccine (5 x 1010 vp).
*The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the time of first 
vaccination (unless the dose escalation IDMC decision can be made based on the evaluation of 
accumulating safety data on fewer subjects) to ensure that at least 64 infants receive two doses of study 
vaccine (ChAd155-RSV or Placebo) (see Section 5.1). Then the number of subjects at each step will be at 
least 16 (approximately 8 subjects per group) at steps 1 and 2 and 32 (approximately 16 subjects per group 
at step 3) (Amended 10 December 2017).
 
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Table 2
Study groups and treatment foreseen in the study
Treatment name
Volume 
administered
Vaccine/Product 
name
Study Groups
Step 1
Step 2
Step 3
RSV-
Ld
Placebo-
Ld
RSV-
Md
Placebo-
Md
RSV-
Hd
Placebo-
Hd
ChAd155 5x109 vp
0.5 ml
ChAd155-RSV
X
ChAd155 1.5x1010 vp
0.15 ml
ChAd155-RSV
X
ChAd155 5x1010 vp
0.5 ml
ChAd155-RSV
X
Placebo 0.5
0.5 ml
Formulation 
buffer S9b
X
X
Placebo 0.15
0.15 ml
Formulation 
buffer S9b
X
RSV-Ld: low dose ChAd155-RSV vaccine (5 x 109 vp); RSV-Md: middle dose ChAd155-RSV vaccine (1.5 x 1010 vp); 
RSV-Hd: high dose ChAd155-RSV vaccine (5 x 1010 vp).

Control: placebo control (Formulation buffer S9b).

Vaccination schedule(s): two IM vaccine doses administered according to a 0, 1-
month schedule (i.e. at Day 0 and Day 30).

Treatment allocation: infants will be randomized using a randomization system on 
internet (SBIR) at first vaccination.

Blinding: observer-blind in Epoch 001 and single-blind in Epoch 002.
Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001
observer-blind
Epoch 002
single-blind

Sampling schedule:

Blood samples for biochemistry will be taken from all infants at Screening (up 
to 29 days before first vaccination to Day 0) and on Day 30, and Day 60 (refer to 
Table 11 for the list of parameters to be tested). Blood samples for hematology
will be taken from all infants at Screening (up to 29 days before first vaccination 
to Day 0) and on Day 1, Day 30, Day 31, and Day 60 (refer to Table 11 for the 
list of parameters to be tested). Day 7 hematology testing will be performed if 
any ≥Grade 1 for platelet decrease is detected on Day 1 after vaccination, to 
ensure its resolution. Similarly, hematology testing on Day 37 will be performed 
if any ≥Grade 1 for platelet decrease is detected on Day 31. A clinical 
examination with special attention given to detection of spontaneous bleeding or 
easy bruising and evidence of bruising or petechiae will be performed by the 
investigator/study staff on Day 1, Day 3 and Day 7 after each vaccination (i.e. 
Day 1, Day 3, Day 7, Day 31, Day 33, and Day 37). The visits on Day 3 and Day 
33 may be replaced by a phone call by the investigator/study staff to inquire of 
the infants' general health and to solicit reports of a rash, spontaneous bleeding or 
easy bruising. On Day 1, and Day 31, special attention will also be given to the 
detection of petechiae or evidence of petechiae induced by the tourniquet. This 
special attention to detection of petechiae or evidence of petechiae induced by 
the tourniquet will also be given on Day 7 and/or Day 37 in case hematology 
 
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testing will be performed on that day. Further testing may be required to 
investigate a finding or guide subject management based on the investigators 
clinical judgment. Subjects’ parent(s)/LAR(s) will be instructed to contact the 
investigator/study staff if their child presents symptoms of spontaneous bleeding 
or easy bruising or if their child develops a rash in the month following 
vaccination, in order to detect any thrombocytopenic petechiae or purpura. The 
investigator will, based on his/her medical judgement, appropriately investigate 
infants with clinical suspicion of low platelets.

Refer to Section 6.6.11.2 and Figure 2 for information about the re-testing of 
samples in case of any Grade 1 abnormality with potential clinical relevance or 
any ≥Grade 2 abnormality.

Blood sample for RSV serostatus will be taken from all infants at Screening.

Blood samples for CMI are limited to those in investigational sites with a 
laboratory in proximity capable to perform WBS necessary for the CMI assay. In 
those sites, samples will be taken from all subjects at Screening and on Day 30, 
Day 60, and Day 365.
Note: Blood samples for CMI taken on Day 7 and Day 37 for subjects enrolled 
under protocol amendment 1 will still be assessed for CMI.

Blood samples for humoral immunogenicity will be taken from all subjects at 
Screening and on Day 30, Day 60, and Day 365.

Blood sample for assessment of mechanism of illness (potential ERD) will be 
taken from subjects hospitalized for LRTI (only for RSV-positive subjects using 
a locally available RSV test).

Nasal swab: there will be monthly nasal swab to detect asymptomatic RSV 
infections during the RSV season and if following active or a passive 
surveillance contacts, a subject presents symptoms of RTI, a nasal swab will be 
collected.

Study visits: Visit 1 (Day 0), Visit 5 (Day 30), Visit 9 (Day 60) and Visit 10 (Day 
365) must be performed at the investigators clinical facility. Visit 2 (Day 1), Visit 4
(Day 7), Visit 6 (Day 31), Visit 8 (Day 37) and Visit 11 (Day 730) (no blood 
sampling for immune response and no vaccine administration) may take place in the 
subject’s home or at the investigators clinical facility as appropriate to the 
circumstances in the judgment of the investigator. Visit 3 (Day 3) and Visit 7 (Day 
33) may take place at the investigators clinical facility or the investigator/clinical 
staff may call the subjects’ parent(s)/LAR(s), as appropriate to the circumstances in 
the judgment of the investigator.

Type of study: e.g. self-contained

Data collection: Electronic Case Report Form (eCRF).

Safety monitoring: iSRC and IDMC (refer to Section 9.10).

Surveillance for RSV-RTI, difficulty in breathing and wheezing episodes.
 
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Surveillance period will be carried out from Visit 1 (after Dose 1) until Visit 11 
(Day 730). In order to detect asymptomatic RSV-RTI, monthly nasal swabs for 
analysis at sponsor laboratory will be performed for all subjects during the RSV 
season. In order to timely detect RSV-RTI and to ensure cases are timely captured by
the study sites, both active and passive surveillance will be conducted:

Passive surveillance: Parent(s)/LAR(s) are instructed to contact the 
investigator/study staff as soon as the subject experiences new RTI symptoms 
(cough, runny nose or blocked nose) or worsening of RTI symptoms, or in case 
of difficulty in breathing or wheezing.

Active surveillance: parent(s)/LAR(s) of all the subjects will be contacted by the 
investigator/study staff on a regular basis (weekly during the RSV season and 
every month outside the RSV season) to identify any potential RSV-RTI and to 
remind the parent(s)/LAR(s) of the subjects to report any new occurrence of RTI 
symptoms (cough, runny nose, blocked nose) or worsening of RTI symptoms, or 
in case of difficulty in breathing or wheezing as soon as possible.
Refer to Section 9.2 for more information about active and passive surveillance.
4.
CASE DEFINITION OF RESPIRATORY TRACT
INFECTION ASSOCIATED WITH RSV INFECTION
It should be noted that for the reporting of safety (unsolicited AEs, AEs of specific 
interest and serious adverse events [SAEs]), the investigator will use all available 
information and his/her medical judgment to make diagnoses. The case definitions 
presented below will be used for a safety analysis complementary to standard safety 
tabulations of events according to Medical Dictionary for Regulatory Activities 
(MedDRA) preferred terms.
4.1.
RTI case definitions
During the analysis of the study, all cases identified during the surveillance of RSV-RTI 
will be definitively classified as either RTI, LRTI, severe LRTI or very severe LRTI
according to the standardized case definitions (see Table 4) based on the available World 
Health Organization (WHO) case definitions.
 
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Table 4
Case definitions for data analysis
RSV-RTI
Runny nose OR blocked nose OR cough
AND 
Confirmed RSV infection 4
RSV-LRTI
History of cough OR difficulty breathing 1
AND 
SpO2 < 95% 2, OR RR increase 3
AND 
Confirmed RSV infection 4
RSV-severe LRTI
Meeting the case definition of RSV-LRTI
AND
SpO2 < 93% 2, OR lower chest wall in-drawing
RSV-very severe 
LRTI
Meeting the case definition of RSV-LRTI 
AND 
SpO2 < 90% 2, OR inability to feed, OR failure to respond / unconscious
RSV hospitalization
Confirmed RSV infection 5
AND
Hospitalized for acute medical condition 6
All-cause LRTI
History of cough OR difficulty breathing 1
AND 
SpO2 < 95% 2, OR RR increase 3
Definitions based on [Modjarrad, 2016]
LRTI = lower respiratory tract infections; RR = respiratory rate; RTI = respiratory tract infections; SpO2 = blood oxygen 
saturation.
1 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.
2 For blood oxygen saturation (SpO2), the lowest value monitored will be used.
3 RR increase defined as 40/minute (12 months of age or above).
4 RSV infection confirmed on nasal swab positive for RSV A or B by quantitative Reverse Transcription Polymerase 
Chain Reaction (qRT-PCR).
5 RSV sampling and testing is based on medical judgment of medical practitioner or driven by algorithm.
6 Hospitalization is defined as a medical decision that the infant requires admission for observation or treatment.
 
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4.2.
RTI episode
4.2.1.
Start date of the RTI episode
The start date of the RTI episode is defined as the point at which the first symptoms of 
cough, runny nose, blocked nose, wheezing, or difficulty breathing were observed.
4.2.2.
End date of the RTI episode
The end date of the RTI episode is defined as the point at which the child is considered 
symptom-free of cough, runny nose, blocked nose, wheezing, or difficulty breathing.
5.
STUDY COHORT
5.1.
Number of subjects
The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the 
time of first vaccination (unless the dose escalation IDMC decision can be made based 
on the evaluation of accumulating safety data on fewer subjects to ensure that at least 
64 infants receive two doses of study vaccine (ChAd155-RSV or Placebo) (Amended 10 
December 2017). Refer to Section 11.4 for the determination of sample size.
Overview of the screening plan:
Upon completion of all screening procedures (Refer to Table 5), the investigator will 
review the inclusion/exclusion criteria for each infant. Infants meeting all eligibility 
criteria will be enrolled in the study. Their screening information will be recorded on the 
appropriate screen of the eCRF.
If the investigator believes there is a reasonable reason to do so, screening procedures 
may be repeated once only. All screening procedures will be repeated except the blood 
sampling for CMI response and humoral response (neutralizing antibody titers against 
RSV-A, RSV F protein antibody concentrations and palivizumab-competing antibody 
concentrations). Blood sampling to assess RSV serostatus (IBL International kit) might 
not be repeated if the infant has been confirmed RSV-seropositive during the first 
screening.
5.2.
Inclusion criteria for enrolment
Deviations from inclusion criteria are not allowed because they can potentially jeopardize 
the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential.
 
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All subjects must satisfy ALL the following criteria at study entry:

Subjects’ parent(s)/LAR(s) who, in the opinion of the investigator, can and will 
comply with the requirements of the protocol (e.g. completion of the diary cards, 
return for follow-up visits).

Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to 
performance of any study specific procedure.

A male or female between, and including, 12 and 23 months (from the day the infant 
becomes 12 months of age until the day before the infant achieves 24 months of age) 
at the time of the first vaccination.

Healthy subjects as established by medical history and clinical examination before 
entering into the study.

Seropositive for RSV as determined by IBL International kit.

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. (Required for Spain)

Subjects’ parent(s)/LAR(s) need to have access to a consistent mean of telephone 
contact (e.g. land line or mobile) or computer.
5.3.
Exclusion criteria for enrolment
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. 
Therefore, adherence to the criteria as specified in the protocol is essential.
The following criteria should be checked at the time of study entry. If ANY exclusion 
criterion applies, the subject must not be included in the study:

Child in care.
Please refer to the glossary of terms for the definition of child in care.

Use of any investigational or non-registered product (drug or vaccine) other than the 
study vaccine during the period starting 30 days before the first dose of study 
vaccine (Day -29 to Day 0), or planned use during the study period.

Any medical condition that in the judgment of the investigator would make IM 
injection unsafe.

Chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs during the period starting six 
months prior to the first vaccine. For corticosteroids, this will mean prednisone (
0.5 mg/kg/day (for pediatric subjects), or equivalent. Inhaled and topical steroids are 
allowed.

Administration of long-acting immune-modifying drugs (e.g. infliximab) or planned 
administration at any time during the study period.
 
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
Administration of immunoglobulins and/or any blood products during the period 
starting three months before the first dose of study vaccine or planned administration 
during the study period.

Planned administration/administration of a vaccine not foreseen by the study 
protocol in the period starting 30 days before the first dose and ending 30 days after 
the last dose of vaccine administration, with the exception of scheduled routine 
pediatric vaccines which may be administered 14 days before a dose or 7 days 
after a dose.

Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal 
functional abnormality, as determined by physical examination or laboratory 
screening tests.

Serious chronic illness.

Major congenital defects.

History of any neurological disorders or seizures.

History of or current autoimmune disease.

History of recurrent wheezing. (Wheezing should have been verified on auscultation 
by doctor).

History of chronic cough (4 weeks or more duration).

Previous hospitalization for respiratory illnesses.

History of thrombocytopenia.

History of anemia.

Previous, current or planned administration of Synagis (palivizumab).

Neurological complications following any prior vaccination.

Born to a mother known or suspected to be HIV-positive (no laboratory testing 
required).

Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing required).

Family history of congenital or hereditary immunodeficiency.

Previous vaccination with a recombinant simian or human adenoviral vaccine.

History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccine.

Hypersensitivity to latex.

Current severe eczema.

Acute disease and/or fever at the time of enrolment.

Fever is defined as temperature ≥ 37.5°C/99.5°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 will be axillary.
 
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
Clinically significant upper respiratory tract infection.

Subjects with a minor illness (such as mild diarrhea) without fever may, be 
enrolled at the discretion of the investigator.

Any clinically significant Grade 1* or any ≥ Grade 2* hematological or biochemical 
laboratory abnormality detected at the last screening blood sampling.
* Refer to Appendix C. For Grade 1 laboratory abnormalities, the investigator should 
use his/her clinical judgment to decide which ones are clinically relevant. Infants 
with hematological/biochemical values out of normal range which are expected to be 
temporary, may be re-screened at a later date.

Any other conditions that the investigator judges may interfere with study procedures 
(e.g. drawing blood) or findings (e.g. immune response).

Any conditions that could constitute a risk for the subjects while participating to this 
study.

Weight below the fifth percentile of the local weight-for-age curve.

Concurrently participating in another clinical study, at any time during the study 
period, in which the subject has been or will be exposed to an investigational or a 
non-investigational vaccine/product (pharmaceutical product or device).

Planned move to a location that will prohibit participating in the trial until study end.
6.
CONDUCT OF THE STUDY
6.1.
Regulatory and ethical considerations, including the 
informed consent process
The study will be conducted in accordance with all applicable regulatory requirements.
The study will be conducted in accordance with the ICH Guideline for Good Clinical 
Practice (GCP), all applicable subject privacy requirements and the guiding principles of 
the Declaration of Helsinki. 
The study has been designed and will be conducted in accordance with the ICH 
Harmonized Tripartite Guideline for clinical investigation of medicinal products in the 
pediatric population (ICH E11) and all other applicable ethical guidelines.
GSK will obtain favorable opinion/approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements, prior to a site 
initiating the study in that country.
Conduct of the study includes, but is not limited to, the following:

Institutional Review Board (IRB)/Independent Ethics Committee (IEC) review and 
favorable opinion/approval of study protocol and any subsequent amendments.

Subject’s parent(s)/LAR(s) informed consent.

Investigator reporting requirements as stated in the protocol.
 
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GSK will provide full details of the above procedures to the investigator, either verbally, 
in writing, or both.
Freely given and written or witnessed/ thumb printed informed consent must be obtained 
from each subject’s parent(s)/LAR(s) prior to participation in the study.
GSK Biologicals will prepare a model Informed Consent Form (ICF) which will embody 
the ICH GCP and GSK Biologicals required elements. While it is strongly recommended 
that this model ICF is to be followed as closely as possible, the informed consent 
requirements given in this document are not intended to pre-empt any local regulations 
which require additional information to be disclosed for informed consent to be legally 
effective. Clinical judgment, local regulations and requirements should guide the final 
structure and content of the local version of the ICF. 
The investigator has the final responsibility for the final presentation of the ICF, 
respecting the mandatory requirements of local regulations. The ICF generated by the 
investigator with the assistance of the sponsor’s representative must be acceptable to 
GSK Biologicals and be approved (along with the protocol, and any other necessary 
documentation) by the IRB/IEC.
6.2.
Subject identification and randomization of treatment
6.2.1.
Subject identification
Subject identification numbers will be assigned sequentially to the subjects who have 
consented to participate in the study, according to the range of subject identification 
numbers allocated to each study center.
6.2.2.
Randomization of treatment
6.2.2.1.
Randomization of supplies
The randomization of supplies within blocks will be performed at GSK Biologicals, using 
MATerial EXcellence (MATEX), a program developed for use in Statistical Analysis 
System (SAS®) (Cary, NC, USA) by GSK Biologicals. Entire blocks will be shipped to 
the study centers /warehouse(s).
6.2.2.2.
Treatment allocation to the subject
The treatment numbers will be allocated by dose.
 
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6.2.2.2.1.
Study group and treatment number allocation
The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the 
time of first vaccination (unless the dose escalation IDMC decision can be made based 
on the evaluation of accumulating safety data on fewer subjects to ensure that at least 
64 infants receive two doses of study vaccine (ChAd155-RSV or Placebo) (see Section 
5.1) (Amended 10 December 2017). Infants will be randomly assigned to two study 
groups per step in a (1:1) ratio (approximately 16 subjects in each group).

In Step 1, between approximately 8 and 16 RSV-seropositive infants will be 
randomly assigned to receive low dose ChAd155-RSV vaccine (5 x 109 vp [RSV-
Ld]; 0.5 mL) and between approximately 8 and 16 RSV-seropositive infants will be 
randomly assigned to receive placebo (0.5 mL). (Amended 10 December 2017)

In Step 2, between approximately 8 and 16 RSV-seropositive infants will be 
randomly assigned to receive middle dose ChAd155-RSV vaccine (1.5 x 1010 vp 
[RSV-Md]; 0.15 mL) and between approximately 8 and 16 RSV-seropositive infants
will be randomly assigned to receive placebo (0.15 mL). (Amended 10 December
2017)

In Step 3, approximately 16 RSV-seropositive infants will be randomly assigned to 
receive high dose ChAd155-RSV vaccine (5 x 1010 vp [RSV-Hd]; 0.5 mL) and 
approximately 16 RSV-seropositive infants will be randomly assigned to receive 
placebo (0.5 mL).
Allocation of the subject to a study group at the investigator site will be performed using 
a randomization system on internet (SBIR). Within each step, the randomization 
algorithm will use a minimization procedure accounting for center.
After obtaining the signed and dated ICF from the subject’s parent(s)/LAR(s) and having 
checked the eligibility of the subject, the study staff in charge of the vaccine
administration will access SBIR. Upon providing the subject identification number, the 
randomization system will determine the study group and will provide the treatment 
number to be used for the first dose.
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen.
When SBIR is not available, please refer to the SBIR user guide or the SPM for specific 
instructions.
6.2.2.2.2.
Treatment number allocation for subsequent doses
For each dose subsequent to the first dose, the study staff in charge of the vaccine
administration will access SBIR, provide the subject identification number, and the 
system will provide a treatment number consistent with the allocated study group.
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen.
 
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6.3.
Method of blinding
Data will be collected in an observer-blind manner. By observer-blind, it is meant that 
during the course of the study, the vaccine recipient and those responsible for the 
evaluation of any study endpoint (e.g. safety, reactogenicity) will all be unaware of which 
vaccine was administered. To do so, vaccine preparation and administration will be done 
by authorized medical personnel who will not participate in any of the study clinical 
evaluation assays.
When all data up to Day 60 are available, a statistical analysis will be performed. This
analysis may lead to the unblinding of some subjects. As a consequence, after Day 60, the 
study cannot be considered as observer-blind, but will be conducted in a single-blind 
manner, with subjects’ parent(s)/ LAR(s) remaining blinded up to study end (Day 730).
The investigators will not have access to the treatment allocation up to study end (Day 
730).
The laboratory in charge of the laboratory testing will be blinded to the treatment, and 
codes will be used to link the subject and study (without any link to the treatment 
attributed to the subject) to each sample.
6.4.
General study aspects
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying SPM. The SPM provides the investigator and the site 
personnel with administrative and detailed technical information that does not impact the 
safety of the subjects.
Vaccination will be limited to a maximum of 10 infants per day. In the same 
investigational center, infants will be vaccinated sequentially, separated by a minimum 
interval of 60 minutes. In addition, to monitor delayed potential reactions following 
vaccination, there will be a 48-hour observation period following Dose 1 and Dose 2
administration to the first eight infants (corresponding to three to five ChAd155-RSV 
vaccine recipients) in each Step (1, 2, and 3) before continuing vaccination of more 
infants (i.e. from the ninth infant). From the ninth infant, infants will be vaccinated 
sequentially, separated by a minimum interval of 60 minutes.
Refer to Section 9.10 for information about limited vaccination, holding rules, safety 
monitoring and safety evaluation by iSRC and IDMC.
 
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6.5.
Outline of study procedures
Table 5
List of study procedures
Epoch
Epoch 001
Epoch 002
Age
12-23 mth
24-35
mth
36-47
mth
Type of contact
Screening Visit 
1
Visit 
2#
Visit 
3##
Visit 
4#
Visit 
5
Visit 
6#
Visit 
7##
Visit 
8#
Visit 
9
Visit 10
Visit 
11#
Unscheduled 
visit for 
safety*
Contact for 
active/passive 
surveillance**
Surveillance 
for 
asymptomatic 
RSV-RTI*** 
Assessment 
of potential 
RSV-RTI****
Timepoints
D-29 to 
D0 
D0
D1
D3
D7
D30 D31 D33 D37 D60
D365
D730
Monthly or 
Weekly
Monthly
Informed consent
●
Check inclusion/exclusion criteria
●
O
Collect demographic data
●a
Collect birth weight and gestation at 
birth in weeks
●
Medical history
●
Physical examinationb
●
O
O
O
O
O
O
O
O
O
O
O
●
Growth monitoringc
●
●
●
●
●
Check contraindications and warnings 
and precautions
O
O
Pre-vaccination body temperature
●
●
Randomization
O
Vaccine administration
●
●
Recording of administered treatment 
number
●
●
60 minutes post-vaccination 
observationd
●
●
Blood sampling for RSV serostatus 
(1.0 mL)
●
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Epoch
Epoch 001
Epoch 002
Age
12-23 mth
24-35
mth
36-47
mth
Type of contact
Screening Visit 
1
Visit 
2#
Visit 
3##
Visit 
4#
Visit 
5
Visit 
6#
Visit 
7##
Visit 
8#
Visit 
9
Visit 10
Visit 
11#
Unscheduled 
visit for 
safety*
Contact for 
active/passive 
surveillance**
Surveillance 
for 
asymptomatic 
RSV-RTI*** 
Assessment 
of potential 
RSV-RTI****
Timepoints
D-29 to 
D0 
D0
D1
D3
D7
D30 D31 D33 D37 D60
D365
D730
Monthly or 
Weekly
Monthly
Blood sampling for assessment of 
mechanisms of illness (potential ERD; 
2.5 mL)
●l
Blood sampling for hematology (1.2 
mL)
●e
●f
●f,p
●f,g
●f
●f,p
●f
●f
Blood sampling for biochemistry (1.1 
mL)
●e
●f,g
●f
●f
Blood sampling for CMI response (2.0 
mL) o
●r
●g
●
●
Blood sampling for humoral response 
(2.5 mL)
●r
●g
●
●
Detection of spontaneous bleeding or 
easy bruising and evidence of bruising 
or petechiae q
●
●
●
●
●
●
Examination of limb for petechiae 
induced by the tourniquet
●
●
●
●
Surveillance for RSV-RTI, difficulty in 
breathing and wheezing
O
O
O
O
O
O
O
O
O
O
O
●
●
Documentation of symptoms and signs 
of RTIj
●
Nasal swab for central testings
●m
●h
Specimen for local testings
●n
Distribution of RTI episode cardsk
O
O
O
O
O
O
O
O
Collection of completed RTI episode 
cardsk
O
O
O
O
O
O
O
O
O
O
O
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Epoch
Epoch 001
Epoch 002
Age
12-23 mth
24-35
mth
36-47
mth
Type of contact
Screening Visit 
1
Visit 
2#
Visit 
3##
Visit 
4#
Visit 
5
Visit 
6#
Visit 
7##
Visit 
8#
Visit 
9
Visit 10
Visit 
11#
Unscheduled 
visit for 
safety*
Contact for 
active/passive 
surveillance**
Surveillance 
for 
asymptomatic 
RSV-RTI*** 
Assessment 
of potential 
RSV-RTI****
Timepoints
D-29 to 
D0 
D0
D1
D3
D7
D30 D31 D33 D37 D60
D365
D730
Monthly or 
Weekly
Monthly
Transcription of completed RTI 
episode cards
●
●
●
●
●
●
●
●
O
●
●
Record any concomitant 
medications/vaccinations
●
●
●
●
●
●
●
●
●
●
●
●
Distribution of the subject card
O
Distribution of diary card
O
O
Return of diary card
O
O
O
O
Diary card transcription by investigator
●
●
●
●
Recording of solicited AEs (Day 0-6)
●
●
●
●
●
●
●i
Recording of unsolicited AEs (Day 0-
29)
●
●
●
●
●
●
●
●
●
●i
Recording of AE leading to study 
withdrawal
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Recording of AE of specific interest 
(RSV-LRTI)
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Recording of AE of specific interest 
(spontaneous or excessive bleeding)
●
●
●
●
●
●
●
●
●
●
●
●
●
Recording of SAEs
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Screening conclusion
●
Study conclusion
●
Signing of investigator signature form 
by investigator after Screening and 
before each analysis
●
●
●
●
● is used to indicate a study procedure that requires documentation in the individual eCRF.
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O is used to indicate a study procedure that does not require documentation in the individual eCRF.
Note: the double-bordered lines following Visit 9 (Day 60), Visit 10 (Day 365) and Visit 11 (Day 730) indicate the statistical analyses which will be performed. After Visit 9 (Day 60) the 
study will be conducted in a single-blind manner, with patients remaining blinded up to study end (Day 730). The investigators will not have access to the treatment allocation up to 
study end (Day 730).
* This visit is applicable for infants with hematological/biochemical values out of normal range or for further evaluation of clinical suspicion of low platelet count.
** Active contacts for surveillance of RSV-RTI will take place weekly during the RSV season and every month outside the RSV season (refer to Section 9.2). Passive phone contacts 
from the subjects’ parent(s)/LAR(s) to the investigator will take place when symptoms occur.
*** In order to detect asymptomatic RSV infection, monthly visits will be performed during the RSV season.
**** This visit is only applicable for infants with potential RSV-RTI.
# Visit 2 (Day 1), Visit 4 (Day 7), Visit 6 (Day 31), Visit 8 (Day 37) and Visit 11 (Day 730) may take place in the subject’s home or at the investigators clinical facility as appropriate to the 
circumstances in the judgment of the investigator.
## On Day 3 and Day 33, a visit may take place at the investigators clinical facility or the investigator /clinical staff may call the subjects’ parent(s)/LAR(s), as appropriate to the 
circumstances in the judgment of the investigator.
a Recording of demographic data includes date of birth, gender, geographic ancestry, and ethnicity.
b At Screening, perform a complete physical examination, including assessment of vital signs (body temperature, heart rate [HR], and RR). At subsequent study visits, perform a 
physical examination only if the subject’s parent(s)/LAR(s) indicate(s) during questioning that there might be some underlying pathology(ies) or if deemed necessary.
c Growth monitoring includes weight and length (for infants < 24 months of age) or height (for subjects 24 months of age).
d Infants will need to remain under observation (visual follow-up as well as measurement of resting vital signs) at the study site for at least 60 minutes after vaccination. Vital signs are 
body temperature, HR and RR. Vital signs are measured preferably when the infant is calm.
e At Screening, for infants with hematological/biochemical values out of normal range which are expected to be temporary, a re-screening visit may be scheduled during which blood 
sample collection for hematology/biochemistry will be repeated (maximum one re-screening visit per infant is allowed; blood for CMI response and humoral response will not be re-
sampled at the re-screening visit, if already done before).
f If any Grade 1 abnormality with potential clinical relevance (according to investigators judgment) or any ≥ Grade 2 abnormality is detected, or for further evaluation of clinical suspicion 
of low platelet count, refer to Section 6.6.11.2 and Figure 2 for re-test.
g Blood samples to be taken before vaccination.
h If during passive or active surveillance contact, the investigator/study staff assesses that an infant presents a potential RSV-RTI (refer to Table 4 for definition), the potential RSV 
infection will be assessed by quantitative RT-PCR.
iOnly when the unscheduled visit occurs within the AE reporting time frame, i.e. from Day 0 to Day 6 for solicited AEs and from Day 0 to Day 29 for unsolicited AEs.
j Signs and symptoms to be recorded in the eCRF are listed in the SPM.
k Subject’s parent(s)/LAR(s) will be instructed to record on the RTI episode card the start date and the end date of the following symptoms (cough, runny nose, blocked nose, difficulty 
in breathing, or wheezing) and to return it to the investigator at the next visit or by mail (e-mail or postal mail).
l Blood sample collected for subjects hospitalized for LRTI(only for RSV-positive subjects using a locally available RSV test); Refer to Section 6.7.3.
m Nasal swab collected at the monthly surveillance for asymptomatic RSV-RTI will be tested by quantitative RT-PCR.
n For RSV testing and respiratory viral panel (RVP) at a local routine laboratory, where available.
o In investigational sites with a laboratory in proximity capable to perform WBS necessary for the CMI assay.
p Day 7 hematology testing will be performed if any ≥ Grade 1 for platelet decrease is detected on Day 1 after vaccination. Similarly, hematology testing on Day 37 will be performed if 
any ≥ Grade 1 for platelet decrease is detected on Day 31.
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q A clinical examination with special attention given to detection of spontaneous bleeding or easy bruising and evidence of bruising or petechiae will be performed by the 
investigator/study staff on Day 1, Day 3 and Day 7 after each vaccination (i.e. Day 1, Day 3, Day 7, Day 31, Day 33 and Day 37). The visits on Day 3 and Day 33 may be replaced by a 
phone call by the investigator/study staff to inquire of the infants' general health and to solicit reports of a rash, spontaneous bleeding or easy bruising. Subjects’ parent(s)/LAR(s) will 
be instructed to contact the investigator/study staff if their child presents symptoms of spontaneous bleeding or easy bruising or if their child develops a rash in the month following 
vaccination, in order to detect any thrombocytopenic petechiae or purpura.
r Blood samples for CMI and for humoral immunogenicity may be postponed until after the RSV serostatus is known and eligibility is confirmed up to or on Day 0 (but before 
vaccination).
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Table 6
Intervals between study visits
Interval
Optimal length of interval
Allowed interval
Screening Visit 1 (Day 0)
1 - 30 days1
-
Visit 1 (Day 0) Visit 2 (Day 1)
1 day
-
Visit 1 (Day 0) Visit 3 (Day 3)
3 days
3 - 4 days
Visit 1 (Day 0) Visit 4 (Day 7)
7 days
7 - 10 days
Visit 1 (Day 0) Visit 5 (Day 30)
30 days
23 - 36 days2
Visit 5 (Day 30) Visit 6 (Day 31)
1 day
-
Visit 5 (Day 30) Visit 7 (Day 33)
3 days
3 - 4 days
Visit 5 (Day 30) Visit 8 (Day 37)
7 days
7 - 10 days
Visit 5 (Day 30) Visit 9 (Day 60)
30 days
28 - 35 days2
Visit 1 (Day 0) Visit 10 (Day 365)
365 days
335 - 395 days2
Visit 1 (Day 0) Visit 11 (Day 730)
730 days
700 - 760 days
1 Visit 1 should take place no longer than 30 days after the Screening visit. When applicable, a re-screening visit may 
be scheduled at any time (but only once to assess eligibility; blood for CMI response and humoral response will not be 
re-sampled, if already done before). All screening procedures need to be performed within 30 days of Visit 1.
2 Immunogenicity data from blood samples collected outside this interval will not be eligible for inclusion in the 
according-to-protocol (ATP) cohort for analysis of immunogenicity.
6.6.
Detailed description of study procedures
6.6.1.
Informed consent
The signed/witnessed/thumb printed informed consent of the subject’s parent(s)/LAR(s) 
must be obtained before study participation. Refer to Section 6.1 for the requirements on 
how to obtain informed consent.
6.6.2.
Check inclusion and exclusion criteria
Check all inclusion and exclusion criteria as described in Sections 5.2 and 5.3 before 
enrolment.
6.6.3.
Collect demographic data
Record demographic data such as date of birth (day, month and year), gender, geographic 
ancestry, and ethnicity in the subject’s eCRF. Collect and record the birth weight and 
gestation at birth (in weeks) in the eCRF.
6.6.4.
Medical history
Obtain the subject’s medical history by interview and/or review of the subject’s medical 
records and record any pre-existing conditions or signs and/or symptoms present in a 
subject prior to the first study vaccination in the eCRF.
 
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6.6.5.
Physical examination
At Screening, perform a physical examination of the subject, including assessment of 
vital signs preferably when the infant is calm. Vital signs are body temperature, heart rate 
(HR) and RR. Collected information needs to be recorded in the eCRF.
At subsequent study visits, perform a physical examination only if the subject’s 
parent(s)/LAR(s) indicate(s) during questioning that there might be some underlying 
pathology(ies) or if deemed necessary.
Treatment of any abnormality observed during physical examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate 
health care provider.
6.6.6.
Growth monitoring
Growth monitoring includes weight and length (for infants < 24 months of age) or height
(for subjects 24 months of age; [United Nations, 1986]). Collected information needs to 
be recorded in the eCRF.
6.6.7.
Check contraindications, warnings and precautions to 
vaccination
Contraindications, warnings and precautions to vaccination must be checked at the 
beginning of each vaccination visit. Refer to Section 7.5 for more details.
6.6.8.
Assess pre-vaccination body temperature
The axillary, rectal, oral, or tympanic body temperature of all subjects needs to be 
measured prior to any study vaccine administration (Amended 10 December 2017). The 
preferred route for recording temperature in this study will be axillary. If the subject has 
fever (fever is defined as temperature 37.5°C/99.5°F for oral, axillary or tympanic 
route, or 38.0°C/100.4°F for rectal route) on the day of vaccination, the vaccination 
visit will be rescheduled within the allowed interval for this visit (see Table 6).
6.6.9.
Randomization
Study group and treatment number allocation will be performed as described in Section 
6.2.2. The number of each administered treatment must be recorded in the eCRF.
6.6.10.
Study Vaccines administration

Across each steps, vaccination will be limited to a maximum of 10 infants per day. In 
the same investigational center, infants will be vaccinated sequentially, separated by 
a minimum interval of 60 minutes. In addition, to monitor delayed potential reactions 
following vaccination, there will be a 48-hour observation period following Dose 1 
and Dose 2 administration to the first eight infants (corresponding to three to five 
 
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ChAd155-RSV vaccine recipients) in each Step (1, 2, and 3) before continuing 
vaccination of more infants (Refer to Section 9.10.1).

After completing all prerequisite procedures prior to vaccination, one dose of study 
vaccine will be administered via IM injection in the deltoid (if the muscle size is 
adequate; otherwise injections might be done in the anterolateral thigh). The site of 
administration of Dose 2 should preferably remain the same as the site of 
administration of Dose 1. Refer to Section 7.3 for detailed description of the vaccines 
administration procedure. If the investigator or delegate determines that the infant’s 
health on the day of administration temporarily precludes vaccine administration, the 
visit will be rescheduled within the allowed interval for this visit (refer to Table 6).

The subjects will be observed closely (visual follow-up as well as measurement of 
resting vital signs) for at least 60 minutes following the administration of the 
vaccines, with appropriate medical treatment readily available in case of 
anaphylaxis. Vital signs are body temperature, HR and RR. Vital signs are preferably 
measured when the infant is calm.
6.6.11.
Sampling
Refer to the Module on Biospecimen Management in the SPM for detailed instructions 
for the collection, handling and processing of the samples.
To minimize any development of needle aversion, pain relief by means of a topical local 
anesthetic may be offered to infants prior to any blood sampling requested by the 
protocol at the discretion of the investigator.
6.6.11.1.
Blood sampling for RSV serostatus, humoral immunity, and cell-
mediated immunity
Blood samples will be taken during certain study visits as specified in Section 6.5 List of 
Study Procedures.

A volume of maximum 1.0 mL of whole blood (to provide at least 300 L of serum) 
should be drawn from all infants for analysis of their RSV serostatus at the screening 
visit. After centrifugation, serum samples should be kept at –20°C/ –4°F or below. 
RSV serostatus assessment will be performed in a laboratory designated by GSK 
Biologicals using an ELISA commercial kit (refer to Table 9). Refer to the SPM for 
more details on sample storage conditions.

A volume of 2.0 mL of whole blood should be drawn from all infants for analysis of 
CMI response at each pre-defined timepoint, in investigational sites with a laboratory 
in proximity capable to perform WBS necessary for the CMI assay. Refer to the 
SPM for more details on sample storage conditions.

A volume of 2.5 mL of whole blood (to provide at least 800 L of serum) should be 
drawn from all infants for analysis of humoral response at each pre-defined 
timepoint. After centrifugation, serum samples should be kept at –20°C/ –4°F or 
below until shipment. Refer to the SPM for more details on sample storage 
conditions.
 
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
Blood sampling for CMI and humoral response will not be repeated in case of 
insufficient volume, at any timepoint.
6.6.11.2.
Blood sampling for hematology and biochemistry

A volume of maximum 1.2 mL of whole blood should be drawn from all infants for 
analysis of the hematology parameters (refer to Table 11) at each pre-defined 
timepoint.

A volume of maximum 1.1 mL of whole blood should be drawn from all infants for 
analysis of the biochemistry parameters (refer to Table 11) at each pre-defined 
timepoint.
Hematology and biochemistry parameters assessment will be performed according to 
laboratory practices.
Day 7 hematology testing will be performed if any ≥Grade 1 for platelet decrease is 
detected on Day 1. Similarly, hematology testing on Day 37 will be performed if any 
≥Grade 1 for platelet decrease is detected on Day 31 (refer to Figure 2 and 
Appendix C).
If any Grade 1 abnormality with potential clinical relevance (according to 
investigators judgment, refer to the glossary of terms) or any ≥Grade 2 abnormality 
is detected (refer to Figure 2 and Appendix C):

at Screening, for infants with hematological/biochemical values out of normal 
range which are expected to be temporary, a re-screening visit may be scheduled 
during which blood sample collection for hematology/biochemistry will be 
repeated (maximum one re-screening visit per infant is allowed within the 
interval planned in Table 6).

at Day 7, the relevant hematology/biochemistry parameter(s) must be re-tested 
before administration of vaccine Dose 2, either during an unscheduled visit or at 
the Dose 2 vaccination visit itself (provided results are obtained before 
vaccination). Only if the concerned parameter(s) is/are within the acceptable 
range (i.e. within normal range or Grade 1 without clinical relevance), vaccine 
Dose 2 can be administered. If the concerned parameter(s) is/are not within the 
acceptable range within the allowed interval for the second dosing visit, Visit 5, 
the infant will not receive Dose 2 but should still continue the study for safety 
follow-up (up to Day 730).

at Days 30, 37 and 60 the relevant hematology/biochemistry parameter(s) may
be re-tested as per the opinion of the investigator.
Note: For safety reasons and specifically for further investigation of an AE of specific 
interest (suspected bleeding or low platelet count), blood can be re-sampled for 
hematology and biochemistry assessment.
 
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Figure 2
Schematic overview of required additional hematology and biochemistry testing during the study
Note: For safety reasons and specifically for further investigation of an AE of specific interest (suspected bleeding or low platelet count), blood can be re-sampled for hematology and 
biochemistry assessment.
Re-testing at screening
Grade 1 abnormality with 
potential clinical 
relevance  or ≥ Grade 2 
abnormality, expected to 
be temporary 
Subject may be 
enrolled in the study 
Testing may be repeated at 
any time (but only once to 
assess eligibility). 
To be performed within 
screening visit window
Grade 1 with potential clinical 
relevance  or ≥ Grade 2
Values within normal range or 
Grade 1 without clinical 
relevance
Subject not 
eligible
Grade 1 abnormality with 
potential clinical 
relevance or ≥ Grade 2 
abnormality
Re-testing during the study
Grade 1 abnormality 
with potential clinical 
relevance or ≥ Grade 
2 abnormality
at Day 7: 
Mandatory re-testing
of concerned 
parameter(s) prior to 
Dose 2 administration.
To be performed within 
the  visit window
If at any other study 
visit: 
Optional re-testing of 
concerned parameter(s) 
at the discretion of the 
investigator
Within normal range or Grade 
1 without clinical relevance 
prior to Dose 2 administration
Not within normal range or 
Grade 1 with potential clinical 
relevance or ≥ Grade 2 by 
Day 35 
Proceed with 
Dose 2 
administration
Withdraw subject 
from Dose 2  
Vaccination
If at Day 1: 
Mandatory re-testing
of concerned 
parameter(s) at Day 7
≥ Grade 1 abnormality of 
platelets
If at Day 31: 
Mandatory re-testing of 
concerned parameter(s) 
at Day 37
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6.6.11.3.
Nasal swab and other specimen for local assay
Nasal swab and other specimen for local assay collected during assessment visit
If during passive or active surveillance contact, the investigator/study staff assesses that 
an infant presents a potential RSV-RTI (refer to 9.2), a nasal swab and another specimen 
for local assay will be collected during an assessment visit:

The nasal swab will allow assessing the potential RSV infection by quantitative RT-
PCR at sponsor laboratory.

The specimen for local assay will allow assessing the potential RSV infection and 
RVP at a local routine laboratory, where available. The specimen type will depend 
on the assay run locally.
Nasal swab collected to detect asymptomatic RSV infections
During RSV season, there will be monthly nasal swabs to detect asymptomatic RSV 
infections. These nasal swabs will allow assessing the potential RSV infection by 
quantitative RT-PCR at sponsor laboratory.
Refer to the SPM for more details about nasal swab.
6.6.12.
Detection of spontaneous bleeding or easy bruising and 
evidence of bruising or petechiae
Subjects’ parent(s)/LAR(s) will be instructed to contact the investigator/study staff if 
their child presents symptoms of spontaneous bleeding or easy bruising or if their child 
develops a rash in the month following vaccination, in order to detect any 
thrombocytopenic petechiae or purpura. Refer to Sections 9.1.5 and 9.4.3 for reporting of 
adverse events of specific interest (spontaneous or excessive bleeding).
At Visit 2 (Day 1), Visit 3 (Day 3)*, Visit 4 (Day 7), Visit 6 (Day 31), Visit 7 (Day 33)*, 
and Visit 8 (Day 37), the investigator will perform a clinical examination with special 
attention given to detection of spontaneous bleeding or easy bruising and evidence of 
bruising or petechiae. Episodes of spontaneous bleeding or easy bruising and evidence of 
bruising or petechiae will be recorded in the eCRF.
* The visits on Day 3 and Day 33 may be replaced by a phone call by the 
investigator/study staff to inquire of the infants' general health and to solicit reports of a 
rash, spontaneous bleeding or easy bruising.
Further testing may be required to investigate a finding or guide subject management 
based on the investigators clinical judgment.
 
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6.6.13.
Detection of petechiae or evidence of petechiae induced by the 
tourniquet
At Visit 2 (Day 1), Visit 6 (Day 31), the investigator will perform an examination of the 
limb where the tourniquet for blood sample has been placed in order to detect petechiae 
or evidence of petechiae induced by the tourniquet. This special attention to detection of 
petechiae or evidence of petechiae induced by the tourniquet will also be given at Visit 4 
(Day 7) and/or Visit 8 (Day 37) in case hematology testing will be performed on that day. 
Episodes of petechiae will be recorded in the eCRF. 
These episodes might be reported as AE based on the investigators clinical judgment.
6.6.14.
Surveillance for RSV-RTI and wheezing
Surveillance period for RSV-RTI and wheezing will start at Visit 1 (after Dose 1) until 
the final visit (Visit 11 [Day 730]). In order to timely detect RSV-RTI and to ensure cases 
are timely captured by the study sites, both active and passive surveillance will be 
conducted as described in Section 9.2. Contacts for active and passive surveillance will 
be recorded in the eCRF.
If an assessment visit is performed (refer to Section 9.2.4), this visit will be recorded in 
the eCRF, as well as signs and symptoms. Signs and symptoms to be recorded in the 
eCRF are listed in the SPM.
At the first vaccination visit (Visit 1 [Day 0]), RTI episode cards will be provided to the 
subject's parent(s)/LAR(s). At subsequent study visits, new RTI episode card(s) will be 
distributed as needed. The subject's parent(s)/LAR(s) will record the start date and the 
end date of the following symptoms: cough, runny nose, blocked nose, difficulty in
breathing, or wheezing. The subject's parent(s)/LAR(s) will be instructed to return the 
completed RTI episode card to the investigator at the next visit or by mail (e-mail or 
postal mail). The investigator will transcribe the collected information into the eCRF. 
Any unreturned RTI episode card will be sought from the subject's parent(s)/LAR(s) 
through telephone call(s) or any other convenient procedure.
6.6.15.
Check and record concomitant medication/vaccination
Concomitant medication/vaccination must be checked and recorded in the eCRF as 
described in Section 7.6.
6.6.16.
Recording of AEs, AEs of specific interest and SAEs

Refer to Section 9.3 for procedures for the investigator to record AEs, AEs of specific 
interest (RSV-LRTI and spontaneous or excessive bleeding) and SAEs.

Refer to Section 9.4 for guidelines and how to report AEs of specific interest and 
SAE reports to GSK Biologicals.
 
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
The subjects’ parent(s)/LAR(s) will be instructed to contact the investigator 
immediately should the subjects manifest any signs or symptoms they perceive as 
serious.

At each vaccination visits (Visit 1 [Day 0] and Visit 5 [Day 30]), a diary card will be 
provided to the subject’s parent(s)/LAR(s). The subject’s parent(s)/LAR(s) will 
record body temperature, any solicited local/general AEs, any unsolicited AEs, and 
concomitant medications/products/vaccinations on the day of vaccination and 6 
subsequent days. The subject’s parent(s)/LAR(s) will be instructed to return the 
completed diary card to the investigator at Visit 4 (Day 7) and Visit 8 (Day 37).
The subject’s parent(s)/LAR(s) will record on the same diary card any unsolicited 
AEs and concomitant medications/products/vaccinations from 7 to 29 days after each 
vaccination. The subject’s parent(s)/LAR(s) will be instructed to return the 
completed diary card to the investigator at Visit 5 (Day 30) and Visit 9 (Day 60).
The investigator will collect and verify completed diary cards during discussion with 
the subject’s parent(s)/LAR(s) on Visit 4 (Day 7), Visit 5 (Day 30), Visit 8 (Day 37) 
and Visit 9 (Day 60). The investigator will transcribe the collected information into 
the eCRF in English.
Any unreturned diary cards will be sought from the subject’s parent(s)/LAR(s) 
through telephone call(s) or any other convenient procedure.
6.6.17.
Screening conclusion
At the end of the screening visit, the investigator will:

Review data collected.

Complete the Screening Conclusion screen in the eCRF.
6.6.18.
Signing of investigator signature form by investigator
At the end of the screening visit, Visit 9 (Day 60), Visit 10 (Day 365) and Visit 11 (Day 
730), the investigator will sign the investigator signature form in the eCRF.
6.6.19.
Study conclusion
At the last visit (Visit 11 [Day 730]), the investigator will:

Review data collected to ensure accuracy and completeness.

Complete the Study Conclusion screen in the eCRF.
 
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6.7.
Biological sample handling and analysis
Please refer to the SPM for details on biospecimen management (handling, storage and 
shipment).
Samples will not be labeled with information that directly identifies the subject but will 
be coded with the identification number for the subject (subject number).

Collected samples will be used for protocol mandated research and purposes related 
to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. This may include the management of the quality of these 
tests, the maintenance or improvement of these tests, the development of new test 
methods, as well as making sure that new tests are comparable to previous methods 
and work reliably.

It is also possible that future findings may make it desirable to use the samples 
acquired in this study for future research, not described in this protocol. Therefore, 
all subjects in countries where this is allowed, will be asked to give a specific 
consent to allow GSK or a contracted partner to use the samples for future research. 
Future research will be subject to the laws and regulations in the respective countries 
and will only be performed once an independent Ethics Committee or Review Board 
has approved this research.
Information on further investigations and their rationale can be obtained from GSK 
Biologicals.
Any sample testing will be done in line with the consent of the individual subject’s 
parent(s)/LAR(s).
Refer also to the Investigator Agreement, where it is noted that the investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s). 
If additional testing is performed, the marker priority ranking given in Section 6.7.4 may 
be changed.
Collected samples will be stored for a maximum of 20 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed 
and agreed with GSK Biologicals.
6.7.1.
Use of specified study materials
When materials are provided by GSK Biologicals, it is MANDATORY that all clinical 
samples (including serum samples) be collected and stored exclusively using those 
materials in the appropriate manner. The use of other materials could result in the 
exclusion of the subject from the ATP analysis (See Section 11.5 for the definition of 
cohorts to be analyzed). The investigator must ensure that his/her personnel and the 
 
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laboratory(ies) under his/her supervision comply with this requirement. However, when 
GSK Biologicals does not provide material for collecting and storing clinical samples, 
appropriate materials from the investigator’s site must be used. Refer to the Module on 
Clinical Trial Supplies in the SPM.
6.7.2.
Biological samples
Table 7
Biological samples (Amended 10 December 2017)
Sample Timepoint
Type of sample†
Subject
Number of 
subjects§
Quantity
Blood Screening
Blood sample for RSV serostatus
All infants
96
1.0 mL
Blood sample for hematology
All infants
96
1.2 mL
Blood sample for biochemistry
All infants
96
1.1 mL
Blood sample for cell-mediated immunogenicity 
response 
All infants††
or96
††, ¥
2.0 mL
Blood sample for humoral response 
All infants
96¥
2.5 mL
Total volume of blood collected for each subject††
7.8 mL
Visit 2 (Day 
1)
Blood sample for hematology
All infants
96
1.2 mL
Total volume of blood collected for each subject
1.2 mL
Visit 4 (Day 
7)
Blood sample for hematology
All infants‡
96‡
1.2 mL
Total volume of blood collected for each subject‡
1.2 mL
Visit 5 (Day 
30)
Blood sample for hematology
All infants
96
1.2 mL
Blood sample for biochemistry
All infants
96
1.1 mL
Blood sample for cell-mediated immunogenicity 
response
All infants††
96††
2.0 mL
Blood sample for humoral response
All infants
96
2.5 mL
Total volume of blood collected for each subject††
6.8 mL
Visit 6 (Day 
31)
Blood sample for hematology
All infants
96
1.2 mL
Total volume of blood collected for each subject
1.2 mL
Visit 8 (Day 
37)
Blood sample for hematology
All infants‡
96‡
1.2 mL
Total volume of blood collected for each subject‡
1.2 mL
Visit 9 (Day 
60)
Blood sample for hematology
All infants
96
1.2 mL
Blood sample for biochemistry
All infants
96
1.1 mL
Blood sample for cell-mediated immunogenicity 
response
All infants††
96††
2.0 mL
Blood sample for humoral response
All infants
96
2.5 mL
Total volume of blood collected for each subject††
6.8 mL
Total volume of blood collected for each subject††,‡ from Screening to Visit 9 (Day 60)*
26.2 mL
Visit 10 (Day 
365)
Blood sample for cell-mediated immunogenicity 
response
All infants††
96††
2.0 mL
Blood sample for humoral response
All infants
96
2.5 mL
Total volume of blood collected for each subject††
4.5 mL
Assessment 
of potential 
RSV-RTI
Blood sample for assessment of mechanism of illness 
(potential ERD)
Hospitalization 
for RSV-LRTI
Hospitalization 
for RSV-LRTI
2.5 mL
Unscheduled 
visit for safety
Blood sample for hematology
Event-driven
Event-driven
1.2 mL
Blood sample for biochemistry
Event-driven
Event-driven
1.1 mL
Total volume of blood collected for each subject††,‡ from Screening to Visit 11 (Day 730)*
30.7 mL
 
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Sample Timepoint
Type of sample†
Subject
Number of 
subjects§
Quantity
Nasal 
swab
Assessment 
of potential 
RSV-RTI
Nasal swab**
Event-driven
Event-driven
-
Surveillance 
for 
asymptomatic 
RSV-RTI
Nasal swab***
All infants
96
-
§ The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the time of first 
vaccination (unless the dose escalation IDMC decision can be made based on the evaluation of accumulating 
safety data on fewer subjects) to ensure that at least 64 infants receive two doses of study vaccine (ChAd155-
RSV or Placebo) (see Section 5.1) (Amended 10 December 2017).
* Total quantity of blood for each subject excludes any unscheduled hematology and biochemistry blood sampling or 
blood sample for assessment of mechanism of illness collected if a subject has been hospitalized for RSV-LRTI.
** If during passive or active surveillance contact, the investigator/study staff assesses that an infant presents a 
potential RSV-RTI (refer to Table 4 for definition), the potential RSV infection will be assessed by quantitative RT-PCR 
of nasal swab specimens taken at an assessment visit.
*** During RSV season, there will be monthly nasal swabs to detect asymptomatic RSV infections. These swabs will be 
tested by quantitative RT-PCR at sponsor laboratory.
These assays will be performed only on enrolled infants.
¥ Blood samples for CMI and for humoral immunogenicity may be postponed until after the RSV serostatus is known 
and eligibility is confirmed up to or on Day 0 (but before vaccination).
† The priority ranking in blood sampling is hematology > biochemistry > humoral response > CMI response. 
Venipuncture will not be repeated for CMI and humoral response in case of insufficient volume, at any timepoint.
†† In investigational sites with a laboratory in proximity capable to perform WBS necessary for the CMI assay.
‡ Day 7 hematology testing will be performed if any ≥ Grade 1 for platelet decrease is detected on Day 1 after 
vaccination. Similarly, hematology testing on Day 37 will be performed if any ≥ Grade 1 for platelet decrease is 
detected on Day 31.
6.7.3.
Laboratory assays
Please refer to Appendix A for a detailed description of the assays performed in the 
study. Please refer to Appendix B for the address of the clinical laboratories planned to be 
used for sample analysis.
The following laboratory assays are planned:

Frequency of interleukin 2, 13, and 17 (IL-2, IL-13 and IL-17), cluster of 
differentiation 40 ligand (CD40L), 41BB, tumor necrosis factor alpha (TNF-), and 
IFN-secreting CD3+/CD4+ and CD3+/CD8+ T-cells will be determined by ICS 
assay on whole blood samples (Table 8).

Serostatus to RSV F and/or G protein will be determined at screening by ELISA 
commercial kit on serum sample, according to the manufacturer instructions (Table 
9).

Functional (neutralizing) antibody titers against RSV-A will be measured by a 
neutralization assay on serum samples (Table 9).

RSV F protein antibody concentrations and palivizumab-competing antibody 
concentrations will be determined by in-house ELISA on serum sample (Table 9).
 
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
RTI will be assessed by:

Quantitative RT-PCR that is able to discriminate RSV-A and RSV-B subtypes
(Table 10).

Qualitative multiplex PCR for detection of a panel of viruses (Table 10).

Local RSV assay and local RVP where available (Table 10).
These assays will be performed at the investigator’s laboratory, at GSK Biologicals’ 
laboratory or at laboratory designated by GSK Biologicals using standardized and 
validated procedures.
Table 8
Cell-Mediated Immunity (CMI)
System
Component
Challenge
Method
Unit
Laboratory
Whole 
blood
IL-2, CD40L, 41BB, 
TNF-, IFN-, IL-13, IL-
17 secreting 
CD3+/CD4+ and 
CD3+/CD8+ T-cells
Peptide pools covering 
the proteins F, N & M2-1
ICS
Events/10E6 cells
GSK Biologicals1 or 
designated laboratory
CD40L: cluster of differentiation 40 ligand; ICS: Intracellular staining; IFN-: interferon gamma, IL (IL-2; IL-13; IL-17): 
interleukin; TNF-: tumor necrosis factor alpha
1 GSK Biologicals laboratory refers to the clinical laboratory sciences (CLS) in Rixensart, Belgium; Wavre, Belgium.
Table 9
Humoral Immunity (Antibody determination)
System
Component
Method
Kit / 
Manufacturer
Unit
Cut-off
Laboratory
SERUM
Respiratory 
Syncytial virus 
Ab.IgG (RSV F 
or G antibody)
ELISA
IBL 
International
Qualitative assay 
(positive/negative)
Qualitative assay 
(positive/negative)
Q2 Solutions
SERUM Respiratory 
Syncytial Virus 
A Ab
NEUTRALIZATION 
In-house
ED60
To be defined
GSK Biologicals1 or 
NÉOMED-LABS
SERUM Respiratory 
Syncytial Virus 
F protein 
Ab.IgG
(Anti-RSV 
PreF antibody)
ELISA 
In-house
EU/ml
To be defined
GSK Biologicals1 or 
NÉOMED-LABS
SERUM Respiratory 
Syncytial Virus 
F protein 
Ab.IgG
(Palivizumab 
competing Ab) 
ELISA 
In-house
µg/ml
To be defined
GSK Biologicals1 or 
NÉOMED-LABS
Ab: antibody; ELISA: enzyme-linked immunosorbent assay; IgG: immunoglobulin G; RSV: respiratory syncytial virus
1 GSK Biologicals laboratory refers to the CLS in Rixensart, Belgium; Wavre, Belgium.
 
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Table 10
Molecular Biology (PCR tests)
System
Component
Kit / Manufacturer
Method
Unit
Laboratory
Nasal 
swab
RSV A RNA
RSV B RNA
In-house
Quantitative
RT-PCR 
Copies/ml
GSK Biologicals1
or designated 
laboratory
Nasal 
swab
Influenza A virus (Flu A)
Influenza B virus (Flu B)
Human respiratory syncytial virus A 
(RSV A)
Human respiratory syncytial virus B 
(RSV B)
Human Influenza A virus subtype H1 
(Flu A-H1)
Human Influenza A virus subtype H3 
(Flu A-H3)
Human Influenza A virus subtype 
H1pdm09 (Flu A-H1pdm09)
Human adenovirus (AdV)
Human metapneumovirus (MPV)
Human enterovirus (HEV)
Human parainfluenza virus 1 (PIV1)
Human parainfluenza virus 2 (PIV2)
Human parainfluenza virus 3 (PIV3)
Human parainfluenza virus 4 (PIV4)
Human bocavirus 1/2/3/4 (HBoV)
Human rhinovirus A/B/C (HRV)
Human coronavirus 229E (229E)
Human coronavirus NL63 (NL63)
Human coronavirus OC43 (OC43) 2
Allplex Respiratory 
Panel or equivalent 2
Multiplex 
PCR
Qualitative 
assay 
(positive/
negative)
GSK Biologicals1
or designated 
laboratory
Other 
specimen
RSV
Not applicable
Locally 
available 
RSV assay
Not 
applicable
Routine local 
laboratory
Other 
specimen
RVP
Not applicable
Locally 
available 
RVP assay
Not 
applicable
Routine local 
laboratory
PCR: polymerase chain reaction; RSV: respiratory syncytial virus; RT: Reverse Transcription; RVP: respiratory viral 
panel
1 GSK Biologicals laboratory refers to the CLS in Rixensart, Belgium; Wavre, Belgium.
2 The list of components might be subject to change in case equivalent kit is used for multiplex RVP testing.
Additional testing on serum and blood samples to characterize the immune response to 
RSV or to the investigational ChAd155-RSV vaccine may be performed if deemed 
necessary for accurate interpretation of the data and/or should such test(s) become 
available in the GSK Biologicals laboratory or a laboratory designated by GSK 
Biologicals.
Additional viral diagnosis testing on the nasal swabs, such as (but not limited to) 
multiplex PCR and/or high-throughput sequencing, may be done, if deemed necessary, 
provided specific assays become available at GSK Biologicals’ laboratory or a laboratory 
designated by GSK Biologicals.
 
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Additional testing may include, but is not limited to, the following:

Anti-vector immunity: neutralization.
For subjects hospitalized for LRTI and RSV-positive using a locally available RSV test 
(refer to Section 9.2.5), an additional blood sample will be collected. The corresponding 
serum sample will be stored at GSK Biologicals laboratory to further characterize the 
mechanisms of illness (potential ERD), if deemed necessary. In this event, the serum 
samples could be tested by RSV neutralization assay and also by ELISA (or alternative 
method) for measurement of protein F antibodies and cytokines.
Hematology and biochemistry assessments will be performed in the investigator’s 
laboratory as per local practice using standardized and validated procedures (Table 11).
Table 11
Hematology and biochemistry tests (Amended 10 December 2017)
System
Discipline
Component
Timepoint
Method
Scale
Laboratory
Whole blood Hematology
Hemoglobin
Screening, Day 1, 
Day 7*, Day 30, 
Day 31, Day 37*, 
Day 60
As per local 
practice
Quantitative
Local 
laboratory
Leukocytes (White Blood 
Cells)**
Platelets
Serum
Biochemistry
Alanine Aminotransferase
Screening, Day 
30, Day 60
As per local 
practice
Quantitative
Aspartate Aminotransferase
Creatinine
* Day 7 hematology testing will be performed if any ≥ Grade 1 for platelet decrease is detected on Day 1 after 
vaccination. Similarly, hematology testing on Day 37 will be performed if any ≥ Grade 1 for platelet decrease is 
detected on Day 31.
** White Blood Cell differential including absolute neutrophil and lymphocyte counts must be recorded in the 
eCRF. (Amended 10 December 2017)
Additional hematology and/or biochemistry testing may be performed or required in
specific circumstances. Refer to Figure 2 for a schematic overview.
Collected samples may be used for purposes related to the quality assurance of the 
laboratory tests described in this protocol. This may include the management of the 
quality of these current tests, the maintenance or improvement of these current tests, the 
development of new test methods for the markers described in this protocol, as well as 
making sure that new tests are comparable to previous methods and work reliably.
The GSK Biologicals’ clinical laboratories have established a Quality System supported 
by procedures. The activities of GSK Biologicals’ clinical laboratories are audited 
regularly for quality assessment by an internal (sponsor-dependent) but laboratory-
independent Quality Department.
 
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6.7.4.
Biological samples evaluation
6.7.4.1.
Immunological read-outs
Table 12
Immunological read-outs (Amended 10 December 2017)
Blood sampling timepoint
No. 
subjects†
Component
Components 
priority rank
Type of contact 
and timepoint*
Sampling timepoint
System
Screening (Day -
29 to Day 0)
Pre-Vaccination
Whole blood
96‡,¥
IL-2, CD40L, 41BB, TNF-, IFN-, 
IL-13, IL-17 secreting T-cells
1
Serum
96
Respiratory Syncytial virus Ab.IgG
(RSV F or G antibody)
1
96¥
Anti-RSV A Neutralizing Antibody
2
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody ) 
3
Respiratory Syncytial Virus F protein 
Ab.IgG (Palivizumab competing Ab) 
4
Visit 5 (Day 30)
Post-Vaccination 1
Whole blood
96‡
IL-2, CD40L, 41BB, TNF-, IFN-, 
IL-13, IL-17 secreting T-cells
1
Serum
~96
Anti-RSV A Neutralizing Antibody
1
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody )
2
Respiratory Syncytial Virus F protein 
Ab.IgG (Palivizumab competing Ab) 
3
Visit 9 (Day 60)
Post-Vaccination 2
Whole blood
96‡
IL-2, CD40L, 41BB, TNF-, IFN-, 
IL-13, IL-17 secreting T-cells
1
Serum
~96
Anti-RSV A Neutralizing Antibody
1
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody ) 
2
Respiratory Syncytial Virus F protein 
Ab.IgG (Palivizumab competing Ab) 
3
Visit 10 (Day 365)
Post-Vaccination 2
Whole blood
96‡
IL-2, CD40L, 41BB, TNF-, IFN-, 
IL-13, IL-17 secreting T-cells
1
Serum
~96
Anti-RSV A Neutralizing Antibody
1
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody ) 
2
CD40L: cluster of differentiation 40 ligand; IFN-: interferon gamma; IgG: immunoglobulin G; IL (IL-2; IL-13; IL-17): 
interleukin; TNF-: tumor necrosis factor alpha; RSV: respiratory syncytial virus.
* Blood samples for CMI taken on Day 7 and Day 37 for subjects enrolled under protocol amendment 1 will still be 
assessed for CMI.
† The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the time of first 
vaccination (unless the dose escalation IDMC decision can be made based on the evaluation of accumulating 
safety data on fewer subjects) to ensure that at least 64 infants receive two doses of study vaccine (ChAd155-
RSV or Placebo) (see Section 5.1) (Amended 10 December 2017).
‡Only in investigational sites with a laboratory in proximity capable to perform WBS necessary for the CMI assay.
¥ Blood samples for CMI and for humoral immunogenicity may be postponed until after the RSV serostatus is known 
and eligibility is confirmed up to or on Day 0(but before vaccination).
In case of insufficient blood sample volume to perform assays for all antibodies, the 
samples will be analyzed according to priority ranking provided in Table 12.
 
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Table 13
Molecular biology for nasal swab and specimen analysis (Amended 
10 December 2017)
Blood sampling timepoint
No. 
subjects†
Component
Components 
priority rank
Type of contact 
and timepoint
Sampling 
timepoint
System
Surveillance for 
asymptomatic 
RSV-RTI
Monthly contact 
during the RSV 
season
Nasal 
swab
~96
Quantitative RT-PCR
(RSV A RNA and RSV B RNA)
Not 
applicable
Assessment of 
potential RSV-
RTI
All subjects 
attending 
assessment visit
Nasal 
swab
Event-
driven
Quantitative RT-PCR
(RSV A RNA and RSV B RNA)
Not 
applicable
Assessment of 
potential RSV-
RTI
All subjects 
attending 
assessment visit 
with positive 
Quantitative RSV 
A/B RT-PCR 
results
Nasal 
swab
Event-
driven
Qualitative multiplex PCR** (Influenza A virus 
(Flu A)
Influenza B virus (Flu B)
Human respiratory syncytial virus A (RSV A)
Human respiratory syncytial virus B (RSV B)
Human Influenza A virus subtype H1 (Flu A-H1)
Human Influenza A virus subtype H3 (Flu A-H3)
Human Influenza A virus subtype H1pdm09 
(Flu A-H1pdm09)
Human adenovirus (AdV)
Human metapneumovirus (MPV)
Human enterovirus (HEV)
Human parainfluenza virus 1 (PIV1)
Human parainfluenza virus 2 (PIV2)
Human parainfluenza virus 3 (PIV3)
Human parainfluenza virus 4 (PIV4)
Human bocavirus 1/2/3/4 (HBoV)
Human rhinovirus A/B/C (HRV)
Human coronavirus 229E (229E)
Human coronavirus NL63 (NL63)
Human coronavirus OC43 (OC43))
Not 
applicable
Assessment of 
potential RSV-
RTI
All subjects 
presenting 
confirmed LRTI* 
(with negative 
Quantitative RSV 
A and B RT-PCR 
results)
Nasal 
swab
Event-
driven
Qualitative multiplex PCR** (Influenza A virus 
(Flu A)
Influenza B virus (Flu B)
Human respiratory syncytial virus A (RSV A)
Human respiratory syncytial virus B (RSV B)
Human Influenza A virus subtype H1 (Flu A-H1)
Human Influenza A virus subtype H3 (Flu A-H3)
Human Influenza A virus subtype H1pdm09 
(Flu A-H1pdm09)
Human adenovirus (AdV)
Human metapneumovirus (MPV)
Human enterovirus (HEV)
Human parainfluenza virus 1 (PIV1)
Human parainfluenza virus 2 (PIV2)
Human parainfluenza virus 3 (PIV3)
Human parainfluenza virus 4 (PIV4)
Human bocavirus 1/2/3/4 (HBoV)
Human rhinovirus A/B/C (HRV)
Human coronavirus 229E (229E)
Human coronavirus NL63 (NL63)
Human coronavirus OC43 (OC43))
Not 
applicable
 
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Blood sampling timepoint
No. 
subjects†
Component
Components 
priority rank
Type of contact 
and timepoint
Sampling 
timepoint
System
Assessment of 
potential RSV-
RTI
All subjects 
attending 
assessment visit
Other 
specimen
Event-
driven
Locally available RSV assay
Not 
applicable
Assessment of 
potential RSV-
RTI
All subjects 
attending 
assessment visit
Other 
specimen
Event-
driven
Locally available RVP assay
Not 
applicable
PCR: polymerase chain reaction; RSV: respiratory syncytial virus; RTI: respiratory tract infection; RVP: respiratory viral 
panel.
† The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the time of first 
vaccination (unless the dose escalation IDMC decision can be made based on the evaluation of accumulating 
safety data on fewer subjects) to ensure that at least 64 infants receive two doses of study vaccine (ChAd155-
RSV or Placebo) (see Section 5.1) (Amended 10 December 2017).
* Refer to Table 4 for the case definitions.
** The list of components might be subject to change in case equivalent kit is used for multiplex RVP testing.
6.7.5.
Immunological correlates of protection
No generally accepted immunological correlate of protection has been established so far 
for the antigens used in the candidate ChAd155-RSV vaccine.
7.
STUDY VACCINES AND ADMINISTRATION
7.1.
Description of study vaccines
The investigational ChAd155-RSV vaccine has been developed and manufactured by 
GSK Biologicals.
The Quality Control Standards and Requirements for the candidate vaccine are described 
in separate Quality Assurance documents (e.g. release protocols, certificate of analysis) 
and the required approvals have been obtained. 
The vaccines are labeled and packed according to applicable regulatory requirements.
 
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Table 14
Study vaccines
Treatment name
Vaccine name
Formulation
Presentation
Volume to be 
administered
Number of 
doses
ChAd155 5x109 vp
ChAd155-RSV
ChAd155-RSV=1*10¹⁰vp/mL
Liquid in 
monodose vial
0.5 ml
2
ChAd155 1.5x1010 vp ChAd155-RSV
ChAd155-RSV=1*10¹¹vp/mL
Liquid in 
monodose vial
0.15 ml
2
ChAd155 5x1010 vp
ChAd155-RSV
ChAd155-RSV=1*10¹¹vp/mL
Liquid in 
monodose vial
0.5 ml
2
Placebo 0.5
Formulation 
buffer S9b
Na₂HPO₄=1.3mg; 
KH₂PO₄=186µg; NaCl=3.85mg; 
KCl=100µg; MgCl₂=50µg *
Clear liquid
0.5 ml
2
Placebo 0.15
Formulation 
buffer S9b
Na₂HPO₄=0.4mg; 
KH₂PO₄=56µg; NaCl=1,16mg; 
KCl=30µg; MgCl₂=15µg *
Clear liquid
0.15 ml
2
* Same concentration of buffer S9b is used for Placebo 0.5 and Placebo 0.15. Values indicated here are the quantities 
contained in the volume to be administered.
7.2.
Storage and handling of study vaccines
The study vaccine must be stored at the respective label storage temperature conditions in 
a safe and locked place. Access to the storage space should be limited to authorized study 
personnel. The storage conditions will be assessed during pre-study activities under the 
responsibility of the sponsor study contact. The storage temperature should be 
continuously monitored with calibrated (if not validated) temperature monitoring 
device(s) and recorded. Refer to the Module on Clinical Trial Supplies in the SPM for 
more details on storage of the study vaccines.
Temperature excursions must be reported in degree Celsius.
For the placebo any temperature excursion outside the range of 0.0 to +8.0C (for +2 to 
+8°C/+36 to +46°F label storage condition) and for the ChAd155-RSV vaccine any 
temperature excursion above -60°C (for -60°C/-76°F label storage condition) or 
below -90°C must be reported in the appropriate (electronic) temperature excursion 
decision form ([e]TDF). The impacted IMPs must not be used and must be stored in 
quarantine at label temperature conditions until usage approval has been obtained from 
the sponsor.
Refer to the Module on Clinical Trial Supplies in the SPM for details and instructions on 
the temperature excursion reporting and usage decision process, packaging and 
accountability of the study vaccines.
 
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7.3.
Dosage and administration of study vaccines
Table 15
Dosage and administration
Type of contact 
and timepoint
Volume to be 
administered Study group
Treatment name
Route1
Site
Side3
Visit 1 (Day 0)
Visit 5 (Day 30)
0.5 ml
RSV-Ld
ChAd155 5x109 vp
IM
Deltoid2
Left
0.5 ml
Placebo-Ld
Placebo 0.5
IM
Deltoid2
Left
0.15 ml
RSV-Md
ChAd155 1.5x1010 vp
IM
Deltoid2
Left
0.15 ml
Placebo-Md
Placebo 0.15
IM
Deltoid2
Left
0.5 ml
RSV-Hd
ChAd155 5x1010 vp
IM
Deltoid2
Left
0.5 ml
Placebo-Hd
Placebo 0.5
IM
Deltoid2
Left
1 IM: Intramuscular.
2 If the muscle size is adequate; otherwise injections might be done in the anterolateral thigh. The site of administration 
of Dose 2 should preferably remain the same as the site of administration of Dose 1.
3 Preferable side for administration.
RSV-Ld: low dose ChAd155-RSV vaccine (5 x 109 vp); RSV-Md: middle dose ChAd155-RSV vaccine (1.5 x 1010 vp); 
RSV-Hd: high dose ChAd155-RSV vaccine (5 x 1010 vp).
Note that ChAd155-RSV vaccine middle dose will be given as a 0.15-mL fractional dose 
of the high dose (0.5 mL). Refer to the SPM for detailed instructions on study vaccine 
administration.
Minimizing environmental contamination with genetically modified organisms
Each product will be used in accordance with the applicable genetically modified 
organism regulations.
To minimize release of the recombinant vectored vaccine virus into the environment, 
each vaccine is produced under good manufacturing practice conditions with the handling 
of live material in appropriate laboratory facilities. This is to ensure that any release of 
modified organism is contained, inactivated and incinerated, using single use equipment 
as much as possible, to avoid release of modified genetic material into the environment.
After each vaccination, the injection site will be covered with a dressing in order to 
absorb any virus that may leak out through the needle track. The dressing will be 
removed only after 30 minutes and will be disposed as genetically modified organism 
waste by autoclaving or in accordance with the applicable guidelines/SOPs at the 
investigator’s site.
7.4.
Replacement of unusable vaccine doses
In addition to the vaccine doses provided for the planned number of subjects (including 
over-randomization when applicable), at least 10% additional vaccine doses will be 
supplied to replace those that are unusable.
The investigator will use SBIR to obtain the replacement vial number. The replacement 
numbers will be allocated by dose. The system will ensure, in a blinded manner, that the 
replacement vial matches the formulation the subject was assigned to by randomization.
 
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7.5.
Contraindications to subsequent vaccination
The following events constitute absolute contraindications to further administration of 
ChAd155-RSV vaccine. If any of these events occur during the study, the subject must 
not receive additional doses of vaccine but may continue other study procedures at the 
discretion of the investigator (see Section 9.5).

Anaphylaxis following the administration of vaccine.

Any confirmed or suspected immunosuppressive or immunodeficient condition, 
including HIV infection.

Any condition that in the judgment of the investigator would make IM injection 
unsafe.

Current autoimmune disease.

Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal 
functional abnormality, as determined by physical examination or laboratory tests.

Failure to thrive.
The following events constitute contraindications to administration of ChAd155-RSV 
vaccine at that point in time; if any of these events occur at the time scheduled for 
vaccination, the subject may be vaccinated at a later date, within the time window 
specified in the protocol (see Section 6.5), or the subject may be withdrawn at the 
discretion of the investigator (see Section 9.5).

Acute disease and/or fever at the time of vaccination. 

Fever is defined as temperature 37.5°C/99.5°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 will be axillary.

Subjects with a minor illness (such as mild diarrhea, mild upper respiratory tract 
infections) without fever can be administered all vaccines.

Any Grade 1 abnormality with potential clinical relevance or any Grade 2 
abnormality in hematological parameters detected in the Day 7 blood sample (refer 
to Section 6.6.11.2, Figure 2 and Appendix C).
7.6.
Concomitant medications/products and concomitant 
vaccinations
At each study visit, the investigator should question the subject’s parent(s)/LAR(s) about 
any medications/products taken and vaccinations received by the subject.
 
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7.6.1.
Recording of concomitant medications/products and 
concomitant vaccinations
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in 
the eCRF.

All concomitant medications/products, except vitamins and dietary supplements, 
administered in the 30 day follow-up period after the administration of each dose of 
study vaccines (Day 0 to Day 29).

Any concomitant vaccination administered in the period starting 30 days before the 
first dose of study vaccines and ending at the last study visit (Day -29 to Day 730).

Prophylactic medication (i.e. medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination or blood sampling).

E.g. an anti-pyretic is considered to be prophylactic when it is given in the 
absence of fever and any other symptom, to prevent fever from occurring [fever 
is defined as temperature 37.5°C/99.5°F for oral, axillary or tympanic route, or 
38.0°C/100.4°F for rectal route].

E.g. a topical local anesthetic used prior to a blood sampling is considered to be 
prophylactic.

Any concomitant medications/products/vaccines listed in Section 7.6.2.

Any concomitant medications/products/vaccines relevant to a SAE to be reported as 
per protocol or administered at any time during the study period for the treatment of 
a SAE. In addition, concomitant medications relevant to SAEs need to be recorded 
on the expedited Adverse Event report.

Any antipyretic administered in the period starting 6 hours before vaccination and 
ending 12 hours after vaccination need to be recorded on the specific page of the 
eCRF.
7.6.2.
Concomitant medications/products/vaccines that may lead to the 
elimination of a subject from ATP analyses
The use of the following concomitant medications/products/vaccines will not require 
withdrawal of the subject from the study but may determine a subject’s evaluability in the 
ATP analysis. See Section 11.5 for cohorts to be analyzed.

Any investigational or non-registered product (drug or vaccine) other than the study 
vaccine used during the study period. 

Immunosuppressants or other immune-modifying drugs administered chronically 
(i.e. more than 14 days in total) during the study period. For corticosteroids, this will 
mean prednisone 0.5 mg/kg/day (for pediatric subjects), or equivalent. Inhaled and 
topical steroids are allowed.

Long-acting immune-modifying drugs administered at any time during the study 
period (e.g. infliximab).
 
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
A vaccine not foreseen by the study protocol administered during the period starting
30 days before the first dose and ending 30 days after the last dose of vaccines
administration*, with the exception of:

Scheduled routine pediatric vaccines which may be administered 14 days 
before a dose and 7 days after a dose of study vaccines.

Vaccines needed for urgent individual medical need (e.g. rabies prophylaxis).
* In case an emergency mass vaccination for an unforeseen public health threat (e.g.: 
a pandemic) is organized by the public health authorities, outside the routine 
immunization program, the time period described above can be reduced if necessary 
for that vaccine provided it is licensed and used according to its Summary of Product 
Characteristics or Prescribing Information and according to the local governmental 
recommendations and provided a written approval of the sponsor is obtained.

Immunoglobulins and/or any blood products administered during the study period.
8.
HEALTH ECONOMICS
Not applicable.
9.
SAFETY
The investigator or site staff is/are responsible for the detection, documentation and 
reporting of events meeting the criteria and definition of an AE or SAE as provided in 
this protocol. 
Each subject’s parent(s)/LAR(s) will be instructed to contact the investigator immediately 
should they/the subject manifest any signs or symptoms they perceive as serious.
9.1.
Safety definitions
9.1.1.
Definition of an adverse event
An AE is 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.
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with 
the use of a medicinal product. For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. 
Examples of an AE include:

Significant or unexpected worsening or exacerbation of the condition/indication 
under study.
 
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
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after investigational vaccine(s) administration 
even though they may have been present prior to the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
investigational vaccine(s) or a concurrent medication (overdose per se should not be 
reported as an AE/SAE).

Signs, symptoms temporally associated with vaccine(s) administration.

Significant failure of expected pharmacological or biological action. 
AEs to be recorded as endpoints (solicited AEs) are described in Section 9.1.3. All other 
AEs will be recorded as UNSOLICITED AEs.
Examples of an AE DO NOT include:

Medical or surgical procedures (e.g. endoscopy, appendectomy); the condition that 
leads to the procedure is an AE/SAE.

Situations where an untoward medical occurrence did not occur (e.g. social and/or 
convenience admission to a hospital, admission for routine examination).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 

Pre-existing conditions or signs and/or symptoms present in a subject prior to the 
first study vaccination. These events will be recorded in the medical history section 
of the eCRF.
9.1.2.
Definition of a serious adverse event
A SAE is any untoward medical occurrence that:
a.
Results in death,
b.
Is life-threatening,
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the subject was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, had it been more severe.
c.
Requires hospitalization or prolongation of existing hospitalization,
Note: In general, hospitalization signifies that the subject has been admitted at the 
hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or in an out-patient setting. Complications 
that occur during hospitalization are also considered AEs. If a complication prolongs 
hospitalization or fulfills any other serious criteria, the event will also be considered 
 
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serious. When in doubt as to whether ‘hospitalization’ occurred or was necessary, the 
AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed prior to informed consent signature) that did not worsen from baseline is 
NOT considered an AE.
d.
Results in disability/incapacity
Note: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include experiences 
of relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhea, influenza like illness, and accidental trauma (e.g. sprained ankle) 
which may interfere or prevent everyday life functions but do not constitute a 
substantial disruption.
Medical or scientific judgment should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be considered serious. 
Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalization.
9.1.3.
Solicited adverse events
9.1.3.1.
Solicited local (injection-site) adverse events
The following local (injection-site) AEs will be solicited:
Table 16
Solicited local adverse events
All age groups
Pain at injection site
Redness at injection site
Swelling at injection site
9.1.3.2.
Solicited general adverse events
The following general AEs will be solicited:
Table 17
Solicited general adverse events
Infant
Drowsiness
Fever*
Irritability/Fussiness
Loss of appetite
* Fever is defined as temperature 37.5°C/99.5°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 will be axillary.
 
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Note: Temperature will be recorded in the evening. Should additional temperature 
measurements be performed at other times of day, the highest temperature will be 
recorded in the eCRF.
9.1.4.
Clinical laboratory parameters and other abnormal assessments 
qualifying as adverse events or serious adverse events 
In absence of diagnosis, abnormal laboratory findings (e.g. clinical chemistry, 
hematology, urinalysis) or other abnormal assessments (e.g. physical examination) that 
are judged by the investigator to be clinically significant will be recorded as AE or SAE 
if they meet the definition of an AE or SAE (refer to Sections 9.1.1 and 9.1.2). Clinically 
significant abnormal laboratory findings or other abnormal assessments that are present at 
baseline and significantly worsen following the start of the study will also be reported as 
AEs or SAEs. 
The investigator will exercise his or her medical and scientific judgment in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant.
9.1.5.
Adverse events of specific interest
9.1.5.1.
Spontaneous or excessive bleeding
Any episode of spontaneous or excessive bleeding occurring within 30 days after each 
vaccination should be fully investigated with a full range of hematological tests to 
identify the underlying cause and reported as an AE of specific interest.
9.1.5.2.
RSV-LRTI
All subjects experiencing a LRTI associated with RSV infection should be reported as 
AE of specific interest in an expedited manner for the duration of their participation to 
the study. These will be detected through the surveillance for RSV-RTI (refer to Section 
9.2).
To identify RSV-LRTI for the purpose of AE of specific interest, the diagnosis should be 
based on the investigators’ clinical judgment taking into account the clinical history, the 
examination, relevant medical investigations and locally-available diagnostic test for 
RSV. Of note the case definition presented in Table 4 is based on a limited set of 
symptoms and signs and is designed for protocol specified analyses pooled across sites at 
study conclusion and should not be used for the purpose of reporting RSV-LRTI as an 
AE of specific interest during the trial conduct.
In addition to report these cases as AE of specific interest, the investigator should 
investigate the case according to the procedures for the surveillance of RSV-RTI (refer to 
Section 9.2) and document it in the eCRF. Of note a nasal swab should be taken for 
confirmatory testing of RSV infection by the sponsor.
 
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9.2.
Surveillance for RSV-RTI, difficulty in breathing and 
wheezing episodes
Each subject will be under surveillance for RSV-RTI, difficulty in breathing and 
wheezing episodes from the administration of Dose 1 (Visit 1) and will continue until the 
final visit (Visit 11). Surveillance will be performed via phone or e-mail contacts and 
assessment visits (refer to Figure 3). The passive and active surveillance contacts can also 
be made by/with the person designated by the parent(s)/LAR(s) (e.g. grandparents, 
nanny) as long as the parent(s)/LAR(s) have given approval.
The safety of the infant is paramount and for any reported illness, the 
investigator/study staff should assess the need for any intervention and provide this 
as part of regular healthcare or instruct/advise the parent(s)/LAR(s) where to 
obtain this care.
 
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Figure 3
Decision tree for passive and active surveillance contacts
1 Active contacts will take place weekly during the RSV season and every month outside the RSV season. Passive 
phone contacts from the carers to the investigator will take place when symptoms occur.
2 Refer to the SPM for signs and symptoms to be collected.
3 RSV-A/B quantitative PCR on all specimens.
4 RVP (Multiplex PCR) on all specimens RSV-A/B positive and on all cases of confirmed LRTI according to case
definition presented in Table 4.
5 For example, in the event that the subject requires urgent medical evaluation and care or has travelled to another
location,…
6 In case of worsening of symptoms, optional sample if the previous specimen was RSV-positive.
7 Where reasonably possible.
Active or Passive surveillance 
contact1
Yes
Yes
No
Yes
No
No
Perform Assessment visit within 72 hours
•
Document signs and symptoms2
•
Record SpO2 and RR
•
Take a specimen (for analysis of RSV and 
RVP at a local routine laboratory)
•
Take a nasal swab (for analysis at sponsor 
laboratory)3,4
Perform Assessment visit within 24 hours
•
Document signs and symptoms2
•
Record SpO2 and RR
•
Take a specimen (for analysis of RSV and RVP at a local routine 
laboratory)6
•
Take a nasal swab (for analysis at sponsor laboratory)3,4
•
Give medical advice as appropriate
OR in the event the Assessment visit within 24 hours is not possible5
•
Advise to seek medical care
•
Record clinical details from medical records2
•
Request a specimen (for analysis of RSV and RVP at a local 
routine laboratory)7
•
Take a nasal swab within 72 hours (for analysis at sponsor 
laboratory)3,4
Note: Report all RSV-LRTI as AE of specific interest within 24 
hours (Expedited AE report)
Suspicion of difficulty in 
breathing, wheezing or 
parental concern?
RTI Symptoms
(cough, runny nose, blocked
nose), difficulty in breathing
or wheezing?
Remind to report any worsening 
of symptoms
Remind to report any future 
symptoms
Worsening of 
symptoms or parental 
concern?
 
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9.2.1.
Passive surveillance
All subjects’ parent(s)/LAR(s) will be instructed to contact investigator/study staff in 
case of any new RTI symptoms (cough, runny nose or blocked nose) or in case of any 
new difficulty in breathing or wheezing. They will be also reminded to record the start 
date and the end date of RTI symptoms on the RTI episode card.

If there is any new difficulty in breathing, wheezing or parental concern, the 
investigator/study staff will schedule an assessment visit as soon as possible (refer to 
Section 9.2.4), but no later than 24 hours after the phone contact to ensure prompt 
assessment of the need for medical care.

If there is no suspicion of difficulty in breathing, nor wheezing, nor parental 
concern, but there are any new symptoms of an RTI (cough, runny nose or blocked 
nose), the investigator/study staff will schedule an assessment visit as soon as 
possible (refer to Section 9.2.4), but no later than 72 hours after the phone contact. 
Performing the visit as soon as possible is important to assess the need for medical 
care, to ensure that early symptoms are captured, and also to collect an optimal nasal 
swab for the detection of RSV.

All passive surveillance contacts will be document in the eCRF.

In the event that it is not possible to schedule an assessment visit, which may arise if 
the family have travelled, then the assessment visit page of the eCRF should be filled 
in as completely as possible using available medical records.
9.2.2.
Surveillance for asymptomatic RSV-RTI

In order to detect asymptomatic RSV-RTI, monthly nasal swabs for analysis at 
sponsor laboratory will be performed for all subjects during the RSV season. This 
nasal swab will be tested by quantitative PCR.

These nasal swabs may be performed in the subject’s home or the investigators 
clinical facility as appropriate to the circumstances in the judgment of the 
investigator.

All surveillance for asymptomatic RSV-RTI visits will be documented in the eCRF.
9.2.3.
Active surveillance
There will be contact between the investigator/study staff and subject’s parent(s)/LAR(s) 
on a regular basis (weekly during the RSV season and every month outside the RSV 
season). If there has not been a contact through a clinic visit/home visit/phone call (i.e. 
Visits 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11), a passive surveillance contact (refer to Section 
9.2.1), an assessment visit (refer to Section 9.2.4) or a surveillance for asymptomatic 
RSV infection (refer to Section 9.2.2), then the investigator/study staff will contact the 
subject’s parent(s)/LAR(s). The active surveillance will be performed by phone, mobile 
phone or e-mail. During each active follow-up contact, the investigator/study staff will:
 
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
Confirm with the subjects’ parent(s)/LAR(s), if the subject has developed new RTI 
symptoms (cough, runny nose or blocked nose) and if he/she has developed any 
symptoms of difficulty in breathing or wheezing (during and between contacts).

If there is any new or ongoing difficulty in breathing, wheezing or parental 
concern, the investigator/study staff will schedule an assessment visit as soon as 
possible (refer to Section 9.2.4), but no later than 24 hours after the contact to 
ensure prompt assessment of the need for medical care. The investigator/study 
staff will remind the subjects’ parent(s)/LAR(s) to record the start date and the 
end date of the RTI symptoms on the RTI episode card.

If there is no suspicion of difficulty in breathing, nor wheezing, nor parental 
concern but any new symptoms of an RTI (cough, runny nose or blocked nose) 
are present, the investigator/study staff will schedule an assessment visit as soon 
as possible (refer to Section 9.2.4), but no later than 72 hours after the contact. 
Performing the visit as soon as possible is important to assess the need for 
medical care, to ensure that early symptoms are captured, and also to collect a 
nasal swab for the detection of RSV.

All active surveillance contacts will be document in the eCRF.

In the event that it is not possible to schedule an assessment visit, which may arise if 
the family have travelled, then the assessment visit page of the eCRF should be filled 
in as completely as possible using available medical records.
9.2.4.
Assessment visit
The purpose of the assessment visit is to objectively document signs and symptoms by an 
appropriately qualified person (i.e. medical or nursing), provide medical advice and to 
take a nasal swab for detection of RSV infection.

Assessment visits may take place in the subject’s home, the investigators clinical 
facility or a medical facility as appropriate to the circumstances in the judgment of 
the investigator.

If the reported symptoms are already of a level of severity that urgent care is 
indicated, the parent(s)/LAR(s) should be redirected to the proper location to receive 
this care (e.g. Emergency Room) and an assessment visit could be scheduled to take 
place there at a suitable time.

During the assessment visit, the investigator/study staff will evaluate the clinical 
signs and symptoms of the RTI. Signs and symptoms to be recorded in the eCRF are 
listed in the SPM.

Specimens for testing of RSV and RVP at a local routine laboratory will be collected 
for all the subjects who have symptoms of an RTI.

Nasal swabs for analysis at sponsor laboratory will be collected for all the subjects 
who have symptoms of an RTI. Note: all subjects experiencing an RSV-LRTI must 
be reported as an AE of specific interest in an expedited manner (refer to Section 
9.4).
 
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
Parent(s)/LAR(s) will be instructed to contact the study staff if the severity of the 
already existing symptoms increases or if the subject develops difficulty in breathing 
or wheezing and this may lead to a repeat assessment visit upon the judgment of the 
investigator.

During subsequent surveillance contacts after an assessment visit, the status and 
evolution of the case will be followed until case resolution.

Each assessment visit will be encoded in the eCRF.
9.2.5.
Subject hospitalized for LRTI
Subjects admitted to hospital and treated for an LRTI will be documented fully as SAEs. 
In addition to establish the severity of the illness, the eCRF screen corresponding to the
assessment visit will be completed as fully as possible from medical records. Signs and 
symptoms to be recorded in the eCRF are listed in the SPM. Study staff will collect a 
nasal swab for all the subjects who have been hospitalized with a RTI for analysis at 
sponsor laboratory. All subjects with clinical suspicion of LRTI must be tested for RSV
and RVP using locally available test. Note: all subjects experiencing an RSV-LRTI must 
be reported as an AE of specific interest in an expedited manner (refer to Section 9.4).
Study staff will also collect a blood sample to be stored at sponsor’s laboratory for future 
assessment of mechanism of illness (potential ERD). This will be done only for RSV-
positive subjects using a locally available RSV test.
9.3.
Detecting and recording adverse events, adverse events of 
specific interest and serious adverse events
9.3.1.
Time period for detecting and recording adverse events, adverse 
events of specific interest and serious adverse events
All AEs starting within 30 days following administration of each dose of study vaccine
(Day 0 to Day 29) must be recorded into the appropriate section of the eCRF, irrespective 
of intensity or whether or not they are considered vaccination-related.
The time period for collecting and recording SAEs will begin at the first receipt of study 
vaccine and will end at study conclusion. See Section 9.4 for instructions on reporting of 
SAEs.
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from 
the time of the first receipt of study vaccines.
In addition to the above-mentioned reporting requirements and in order to fulfill
international reporting obligations, SAEs that are related to study participation (i.e. 
protocol-mandated procedures, invasive tests, a change from existing therapy) or are 
related to a concurrent GSK medication/vaccine will be collected and recorded from the 
time the subject consents to participate in the study until she/he is discharged from the 
study.
 
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The time period for collecting AEs of specific interest (RSV-LRTI) will begin at the first 
receipt of study vaccine and will end at study conclusion. The time period for collecting 
AEs of specific interest (spontaneous or excessive bleeding) will begin at the first receipt 
of study vaccine and will end 30 days after the last vaccination. See Section 9.4 for 
instructions on reporting of AEs of specific interest.
An overview of the protocol-required reporting periods for AEs, AEs of specific interest 
and SAEs is given in Table 18.
 
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Table 18
Reporting periods for collecting safety information
Visit
SCR
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
Days
-29 to 0
0
1
3
6
7
29
30
31
33
36
37
59
60
365
730
Solicited local and general AEs
Unsolicited AEs
Clinical examination with special attention given 
to the detection of episodes of spontaneous 
bleeding or easy bruising and evidence of 
bruising or petechiae*
Examination of limb for petechiae induced by 
the tourniquet**
AEs/SAEs leading to withdrawal from the study
AE of specific interest (RSV-LRTI)
AE of specific interest (spontaneous or 
excessive bleeding)
SAEs
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Visit
SCR
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
Days
-29 to 0
0
1
3
6
7
29
30
31
33
36
37
59
60
365
730
SAEs related to study participation (start at 
signature of informed consent form) or concurren
GSK medication/vaccine
SCR: Screening
* Clinical examination with special attention given to the detection of spontaneous bleeding or easy bruising and evidence of bruising or petechiae will be performed by the 
investigator/study staff on Day 1, Day 3, and Day 7 after each vaccination. The visits on Day 3 and Day 33 may be replaced by a phone call by the investigator/study staff to inquire of 
the infants' general health and to solicit reports of a rash, spontaneous bleeding or easy bruising. Subjects’ parent(s)/LAR(s) will be instructed to contact the investigator/study staff if 
their child presents symptoms of spontaneous bleeding or easy bruising or if their child develops a rash in the month following vaccination, in order to detect any thrombocytopenic 
petechiae or purpura.
**On Day 7 and/or Day 37, special attention to detection of petechiae or evidence of petechiae induced by the tourniquet will be given in case hematology testing will be performed on 
that day.
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9.3.2.
Post-Study adverse events and serious adverse events
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting period defined in Table 18. Investigators are not obligated to actively seek AEs 
or SAEs in former study participants. However, if the investigator learns of any SAE at
any time after a subject has been discharged from the study, and he/she considers the 
event reasonably related to the investigational vaccines, the investigator will promptly 
notify the Study Contact for Reporting SAEs.
9.3.3.
Evaluation of adverse events and serious adverse events
9.3.3.1.
Active questioning to detect adverse events and serious adverse 
events
As a consistent method of collecting AEs, the subject’s parent(s)/LAR(s) should be asked 
a non-leading question such as:
‘Has your child acted differently or felt different in any way since receiving the vaccines
or since the last visit?’
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the 
subject’s medical records to GSK Biologicals instead of appropriately completing the 
eCRF. However, there may be instances when copies of medical records for certain cases 
are requested by GSK Biologicals. In this instance, all subject identifiers will be blinded 
on the copies of the medical records prior to submission to GSK Biologicals.
The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms.
 
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9.3.3.2.
Assessment of adverse events
9.3.3.2.1.
Assessment of intensity
The intensity of the following solicited AEs will be assessed as described:
Table 19
Intensity scales for solicited symptoms in infants
Infants
Adverse Event
Intensity grade
Parameter
Pain at injection site
0
None
1
Mild: Minor reaction to touch
2
Moderate: Cries/protests on touch
3
Severe: Cries when limb is moved/spontaneously painful
Redness at injection site
Record greatest surface diameter in mm
Swelling at injection site
Record greatest surface diameter in mm
Fever*
Record temperature in °C/°F
Irritability/Fussiness
0
Behavior as usual
1
Mild: Crying more than usual/no effect on normal activity
2
Moderate: Crying more than usual/interferes with normal 
activity
3
Severe: Crying that cannot be comforted/prevents normal 
activity
Drowsiness
0
Behavior as usual
1
Mild: Drowsiness easily tolerated
2
Moderate: Drowsiness that interferes with normal activity
3
Severe: Drowsiness that prevents normal activity
Loss of appetite
0
Appetite as usual
1
Mild: Eating less than usual/no effect on normal activity
2
Moderate: Eating less than usual/interferes with normal activity
3
Severe: Not eating at all
*Fever is defined as temperature 37.5°C / 99.5°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 will be axillary.
The maximum intensity of local injection site redness and swelling will be scored at GSK 
Biologicals as follows:
0
:
None
1
:
< 5 mm
2
:
5 to 20 mm
3
:
> 20 mm
The maximum intensity of fever will be scored at GSK Biologicals as follows:
0
:
< 37.5°C/99.5°F
1
:
37.5°C/99.5°F to 38.5°C/101.3°F
2
:
> 38.5°C/101.3°F to 39.5°C/103.1°F
3
:
> 39.5°C/103.1°F
 
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The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the investigator’s clinical judgment.
The intensity should be assigned to one of the following categories:
1 (mild)
=
An AE which is easily tolerated by the subject, causing minimal 
discomfort and not interfering with everyday activities.
2 (moderate)
=
An AE which is sufficiently discomforting to interfere with 
normal everyday activities.
3 (severe)
=
An AE which prevents normal, everyday activities. Such an AE 
would, for example, prevent attendance at kindergarten/a day-care 
center and would cause the parent(s)/LAR(s) to seek medical 
advice.
An AE that is assessed as Grade 3 (severe) should not be confused with a SAE. Grade 
3 is a category used for rating the intensity of an event; and both AEs and SAEs can be 
assessed as Grade 3. An event is defined as ‘serious’ when it meets one of the pre-
defined outcomes as described in Section 9.1.2.
9.3.3.2.2.
Assessment of causality
The investigator is obligated to assess the relationship between investigational vaccine
and the occurrence of each AE/SAE. The investigator will use clinical judgment to 
determine the relationship. Alternative plausible causes, such as natural history of the 
underlying diseases, concomitant therapy, other risk factors, and the temporal 
relationship of the event to the investigational vaccines will be considered and 
investigated. The investigator will also consult the IB to determine his/her assessment.
There may be situations when a SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK Biologicals. However, it is very 
important that the investigator always makes an assessment of causality for every event 
prior to submission of the Expedited Adverse Events Report to GSK Biologicals. The 
investigator may change his/her opinion of causality in light of follow-up information and 
update the SAE information accordingly. The causality assessment is one of the criteria 
used when determining regulatory reporting requirements.
In case of concomitant administration of multiple vaccines/products, it may not be 
possible to determine the causal relationship of general AEs to the individual vaccine
administered. The investigator should, therefore, assess whether the AE could be causally 
related to vaccination rather than to the individual vaccines.
 
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All solicited local (injection site) reactions will be considered causally related to 
vaccination. Causality of all other AEs should be assessed by the investigator using the 
following question:
Is there a reasonable possibility that the AE may have been caused by the investigational 
vaccine?
YES
:
There is a reasonable possibility that the vaccine contributed to the 
AE.
NO
:
There is no reasonable possibility that the AE is causally related to 
the administration of the study vaccine. There are other, more 
likely causes and administration of the study vaccine is not 
suspected to have contributed to the AE.
If an event meets the criteria to be determined as ‘serious’ (see Section 9.1.2), additional 
examinations/tests will be performed by the investigator in order to determine ALL 
possible contributing factors for each SAE.
Possible contributing factors include:

Medical history.

Other medication.

Protocol required procedure.

Other procedure not required by the protocol.

Lack of efficacy of the vaccines, if applicable.

Erroneous administration.

Other cause (specify).
9.3.3.3.
Assessment of outcomes
The investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as:

Recovered/resolved.

Recovering/resolving.

Not recovered/not resolved.

Recovered with sequelae/resolved with sequelae.

Fatal (SAEs only).
 
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9.3.3.4.
Medically attended visits
For each solicited and unsolicited symptom the subject experiences, the subject’s 
parent(s)/LAR(s) will be asked if the subject received medical attention defined as 
hospitalization, or an otherwise unscheduled visit to or from medical personnel for any 
reason, including emergency room visits. This information will be recorded in the eCRF.
9.4.
Reporting of serious adverse events and adverse events of 
specific interest
9.4.1.
Prompt reporting of serious adverse events and adverse events 
of specific interest to GSK Biologicals
SAEs that occur in the time period defined in Section 9.3 will be reported promptly to 
GSK within the timeframes described in Table 20, once the investigator determines that 
the event meets the protocol definition of a SAE.
AEs of specific interest (RSV-LRTI and spontaneous or excessive bleeding) that occur in 
the time period defined in Section 9.3 will be reported promptly to GSK within the 
timeframes described in Table 20.
Table 20
Timeframes for submitting serious adverse event and adverse 
events of specific interest reports to GSK Biologicals
Type of Event
Initial Reports
Follow-up of Relevant Information on a 
Previous Report
Timeframe
Documents
Timeframe
Documents
SAEs
24 hours*‡
electronic Expedited 
Adverse Events Report
24 hours*
electronic Expedited Adverse 
Events Report
AEs of specific 
interest
24 hours*‡
electronic Expedited 
Adverse Events Report
24 hours*
electronic Expedited Adverse 
Events Report
* Timeframe allowed after receipt or awareness of the information.
‡ The investigator will be required to confirm review of the SAE/AEs of specific interest causality by ticking the 
‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 hours of submission of the SAE/AEs of 
specific interest.
 
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9.4.2.
Contact information for reporting serious adverse events and 
adverse events of specific interest
Study Contact for Reporting SAEs and AEs of specific interest
Refer to the local study contact information document.
Back-up Study Contact for Reporting SAEs and AEs of specific interest
24/24 hour and 7/7 day availability:
GSK Biologicals Clinical Safety & Pharmacovigilance
Outside US & Canada sites:
Fax: 
 or 
Email address: 
US sites only:
Fax: 
Canadian sites only:
Fax: 
 
9.4.3.
Reporting of adverse events of specific interest (RSV-LRTI and 
spontaneous or excessive bleeding) to GSK Biologicals
Once an Investigator becomes aware that an AE of specific interest (RSV-LRTI and 
spontaneous or excessive bleeding) has occurred in a subject, the Investigator (or 
designate) must complete the information in the electronic Expedited Adverse Events 
Report WITHIN 24 HOURS. The report will always be completed as thoroughly as 
possible with all available details of the event. Even if the Investigator does not have all 
information regarding an AE of specific interest (RSV-LRTI and spontaneous or 
excessive bleeding), the report should still be completed within 24 hours. Once additional 
relevant information is received, the report should be updated WITHIN 24 HOURS.
The Investigator will always provide an assessment of causality at the time of the initial 
report. The Investigator will be required to confirm the review of causality by ticking the 
‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 hours of 
submission of the AE of specific interest.
Refer to Section 9.4.4.1 for the back-up system in case the electronic reporting system 
does not work.
9.4.4.
Completion and transmission of SAE reports to GSK Biologicals
Once an investigator becomes aware that a SAE has occurred in a study subject, the 
investigator (or designate) must complete the information in the electronic Expedited 
Adverse Events Report WITHIN 24 HOURS. The report will always be completed as 
thoroughly as possible with all available details of the event. Even if the investigator does 
not have all information regarding a SAE, the report should still be completed within 24 
hours. Once additional relevant information is received, the report should be updated 
WITHIN 24 HOURS.
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The investigator will always provide an assessment of causality at the time of the initial 
report. The investigator will be required to confirm the review of the SAE causality by 
ticking the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 
hours of submission of the SAE.
9.4.4.1.
Back-up system in case the electronic reporting system does not work
If the electronic reporting system does not work, the investigator (or designate) must 
complete, then date and sign a paper Expedited Adverse Events Report and fax it to the 
Study Contact for Reporting SAEs (refer to the Sponsor Information) or to GSK 
Biologicals Clinical Safety and Pharmacovigilance department within 24 hours. 
This back-up system should only be used if the electronic reporting system is not working 
and NOT if the system is slow. As soon as the electronic reporting system is working 
again, the investigator (or designate) must complete the electronic Expedited Adverse 
Events Report within 24 hours. The final valid information for regulatory reporting will 
be the information reported through the electronic SAE reporting system. 
9.4.5.
Updating of serious adverse event and adverse event of specific 
interest information after removal of write access to the subject’s
eCRF
When additional SAE or AEs of specific interest information is received after removal of 
the write access to the subject’s eCRF, new or updated information should be recorded on 
the appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be faxed to the Study Contact for Reporting SAEs (refer to the 
Sponsor Information) or to GSK Biologicals Clinical Safety and Pharmacovigilance 
department within the designated reporting time frames specified in Table 20.
9.4.6.
Regulatory reporting requirements for serious adverse events
The investigator will promptly report all SAEs to GSK in accordance with the procedures 
detailed in Section 9.4.1. GSK Biologicals has a legal responsibility to promptly notify, 
as appropriate, both the local regulatory authority and other regulatory agencies about the 
safety of a product under clinical investigation. Prompt notification of SAEs by the 
investigator to the Study Contact for Reporting SAEs is essential so that legal obligations 
and ethical responsibilities towards the safety of other subjects are met.
Investigator safety reports are prepared according to the current GSK policy and are 
forwarded to investigators as necessary. An investigator safety report is prepared for a 
SAE(s) that is both attributable to the investigational vaccines and unexpected. The 
purpose of the report is to fulfill specific regulatory and GCP requirements, regarding the 
product under investigation.
 
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9.5.
Follow-up of adverse events, serious adverse events and 
adverse events of specific interest
9.5.1.
Follow-up during the study
After the initial AE, AE of specific interest or SAE report, the investigator is required to 
proactively follow each subject and provide additional relevant information on the 
subject’s condition to GSK Biologicals (within 24 hours for AE of specific interest and 
SAEs; refer to Table 20).
All AE of specific interest (RSV-LRTI) and SAEs documented at a previous visit/contact 
and designated as not recovered/not resolved or recovering/resolving will be reviewed at 
subsequent visits/contacts until the end of the study.
All AE of specific interest (spontaneous or excessive bleeding) documented at a previous 
visit/contact and designated as not recovered/not resolved or recovering/resolving will be 
reviewed at subsequent visits/contacts until 30 days after the last vaccination.
All AEs documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until 30 
days after the last vaccination.
9.5.2.
Follow-up after the subject is discharged from the study
The investigator will follow subjects:

with SAEs, with AEs of specific interest or subjects withdrawn from the study as a 
result of an AE, until the event has resolved, subsided, stabilized, disappeared, or 
until the event is otherwise explained, or the subject is lost to follow-up.
If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to GSK Biologicals using electronic Expedited 
Adverse Events Report.
GSK Biologicals may request that the investigator performs or arranges the conduct of 
additional clinical examinations/tests and/or evaluations to elucidate as fully as possible 
the nature and/or causality of the AE or SAE. The investigator is obliged to assist. If a 
subject dies during participation in the study or during a recognized follow-up period, 
GSK Biologicals will be provided with any available post-mortem findings, including 
histopathology.
9.6.
Treatment of adverse events
Treatment of any AE is at the sole discretion of the investigator and according to current 
good medical practice. Any medication administered for the treatment of an AE should 
be recorded in the subject’s eCRF (refer to Section 7.6).
 
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9.7.
Unblinding
GSK Biologicals’ policy (which incorporates ICH E2A guidance, EU Clinical Trial 
Directive and US Federal Regulations) is to unblind the report of any SAE which is 
unexpected and attributable/suspected to be attributable to the investigational vaccines, 
prior to regulatory reporting. The GSK Biologicals’ Central Safety Physician is 
responsible for unblinding the treatment assignment in accordance with the specified 
timeframes for expedited reporting of SAEs (refer to Section 9.4.1).
9.8.
Emergency unblinding
Unblinding of a subject’s individual treatment code should occur only in the case of a 
medical emergency, or in the event of a serious medical condition, when knowledge of 
the treatment is essential for the clinical management or welfare of the subject, as judged 
by the investigator.
The emergency unblinding process consists of the automated system SBIR that allows the 
investigator to have unrestricted, immediate and direct access to the subject’s individual 
study treatment.
The investigator has the option of contacting a GSK Biologicals’ On-call Central Safety 
Physician (or Backup) if he/she needs medical advice or needs the support of GSK to 
perform the unblinding (i.e. he/she cannot access SBIR).
 
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Any emergency unblinding must be fully documented by using the Emergency 
Unblinding Documentation Form, which must be appropriately completed by the 
investigator and sent within 24 hours to GSK Biologicals.
GSK Biologicals’ Contact information for Emergency Unblinding
24/24 hour and 7/7 day availability
GSK Biologicals’ Central Safety Physician: 
Outside US:
 (GSK Biologicals Central Safety Physician on-call)
For US:
(GSK Biologicals Central Safety Physician on-call)
GSK Biologicals’ Central Safety Physician Back-up:
Outside US:
US only:
Emergency Unblinding Documentation Form transmission:
Outside US:
Fax: 
 or 
US only:
Fax: 
9.9.
Subject card
Study subjects’ parent(s)/LAR(s) must be provided with the address and telephone 
number of the main contact for information about the clinical study.
The investigator (or designate) must therefore provide a “subject card” to each subject’s 
parent(s)/LAR(s). In an emergency situation this card serves to inform the responsible 
attending physician that the subject is in a clinical study and that relevant information 
may be obtained by contacting the investigator.
Subjects’ parent(s)/LAR(s) must be instructed to keep subject cards in their possession at 
all times.
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9.10.
Holding rules and safety monitoring
The investigational ChAd155-RSV vaccine has never been administered to infants. 
Safety precautions such as staggered enrolment, dose-escalation, limited vaccination, 
safety evaluations by an iSRC and an IDMC, and study holding rules have therefore been 
defined.
9.10.1.
Limited vaccination
Limited vaccination in Steps 1, 2 and 3:

During vaccination days, vaccination will be limited to maximum 10 infants per day.
In the same investigational center, all infants should be vaccinated sequentially and at 
least 60 minutes apart to allow monitoring of any acute events (e.g. hypersensitivity 
reaction). All infants should be closely observed (visual follow-up as well as 
measurement of vital signs) for at least 60 minutes after vaccination. Vital signs are body 
temperature, HR, and RR. Vital signs are preferably measured when the infant is calm. In 
addition, to monitor delayed potential reactions following vaccination, there will be a 48-
hour observation period following Dose 1 and Dose 2 administration to the first eight 
infants (corresponding to three to five ChAd155-RSV vaccine recipients) in each Step (1, 
2, and 3) before continuing vaccination of more infants (i.e. from the ninth infant). From 
the ninth infant, infants will be vaccinated sequentially, separated by a minimum interval 
of 60 minutes. Refer to the SPM for more details about the 48-hour observation period 
after the first eight subjects vaccinated in each Step.
9.10.2.
Internal safety review committee (iSRC) oversight
This study will be overseen by an iSRC operating under a charter. Core members of the 
iSRC will include a GSK Biologicals’ safety physician, a CRDL, and a biostatistician 
who are not otherwise involved in the conduct of the project. The iSRC safety reviews 
will be conducted using unblinded data. The iSRC has access to the subject 
randomization and reviews unblinded data.
The iSRC will review all accumulating safety data three weeks after the start of 
vaccination and then about every three weeks (until the IDMC has reviewed all safety 
data up to 30 days after administration of Dose 2 in Step 3 (i.e. Day 60). The iSRC 
members will determine if a safety signal should be escalated to the IDMC. The iSRC 
members will determine whether any of the predefined holding rules are met (refer to 
Section 9.10.5) or if there is any other safety signal. In this case, vaccination in the study 
will be immediately put on hold (refer to Section 9.10.6).
The iSRC will receive the following safety data within 48 hours upon GSK becoming 
aware of:

Fatal SAEs.

Life-threatening SAEs.
 
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
Related SAEs.

SAEs occurring within 30 days of vaccination.

LRTI associated with RSV infection (AE of specific interest) occurring from Day 0 
to Day 730.

Spontaneous or excessive bleeding (AE of specific interest) occurring within 30 days 
after each vaccination.
In addition, the iSRC will receive:

Unblinded summary reports of accumulated solicited AEs, unsolicited AEs, results 
of laboratory monitoring of hematology and biochemistry.

New information that may adversely affect the safety of the subjects or the conduct 
of the study.

All subsequent protocol amendments, informed consent changes or revisions or other 
documents originally submitted for review.

All subsequent protocol administrative changes (for information).
9.10.3.
Independent Data Monitoring Committee (IDMC) oversight
This study will be overseen by an IDMC operating under a charter. Overall, the role of 
the IDMC includes the review and protection of data integrity and rights and safety of 
study participants throughout the study period. It will provide initial, regular, and closing 
advice to GSK Biologicals on medical, ethical, scientific and safety-related issues. Its 
advice will be based on the interpretation of study data with reference to the study 
protocol.
The IDMC will review the protocol and statistical analysis plan. Meetings will be 
documented and minutes of open sessions of the IDMC meetings made available to the 
sponsor. The IDMC may, if deemed necessary, convene a meeting with, or request 
further information from the principal investigators and GSK Biologicals’ designated 
project representatives at any stage of the study.
The IDMC may recommend to the sponsor to suspend the enrolment to the study and/or 
vaccination based on their review of safety data arising in this study (refer to Section 
9.10.6).
The IDMC safety reviews will be conducted using unblinded data. The IDMC will 
review all available safety data while taking into account any other findings that could 
have an impact on the safety of the subjects.
The IDMC members will determine whether any of the predefined study holding rules 
are met (refer to Section 9.10.5) or if there is any other safety signal. If this is the case, 
vaccination in the study will be immediately put on hold. If no safety signal is observed, 
the favorable outcome of the safety evaluation authorizing the investigator to proceed 
with vaccination of infants as outlined in Figure 1, will be also documented and provided 
in writing.
 
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
The IDMC will receive the following safety data within 48 hours upon GSK 
becoming aware of:

Fatal SAEs occurring from Day 0 to Day 730.

Life-threatening SAEs occurring from Day 0 to Day 730.

Related SAEs occurring from Day 0 to Day 730.

SAEs occurring within 30 days of vaccination.

LRTI associated with RSV infection (AE of specific interest) occurring from Day 
0 to Day 730.

Spontaneous or excessive bleeding (AE of specific interest) occurring within 30 
days after each vaccination.

The IDMC will receive the following safety data monthly throughout the period of 
vaccination (up to 30 days after administration of Dose 2 in Step 3, i.e. Day 60):

Summary reports of solicited and unsolicited AEs, SAEs and laboratory toxicity.

The IDMC will receive the following safety data approximately monthly from 
beginning of the first RSV season and the frequency will be adapted based on the 
instruction of the IDMC:

Cumulative reports of the incidence of RSV-RTI, RSV-LRTI, RSV-severe LRTI
and RSV-RTI leading to hospitalization.

Cumulative tables of incidence of all SAEs.
In addition, the IDMC will receive from GSK Biologicals:

New information that may adversely affect the safety of the subjects or the conduct
of the study.

All subsequent protocol amendments, informed consent changes or revisions or other 
documents originally submitted for review.

All subsequent protocol administrative changes (for information).
9.10.4.
Dose-escalation and safety evaluations by iSRC and IDMC
The study will be conducted in a staggered manner to ensure maximum safety of the 
participating infants progressing sequentially through the 3 dose levels (Figure 1):

Step 1: vaccination of a maximum of 32 infants (approximately 16 infants in the 
RSV-Ld group and approximately 16 infants in the placebo-Ld group). An iSRC will 
review all accumulating safety data three weeks after the start of vaccination in Step 
1 and then about every three weeks (until the IDMC has reviewed all safety data up 
to 30 days after administration of Dose 2 in Step 3 (i.e. Day 60). The IDMC will 
review all accumulating reactogenicity and safety data monthly throughout the 
period of vaccination (up to 30 days after administration of Dose 2 in Step 3, i.e. Day 
60). Dose escalation to Step 2 will proceed after completion of vaccination for 32
subjects, and in the absence of a significant safety concern detected by the IDMC in 
 
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the regular monitoring of accumulating safety data. However, in the absence of a 
significant safety concern detected in the regular monitoring of accumulating 
safety data on at least 16 subjects, the IDMC may recommend for dose escalation 
to proceed without the requirement of enrolling and evaluating the full group size 
of 32 subjects. A subsequent dose escalation will proceed after administration of 
two doses of the vaccine to between a maximum of 32 to a minimum of 16 subjects 
in the absence of a significant safety concern detected by the IDMC in the regular 
monitoring of accumulating safety data. It will be ensured that, as a minimum the 
IDMC will have reviewed safety data of at least 16 subjects for two doses (in Step 1) 
and given their formal approval prior to enrolling subjects to the next dose level 
(Step 2). (Amended 10 December 2017)

Step 2: vaccination of a maximum of 32 infants (approximately 16 infants in the 
RSV-Md group and approximately 16 infants in the placebo-Md group). An iSRC 
will review all accumulating safety data three weeks after the start of vaccination in 
Step 2 and then about every three weeks (until the IDMC has reviewed all safety data 
up to 30 days after administration of Dose 2 in Step 3 (i.e. Day 60). The IDMC will 
review accumulating reactogenicity and safety data monthly throughout the period of 
vaccination (up to 30 days after administration of Dose 2 in Step 3, i.e. Day 60). 
Dose escalation to Step 3 will proceed after administration of two doses of the 
vaccine to 32 subjects, and in the absence of a significant safety concern detected by 
the IDMC in the regular monitoring of accumulating safety data. However, as for the 
dose escalation from Step 1 to Step 2, in the absence of a significant safety concern 
detected in the regular monitoring of accumulating safety data on at least 16 
subjects, the IDMC may again allow for dose escalation to proceed without the 
requirement of enrolling and evaluating the full group size of 32 subjects. A 
subsequent dose escalation will proceed after administration of two doses of the 
vaccine to between a maximum of 32 to a minimum of 16 subjects in the absence 
of a significant safety concern detected by the IDMC in the regular monitoring of 
accumulating safety data. It will be ensured that, as a minimum the IDMC will have 
reviewed safety data of at least 16 subjects for two doses (in Step 2) and given their 
formal approval prior to enrolling subjects to the next dose level (Step 3). (Amended 
10 December 2017)

Step 3: vaccination of 32 infants (approximately 16 infants in the RSV-Hd group and 
approximately 16 infants in the placebo-Hd group). An iSRC will review all 
accumulating safety data three weeks after the start of vaccination in Step 3 and then 
about every three weeks (until the IDMC has reviewed all safety data up to 30 days 
after administration of Dose 2 in Step 3 (i.e. Day 60). A review of the entire set of 
safety data from Steps 1, 2 and 3 will be performed by the IDMC after availability of 
safety data up to 30 days after administration of Dose 2 in Step 3 (i.e. Day 60).
Refer to Section 9.10.2 for iSRC oversight and to Section 9.10.3 for IDMC oversight.
9.10.5.
Holding rules
The safety holding rules which will be assessed by the investigator are defined in Table 
21 and the safety holding rules which will be assessed by the iSRC and the IDMC during 
the safety evaluation are defined in Table 22.
 
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Table 21
Holding rules assessed by the investigator
Holding 
Rule
Event
Number of infants/group
Step 1
Step 2
Step 3
1a
Death or any life-threatening serious adverse event (SAE) 
that can be causally related to vaccination, according to 
investigator’s assessment.
≥ 1
≥ 1
≥ 1
1b
Any withdrawal from the study (by investigator or 
parent(s)/LAR(s) of the subject request) following a Grade 3 
AE that cannot reasonably be attributed to a cause other than 
vaccination.
≥ 1
≥ 1
≥ 1
1c
Any local or general solicited AE leading to hospitalization
that cannot reasonably be attributed to a cause other than 
vaccination.
≥ 1
≥ 1
≥ 1
1d
Within 30 days post-vaccination,
Any spontaneous local or general bleeding
AND
Thrombocytopenia < 50000/mm3
≥ 1
≥ 1
≥ 1
If an investigator detects one of the holding rules mentioned above, he/she will 
immediately put the enrolment or the vaccination on hold (refer to Section 9.10.6) and 
he/she will immediately inform the sponsor and enter the data in the eCRF. It is sponsor’s 
responsibility to put the enrolment or the vaccination on hold at all sites.
Table 22
Holding rules during the planned iSRC and IDMC evaluation
Holding 
Rule
Event
Number of infants/group
Step 1
Step 2
Step 3
2a
Any Grade 3 solicited local AE lasting 48 hours or more in an 
investigational RSV vaccine group, within the 7-day (Days 0-
6) post-vaccination period.
≥ 25% & ≥ 2 
infants/group
≥ 25% & ≥ 2 
infants/group
≥ 25% & ≥ 2 
infants/group
2b
Any Grade 3 solicited general AE lasting 48 hours or more in 
an investigational RSV vaccine group, that cannot reasonably 
be attributed to a cause other than vaccination, within the 7-
day (Days 0-6) post-vaccination period.
≥ 25% & ≥ 2 
infants/group
≥ 25% & ≥ 2 
infants/group
≥ 25% & ≥ 2 
infants/group
2c
Any Grade 3 unsolicited AE in an investigational RSV 
vaccine group, that cannot reasonably be attributed to a 
cause other than vaccination, within the 7-day (Days 0-6) 
post-vaccination period
OR
Any ≥ Grade 3 abnormality in pre-specified hematological or 
biochemical laboratory parameters in an investigational RSV 
vaccine group, if it cannot reasonably be attributed to a cause 
other than vaccination, up to the Day 7 post-vaccination visit1
≥ 25% & ≥ 2 
infants/group
≥ 25% & ≥ 2 
infants/group
≥ 25% & ≥ 2 
infants/group
1 Refer to Appendix C.
Of note, no formal holding rules will be applied for other safety data collected. However, 
these data will also be reviewed by the iSRC and the IDMC in order to allow for an 
overall assessment of the benefit/risk ratio of vaccination.
 
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Risk assessment
Figure 4 gives the probability of not meeting holding rule 1-2 for 16 subjects per study 
group in each step.
Figure 4
Evaluations based on 16 subjects - Risk assessment curve for one 
formulation based on the proposed safety holding rules
The above figure illustrates that, with a maximum of 16 subjects per study group
(Amended 10 December 2017):

Each holding rule 1 (a - d) has more than 85% chance of not being met for 
vaccination with a true incidence rate below 1% and has more than 80% chance of 
being met for vaccination with a true incidence rate above 10%.

Each holding rule 2 (a - c) has more than 90% chance of not being met for 
vaccination with a true incidence rate below 10% and more than 60% chance of 
being met for vaccination with a true incidence rate above 25%.
9.10.6.
Procedure if the trial is put on hold
If the trial is put on hold by the investigator, iSRC or IDMC because a pre-defined 
holding rule is met or because of a safety concern, then all enrolment in the study and all 
vaccination will cease immediately, but all other procedures relating to safety,
immunology and disease monitoring will continue. The IDMC will review all available 
safety information and may ask for additional information to be provided by the 
investigators or the sponsor. The IDMC will make a recommendation to the sponsor 
whether the study should be stopped permanently, modified or continued unchanged.
The sponsor will review all data and IDMC recommendation and will decide whether to 
stop permanently, modify or continue the conduct of the study. The decision of the 
Vaccine safety monitoring board (VSMB) regarding the further conduct of the study will 
be documented and provided in writing to the investigators.
 
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10.
SUBJECT COMPLETION AND WITHDRAWAL
10.1.
Subject completion
A subject who returns for the concluding visit foreseen in the protocol is considered to 
have completed the study.
10.2.
Subject withdrawal
Withdrawals will not be replaced.
10.2.1.
Subject withdrawal from the study
From an analysis perspective, a ‘withdrawal’ from the study refers to any subject who did 
not come back for the concluding visit foreseen in the protocol.
All data collected until the date of withdrawal/last contact of the subject will be used for 
the analysis.
A subject is considered a ‘withdrawal’ from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this subject from the date of withdrawal/last contact.
Investigators will make an attempt (e.g. three telephone calls and a certified letter to the 
last known address) to contact those subjects who do not return for scheduled visits or 
follow-up.
Information relative to the withdrawal will be documented in the eCRF. The investigator 
will document whether the decision to withdraw a subject from the study was made by 
the subject’s parent(s)/LAR(s), or by the investigator, as well as which of the following 
possible reasons was responsible for withdrawal:

SAE.

Non-SAE.

Protocol violation (specify).

Consent withdrawal, not due to an AE*.

Moved from the study area.

Lost to follow-up.

Other (specify).
*In case a subject is withdrawn from the study because the subject’s parent(s)/LAR(s)
has withdrawn consent, the investigator will document the reason for withdrawal of 
consent, if specified by the subject’s parent(s)/LAR(s), in the eCRF.
 
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Subjects who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from subjects who are withdrawn for other reasons. Investigators will 
follow subjects who are withdrawn from the study as result of a SAE/AE until resolution 
of the event (see Section 9.5.2).
10.2.2.
Subject withdrawal from investigational vaccine
A ‘withdrawal’ from the investigational vaccine refers to any subject who does not 
receive the complete treatment, i.e. when no further planned dose is administered from 
the date of withdrawal. A subject withdrawn from the investigational vaccine may not 
necessarily be withdrawn from the study as further study procedures or follow-up may be 
performed (safety or immunogenicity) if planned in the study protocol. The investigator 
should make all efforts to ensure that the subjects remain in the study to ensure a proper 
safety follow-up and medical care if needed.
Information relative to premature discontinuation of the investigational vaccine will be 
documented on the Vaccine Administration screen of the eCRF. The investigator will 
document whether the decision to discontinue further vaccination was made by the 
subject’s parent(s)/LAR(s), or by the investigator, as well as which of the following 
possible reasons was responsible for withdrawal:

SAE.

Non-SAE.

Other (specify).
10.3.
Extension study
At the end of the study (study conclusion visit), the investigator will ask each subject’s 
parent(s)/LAR(s) if they are interested to allow the subject to participate in a booster 
study/long-term study. If subject’s parent(s)/LAR(s) are not interested in participating in 
the booster study/long-term study the reason for refusal will be documented in the 
subject’s eCRF.
10.4.
Screen and baseline failures
Screening failures are defined as subjects who are withdrawn from the study after giving 
informed consent, but who do not meet the inclusion and exclusion criteria.
The following information will be collected for screening failures:

Informed consent.

Inclusion/exclusion criteria.

Demographic data.

Medical history.
 
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
Physical examination.

Growth monitoring.

Blood samples for RSV serostatus, hematology and biochemistry, CMI response and 
humoral response.

SAEs related to study participation, to concomitant use of GSK products or any fatal 
SAEs.

Screening conclusion.
11.
STATISTICAL METHODS
11.1.
Primary endpoint

Occurrence of AEs from first vaccination (Day 0) up to Day 60.

Occurrence of each solicited local and general AE, during a 7-day follow-up 
period after each vaccination (i.e. the day of vaccination and 6 subsequent days).

Occurrence of any unsolicited AE, during a 30-day follow-up period after each 
vaccination (i.e. the day of vaccination and 29 subsequent days).

Occurrence of any SAE from Day 0 up to Day 60.

Occurrence of episode of spontaneous or excessive bleeding (AE of specific 
interest), during a 30-day follow-up period after each vaccination.

Occurrence of any hematological (hemoglobin level, white blood cells and 
platelets) laboratory abnormalities at Screening, Day 1, Day 7, Day 30, Day 31, 
Day 37, and Day 60.

Occurrence of any biochemical (alanine aminotransferase, aspartate 
aminotransferase and creatinine) laboratory abnormalities at Screening, Day 30, 
and Day 60.
11.2.
Secondary endpoints

Occurrence of SAEs from study start (Day 0) up to study conclusion (Day 730).

Occurrence of RSV-LRTI (AE of specific interest) as from Dose 1 administration up 
to study conclusion (Day 730).

Occurrence of RSV-RTI, RSV-LRTI, severe RSV-LRTI (according to standardized 
case definitions) as from Dose 1 administration up to study conclusion (Day 730).

Magnitude of the CMI response to the investigational RSV vaccine, pre-vaccination 
(Screening), post-Dose 1 (Day 30) and post-Dose 2 (Day 60 and Day 365).

CD3+/CD4+ T-cells expressing at least two markers among CD40L, IL-2, TNF-
α, and IFN-γ upon stimulation with F, N and M2-1 peptide pools.
 
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
Humoral response to the investigational RSV vaccine, pre-vaccination (Screening), 
post-Dose 1 (Day 30) and post-Dose 2 (Day 60 and Day 365):

Neutralizing antibody titers against RSV-A.

RSV F antibody concentrations.

Humoral response to the investigational RSV vaccine, pre-vaccination (Screening), 
post-Dose 1 (Day 30) and post-Dose 2 (Day 60):

Palivizumab-competing antibody concentrations.
11.3.
Tertiary endpoints

CMI response profile (Th1, Th2, Th17) to the investigational RSV vaccine, pre-
vaccination (Screening), post-Dose 1 (Day 30) and post-Dose 2 (Day 60 and Day 
365).

CD3+/CD4+ and/or CD3+/CD8+ T-cells expressing at least one or any 
combination of immune marker(s) among CD40L, 41BB, IL-2, TNF-α, IFN-γ, 
IL-13 and IL-17 upon stimulation with F, N and M2-1 peptide pools.

Any further exploratory immunology to detect disease-related or vaccine-related 
immune responses, such as but not limited to:

Anti-vector immunity: neutralization.
11.4.
Determination of sample size
No hypothesis driven sample size calculation was conducted due to the nature of 
descriptive summary of the study objectives. The sample size of 32 subjects per dose 
cohort/Step, randomized 1:1 to vaccine or placebo, was based on conventional study 
designs for Phase 1/2 trials. Specifically, if no adverse event was observed among 16 
RSV vaccinated subjects, the exact, two-sided 95% confidence interval (CI) would rule 
out an AE rate of 20% or more; if the incidence rate of AEs is more than 10%, there 
will still be more than an 80% chance of observing at least one subject with this AE. 
Combining all RSV vaccinees across all dose levels, there will be more than a 99% 
chance of observing at least one subject with this AE.
Furthermore, with 16 RSV vaccinees, the maximum width of a 95% CI for the 
proportion of subjects with adverse events among 16 vaccinees is about 50% (see 
Figure 5). (Amended 10 December 2017)
Figure 5 illustrates the precision on the percentage of subjects with symptoms following 
vaccination.
 
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Figure 5
Exact 95% confidence interval on the percentage of subjects with
adverse events following vaccination for 16 subjects per group
Taking the a priori safety concern of thrombocytopenia, both Frequentist and 
Bayesian approaches will be applied here to provide complementary assurance on the
possibility to exclude a signal based on the accumulated safety data. The Frequentist 
approach examines the statistical power to rule out a significant decrease in platelet 
counts due to vaccination that would suggest a four-fold or greater increase in the risk 
of a Grade 3 or higher thrombocytopenia with 16 subjects per dose cohort. The 
Bayesian approach calculates the posterior predictive probability of not observing any 
subject with a Grade 3 or higher thrombocytopenia among the future 16 subjects by 
basing it on what we have observed in the first 16 subjects.
If we assume platelet counts in healthy infants between 12 and 23 months follow a 
normal distribution with a mean of 300,000 platelets/mm³ and a standard deviation of 
75,000 platelets/mm³, then we would expect 0.04% of unvaccinated infants to have a 
count below 50000 platelets/mm³, which is the cut-off for a Grade 3 thrombocytopenia. 
To rule out a four-fold or greater increase, we would need to show that the mean 
platelet count does not fall below 190,000 platelets/mm³ with a standard deviation of 
47,500. The sample size needed to rule out a 110,000 platelets/mm³ decrease due to 
vaccination with 84% power when vaccination has no effect on platelet count is 16 
infants per dose cohort (8 per group). Sample size is based on a one-sided 0.025 test of 
non-inferiority using the Mann-Whitney statistic (PASS 12, Non-inferiority Tests for 
Two Means using Differences).
The Bayesian approach to predict the probability of no Grade 3 or higher 
thrombocytopenia in the future 16 subjects per dose cohort will be conducted by 
treating the mean of platelet counts µ as a random variable with a normal prior 
distribution N(µ0, σ0
2), where µ0 and σ0 will be determined by using laboratory normal 
 
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range. For this analysis the range of 150,000 to 450,000 platelets/mm³ will be the 
focus. Based on this laboratory range, µ0 would be 300,000, a mean of the range, and 
σ0 would be 75000, an approximate of a standard deviation of data sampled from this 
normal range. After 16 infants complete the two-dose vaccination schedule, a posterior 
distribution of µ will be calculated based on the prior of µ and the observed platelet 
counts from Day 31. The posterior predictive probability of no Grade 3 or higher 
thrombocytopenia in the future 16 subjects per dose cohort will be calculated, and 
sensitivity on the prior will be assessed.
After the first 16 infants of a dose cohort have completed the two-dose vaccination 
schedule, the 95% CI for the difference in mean platelets at Day 31 between vaccinees 
and placebo recipients will be calculated along with the posterior predictive probability 
of no Grade 3 or higher thrombocytopenia in the future 16 infants. If the lower 
boundary of the 95% CI is above 110,000 platelets/mm³ and the predictive probability is 
sufficiently high (e.g., 80% or more), the IDMC may recommend enrolling infants into 
the next dose cohort without completing enrolment in the current cohort. However, if a 
Grade 3 or higher thrombocytopenia occurs in a vaccinated infant at any time point or 
if there is a significant safety concern with another laboratory parameter such as 
hemoglobin or neutrophils, the IDMC may recommend continuing enrolment into the 
lower dose cohort. (Amended 10 December 2017)
11.5.
Cohorts for Analyses
11.5.1.
Total vaccinated cohort
The total vaccinated cohort (TVC) will include all subjects with at least one study 
vaccine administration documented.
A safety analysis based on the TVC will include all vaccinated subjects.
An immunogenicity analysis based on the TVC will include all vaccinated subjects for 
whom immunogenicity data are available.
The TVC analysis will be performed per treatment actually administered at Dose 1.
11.5.2.
According-to-protocol cohort for analysis of immunogenicity
The ATP cohort for analysis of immunogenicity will be defined by timepoint and will 
consist of all subjects from the TVC who complied with eligibility criteria, study 
procedures up to the end of the study and had immunogenicity results in the epoch as 
described below.
More specifically, the ATP cohort for analysis of immunogenicity up to Visit 9 (Day 
60)/at Visit 10 (Day 365) will include all evaluable subjects:

Who met all eligibility criteria (i.e. no protocol violation linked to the 
inclusion/exclusion criteria, including age).
 
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
Who received at least one dose of study vaccine.

For whom the administration route and site of the vaccine was as according to 
protocol.

Who received the vaccine according to protocol procedures.

Who complied with the vaccination schedule, as specified in Table 5.

Who did not receive a concomitant medication/product leading to exclusion from an 
ATP analysis, as described in Section 7.6.2, up to Visit 9 (Day 60)/up to Visit 10
(Day 365).

Who complied with the timings of the post vaccination blood sampling for immune 
response evaluation, up to Visit 9 (Day 60) /at Visit 10 (Day 365), as specified in 
Table 5.

For whom post-vaccination immunogenicity results are available for at least one 
assay up to Visit 9 (Day 60) /at Visit 10 (Day 365).
11.6.
Derived and transformed data
11.6.1.
Demography
For a given subject and a given demographic variable, missing measurements will not be 
replaced.
11.6.2.
Safety
For a given subject and the analysis of solicited AEs during the 7-day follow-up period 
after vaccination, missing or non-evaluable measurements will not be replaced. Therefore 
the analysis of the solicited symptoms based on the TVC will include only vaccinated
subjects with documented safety data (i.e. symptom screen completed).
For analysis of unsolicited AEs, SAEs and for the analysis of concomitant medications, 
all vaccinated subjects will be considered. Subjects who did not report an event or 
concomitant medication will be considered as subjects without the event or the 
concomitant medication respectively.
11.6.3.
Immunogenicity
Any missing or non-evaluable immunogenicity measurement will not be replaced:

For the within-group assessment, the descriptive analysis performed for each assay at 
each timepoint will exclude subjects with a missing or non-evaluable measurement.
Kinetics will be plotted on subjects with results available at all timepoints.
The geometric mean titers/concentrations (GMTs/GMCs) will be computed by taking the 
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A seronegative subject will be defined as a subject whose antibody titers/concentrations
is below the cut-off value of the assay. A seropositive subject is a subject whose antibody 
titers/concentrations is greater than or equal to the cut-off value of the assay.
Vaccine response in terms of RSV neutralizing antibodies will be defined in the statistical 
analysis plan.
The description of the handling of data below the lower limit of quantification for GMC 
calculation and fold increase will be described in the statistical analysis plan.
11.6.4.
RTI and LRTI
For the analysis of RTI and LRTI, all cases will be definitively classified as either RTI, 
LRTI or severe LRTI according to standardized case definitions (see Table 4) based on 
the available WHO case definitions, and the association to RSV infection will be assessed 
by quantitative PCR as primary analysis.
All confirmed LRTI will also be investigated for a panel of respiratory viruses (multiplex 
PCR; refer to Table 10), as a supplementary analysis of the occurrence of RSV-LRTI 
diagnosed upon the multiplex PCR.
For the analysis of RTI episode, a new RTI episode will be defined as any occurrence of 
cough, runny nose, blocked nose or difficulty breathing with an interval of at least 7 
symptom free days since the last episode of RTI that was diagnosed (refer to Section 4.2
for the definition of start and end dates of RTI episode).
11.7.
Analysis of demographics
The analysis of demographics will be performed on the TVC and on the ATP cohort for 
immunogenicity.
Demographic characteristics (age at vaccination in months, gender, race), weight, height 
or length, and vital signs, and cohort description will be summarized by group using 
descriptive statistics:

Frequency tables will be generated for categorical variable such as race.

Mean, median, standard error and range will be provided for continuous data such as 
age.
The distribution of subjects will be tabulated as a whole and per group.
Withdrawal status will be summarized by group using descriptive statistics:

The number of subjects enrolled into the study as well as the number of subjects 
excluded from ATP analyses will be tabulated.

The numbers of withdrawn subjects will be tabulated according to the reason for 
withdrawal.
 
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11.8.
Analysis of safety
11.8.1.
Within groups assessment
The analysis will be performed on the TVC.
The percentage of subjects with at least one local AE (solicited and unsolicited), with at 
least one general AE (solicited and unsolicited) and with any AE during the 7-day or 
30-day follow-up period will be tabulated with exact 95% CI after each vaccine dose and 
overall (Amended 10 December 2017). The percentage of doses followed by at least one 
local AE (solicited and unsolicited), by at least one general AE (solicited and unsolicited) 
and by any AE during the 7-day or 30-day follow-up period will be tabulated, overall 
vaccination course, with exact 95% CI. The same computations will be done for Grade 3 
AEs, for any AEs considered related to vaccination and for any Grade 3 AEs considered 
related to vaccination.
The percentage of subjects reporting each individual solicited local AE (any grade, 
Grade 2, Grade 3, resulting in a medically attended visit) and solicited general AE (any 
grade, Grade 2, Grade 3, any related, Grade 2 related, Grade 3 related, resulting in 
medically attended visit) during the 7-day follow-up period (Day 0-6) will be tabulated 
for each group after each vaccine dose and overall. Similarly, the percentage of doses 
followed by each individual solicited local and general AE and their sub-categories, will 
be tabulated, overall vaccination course, with exact 95% CI.
For fever, the number and percentage of subjects reporting fever by half degree (°C) 
cumulative increments during the 7-day follow-up period (Day 0-6) will be tabulated for 
each group after each vaccine dose and overall. Similar tabulations will be performed for 
any fever with a causal relationship to vaccination, Grade 3 (> 39.5°C) causally related 
fever and for any fever resulting in a medically attended visit. In addition, the prevalence 
of any and Grade 3 fever will be presented graphically over time after vaccination.
For each group and for each hematology and biochemistry parameter:

The percentage of subjects having hematology and biochemistry results below or 
above the local laboratory normal ranges will be tabulated by timepoint.
The maximum grading from Screening up to Visit 9 (Day 60) will be tabulated
(Refer to Appendix C).
The percentage of subjects with unsolicited AEs within 30 days (Day 0-29) after each 
vaccine dose (overall doses) with its exact 95% CI will be tabulated by group and by 
MedDRA preferred term. Similar tabulation will be done for Grade 3 unsolicited AEs, for 
any causally related unsolicited AEs, for Grade 3 causally related unsolicited AEs and for 
unsolicited AEs resulting in a medically attended visit. The verbatim reports of 
unsolicited AEs will be reviewed by a physician and the signs and AEs will be coded 
according to the MedDRA Dictionary for Adverse Reaction Terminology. Every 
verbatim term will be matched with the appropriate Preferred Term.
 
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SAEs reported throughout the study and AE of specific interest will be described in 
detail.
The percentage of subjects using concomitant medication (any medication, any 
antipyretic and any antipyretic taken prophylactically, respectively) during the 7-day 
follow-up period (Day 0-6) and during the 30-day follow-up period (Day 0-29) will be 
summarized by group after each vaccine dose and overall.
11.8.2.
Between groups assessment
Exploratory comparisons between the investigational RSV groups and the Placebo groups 
will be done in terms of the percentage of subjects, overall doses, reporting any Grade 2/3 
AE during the 7-day follow-up period (Day 0-6) after vaccination, and/ or any fever 
>38.5°C during the 7-day follow-up period (Day 0-6) after vaccination, and/ or any 
vaccine-related SAE during the 7-day follow-up period (Day 0-6) after vaccination.
The standardized asymptotic 95% CI for the difference between the RSV groups and 
(minus) the Placebo groups will be computed.
11.9.
Analysis of immunogenicity
The primary analysis will be performed on the ATP cohort for immunogenicity and, if in 
any group the percentage of vaccinated subjects with serological results excluded from 
the ATP cohort for analysis of immunogenicity is more than 10%, a second analysis will 
be performed on the TVC.
11.9.1.
Within groups assessment
11.9.1.1.
Analysis of secondary objectives
The following parameters will be summarized by group using descriptive statistics, at 
each timepoint during which blood samples are collected for CMI in investigational sites 
with a laboratory in proximity capable to perform WBS necessary for the CMI assay:

Frequency of CD3+/CD4+ T-cells expressing at least two markers among CD40L, 
IL-2, TNF-α, and IFN-γ upon stimulation with F, N and M2-1 peptide pools.
For each group, at each timepoint that blood samples are collected for humoral immune 
response against the investigational RSV vaccine (neutralizing antibody titers against 
RSV-A, RSV F antibody concentrations, and palivizumab-competing antibody 
concentrations):

GMTs/GMCs will be tabulated with 95% CI and represented graphically.

Percentage of subjects above the seropositivity threshold will be tabulated with exact 
95% CI.

Antibody titers/concentrations will be displayed using reverse cumulative curves.
 
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
The distributions of neutralizing antibody titers/concentrations will be tabulated.

Percentage of responders in terms of neutralizing antibody titers will be tabulated 
with exact 95% CI.

Individual post-vaccination versus pre-vaccination results will be plotted using 
scatter plots. Results of the Placebo groups will be used as a reference.

Geometric mean of ratios of antibody titers/concentrations at each post-vaccination 
timepoint over pre-vaccination will be tabulated with 95% CI.

Distribution of the fold increase of the neutralizing antibody titers will be tabulated
by pre-vaccination titer category.

The kinetics of individual antibody titer/antibody concentration results will be 
plotted as a function of time for subjects with results available at all timepoints.
11.9.1.2.
Analysis of tertiary objectives
The cellular immune response will be further characterized using descriptive analysis of 
the frequency of CD3+/CD8+ T-cells and CD3+/CD4+ T-helper cell profile (Th1, Th2, 
Th17) expressing at least one or any combination of marker(s) among IL-2, CD40L, 
41BB, TNF-, IFN-, IL-13, and IL-17. 
If available, any further exploratory immunology results (including, but not limited to 
anti-vector immunity) will be reported by group and timepoint using descriptive 
summary statistics.
11.10.
Analysis of RTI and LRTI
The analysis will be performed on the TVC on two pooled groups (i.e. pooled RSV and 
pooled Placebo) separately for first and second RSV seasons and overall.
The proportion of subjects with at least one RSV-associated RTI (with 95 % CI) will be 
calculated. The same descriptive analysis will be performed for subjects with at least one 
RSV-associated LRTI and those with at least one RSV-associated severe LRTI.
As primary analysis, the assessment of RSV infection will be performed using the 
quantitative RT-PCR according to standardized case definitions (see Table 4) based on 
the available WHO case definitions.
Descriptive analyses (mean, median, min, max) of viral load assessed by the quantitative 
RT-PCR (RSV-A/B) of RSV-RTI, RSV-associated LRTI and severe LRTI cases will be 
tabulated. This analysis will also be done by study group.
The incidence rate of all-cause RTI (with 95% CI) will be calculated by group. The same 
descriptive analysis will be performed for all cause LRTI and all cause severe LRTI. 
These will also be presented for each viral etiology identified by multiplex PCR.
The incidence rate of asymptomatic RSV infections (with 95% CI) detected by the 
quantitative PCR (RSV-A/B) will be tabulated by group. Descriptive analyses (mean, 
 
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median, min, max) of viral load assessed by the quantitative RT-PCR (RSV-A/B) of 
those asymptomatic RSV infections will also be done by group.
11.11.
Interpretation of analyses
Comparative analyses will be exploratory and should be interpreted with caution 
considering that there is no adjustment for multiplicity and that group sizes are small for 
these comparisons.
11.12.
Conduct of analyses
Any deviation(s) or change(s) from the original statistical plan outlined in this protocol 
will be described and justified in the final study report.
11.12.1.
Sequence of analyses
In preparation of the planned IDMC and iSRC evaluations, analyses of all available 
safety data (data that are as clean as possible) will be performed (see Section 9.10 for 
more information). These analyses will be done by an unblinded statistician outside GSK 
to maintain the study blind, and will be documented in a statistical analysis report. Only 
the outcome of the IDMC and iSRC reviews will be communicated to the RSV study 
team (no safety signal or safety signal). No clinical study report will be written.
The statistical analyses will be performed in 3 steps:

A first analysis will be performed when all data up to Day 60 (i.e. data that are as 
clean as possible) are available. Additional safety data available at the time of this 
analysis will be described. At this point, the statistician will be unblinded (i.e. 
individual subject treatment assignments will be available) and the study will be 
conducted in a single-blind manner, with patients remaining blinded up to study end 
(Day 730). Summary results may unblind some specific subjects but no individual 
listings will be provided and the investigators will not have access to the treatment 
allocation up to study end (Day 730), except in case of emergency unblinding (see 
Section 9.8).

An analysis will be performed when all data up to Visit 10 (Day 365; i.e. data that 
are as clean as possible) are available. No individual listings will be provided.

The final analysis will be performed when all data up to study conclusion (Day 730) 
are available. An integrated clinical study report containing all data will be written 
and made available to the investigators at that time.
If the data for tertiary endpoints become available at a later stage, (an) additional 
analysis/ analyses will be performed. These data will be documented in annex(es) to 
the study report and will be made available to the investigators at that time.
11.12.2.
Statistical considerations for interim analyses
No interim analyses are planned.
 
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12.
ADMINISTRATIVE MATTERS
To comply with ICH GCP administrative obligations relating to data collection, 
monitoring, archiving data, audits, confidentiality and publications must be fulfilled.
12.1.
electronic Case Report Form instructions
A validated GSK defined electronic data collection tool will be used as the method for 
data collection. 
In all cases, subject initials will not be collected nor transmitted to GSK. Subject data 
necessary for analysis and reporting will be entered/transmitted into a validated database 
or data system. Clinical data management will be performed in accordance with 
applicable GSK standards and data cleaning procedures.
While completed eCRFs are reviewed by a GSK Biologicals’ Site Monitor at the study 
site, omissions or inconsistencies detected by subsequent eCRF review may necessitate 
clarification or correction of omissions or inconsistencies with documentation and 
approval by the investigator or appropriately qualified designee. In all cases, the 
investigator remains accountable for the study data. 
The investigator will be provided with a CD-ROM of the final version of the data 
generated at the investigational site once the database is archived and the study report is 
complete and approved by all parties.
12.2.
Study Monitoring by GSK Biologicals
GSK will monitor the study to verify that, amongst others, the: 

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol, any other 
study agreements, GCP and all applicable regulatory requirements. 
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents.
The investigator must ensure provision of reasonable time, space and qualified personnel 
for monitoring visits.
Direct access to all study-site related and source data is mandatory for the purpose of 
monitoring review. The monitor will perform an eCRF review and a Source Document 
Verification. By Source Document Verification we understand verifying eCRF entries by 
comparing them with the source data that will be made available by the investigator for 
this purpose. 
 
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The Source Documentation Agreement Form describes the source data for the different 
data in the eCRF. This document should be completed and signed by the site monitor and 
investigator and should be filed in the monitor’s and investigator’s study file. Any data 
item for which the eCRF will serve as the source must be identified, agreed and 
documented in the source documentation agreement form.
For eCRF, the monitor freezes completed and approved screens at each visit.
Upon completion or premature discontinuation of the study, the monitor will conduct site 
closure activities with the investigator or site staff, as appropriate, in accordance with 
applicable regulations, GCP, and GSK procedures.
12.3.
Record retention
Following closure of the study, the investigator must maintain all site study records 
(except for those required by local regulations to be maintained elsewhere) in a safe and 
secure location. The records must be easily accessible, when needed (e.g. audit or 
inspection), and must be available for review in conjunction with assessment of the 
facility, supporting systems, and staff. Where permitted by applicable laws/regulations or 
institutional policy, some or all of these records can be maintained in a validated format 
other than hard copy (e.g. microfiche, scanned, electronic); however, caution needs to be 
exercised before such action is taken. The investigator must ensure that all reproductions 
are legible and are a true and accurate copy of the original and meet accessibility and 
retrieval standards, including re-generating a hard copy, if required. Furthermore, the 
investigator must ensure that an acceptable back-up of the reproductions exists and that 
there is an acceptable quality control procedure in place for making these reproductions.
GSK will inform the investigator/institution of the time period for retaining these records 
to comply with all applicable regulatory requirements. However, the 
investigator/institution should seek the written approval of the sponsor before proceeding 
with the disposal of these records. The minimum retention time will meet the strictest 
standard applicable to a particular site, as dictated by ICH GCP, any institutional 
requirements, applicable laws or regulations, or GSK standards/procedures. 
The investigator/institution must notify GSK of any changes in the archival 
arrangements, including, but not limited to archival at an off-site facility, transfer of 
ownership of the records in the event the investigator leaves the site. 
12.4.
Quality assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory 
inspection of this study. Such audits/inspections can occur at any time during or after 
completion of the study. If an audit or inspection occurs, the investigator and institution 
agree to allow the auditor/inspector direct access to all relevant documents and to allocate 
his/her time and the time of his/her staff to the auditor/inspector to discuss findings and 
any relevant issues.
 
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12.5.
Posting of information on publicly available clinical trial 
registers and publication policy
GSK assures that the key design elements of this protocol will be posted on the GSK 
website and in publicly accessible database(s) such as clinicaltrials.gov, in compliance 
with the current regulations.
GSK also assures that results of this study will be posted on the GSK website and in 
publicly accessible regulatory registry(ies) within the required time-frame, in compliance 
with the current regulations. The minimal requirement is to have primary endpoint 
summary results disclosed at latest 12 months post primary completion date and to have 
secondary endpoint disclosed at latest 12 months after the last subject last visit as 
described in the protocol.
As per EU regulation, summaries of the results of GSK interventional studies (phase I-
IV) in pediatric population conducted in at least one EU member state will be posted on 
publicly available EMA registers within 6 months of end of study (as defined in the 
protocol) in the concerned EU member state. However, where, for scientific reasons 
detailed in the protocol, it is not possible to submit a summary of the results within 6 
months in the concerned EU member state, the summary of results shall be submitted as 
soon as it is available. In this case, the protocol shall specify when the results are going to 
be submitted, together with a justification.
GSK also aims to publish the results of these studies in searchable, peer reviewed 
scientific literature and follows the guidance from the International Committee of 
Medical Journal Editors.
12.6.
Provision of study results to investigators
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually-
agreeable location.
GSK Biologicals will also provide the investigator with the full summary of the study 
results. The investigator is encouraged to share the summary results with the study 
subjects, as appropriate.
13.
COUNTRY SPECIFIC REQUIREMENTS
In each participating country all children will be offered locally recommended vaccines 
for their age. These vaccines could be administered from Day 60 (Visit 9) onwards until 
the end of the study. Such vaccines will be provided by the investigator and where 
required will be sourced by GSK. The Investigator is responsible for reporting adverse 
events associated to the use of these vaccines according to local laws and regulations in 
addition to the safety reporting procedures foreseen in this study.
 
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14.
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APPENDIX A
LABORATORY ASSAYS
Assay descriptions could be subjects to change, due to assay re-development and/or 
qualification.
Serostatus to RSV F and/or G protein
The selection of seropositive infants at screening will be based on ELISA with F and G 
protein coating antigens using a commercial kit (IBL kit).
Intracellular staining (ICS)
ICS has been used to assess CMI responses as previously described [Díez-Domingo, 
2010; Moris, 2011].
Within 4 hours post phlebotomy, approximately 350 µL of undiluted whole blood are 
incubated at 37°C with the relevant antigen (in this case pools of 15-mer peptides 
overlapping by 11 amino acids and spanning the sequences of F, N, and M2-1 proteins), 
negative control (medium), or positive control (staphylococcal enterotoxin B) for 2 hours 
in the presence of anti-CD28 and anti-CD49d antibodies. Brefeldin A, a protein secretion 
inhibitor, is then added and the mix is incubated overnight. Red cells are then lysed and 
white cells washed, fixed, cryopreserved, and stored until analysis by cytometry.
Once ready for cytometry analysis, white cells are thawed in batches, washed, and 
incubated with fluorochrome-conjugated antibodies specific to CD4 and CD8 surface 
markers. Then, cells are permeabilized and stained with fluorochrome-conjugated 
antibodies specific for the following immune markers: IL-2, IFN-, TNF-, CD40L, IL-
13, IL-17, and 41BB. After washing, acquisition of data is performed via a flow 
cytometer.
The results are expressed as the frequency of CD4+ or CD8+ T-cells expressing, per 
million of CD4+ or CD8+ T-cells:

CD3+/CD4+ T-cells expressing at least two markers among CD40L, IL-2, TNF-α, 
and IFN-γ (poly-functional CD4+ T-cells). 

CD3+/CD4+ and/or CD3+/CD8+ T-cells expressing at least one or any combination 
of immune marker(s) among CD40L, 41BB, IL-2, TNF-α, IFN-γ, IL-13 and IL-17 
(for determination of Th profile). 
Neutralization assay
The serum neutralization assay is a functional assay that measures the ability of serum 
antibodies to neutralize RSV entry and replication in a host cell line.
First, virus neutralization is performed by incubating a fixed amount of RSV-A long 
strain (ATCC No. VR-26) with serial dilutions of the test serum. Then, the serum-virus 
mixture is transferred onto a monolayer of Vero cells (African Green Monkey, kidney, 
Cercopitheus aethiops, ATCC CCL-81) and incubated for three days to allow infection of 
Vero cells by non-neutralized viruses and the formation of plaques in the cell monolayer. 
 
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Following the fixation period, RSV-infected cells are detected using a primary antibody 
directed against RSV (anti-RSV IgG) and a secondary antibody conjugated with 
fluorescein isothiocyanate, allowing the visualization of plaques by immunofluorescence. 
Viral plaques are counted using an automated microscope coupled to an image analyzer 
(Scanlab system with Axiovision software). For each serum dilution, a ratio, expressed as 
a percentage, is calculated between the number of plaques at that dilution and the number 
of plaques in the virus control wells (no serum added). The serum neutralizing antibody 
titer is expressed in ED60 (Estimated Dilution 60) and corresponds to the inverse of the 
interpolated serum dilution that yields a 60% reduction in the number of plaques 
compared to the virus control wells as described by others [Barbas, 1992; Bates, 2014].
ELISA

Anti-RSV protein F ELISA
The anti-F protein IgG ELISA is an indirect ELISA allowing the detection and the 
quantitation of specific IgG antibodies directed against the RSV F protein in human 
serum samples. (Amended 10 December 2017)

Palivizumab competitive assay
Palivizumab monoclonal antibody (Synagis) is used as a passive treatment that 
protects against RSV infection by binding to the antigenic site II epitope of the RSV 
F antigen.
First, F protein antigens purified from CHO expression system are coated onto 96-
well microplates. Then, after a washing and a blocking step, serial two-fold dilutions 
of test sera, positive control serum, and palivizumab antibody reference standard are 
added in sequence with competitor antibodies (horseradish peroxidase-conjugated 
palivizumab) and incubated to allow specific binding of antibodies directed against 
the F protein antigens. If palivizumab-like antibodies are present in serum samples, 
they will compete with the horseradish peroxidase-conjugated palivizumab
antibodies for binding to the F protein coated antigen. After a washing step, the 
horseradish peroxidase substrate solution (TMB/H2O2) is added and a colored 
product develops in a manner that is inversely proportional to the amount of 
palivizumab-like antibodies contained in the test serum. The color is quantified by 
reading the optical densities at 450-620 nm using a spectrophotometer. Antibody 
concentrations of individual serum and control samples are determined after 
interpolation from the ELISA standard curve using a four-parameter equation and are 
expressed as palivizumab-equivalent antibodies in microgram per millilitre (µg/mL).
PCR

Quantitative PCR able to discriminate RSV-A and RSV-B subtypes:
Briefly, RSV A and RSV B RNAs extracted from the nasal swabs are detected in a 
duplex PCR format using specific amplification primers and fluorescent probes 
designed in the RSV N gene, encoding the RSV nucleocapsid protein. The process 
involves nucleic acids extraction, conversion of RNA to complementary 
deoxyribonucleic acid by reverse transcription and detection by real- time PCR 
reaction using a calibration curve (absolute quantitation). The RSV viral load is 
reported as copies of RSV RNA per mL of sample.
 
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
Qualitative multiplex PCR for detection of a panel of viruses.
A qualitative PCR multiplex assay is used for the detection and identification of 
multiple respiratory virus nucleic acids in nasal swabs from individuals suspected of 
respiratory tract infections. The following virus types and subtypes can be identified 
in the assay:

Influenza A virus (Flu A)

Influenza B virus (Flu B)

Human Influenza A virus subtype H1 (Flu A-H1)

Human Influenza A virus subtype H3 (Flu A-H3)

Human Influenza A virus subtype H1pdm09 (Flu A-H1pdm09)

Human respiratory syncytial virus A (RSV A)

Human respiratory syncytial virus B (RSV B)

Human adenovirus (AdV)

Human metapneumovirus (MPV)

Human enterovirus (HEV)

Human parainfluenza virus 1 (PIV1)

Human parainfluenza virus 2 (PIV2)

Human parainfluenza virus 3 (PIV3)

Human parainfluenza virus 4 (PIV4)

Human bocavirus 1/2/3/4 (HBoV)

Human rhinovirus A/B/C (HRV)

Human coronavirus 229E (229E)

Human coronavirus NL63 (NL63)

Human coronavirus OC43 (OC43)
Following total nucleic acids extraction, viruses are detected by multiplex real-time 
RT-PCR assays targeting the above mentioned viruses. A comparative analysis of 
the fluorescence intensities of each target is performed to detect the viruses present 
in the sample.
 
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APPENDIX B
CLINICAL LABORATORIES
Table 23
GSK Biologicals’ laboratories
Laboratory
Address
GSK Biologicals Clinical Laboratory Sciences, 
Rixensart
Biospecimen Reception - B7/44
Rue de l'Institut, 89 - B-1330 Rixensart - Belgium
GSK Biologicals Clinical Laboratory Sciences, 
Wavre-Nord Noir Epine
Avenue Fleming, 20 - B-1300 Wavre - Belgium
Table 24
Outsourced laboratories
Laboratory
Address
NÉOMED-LABS Inc.
525, Cartier Ouest Laval,
Quebec
Canada H7V 3S8
Q2 Solutions Clinical Trials (US)
27027 Tourney Road, Suite 2E
Valencia, CA 91355
USA
 
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APPENDIX C
TOXICITY GRADING FOR HEMATOLOGY AND 
BIOCHEMISTRY PARAMETERS
Table 25
Toxicity grading scales for hematology and biochemistry 
parameters applicable for this study (Amended 10 December 2017)
Component
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin (g/dL)
9.0 to < 10.5
8.0 to < 9.0
7.0 to < 8.0
< 7.0
Leukocytes decreased 
(cell/mm3)
2500 to < 3500
1500 to < 2500
1000 to < 1500
< 1000
Absolute neutrophil count
decreased (cell/mm³)
1000 to < 1300
750 to < 1000
500 to < 750
< 500
Absolute lymphocyte count
decreased (cell/mm³)
600 to < 650
500 to < 600
350 to < 500
< 350
Platelets decreased (cell/mm3) 
75000 to < 150000
50000 to < 75000
25000 to < 50000
< 25000
Alanine Aminotransferase
(increase by factor)
1.1 to < 2.0 xULN
2.0 to < 3.0 xULN
3.00 to ≤8.0 xULN
> 8.0 xULN
Aspartate Aminotransferase
(increase by factor)
1.1 to < 2.0 xULN
2.0 to < 3.0 xULN
3.00 to ≤8.0 xULN
> 8.0 xULN
Creatinine (mg/dL) 
0.6 to < 0.9
0.9 to < 1.2
1.2 to ≤1.5
> 1.5
Grading scale adapted from [Division of AIDS, 2003], [Division of AIDS, 2004] and [Division of AIDS, 2007].
ULN: upper limit of normal
 
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APPENDIX D
AMENDMENTS AND ADMINISTRATIVE 
CHANGES TO THE PROTOCOL
GlaxoSmithKline Biologicals SA
Vaccines R &D
Protocol Administrative Change 1
eTrack study number and 
Abbreviated Title
204838 (RSV PED-002) 
IND number
16999
EudraCT number
2016-000117-76 
Administrative change 
number:
Administrative change 1
Administrative change 
date:
06 July 2016
Co-ordinating author:
 (Project Manager Scientific Writer, Keyrus 
Biopharma contractor for GSK Biologicals)
Rationale/background for changes: 
!
The IND number has been added on the protocol cover page, the Sponsor Signatory 
Approval page and the Investigator agreement page.
!
Change in study personnel has been mentioned on the protocol cover page.
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
!
On the protocol cover page, the Sponsor Signatory Approval page and the 
Investigator agreement page, IND number has been added:
Investigational New 
Drug (IND) number
16999
!
On the protocol cover page, a contributing author has been added.
Contributing authors 
(continued)
 (Global Regulatory 
Representative)
In the List of abbreviations, definition of the abbreviation “IND” has been added:
IND:
Investigational New Drug
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GlaxoSmithKline Biologicals SA
Vaccines R &D
Protocol Administrative Change 2
eTrack study number and 
Abbreviated Title
204838 (RSV PED-002) 
IND number
16999
EudraCT number
2016-000117-76 
Administrative change 
number:
Administrative change 2
Administrative change 
date:
13 September 2016
Co-ordinating author:
 (Project Manager Scientific Writer, Keyrus 
Biopharma contractor for GSK Biologicals)
Rationale/background for changes: 
!
The GSK Biologicals’ Contact information for Emergency Unblinding for US and 
Canada have changed. This protocol administrative change provides the new 
numbers.
!
Change in study personnel has been mentioned on the protocol cover page.
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
!
On the protocol cover page, the following contributing authors have been added.
Contributing authors 
(continued)
!
 (Vaccine Supply Coordinator)
!
 (Oversight Data Manager, 
Keyrus Biopharma contractor for GSK 
Biologicals)
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!
In Section 9.8. Emergency unblinding, the GSK Biologicals’ Contact information 
for Emergency Unblinding for US and Canada have been changed.
GSK Biologicals’ Contact information for Emergency Unblinding
24/24 hour and 7/7 day availability
GSK Biologicals’ Central Safety Physician: 
Outside US:
 (GSK Biologicals Central Safety Physician on-call)
For US:
(GSK Biologicals Central Safety Physician on-call)
GSK Biologicals’ Central Safety Physician Back-up:
Outside US:
US only:
Emergency Unblinding Documentation Form transmission:
Outside US:
Fax: 
 or 
US only:
Fax: 
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GlaxoSmithKline Biologicals SA
Vaccines R &D
Protocol Amendment 1
eTrack study number and 
Abbreviated Title:
204838 (RSV PED-002) 
IND number:
16999
EudraCT number:
2016-000117-76 
Amendment number:
Amendment 1
Amendment date:
16 January 2017
Co-ordinating author:
 (Project Manager Scientific Writer, Keyrus 
Biopharma contractor for GSK Biologicals)
Rationale/background for changes:
!
The Spanish competent authorities (Agencia Española de Medicamentos y Productos 
Sanitarios [AEMPS]) requested the Sponsor to extend the long term medical follow-
up for one additional year. The purpose of this amendment is to respond to this 
request by increasing the follow-up of the subjects from one year to two years. This 
will include the collection of adverse events (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 (Agenzia Italiana del Farmaco [AIFA]) requested 
that, in addition to the 60 minutes observation planned per protocol between each 
infants receiving ChAd155-RSV vaccination, the Sponsor monitors potential 
hypersensitivity reactions for a longer period following both vaccine administrations 
(one month apart) in a sufficient number of infants before another one can 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. The purpose of this amendment is to respond to this 
request.
!
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.
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!
The holding rule for hospitalization due to any local or general solicited AE has been 
restricted to any local or general solicited AE that cannot 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.
!
In addition, some typos have been corrected and other administrative changes have 
been made throughout the protocol in order to harmonize wording across the 
different RSV project documents and to add clarity.
!
Finally, changes in study personnel have been included on the protocol cover page.
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
On the protocol cover page, the following changes have been made:
Contributing authors 
!
 (Lead Statistician)
!
 (Project Statistician)
!
 (Study Delivery Lead)
!
 (Vaccine Supply Coordinator, Aixial 
contractor for GSK Biologicals)
!
 (Oversight Data Manager, 
Keyrus Biopharma contractor for GSK Biologicals)
!
 (Global Regulatory 
Representative)
In the Synopsis, the following changes have been made:
Rationale for the study 
and study design
!
Study population: The immunogenicity, safety and 
reactogenicity of the pediatric candidate RSV vaccine 
(ChAd155-RSV vaccine) are currently being 
evaluated in healthy adult subjects aged 18 to 45 
years (study 201974 [RSV PED-001]). The 
ChAd155-RSV vaccine is being developed for the 
active immunization of infants as from 6 weeks of 
age. To allow age de-escalation from the adult 
population to the targeted population and to not enroll 
and administer the ChAd155-RSV vaccine to older 
children who are beyond the age of severe RSV
disease and would not benefit from this vaccine, the 
present study will be performed on RSV-seropositive 
infants aged 12 to 17 months, pending satisfactory
after the safety profile of the ChAd155-RSV vaccine 
in adults (study 201974 [RSV PED-001; 
NCT02491463]) was evaluated as satisfactory by an 
Independent Data Monitoring Committee (IDMC). 
The present study will provide critical information on 
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the safety and immunogenicity profile of the 
ChAd155-RSV vaccine before a subsequent trial in 
seronegative infants.

Study blinding: Given the different appearance and 
storage conditions of the investigational RSV vaccine 
and placebo, double blinding is not possible and the 
study will be conducted in an observer-blind manner.
When all data up to Day 60 are available, a statistical 
analysis will be performed. This analysis may lead to 
the unblinding of some subjects. As a consequence, 
after Day 60, the study cannot be considered as 
observer-blind, but will be conducted in a single-
blind manner, with subjects’ parent(s)/ legally 
acceptable representative (LAR[s]) remaining blinded 
up to study end (Day 365Day 730). The investigators 
will not have access to the treatment allocation up to 
study end (Day 365Day 730).

Staggered design with 3 steps:
Vaccination will be limited to a maximum of 10 
infants per day. In the same investigational center, 
infants will be vaccinated sequentially, separated by a 
minimum interval of 60 minutes to allow monitoring 
of any acute events (e.g. hypersensitivity reaction). In 
addition, to monitor delayed potential reactions 
following vaccination, there will be a 48-hour 
observation period following Dose 1 and Dose 2 
administration to the first eight infants 
(corresponding to three to five ChAd155-RSV 
vaccine recipients) in each Step (1, 2, and 3) before 
continuing vaccination of more infants (i.e. from 
the ninth infant). From the ninth infant, infants will 
be vaccinated sequentially, separated by a minimum 
interval of 60 minutes. Refer to the study procedures 
manual (SPM) for more details about the 48-hour 
observation period after the first eight subjects 
vaccinated in each Step.
Within each step, an internal Safety Review 
Committee (iSRC) will review accumulated safety 
data three weeks after the start of vaccination and 
then about every three weeks (until the Independent 
Data Monitoring Committee [IDMC] reviews the 
data).
 
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Objectives
Secondary

To evaluate the safety of two IM doses of three dose 
levels of the RSV investigational vaccine when 
administered according to a 0, 1-month schedule 
from study start (Day 0) up to study conclusion (Day 
365730) in RSV-seropositive infants aged 12 to 17 
months.

To evaluate the occurrence of RSV respiratory tract 
infections in RSV-seropositive infants from Visit 1 
(Day 0, after Dose 1) up to study conclusion (Day 
365730).
Study design

Duration of the study: approximately 12 24 months:

Epoch 002: follow-up starting at Visit 10 (Day 365) 
and ending at Visit 10 11 (Day 365 730).

End of Study: Last testing results released of samples 
collected at Visit 10 11 (Day 365 730).

Sampling schedule:

Blood samples for biochemistry will be taken 
from all infants at Screening (14 29 days before 
first vaccination to Day 0) and on Day 7, Day 30, 
Day 37, and Day 60. Blood samples for 
hematology will be taken from all infants at 
Screening (14 29 days before first vaccination to 
Day 0) and on Day 1, Day 7, Day 30, Day 31, 
Day 37, and Day 60. A clinical history and 
examination with special attention given to 
detection of spontaneous bleeding or easy 
bruising and evidence of bruising or petechiae 
will be performed on Day 1, Day 3 and Day 7 
after each vaccination (i.e. Day 1, Day 3, Day 7, 
Day 31, Day 33, and Day 37). On Day 1, Day 7, 
Day 31, and Day 37, special attention will also be 
given to the detection of petechiae or evidence of 
petechiae induced by the tourniquet. Further 
testing may be required to investigate a finding or 
guide subject management based on the 
investigators clinical judgment. Subjects’ 
parent(s)/LAR(s) will be instructed to contact the 
investigator/study staff if their child presents 
symptoms of spontaneous bleeding or easy 
bruising following vaccination.

Surveillance for RSV-RTI, difficulty in breathing and 
wheezing episodes.
 
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Surveillance period will be carried out from Visit 1 
(after Dose 1) until Visit 10 11 (Day 365730). In 
order to detect asymptomatic RSV-RTI, monthly 
nasal swabs for analysis at sponsor laboratory will be 
performed for all subjects during the RSV season. In 
order to timely detect RSV-RTI and to ensure cases 
are timely captured by the study sites, both active and 
passive surveillance will be conducted:
Case definition
During the analysis of the study, all cases identified 
during the surveillance of RSV-RTI will be definitively 
classified as either RTI, LRTI or severe LRTI according 
to the case definitions described in Synopsis Table 4. The 
analysis may also be done using the available World 
Health Organization (WHO) case definitions for RTI, 
LRTI and severe LRTI.
Endpoints
Secondary

Occurrence of SAEs from study start (Day 0) up to 
study conclusion (Day 365730) in all subjects.

Occurrence of RSV-LRTI (AE of specific interest) as 
from Dose 1 administration up to study conclusion 
(Day 365730) in all subjects.

Occurrence of RSV-RTI, RSV-LRTI, severe RSV-
LRTI (according to case definitions) as from Dose 1 
administration up to study conclusion (Day 365730) 
in all subjects.
 
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In Section 1.2.2.1 Study population, the following changes have been made:

The immunogenicity, safety and reactogenicity of the pediatric candidate RSV 
vaccine (ChAd155-RSV vaccine) are currently being evaluated in healthy adults 
aged 18 to 45 years (study 201974 [RSV PED-001; NCT02491463]). The ChAd155-
RSV vaccine is being developed for the active immunization of infants as from 6 
weeks of age. To allow age de-escalation from the adult population to the targeted 
population and to not enroll and administer the ChAd155-RSV vaccine to older 
children who are beyond the age of severe RSV disease and would not benefit from 
this vaccine, the present study will be performed on RSV-seropositive infants aged 
12 to 17 months, pending satisfactory after the safety profile of the ChAd155-RSV 
vaccine in adults (study 201974 [RSV PED-001; NCT02491463]) was evaluated as 
satisfactory by an Independent Data Monitoring Committee (IDMC). The present 
study will provide critical information on the safety and immunogenicity profile of 
the ChAd155-RSV vaccine before a subsequent trial in seronegative infants.
In Section 1.2.2.2 RSV serostatus using IBL International kit and choice of study 
population, the following changes have been made:

Despite the assay characterization performed by the manufacturer, a potential lack of 
sensitivity of the IBL International kit compared to a RSV neutralization assay has 
been reported [Malkin, 2013]. GSK considers that the specificity and sensitivity 
characteristics of the assay indicate a reduced a lower sensitivity reduces the risk of 
enrolling RSV-seronegative infants identified RSV-seropositive in the assay (i.e. 
false RSV-seropositive infants results) and that this is acceptable in this screening 
context.
In Section 1.2.4.1 Staggered design with 3 steps, the following change has been made:

Vaccination will be limited to a maximum of 10 infants per day. In the same 
investigational center, infants will be vaccinated sequentially, separated by a 
minimum interval of 60 minutes to allow monitoring of any acute events (e.g. 
hypersensitivity reaction). In addition, to monitor delayed potential reactions 
following vaccination, there will be a 48-hour observation period following Dose 1 
and Dose 2 administration to the first eight infants (corresponding to three to five 
ChAd155-RSV vaccine recipients) in each Step (1, 2, and 3) before continuing 
vaccination of more infant (i.e. from the ninth infant). From the ninth infant, 
infants will be vaccinated sequentially, separated by a minimum interval of 60 
minutes. Refer to the study procedures manual (SPM) for more details about the 
48-hour observation period after the first eight subjects vaccinated in each Step.

Within each step, an internal Safety Review Committee (iSRC) will review 
accumulated safety data three weeks after the start of vaccination and then about 
every three weeks (until the Independent Data Monitoring Committee [IDMC]
reviews the data). Ad-hoc iSRC meetings may be held should safety concerns 
warrant a safety review. Refer to Section 9.10.2 for more information about iSRC.
 
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In Section 1.2.4.2 Rationale for monitoring of hematology parameters, the following 
changes have been made:

Emphasis on “minimal risk” is imperative for the protection of the pediatric 
population participating to research studies where blood sample volume limits is a 
critical parameter. To stay within blood sampling limits that are consistent with 
physiological “minimal risk” in this young and vulnerable population, but also to 
minimize any development of needle aversion, no blood draw will be performed for 
immunological assays and for biochemistry tests at Day 1 and none for hematology 
and biochemistry tests at Day 3. Blood samples collected within the screening 
window (limited to maximum 14 days) will serve as baseline for the immunological 
analysis and for the hematology and biochemistry check-up before vaccination. 
Consequently, the maximum blood draw volumes collected per protocol have been 
restricted to 9.0 mL within 24 hours and 32.4 mL over eight weeks (refer to Table 5 
and Table 7). Of note, it is considered that blood sample volumes ranging from 1 to 
5% of total blood volume within 24 hours and up to 10% of total blood volume over 
8 weeks are consistent with the limited evidence available on the minimal 
physiological risk for healthy children [Howie; 2011]. The total blood volume of a 
child is around 75 to 80 mL/kg (85 to 105 mL/kg in the neonatal period). 
Considering a girl of 12 months of age with a low weight of 7.3 kg (5th percentile 
[WHO; 2006]), the minimal individual total blood volume in the study population 
would be 547.5 mL and therefore the safer limits of blood draw volumes would 
range from 5.5 to 27.4 mL within 24 hours and be limited to 54.7 mL over 8 weeks. 
To minimize any development of needle aversion, pain relief by means of a topical 
local anesthetic may be offered to infants prior to any blood sampling requested by 
the protocol at the discretion of the investigator.
In Section 1.2.5 Rationale for study blinding, the following changes have been made:

When all data up to Day 60 are available, a statistical analysis will be performed. 
This analysis may lead to the unblinding of some subjects. As a consequence, after 
Day 60, the study cannot be considered as observer-blind, but will be conducted in a 
single-blind manner, with subjects’ parent(s)/ LAR(s) remaining blinded up to study 
end (Day 365730). The investigators will not have access to the treatment allocation 
up to study end (Day 365730).
In Section 2.2 Secondary objectives, the following changes have been made:

To evaluate the safety of two IM doses of three dose levels of the RSV 
investigational vaccine when administered according to a 0, 1-month schedule from 
study start (Day 0) up to study conclusion (Day 365730) in RSV-seropositive infants 
aged 12 to 17 months. 

To evaluate the occurrence of RSV respiratory tract infections in RSV-seropositive 
infants from Visit 1 (Day 0, after Dose 1) up to study conclusion (Day 365730).
 
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In Section 3 Study Design Overview, the following changes have been made:
Figure 1
Study design
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Figure 1
Study design
¥ Visit 2 (Day 1), Visit 3 (Day 3), Visit 6 (Day 31), and Visit 7 (Day 33), and Visit 11 (Day 730) may take place in the subject’s home or at the investigators clinical facility as appropriate
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
Duration of the study: approximately 12 24 months:

Epoch 002: follow-up starting at Visit 10 (Day 365) and ending at Visit 10 11 
(Day 365 730).

End of Study: Last testing results released of samples collected at Visit 10 11 (Day 
365 730).

Sampling schedule:

Blood samples for biochemistry will be taken from all infants at Screening (up 
to 14 29 days before first vaccination to Day 0) and on Day 7, Day 30, Day 37, 
and Day 60 (refer to Table 11 for the list of parameters to be tested). Blood 
samples for hematology will be taken from all infants at Screening (up to 14 29
days before first vaccination to Day 0) and on Day 1, Day 7, Day 30, Day 31, 
Day 37, and Day 60 (refer to Table 11 for the list of parameters to be tested). A 
clinical history and examination with special attention given to detection of 
spontaneous bleeding or easy bruising and evidence of bruising or petechiae will 
be performed on Day 1, Day 3 and Day 7 after each vaccination (i.e. Day 1, Day 
3, Day 7, Day 31, Day 33, and Day 37). On Day 1, Day 7, Day 31, and Day 37, 
special attention will also be given to the detection of petechiae or evidence of 
petechiae induced by the tourniquet. Further testing may be required to 
investigate a finding or guide subject management based on the investigators 
clinical judgment. Subjects’ parent(s)/LAR(s) will be instructed to contact the 
investigator/study staff if their child presents symptoms of spontaneous bleeding 
or easy bruising following vaccination. Refer to Section 6.6.11.2 and Figure 2 for 
information about the re-testing of samples in case of any Grade 1 abnormality 
with potential clinical relevance or any ≥Grade 2 abnormality.

Surveillance for RSV-RTI, difficulty in breathing and wheezing episodes.
Surveillance period will be carried out from Visit 1 (after Dose 1) until Visit 10 11
(Day 365730). In order to detect asymptomatic RSV-RTI, monthly nasal swabs for 
analysis at sponsor laboratory will be performed for all subjects during the RSV 
season. In order to timely detect RSV-RTI and to ensure cases are timely captured by 
the study sites, both active and passive surveillance will be conducted:
In Section 4.1 RTI case definitions, the following change has been made:

During the analysis of the study, all cases identified during the surveillance of RSV-
RTI will be definitively classified as either RTI, LRTI or severe LRTI according to 
the case definitions described in Table 4. The analysis may also be done using the 
available World Health Organization (WHO) case definitions for RTI, LRTI and 
severe LRTI.
In Section 4.2.1 Start date of the RTI episode, the following change has been made:

The start date of the RTI episode is defined as the point at which the first symptoms 
of cough, runny nose, blocked nose, wheezing, or difficulty breathing were observed.
 
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In Section 4.2.2 End date of the RTI episode, the following change has been made:

The end date of the RTI episode is defined as the point at which the child is 
considered symptom-free of cough, runny nose, blocked nose, wheezing, or 
difficulty breathing.
In Section 5.3 Exclusion criteria for enrolment, the following changes have been made:

History of recurrent wheezing. (Wheezing should have been verified on 
auscultation by doctor).

History of chronic cough (4 weeks or more duration).
In Section 6.2.2.2.1 Study group and treatment number allocation, the following 
change has been made:

When SBIR is not available, please refer to the SBIR user guide or the Study 
Procedures Manual (SPM) for specific instructions.
In Section 6.3 Method of blinding, the following changes have been made:

When all data up to Day 60 are available, a statistical analysis will be performed. 
This analysis may lead to the unblinding of some subjects. As a consequence, after 
Day 60, the study cannot be considered as observer-blind, but will be conducted in a 
single-blind manner, with subjects’ parent(s)/ LAR(s) remaining blinded up to study 
end (Day 365730). The investigators will not have access to the treatment allocation 
up to study end (Day 365730).
In Section 6.4 General study aspects, the following changes have been made:

Vaccination will be limited to a maximum of 10 infants per day. In the same 
investigational center, infants will be vaccinated sequentially, separated by a 
minimum interval of 60 minutes. In addition, to monitor delayed potential reactions 
following vaccination, there will be a 48-hour observation period following Dose 1 
and Dose 2 administration to the first eight infants (corresponding to three to five 
ChAd155-RSV vaccine recipients) in each Step (1, 2, and 3) before continuing 
vaccination of more infants (i.e. from the ninth infant). From the ninth infant, 
infants will be vaccinated sequentially, separated by a minimum interval of 60 
minutes.
 
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In Section 6.5 Outline of study procedures, the following changes have been made:
Table 5
List of study procedures
Epoch
Epoch 001 
Epoch 002 
Age
12-17 mth
24-29 
mth
36-41 
mth
Type of contact
Screening Visit 
1 
Visit 
2#
Visit 
3#
Visit 
4 
Visit 
5 
Visit 
6#
Visit 
7#
Visit 
8 
Visit 
9 
Visit 10 
Visit 
11 
Unscheduled 
visit for 
safety*
Contact for 
active/passive 
surveillance**
Surveillance 
for 
asymptomatic 
RSV-RTI*** 
Assessment 
of potential 
RSV-RTI****
Timepoints
D-14-29 to 
D0
D0
D1
D3
D7
D30 D31 D33 D37 D60
D365
D730
Monthly or 
Weekly
Monthly
Informed consent
●
Informed consent Addendum
●
Check inclusion/exclusion criteria
●
O
Collect demographic data
●a
Medical history
●
Physical examinationb
●
O
O
O
O
O
O
O
O
O
O
O
O
O
●
Growth monitoringc
●
●
●
●
●
Check contraindications and warnings 
and precautions
O
O
Pre-vaccination body temperature
●
●
Randomization
O
Vaccine administration
●
●
Recording of administered treatment 
number
●
●
60 minutes post-vaccination 
observationd
●O
●O
Blood sampling for RSV serostatus 
(1.0 mL)
●
Blood sampling for assessment of 
mechanisms of illness (potential ERD; 
2.5 mL) 
●l
Blood sampling for hematology (1.2 
mL) 
●e
●f
●f
●f,g
●f
●f
●f
●f
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Epoch
Epoch 001 
Epoch 002 
Age
12-17 mth
24-29 
mth
36-41 
mth
Type of contact
Screening Visit 
1 
Visit 
2#
Visit 
3#
Visit 
4 
Visit 
5 
Visit 
6#
Visit 
7#
Visit 
8 
Visit 
9 
Visit 10 
Visit 
11 
Unscheduled 
visit for 
safety*
Contact for 
active/passive 
surveillance**
Surveillance 
for 
asymptomatic 
RSV-RTI*** 
Assessment 
of potential 
RSV-RTI****
Timepoints
D-14-29 to 
D0
D0
D1
D3
D7
D30 D31 D33 D37 D60
D365
D730
Monthly or 
Weekly
Monthly
Blood sampling for biochemistry (1.1 
mL)
●e
●f
●f,g
●f
●f
●f
Blood sampling for CMI response (2.0 
mL)
●
●
●g
●
●
●
Blood sampling for humoral response 
(2.5 mL) 
●
●g
●
●
Detection of spontaneous bleeding or 
easy bruising and evidence of bruising 
or petechiae
●
●
●
●
●
●
Examination of limb for petechiae 
induced by the tourniquet 
●
●
●
●
Surveillance for RSV-RTI, difficulty in 
breathing and wheezing
O
O
O
O
O
O
O
O
O
O
O
●
●
Documentation of symptoms and signs 
of RTIj
●
Nasal swab for central testings
●m
●h
Specimen for local testings 
●n
Distribution of RTI episode cardsk
O
Collection of completed RTI episode 
cardsk
O
O
O
O
O
O
O
O
O
O
O
O
O
Transcription of completed RTI 
episode cards
●
●
●
●
●
●
●
●
●
●
O
●
●
Record any concomitant 
medications/vaccinations
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Distribution of the subject card
O
Distribution of diary card
O
O
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Epoch
Epoch 001 
Epoch 002 
Age
12-17 mth
24-29 
mth
36-41 
mth
Type of contact
Screening Visit 
1 
Visit 
2#
Visit 
3#
Visit 
4 
Visit 
5 
Visit 
6#
Visit 
7#
Visit 
8 
Visit 
9 
Visit 10 
Visit 
11 
Unscheduled 
visit for 
safety*
Contact for 
active/passive 
surveillance**
Surveillance 
for 
asymptomatic 
RSV-RTI*** 
Assessment 
of potential 
RSV-RTI****
Timepoints
D-14-29 to 
D0
D0
D1
D3
D7
D30 D31 D33 D37 D60
D365
D730
Monthly or 
Weekly
Monthly
Return of diary card
O
O
O
O
Diary card transcription by investigator
●
●
●
●
Recording of solicited AEs (Day 0-6)
●
●
●
●
●
●
●i
Recording of unsolicited AEs (Day 0-
29)
●
●
●
●
●
●
●
●
●
●i
Recording of AE leading to study 
withdrawal 
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Recording of AE of specific interest 
(RSV-LRTI) 
●
●
●
●
●
●
●
●
●
●
●
●
●
Recording of AE of specific interest 
(spontaneous or excessive bleeding)
●
●
●
●
●
●
●
●
●
Recording of SAEs 
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Screening conclusion
●
Study conclusion
●
● 
Study conclusion for GSK data 
management
●
●
Note: the double-bordered lines following Visit 9 (Day 60), and Visit 10 (Day 365) and Visit 11 (Day 730) indicate the statistical analyses which will be performed. After Visit 9 (Day 60) 
the study will be conducted in a single-blind manner, with patients remaining blinded up to study end (Day 365 730). The investigators will not have access to the treatment allocation 
up to study end (Day 365 730).
# Visit 2 (Day 1), Visit 3 (Day 3), Visit 6 (Day 31), and Visit 7 (Day 33), and Visit 11 (Day 730) may take place in the subject’s home or at the investigators clinical facility as appropriate 
to the circumstances in the judgment of the investigator.
$ This is only applicable for subject’s parent(s)/LAR(s) who have previously signed the Version 1 of the model ICF
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Table 6
Intervals between study visits
Interval
Optimal length of interval
Allowed interval
Screening Visit 1 (Day 0)
1 - 14 30 days1
-
Visit 1 (Day 0) Visit 5 (Day 30)
30 days
2823 - 3536 days2
Visit 1 (Day 0) Visit 11 (Day 730)
730 days 
700 - 760 days
1 Visit 1 should take place no longer than 14 30 days after the Screening visit. When applicable, a re-screening visit may be scheduled at any time (but only once to assess eligibility; 
blood for CMI response and humoral response will not be re-sampled). All screening procedures need to be performed within 14 30 days of Visit 1.
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In Section 6.6.10 Study vaccines administration, the following change has been made:

Across each steps, vaccination will be limited to a maximum of 10 infants per day. In 
the same investigational center, infants will be vaccinated sequentially, separated by 
a minimum interval of 60 minutes. In addition, to monitor delayed potential 
reactions following vaccination, there will be a 48-hour observation period 
following Dose 1 and Dose 2 administration to the first eight infants 
(corresponding to three to five ChAd155-RSV vaccine recipients) in each Step (1, 
2, and 3) before continuing vaccination of more infants (Refer to Section 9.10.1).
In Section 6.6.11.2 Blood sampling for hematology and biochemistry, the following 
change has been made:

at Day 7, the relevant hematology/biochemistry parameter(s) must be re-tested 
before administration of vaccine Dose 2, either during an unscheduled visit or at the 
Dose 2 vaccination visit itself (provided results are obtained before vaccination). 
Only if the concerned parameter(s) is/are within the acceptable range (i.e. within 
normal range or Grade 1 without clinical relevance), vaccine Dose 2 can be 
administered. If the concerned parameter(s) is/are not within the acceptable range by 
Day 35 (which is the maximum allowed interval for the second dosing visit, Visit 5), 
the infant will not receive Dose 2 but should still continue the study for safety 
follow-up (up to Day 365730).
In Section 6.6.14 Surveillance for RSV-RTI and wheezing, the following changes have 
been made:

Surveillance period for RSV-RTI and wheezing will start at Visit 1 (after Dose 1) 
until the final visit (Visit 10 11 [Day 365 730]). In order to timely detect RSV-RTI 
and to ensure cases are timely captured by the study sites, both active and passive 
surveillance will be conducted as described in Section 9.2. Contacts for active and 
passive surveillance will be recorded in the eCRF.

At the first vaccination visit (Visit 1 [Day 0]), an RTI episode cards will be provided 
to the subject's parent(s)/LAR(s). The subject's parent(s)/LAR(s) will record the start 
date and the end date of the following symptoms: cough, runny nose, blocked nose, 
difficulty in breathing, or wheezing. The subject's parent(s)/LAR(s) will be 
instructed to return the completed RTI episode card to the investigator at the next 
visit or by mail (e-mail or postal mail). The investigator will transcribe the collected 
information into the eCRF. Any unreturned RTI episode card will be sought from the 
subject's parent(s)/LAR(s) through telephone call(s) or any other convenient 
procedure.
In Section 6.6.18 Study conclusion, the following changes have been made:

At the last visit (Visit 10 11 [Day 365 730]), the investigator will:
 
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In Section 6.7.2 Biological samples, the following changes have been made:
Table 7
Biological samples
Total volume of blood collected for each subject from Screening to Visit 10 11 (Day 
365730)*
36.9 mL
In Section 6.7.4.1 Immunological read-outs, the following changes have been made:
Table 12
Immunological read-outs
Blood sampling timepoint
No. 
subjects
Component
Components 
priority rank
Type of contact 
and timepoint
Sampling timepoint
System
Screening (Day -
1429 to Day 0)
Pre-Vaccination
Whole blood
~96
IL-2, CD40L, 41BB, TNF-, IFN-, IL-
13, IL-17 secreting T-cells
1
Serum
96
Respiratory Syncytial virus Ab.IgG 
(RSV F or G antibody)
1
~96
Anti-RSV A Neutralizing Antibody 
2
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody ) 
3
Respiratory Syncytial Virus F protein 
Ab.IgG (Palivizumab competing Ab) 
4
In Section 7.1 Description of study vaccines, the following changes have been made:
Table 14
Study vaccines
Placebo 0.5 
Formulation 
buffer S9b 
Na2HPO4=1.3mg; 
KH2PO4=186µg; NaCl=3.85mg; 
KCl=100µg; MgCl2=50µg *
Clear liquid 
0.5 ml 
2
Placebo 0.15 
Formulation 
buffer S9b 
Na2HPO4=0.4mg; KH2PO4=56µg; 
NaCl=1,16mg; KCl=30µg; 
MgCl2=15µg *
Clear liquid 
0.15 ml 
2
In Section 7.6.1 Recording of concomitant medications/products and concomitant 
vaccinations, the following change has been made:

Any concomitant vaccination administered in the period starting 30 days before the 
first dose of study vaccines and ending at the last study visit (Day -29 to Day 
365730).
In Section 9.2 Surveillance for RSV-RTI, difficulty in breathing and wheezing 
episodes, the following changes have been made:

Each subject will be under surveillance for RSV-RTI, difficulty in breathing and 
wheezing episodes from the administration of Dose 1 (Visit 1) and will continue 
until the final visit (Visit 10 11). Surveillance will be performed via phone or e-mail 
contacts and assessment visits (refer to Figure 3). The passive and active surveillance 
contacts can also be made by/with the person designated by the parent(s)/LAR(s) 
(e.g. grandparents, nanny) as long as the parent(s)/LAR(s) have given approval.
 
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Figure 3
Decision tree for passive and active surveillance contacts
6 In case of worsening of symptoms, optional sample if the previous swab specimen was RSV-positive.
In Section 9.2.3 Active surveillance, the following changes have been made:

There will be contact between the investigator/study staff and subject’s 
parent(s)/LAR(s) on a regular basis (weekly during the RSV season and every month 
outside the RSV season). If there has not been a contact through a clinic visit (i.e. 
Visits 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11), a passive surveillance contact (refer to Section 
9.2.1), an assessment visit (refer to Section 9.2.4) or a surveillance for asymptomatic 
RSV infection (refer to Section 9.2.2), then the investigator/study staff will contact 
the subject’s parent(s)/LAR(s). The active surveillance will be performed by phone, 
mobile phone or e-mail. During each active follow-up contact, the investigator/study 
staff will:
In Section 9.3.1 Time period for detecting and recording adverse events, adverse 
events of specific interest and serious adverse events, the following changes have been 
made:
Table 18
Reporting periods for collecting safety information
Visit
SCR
V1 V2 V3
V4
V5 V6 V7
V8
V9
V10
V11
Days
-1429
to 0
0
1
3
6
7
29 30 31 33 36 37
59 60
365
730
AEs/SAEs leading to 
withdrawal from the study
AE of specific interest (RSV-
LRTI)
SAEs
SAEs related to study 
participation (start at signature 
of informed consent form) or 
concurrent GSK 
medication/vaccine
In Section 9.10.1 Limited vaccination, the following change has been made:

In the same investigational center, all infants should be vaccinated sequentially and 
at least 60 minutes apart to allow monitoring of any acute events (e.g. 
hypersensitivity reaction). All infants should be closely observed (visual follow-up 
as well as measurement of vital signs) for at least 60 minutes after vaccination. Vital 
signs are body temperature, HR, and RR. Vital signs are preferably measured when 
the infant is calm. In addition, to monitor delayed potential reactions following 
vaccination, there will be a 48-hour observation period following Dose 1 and 
 
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Dose 2 administration to the first eight infants (corresponding to three to five 
ChAd155-RSV vaccine recipients) in each Step (1, 2, and 3) before continuing 
vaccination of more infants (i.e. from the ninth infant). From the ninth infant, 
infants will be vaccinated sequentially, separated by a minimum interval of 60 
minutes. Refer to the SPM for more details about the 48-hour observation period 
after the first eight subjects vaccinated in each Step.
In Section 9.10.2 Internal safety review committee (iSRC) oversight, the following 
change has been made:

LRTI associated with RSV infection (AE of specific interest) occurring from Day 0 
to Day 365730.
In Section 9.10.3 Independent Data Monitoring Committee (IDMC) oversight, the 
following changes have been made:

The IDMC will receive the following safety data within 48 hours upon GSK 
becoming aware of:

Fatal SAEs occurring from Day 0 to Day 365730.

Life-threatening SAEs occurring from Day 0 to Day 365730.

Related SAEs occurring from Day 0 to Day 365730.

LRTI associated with RSV infection (AE of specific interest) occurring from Day 
0 to Day 365730.

The IDMC will receive the following safety data approximately monthly from 
beginning of the first RSV season and the frequency will be adapted based on the 
instruction of the IDMC:

Cumulative reports of the incidence of RSV-RTI, RSV-LRTI and RSV-severe 
LRTI. The frequency will be initially monthly from the beginning of the RSV 
season and will be adapted based on the instruction of the IDMC.
In Section 9.10.5 Holding rules, the following change has been made:
Table 21
Holding rules assessed by the investigator
Holding 
Rule
Event
Number of infants/group
Step 1
Step 2
Step 3
1c
Any local or general solicited AE leading to hospitalization
that cannot reasonably be attributed to a cause other 
than vaccination.
≥ 1
≥ 1
≥ 1
In Section 11.2 Secondary endpoints, the following changes have been made:

Occurrence of SAEs from study start (Day 0) up to study conclusion (Day 365730) 
in all subjects.
 
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
Occurrence of RSV-LRTI (AE of specific interest) as from Dose 1 administration up 
to study conclusion (Day 365730) in all subjects.

Occurrence of RSV-RTI, RSV-LRTI, severe RSV-LRTI (according to case 
definitions) as from Dose 1 administration up to study conclusion (Day 365730) in 
all subjects.
In Section 11.5.2 According-to-protocol cohort for analysis of immunogenicity, the 
following changes have been made:

Who received two doses at least one dose of study vaccine.
In Section 11.6.4 RTI and LRTI, the following changes have been made:

For the analysis of RTI and LRTI, all cases will be definitively classified as either 
RTI, LRTI or severe LRTI according to the case definitions presented in Table 4, 
and the association to RSV infection will be assessed by quantitative PCR as primary 
analysis. The analysis may also be done using the available WHO case definitions 
for RTI, LRTI and severe LRTI.
In Section 11.10 Analysis of RTI and LRTI, the following change has been made:

The analysis will be performed on the TVC on two pooled groups (i.e. pooled RSV 
and pooled Placebo) separately for first and second RSV seasons and overall.

As primary analysis, the assessment of RSV infection will be performed using the 
quantitative PCR according to case definitions presented in Table 4. The analysis 
may also be done using the available WHO case definitions for RTI, LRTI and 
severe LRTI.
In Section 11.12.1 Sequence of analyses, the following changes have been made:

The statistical analyses will be performed in 2 3 steps:

A first analysis will be performed when all data up to Day 60 (i.e. data that are as 
clean as possible) are available. Additional safety data available at the time of 
this analysis will be described. At this point, the statistician will be unblinded 
(i.e. individual subject treatment assignments will be available) and the study will 
be conducted in a single-blind manner, with patients remaining blinded up to 
study end (Day 365730). Summary results may unblind some specific subjects 
but no individual listings will be provided and the investigators will not have 
access to the treatment allocation up to study end (Day 365730), except in case 
of emergency unblinding (see Section 9.8).

An analysis will be performed when all data up to Visit 10 (Day 365; i.e. data
that are as clean as possible) are available. No individual listings will be 
provided.

The final analysis will be performed when all data up to study conclusion (Day 
365730) are available. An integrated clinical study report containing all data will 
be written and made available to the investigators at that time.
 
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In Appendix A “Laboratory Assays”, the description of the different assays performed 
during the study has been updated in order to be consistent throughout the different RSV 
project documents.
Intracellular staining (ICS)
Within 4 hours post phlebotomy, approximately 350 µL of undiluted whole blood are 
incubated at 37°C with the relevant antigen (in this case pools of 15-mer peptides 
overlapping by 11 amino acids and spanning the sequences of F, N, and M2-1 
proteins), negative control (medium), or positive control (staphylococcal enterotoxin B) 
for 2 hours in the presence of anti-CD28 and anti-CD49d antibodies. Brefeldin A, a 
protein secretion inhibitor, is then added and the mix is incubated overnight. Red cells 
are then lysed and white cells washed, fixed, cryopreserved, and stored until analysis by 
cytometry.
Once ready for cytometry analysis, white cells are thawed in batches, washed, and 
incubated with fluorochrome-conjugated antibodies specific to CD4 and CD8 surface 
markers. Then, cells are permeabilized and stained with fluorochrome-conjugated 
antibodies specific for the following immune markers: For pediatric blood samples, 
undiluted whole blood is stimulated at 37°C with the relevant antigen – in this case 
peptide pools covering proteins F, N and M2-1 - for 2 hours in the presence of anti-CD28 
and anti-CD49d antibodies. An inhibitor of intracellular protein transport (Brefeldin A) is 
added and cells are incubated overnight. Red cells are then lysed and white cells washed, 
fixed, cryopreserved, and stored until cytometric analysis.
Cells are subsequently thawed in batches, washed, and incubated with fluorochrome-
conjugated antibodies specific to CD3, CD4 and CD8 surface markers. Cells are then 
permeabilized and stained with fluorochrome-conjugated antibodies specific for immune 
markers such as IL-2, IFN-, TNF-, CD40L, IL-13, IL-17, and 41BB. After washing, 
flow cytometric acquisition is performed and the results are expressed as the frequency of 
CD4+ and CD8+ T-cells expressing any cytokine or a combination of cytokines.
Other immune markers could be added to characterize further the antigen-specific CD4+ 
or CD8+ T-cells.
After washing, acquisition of data is performed via a flow cytometer.
The results are expressed as the frequency of CD4 or CD8 T-cells expressing, per 
million of CD4 or CD8 T-cells:

At least one immune marker (to detect and measure the CD4 or CD8 T-cell 
response).

Any Th specific immune marker (to determine the Th profile of the CD4 response).
Neutralization assay
The assay comprises several steps. First, a virus neutralization step is performed by 
incubating fixed quantity of live RSV virus (RSV A long strain) with serial dilutions of 
test serum. The serum-virus reaction mixture is then transferred onto a monolayer of 
 
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Vero cells (African Green Monkey, kidney, Cercopitheus aethiops) and incubated for 3 
days. Virus-infected cells are detected by an immunofluorescence assay, using a two-step 
detection system with a primary goat anti-RSV antibody and a secondary fluorochrome-
tagged antibody (anti-Goat IgG-FITC). This antibody system detects host cell-associated 
RSV antigens and allows visualization of plaques appearing on the cell monolayer by 
immunofluorescence. The viral plaques are counted as plaque-forming units using an 
automated microscope reader.
The serum neutralizing antibody titer is reported as the inverse of the serum dilution 
which yields a 60% reduction in the number of viral plaques compared to the virus 
control without serum (Effective Dose: ED60) First, virus neutralization is performed 
by incubating a fixed amount of RSV-A long strain (ATCC No. VR-26) with serial 
dilutions of the test serum. Then, the serum-virus mixture is transferred onto a 
monolayer of Vero cells (African Green Monkey, kidney, Cercopitheus aethiops, ATCC 
CCL-81) and incubated for three days to allow infection of Vero cells by non-
neutralized viruses and the formation of plaques in the cell monolayer. Following the 
fixation period, RSV-infected cells are detected using a primary antibody directed 
against RSV (anti-RSV IgG) and a secondary antibody conjugated with fluorescein 
isothiocyanate, allowing the visualization of plaques by immunofluorescence. Viral 
plaques are counted using an automated microscope coupled to an image analyzer 
(Scanlab system with Axiovision software). For each serum dilution, a ratio, expressed 
as a percentage, is calculated between the number of plaques at that dilution and the 
number of plaques in the virus control wells (no serum added). The serum neutralizing 
antibody titer is expressed in ED60 (Estimated Dilution 60) and corresponds to the 
inverse of the interpolated serum dilution that yields a 60% reduction in the number of 
plaques compared to the virus control wells as described by others [Barbas, 1992; Bates, 
2014].
ELISA

Anti-RSV protein F ELISA
The anti-RSV protein F ELISA is an indirect ELISA allowing the detection and the 
quantification of specific IgG antibodies directed against the RSV F protein in 
human serum samples.
In summary, protein F antigen purified from Chinese Hamster Ovary expression 
system is adsorbed onto a 96-well polystyrene microplate. After a washing and a 
blocking step, dilutions of serum samples, controls and standards are added to the 
coated microplate. After incubation, the microplate is washed to remove unbound 
primary antibodies. Bound IgGs are detected by the addition of a goat anti-human 
IgG antibody, conjugated to horse-radish peroxidase. Bound antibodies are 
quantified by the addition of the horse-radish peroxidase substrate, 
tetramethylbenzidine and hydrogen peroxide, whereby a colored product develops 
proportionally to the amount of anti-RSV PreF IgG antibodies present in the serum 
sample. The antibody concentration is expressed in arbitrary EU/mL.
The anti-F protein IgG ELISA is an indirect ELISA allowing the detection and the 
quantitation of specific IgG antibodies directed against the RSV F protein in 
human serum samples. 
 
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First, F protein antigens purified from CHO expression system are coated onto 96-
well microplates. Then, after a washing and a blocking step, serial two-fold 
dilutions of test sera, controls, and reference standard are incubated to allow 
specific binding of antibodies directed against the F protein antigens. Bound IgG 
are detected by addition of a goat anti-human IgG antibody conjugated to 
horseradish peroxidase. After a washing step, the horseradish peroxidase substrate 
solution (TMB/H2O2) is added and a colored product develops proportionally to the 
amount of anti-F protein IgG antibodies present in the test serum. The color is 
quantified by reading the optical densities at 450-620 nm using a 
spectrophotometer. Antibody concentrations of individual serum and control 
samples are determined after interpolation from the reference standard curve 
using a four-parameter equation and are expressed in arbitrary ELISA units 
(EU)/mL.

Palivizumab competitive assay
Palivizumab monoclonal antibody (Synagis) is used as a passive treatment that 
protects against RSV infection by binding to the antigenic site II epitope of the RSV 
F antigen. The palivizumab competitive assay is based on the competitive binding 
process between the labeled antibody (biotinylated palivizumab) and non-labeled 
antibody (palivizumab-equivalent antibodies in serum used as reference) targeting 
the same epitope on a coated antigen. The results of the palivizumab competitive 
assay ELISA are expressed as palivizumab equivalent antibodies in µg/mL.
First, F protein antigens purified from CHO expression system are coated onto 96-
well microplates. Then, after a washing and a blocking step, serial two-fold 
dilutions of test sera, positive control serum, and palivizumab antibody reference 
standard are added in sequence with competitor antibodies (horseradish 
peroxidase-conjugated palivizumab) and incubated to allow specific binding of 
antibodies directed against the F protein antigens. If palivizumab-like antibodies 
are present in serum samples, they will compete with the horseradish peroxidase-
conjugated palivizumab antibodies for binding to the F protein coated antigen. 
After a washing step, the horseradish peroxidase substrate solution (TMB/H2O2) is 
added and a colored product develops in a manner that is inversely proportional to 
the amount of palivizumab-like antibodies contained in the test serum. The color is 
quantified by reading the optical densities at 450-620 nm using a 
spectrophotometer. Antibody concentrations of individual serum and control 
samples are determined after interpolation from the ELISA standard curve using a 
four-parameter equation and are expressed as palivizumab-equivalent antibodies 
in microgram per millilitre (µg/mL).
PCR

Quantitative PCR able to discriminate RSV-A and RSV-B subtypes:
RSV-A and RSV-B RNAs, extracted from the nasal swab are detected in a duplex 
format using specific amplification primers and fluorescent TaqMan™ probes. The 
process involves viral RNA extraction, conversion of RNA to complementary 
deoxyribonucleic acid by reverse transcription and detection by real- time PCR 
reaction using a calibration curve (absolute quantification).
 
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Briefly, RSV A and RSV B RNAs extracted from the nasal swabs are detected in a 
duplex PCR format using specific amplification primers and fluorescent probes 
designed in the RSV N gene, encoding the RSV nucleocapsid protein. The process 
involves nucleic acids extraction, conversion of RNA to complementary 
deoxyribonucleic acid by reverse transcription and detection by real- time PCR 
reaction using a calibration curve (absolute quantitation). The RSV viral load is 
reported as copies of RSV RNA per mL of sample.

Qualitative multiplex PCR for detection of a panel of 17 viruses: xTAG™ RVP 
FAST assay:
xTAG™ RVP FAST assay is a qualitative nucleic acid multiplex tests intended for 
the simultaneous detection and identification of multiple respiratory virus nucleic 
acids in nasal/nasopharyngeal swabs from individuals suspected of respiratory tract 
infections. After nucleic acid extraction, a multiplexed PCR reaction is performed to 
amplify the regions of interest in the targeted infectious agent genes. The PCR 
reaction product is then subjected to a hybridization/detection step and attached to an 
xTAG universal tag sequence. The 5’ universal tag sequence is hybridized to the 
complementary anti-tag sequence coupled to a particular bead set. The hybridized 
beads are detected and results are analyzed by the data analysis software.
After extraction of nucleic acids from the sample, a single multiplex RT-PCR is 
performed using random primers. Then, each complementary deoxyribonucleic 
acid is detected by virus-specific primers, each primer containing a unique tag 
sequence. A deoxyribonucleic acid polymerase extends the primer when there is a 
perfect match on the 3’ end of the virus specific primer. Biotin-dCTP is 
incorporated into the extending chain if extension occurs. 
Tagged amplified deoxyribonucleic acid is mixed with Luminex beads. These 
beads are coated with anti-tag oligonucleotides complementary to the tag 
sequences included in the virus-specific primers. These beads are colored making 
them spectrally distinguishable from each other. Each tagged primer hybridizes 
only to its unique anti-tag complement; therefore, each bead color represents a 
specific virus through the bead/anti-tag/tagged primer association. 
Revelation is performed by using a fluorescent reporter molecule (streptavidin-
phycoerythrin) that binds to the Biotin-dCTP included in the extended sequences. 
The beads are then analyzed by the Luminex® 200 instrument which corresponds 
to a flow-cytometer containing two lasers: one laser allows identification of the 
color-coded bead associated to each virus and one laser allows identification of the 
presence or absence of extended primer through the reporter molecule. The data 
generated by the Luminex® 200 system are expressed in Median Fluorescence 
Intensity units per bead, which are translated in a positive or negative status for 
each target.
 
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GlaxoSmithKline Biologicals SA
Vaccines R &D
Protocol Amendment 2
eTrack study number and 
Abbreviated Title:
204838 (RSV PED-002) 
IND number:
16999
EudraCT number:
2016-000117-76 
Amendment number:
Amendment 2
Amendment date:
08 June 2017
Co-ordinating author:
 (Scientific Writer, Keyrus Biopharma 
contractor for GSK Biologicals)
Rationale/background for changes:
!
During initial implementation of this study, parents have given feedback that the 
number of visits and blood tests is challenging to accommodate with busy family 
schedules and is demanding for young children. This amendment reduces 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. Assessment of platelet counts (currently at Days 1, 
7, 31 and 37) will now be repeated at Day 7 and/or Day 37 in those infants with a 
Grade 1 or greater abnormality detected at either Day 1 and/or Day 31. This is 
because the nadir of the platelet count occurred on the first day following dosing in 
the preclinical data. This modification of monitoring is judged by the Independent 
Data Monitoring Committee (IDMC) and GSK to be appropriate, as the sampling 
plan captures any potential initial fall and then subsequent recovery. The clinic visits 
at Day 3 and Day 33 including a clinical examination of the child for evidence of 
petechiae may be replaced by a phone call to inquire of the infants’ general health 
and to solicit reports of a rash, spontaneous bleeding or easy bruising, which are all 
indicative of thrombocytopenia. As an additional safety measure the subjects’ 
parent(s)/legally acceptable representative(s) (LAR[s]) will be instructed to contact 
the investigator/study staff immediately if their child develops a rash, in order to 
detect any thrombocytopenic petechiae or purpura. This will supplement the current 
instruction to report spontaneous bleeding or easy bruising in the month following 
vaccination. As there is no absolute requirement for sampling for hematology on Day 
7 or 37, the other tests of biochemistry and cell mediated immunity (CMI) are not 
requested under this amendment at these timepoints.
!
It has been clarified that blood samples for CMI and for humoral immunogenicity 
may be postponed until after the RSV serostatus is known and eligibility is 
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. These children are still at risk of respiratory 
syncytial virus (RSV) disease and could potentially benefit from this vaccine. This 
would also increase the number of subjects screened who are likely to be previously 
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exposed to RSV. Increasing the pool of RSV-seropositive children will decrease the 
number of failures to enroll after screening.

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 will exclude 
infants who have experienced prematurity and its associated complications.

Because enrolment in the trial is slower than anticipated, the safety monitoring 
oversight plan of the IDMC is 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. Moving to a next dose level will be done in the absence of a safety 
concern detected by the IDMC on the four weekly reports and after administration of 
the vaccine to all 32 subjects in the previous Step. It will be ensured that, as a 
minimum, the IDMC will have reviewed safety data of at least 16 subjects for two 
doses and given their formal approval prior to enrolling subjects to the next 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 will be allowed to participate. Therefore, blood 
sampling for the assessment of CMI will only be performed for subjects recruited in 
sites with a WBS capable laboratory in proximity. 
The following minor changes and clarifications have been made:

Further clarification is made on which visits may take place in the subject’s home as 
appropriate to the circumstances and in the judgment of the investigator (not allowed 
if blood sampling for immune response and/or vaccine administration). 

The priority ranking in blood sampling is amended to hematology > biochemistry > 
humoral response > CMI response. This is primarily a study of safety and so 
venipuncture will not be repeated for CMI or humoral response in case of 
insufficient volume at any timepoint, if safety samples have been secured. 

Safety data from study 201974 (RSV PED-001) in healthy adults have been added.

It has been clarified that RSV infections will be assessed using standardized case 
definitions based on the available World Health Organization (WHO) case 
definitions [Modjarrad, 2016].

Clarification on the reporting of temperature excursions has been added. 
Temperature excursion above -60°C and below -90°C for the ChAd155-RSV vaccine 
should be reported.

The endpoints related to CMI evaluation have been clarified.

The kit used for multiplex respiratory viral panel testing has been changed.

In addition, some typos have been corrected and other administrative changes have 
been made throughout the protocol in order to add clarity.
 
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!
Finally, changes in study personnel have been included on the protocol cover page.
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
Throughout the document, the following changes have been made:
!
The age range of infants to be enrolled has been widened, from 12 to 17 months 
initially, to 12 to 23 months.
On the protocol cover page, the following changes have been made:
Contributing authors 
!
 (Expert Scientific Writer, Keyrus 
Biopharma contractor for GSK Biologicals)
!
 (Scientific Writer, Keyrus Biopharma 
contractor for GSK Biologicals)
!
 (Lead Statistician)
!
 (Vaccine Clinical Trial Supply 
Manager Coordinator, Aixial contractor for GSK 
Biologicals)
!
 (Oversight Data Manager, Keyrus 
Biopharma contractor for GSK Biologicals)
Copyright© 2016-2017 the GlaxoSmithKline GSK group of companies or its licensor. All rights 
reserved. Unauthorized copying or use of this information is prohibited.
In the Synopsis, the following changes have been made:
Rationale for the 
study and study 
design
Rationale for the study design
!
Study population: The immunogenicity, safety and 
reactogenicity of the pediatric candidate RSV vaccine 
(ChAd155-RSV vaccine) are currently being has been 
evaluated in healthy adult subjects aged 18 to 45 years (study 
201974 [RSV PED-001]). 
!
Staggered design with 3 steps:
Within each step, aAn internal Safety Review Committee 
(iSRC) will review all accumulating accumulated safety 
data three weeks after the start of vaccination and then about 
every three weeks until the IDMC reviews the data has 
reviewed all safety data up to 30 days after administration 
of Dose 2 in Step 3 (i.e. Day 60).
The IDMC will review accumulating reactogenicity and 
safety data monthly throughout the period of vaccination 
(up to 30 days after administration of Dose 2 in Step 3, i.e. 
Day 60). The IDMC will also review incidence of all serious 
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adverse events (SAEs) and incidence of RSV-respiratory 
tract infections (RTI), RSV-LRTI, RSV-severe LRTI and 
RSV-RTI leading to hospitalization monthly after the start 
of vaccination and from beginning of the first RSV season 
to the end of the study. 
Both iSRC and IDMC will receive critical safety data (i.e. 
SAEs and adverse events of specific interest) within 48 
hours upon GSK becoming aware of it.
The iSRC and IDMC will determine whether any of the 
predefined study holding rules are met. If this is the case, 
vaccination in the study will be immediately put on hold. At 
any time, the IDMC may recommend to the sponsor to 
suspend the enrolment to the study and/or vaccination 
based on the safety data regularly arising in this study.
Moving to a next step will be conditional to the favorable 
outcome of the evaluation of safety data obtained up to 
7 days after administration of the second vaccine dose in the 
previous step (for all subjects), performed by an IDMC. Dose 
escalation will proceed after administration of the vaccine 
to all 32 subjects in the previous Step, and in the absence of 
a safety concern detected by the IDMC in the regular 
monitoring of accumulating safety data. It will be ensured 
that, as a minimum, the IDMC will have reviewed safety 
data of at least 16 subjects for two doses and given their 
formal approval prior to enrolling subjects to the next dose 
level. 
Objectives
Tertiary

To further evaluate the CMI profile induced by two IM doses 
of three dose levels of the RSV investigational vaccine when 
administered according to a 0, 1-month schedule, up to Day 
365 in RSV-seropositive infants aged 12 to 1723 months.
Study design

End of Study: Last testing results released of samples 
collected at Visit 11 (Day 730)*.
* Up to Visit 11 (Day 730), there will be monthly nasal 
swab to detect asymptomatic RSV infections during the 
RSV season and if following active or a passive 
surveillance contacts, a subject presents symptoms of RTI, 
a nasal swab will be collected.

Sampling schedule:

Blood samples for biochemistry will be taken from all 
infants at Screening (29 days before first vaccination to 
Day 0) and on Day 7, Day 30, Day 37, and Day 60. 
Blood samples for hematology will be taken from all 
infants at Screening (29 days before first vaccination to 
 
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Day 0) and on Day 1, Day 7, Day 30, Day 31, Day 37,
and Day 60. Day 7 hematology testing will be performed 
if any ≥ Grade 1 for platelet decrease is detected on Day 
1 after vaccination, to ensure its resolution. Similarly, 
hematology testing on Day 37 will be performed if any ≥ 
Grade 1 for platelet decrease is detected on Day 31. A 
clinical history and examination with special attention 
given to detection of spontaneous bleeding or easy 
bruising and evidence of bruising or petechiae will be 
performed by the investigator/study staff on Day 1, Day 
3 and Day 7 after each vaccination (i.e. Day 1, Day 3, 
Day 7, Day 31, Day 33, and Day 37). The visits on Day 3 
and Day 33 may be replaced by a phone call by the 
investigator/study staff to inquire of the infants' general 
health and to solicit reports of a rash, spontaneous 
bleeding or easy bruising. On Day 1, Day 7, and Day 31, 
and Day 37, special attention will also be given to the 
detection of petechiae or evidence of petechiae induced 
by the tourniquet. This special attention to detection of 
petechiae or evidence of petechiae induced by the 
tourniquet will also be given on Day 7 and/or Day 37 in 
case hematology testing will be performed on that day. 
Further testing may be required to investigate a finding or 
guide subject management based on the investigator’s
clinical judgment. Subjects’ parent(s)/LAR(s) will be
instructed to contact the investigator/study staff if their 
child presents symptoms of spontaneous bleeding or easy 
bruising or if their child develops a rash in the month 
following vaccination, in order to detect any 
thrombocytopenic petechiae or purpura. The 
investigator will, based on his/her medical judgement, 
appropriately investigate infants with clinical suspicion 
of low platelets.

Blood samples for CMI are limited to those in 
investigational sites with a laboratory in proximity 
capable to perform WBS necessary for the CMI assay. 
In those sites, samples will be taken from all subjects at 
Screening (or alternatively during an additional visit 
before Day 0) and on Day 7, Day 30, Day 37, Day 60, 
and Day 365.

Blood samples for humoral immunogenicity will be 
taken from all subjects at Screening (or alternatively 
during an additional visit before Day 0) and on Day 30, 
Day 60, and Day 365.

Study visits: Visit 1 (Day 0), Visit 5 (Day 30), Visit 9 (Day 
60) and Visit 10 (Day 365) must be performed at the
 
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investigators clinical facility. Visit 2 (Day 1), Visit 4 (Day 
7), Visit 6 (Day 31), Visit 8 (Day 37) and Visit 11 (Day 730) 
(no blood sampling for immune response and no vaccine 
administration) may take place in the subject’s home or at 
the investigators clinical facility as appropriate to the 
circumstances in the judgment of the investigator. Visit 3 
(Day 3) and Visit 7 (Day 33) may take place at the 
investigators clinical facility or the investigator/clinical 
staff may call the subjects’ parent(s)/LAR(s), as appropriate 
to the circumstances in the judgment of the investigator.
Case definition
During the analysis of the study, all cases identified during the 
surveillance of RSV-RTI will be definitively classified as either 
RTI, LRTI, and severe LRTI or very severe LRTI according to 
the standardized case definitions described in (see Synopsis 
Table 4) based on the available World Health Organization 
(WHO) case definitions. The analysis may also be done using the 
available World Health Organization (WHO) case definitions for 
RTI, LRTI and severe LRTI.
 
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Synopsis Table 4
Case definitions for data analysis
RSV-RTI
RSV-LRTI
severe RSV-LRTI
RSV A or B 
positive by 
quantitative PCR 
AND
Runny nose, OR
Blocked nose, 
OR
Cough
RSV A or B positive by quantitative PCR AND
Infant with RTI AND
SpO2 < 95% (measured in room air by pulse 
oximetry), OR
RR increase:
> 40/minutes 12 - 30 months of age
RSV A or B positive by quantitative PCR AND
Infant with LRTI AND
SpO2 < 92% (measured in room air by pulse 
oximetry), OR
Difficulty breathing leading to:
Irritability/agitation, OR
Lethargy/sleepiness, OR
Lower chest wall indrawing, OR
Reduced/no vocalization, OR
Apnea > 20 seconds, OR
Cyanosis, OR
Stop feeding well/dehydration
All-cause RTI
All-cause LRTI
All-cause severe LRTI
Runny nose, OR
Blocked nose, 
OR
Cough
Infant with RTI AND
SpO2 < 95% (measured in room air by pulse 
oximetry), OR
RR increase:
> 40/minutes 12 - 30 months of age
Infant with LRTI AND
SpO2 < 92% (measured in room air by pulse 
oximetry), OR
Difficulty breathing leading to:
Irritability/agitation, OR
Lethargy/sleepiness, OR
Lower chest wall indrawing, OR
Reduced/no vocalization, OR
Apnea > 20 seconds, OR
Cyanosis, OR
Stop feeding well/dehydration
PCR: polymerase chain reaction; RR: respiratory rate; SpO2: blood oxygen saturation; RTI: respiratory tract infections; 
LRTI: lower respiratory tract infections
RSV-RTI
Runny nose OR blocked nose OR cough
AND 
Confirmed RSV infection 4
RSV-LRTI
History of cough OR difficulty breathing 1
AND 
SpO2 < 95% 2, OR RR increase 3
AND 
Confirmed RSV infection 4
RSV-severe LRTI
Meeting the case definition of RSV-LRTI
AND
SpO2 < 93% 2, OR lower chest wall in-drawing
 
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RSV-very severe LRTI
Meeting the case definition of RSV-LRTI 
AND 
SpO2 < 90% 2, OR inability to feed, OR failure to respond / unconscious
RSV hospitalization
Confirmed RSV infection 5
AND
Hospitalized for acute medical condition 6
All-cause LRTI
History of cough OR difficulty breathing 1
AND 
SpO2 < 95% 2, OR RR increase 3
Definitions based on [Modjarrad, 2016]
LRTI = lower respiratory tract infections; RR = respiratory rate; RTI = respiratory tract infections; SpO2 = blood 
oxygen saturation.
1 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.
2 For blood oxygen saturation (SpO2), the lowest value monitored will be used.
3 RR increase defined as 40/minute (12 months of age or above).
4 RSV infection confirmed on nasal swab positive for RSV A or B by quantitative Reverse Transcription 
Polymerase Chain Reaction (qRT-PCR).
5 RSV sampling and testing is based on medical judgment of medical practitioner or driven by algorithm.
6 Hospitalization is defined as a medical decision that the infant requires admission for observation or 
treatment.
Endpoints
Primary

Occurrence of AEs from first vaccination (Day 0) up to Day 
60, in all infants. 

Occurrence of episode of spontaneous or excessive 
bleeding (AE of specific interest), during a 30-day follow-
up period after each vaccination, in all subjects.

Occurrence of any biochemical (alanine aminotransferase, 
aspartate aminotransferase and creatinine) laboratory 
abnormalities at Screening, Day 7, Day 30, Day 37, and 
Day 60.
Secondary

Occurrence of SAEs from study start (Day 0) up to study 
conclusion (Day 730) in all subjects.

Occurrence of RSV-LRTI (AE of specific interest) as from 
Dose 1 administration up to study conclusion (Day 730) in all 
subjects.

Occurrence of RSV-RTI, RSV-LRTI, severe RSV-LRTI 
(according to standardized case definitions) as from Dose 1 
administration up to study conclusion (Day 730) in all 
subjects.
 
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
Magnitude of the CMI response to the investigational RSV 
vaccine, pre-vaccination (Screening), post-Dose 1 (Day 7 and 
Day 30) and post-Dose 2 (Day 37, Day 60 and Day 365), in 
all subjects.

CD3+/CD4+ and CD3+/CD8+ T-cells expressing at least 
one marker at least two markers among CD40L, IL-2, 
TNF-α, and IFN-γ upon stimulation with F, N and M2-1 
peptide pools.

Humoral response to the investigational RSV vaccine, pre-
vaccination (Screening), post-Dose 1 (Day 30) and post-Dose 
2 (Day 60 and Day 365), in all subjects: 

Humoral response to the investigational RSV vaccine, pre-
vaccination (Screening), post-Dose 1 (Day 30) and post-Dose 
2 (Day 60), in all subjects:
Tertiary

CMI response profile (Th1, Th2, Th17) to the investigational 
RSV vaccine, pre-vaccination (Screening), post-Dose 1 (Day 
7 and Day 30) and post-Dose 2 (Day 37, Day 60 and Day 
365), in all subjects.

CD3+/CD4+ and/or CD3+/CD8+ T-cells expressing any 
marker or a combination of markers, for determination of 
Th profile at least one or any combination of immune 
marker(s) among CD40L, 41BB, IL-2, TNF-α, IFN-γ, 
IL-13 and IL-17 upon stimulation with F, N and M2-1 
peptide pools.

Any further exploratory immunology to detect disease-related 
or vaccine-related immune responses, such as but not limited 
to:
 
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In the List of abbreviations, the following changes have been made:
WBS:
Whole blood stimulation
In Section Trademarks, the following changes have been made:
Trademarks of the GSK group of 
companies
Generic description
Bexsero
Meningococcal group B vaccine 
(recombinant, adsorbed)
Trademarks not owned by the 
GlaxoSmithKline GSK group of 
companies
Generic description
SynagisTM (MedImmune)
Recombinant humanized monoclonal anti-
RSV antibodies
Allplex (Seegene)
Respiratory panel assay
 
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In Section 1.1.6 Pre-clinical and clinical experience, the following changes have been 
made:
The immunogenicity, safety and reactogenicity of the pediatric candidate RSV vaccine 
(ChAd155-RSV vaccine) have been evaluated in healthy adults aged 18 to 45 years 
(study 201974 [RSV PED-001; NCT02491463]) There were no significant safety 
concerns identified up to Day 60 in study RSV PED-001. Overall, the ChAd155-RSV 
vaccine high dose (Hd) (5 x 1010 vp) seems to be more reactogenic (local and general) 
than the ChAd155-RSV vaccine low dose (Ld) (5 x 109 vp), however, the reactogenicity 
profile was less than that observed in the Bexsero group. No safety signal from the 
assessed hematology parameters (hemoglobin, platelet count, prothrombin time and 
APTT) was observed in subjects receiving the ChAd155-RSV vaccine. No significant 
reductions in platelet count or clinically significant changes in coagulation parameters 
were observed up to 30 days post Dose 2. An approximately 2.4-fold increase in RSV-A 
neutralizing antibody titers (geometric mean titer [GMT] from baseline) was observed 
in both RSV-Ld and RSV-Hd after Dose 1. No booster effect was evident after Dose 2. 
An anti-F IgA and IgG antibody secreting B-cells response and an RSV F, N and M2-1 
specific IFN-γ secreting T-cells response in RSV-Hd group after the first dose were 
observed with ELISpot. There was no booster response after the second vaccination. 
There was no specific vaccine-induced CD4 T-cellular response observed with 
intracellular staining (ICS). For CD8 T-cells only a weak CD8 IFN-γ response to N 
was shown with ICS for some subjects.
Please refer to the current IB for information regarding the pre-clinical and clinical
studies of GlaxoSmithKline (GSK) Biologicals’ investigational ChAd155-RSV vaccine.
In Section 1.2.2.1. Study population, the following changes have been made:
The immunogenicity, safety and reactogenicity of the pediatric candidate RSV vaccine 
(ChAd155-RSV vaccine) are currently being has been evaluated in healthy adults aged 
18 to 45 years (study 201974 [RSV PED-001; NCT02491463]).
In Section 1.2.3. Rationale for regimen, dose and route of administration, the 
following changes have been made:
Please refer to the current IB for information regarding the pre-clinical, clinical and 
toxicology studies of GSK Biologicals’ investigational ChAd155-RSV vaccine.
In Section 1.2.4.1. Staggered design with 3 steps, the following changes have been 
made:
Within each step, aAn internal Safety Review Committee (iSRC) will review all 
accumulating accumulated safety data three weeks after the start of vaccination and then 
about every three weeks until the IDMC reviews has reviewed all safety data up to 30 
days after administration of Dose 2 in Step 3 (i.e. Day 60)the data. Ad-hoc iSRC 
meetings may be held should safety concerns warrant a safety review. Refer to Section 
9.10.2 for more information about iSRC.
 
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The IDMC will review accumulating reactogenicity and safety data monthly 
throughout the period of vaccination (up to 30 days after administration of Dose 2 in 
Step 3, i.e. Day 60). The IDMC will also review incidence of all serious adverse events 
(SAEs) and incidence of RSV-respiratory tract infections (RTI), RSV-LRTI, RSV-
severe LRTI and RSV-RTI leading to hospitalization monthly after the start of 
vaccination and from beginning of the first RSV season to the end of the study. 
Both iSRC and IDMC will receive critical safety data (i.e. SAEs and adverse events of 
specific interest) within 48 hours upon GSK becoming aware of it.
The iSRC and IDMC will determine whether any of the predefined study holding rules 
are met. If this is the case, vaccination in the study will be immediately put on hold. At 
any time, the IDMC may recommend to the sponsor to suspend the enrolment to the 
study and/or vaccination based on the safety data regularly arising in this study.
Moving to a next step will be conditional to the favorable outcome of the evaluation of 
safety data obtained up to 7 days after administration of the second vaccine dose in the 
previous step (for all subjects), performed by an IDMC. Dose escalation will proceed 
after administration of the vaccine to all 32 subjects in the previous Step, and in the 
absence of a safety concern detected by the IDMC in the regular monitoring of 
accumulating safety data. It will be ensured that, as a minimum the IDMC will have 
reviewed safety data of at least 16 subjects for two doses and given their formal 
approval prior to enrolling subjects to the next dose level.
In Section 1.2.4.2. Rationale for monitoring of hematology parameters, the following 
changes have been made:
To stay within blood sampling limits that are consistent with physiological “minimal 
risk” in this young and vulnerable population, but also to minimize any development of 
needle aversion, no blood draw will be performed for immunological assays and for 
biochemistry tests at Day 1 and none for hematology and biochemistry tests at Day 3
blood draws for the determination of hematological parameters are scheduled at Day 1 
and Day 31 (corresponding to the first day after administration of the vaccine). 
Additional specimens will be drawn if any ≥ Grade 1 for platelet decrease is detected at 
Day 1 or Day 31 to investigate clinical symptoms suggestive of low platelets. Blood 
samples collected within the screening window will serve as baseline for the 
immunological analysis and for the hematology and biochemistry check-up before 
vaccination. Consequently, the maximum blood draw volumes collected per protocol 
have been restricted to 9.0 mL within 24 hours and 32.4 26.2 mL over eight weeks (refer 
to Table 5 and Table 7). For investigational sites without a laboratory in proximity 
capable to perform whole blood stimulation [WBS] necessary for the CMI assay the 
volumes will be less.
In light of these data, a clinical examination with special attention given to the detection 
of spontaneous bleeding or easy bruising and evidence of bruising or petechiae will be 
performed by the investigator/study staff on Day 1, Day 3, and Day 7, Day 31, Day 33 
and Day 37 after each vaccination. The visits on Day 3 and Day 33 may be replaced by a 
phone call by the investigator/study staff to inquire of the infants' general health and 
to solicit reports of a rash, spontaneous bleeding or easy bruising. On Day 1 after each 
 
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vaccination, special attention will also be given to the detection of petechiae or evidence 
of petechiae induced by the tourniquet. This special attention to detection of petechiae 
or evidence of petechiae induced by the tourniquet will also be given on Day 7 and Day 
37 in case hematology testing will be performed on that day. Subjects’ parent(s)/ legally 
acceptable representative(s) (LAR[s]) will be instructed to contact the investigator/study 
staff if their child presents symptoms of spontaneous bleeding or easy bruising or if their
child develops a rash in the month following vaccination, in order to detect any 
thrombocytopenic petechiae or purpura. The investigator will, based on his/her 
medical judgement, appropriately investigate infants with clinical suspicion of low 
platelets.
Note that a broad safety hematology and biochemistry evaluation was performed at 
each study visit in adults during study RSV PED-001 (201974; NCT02491463). In this 
study, blood samples for hematology/biochemistry were taken from all subjects at all 
study visits, i.e. at Screening, on the day of vaccination (Day 0 and Day 30), 1 day post 
vaccination (Day 1 and Day 31), 3 days post vaccination (Day 3 and 33), 7 days post 
vaccination (Day 7 and 37), 30 days post Dose 2 (Day 60), on Day 180 and on Day 360. 
The safety profile of the ChAd155-RSV vaccine was found to be satisfactory by an 
IDMC. No safety signal from the assessed hematology parameters (hemoglobin, 
platelet count, prothrombin time and APTT) was observed in subjects receiving the 
ChAd155-RSV vaccine. No significant reductions in platelet count or clinically 
significant changes in coagulation parameters were observed up to 30 days post Dose 2 
(refer to Section 1.1.6 and current IB).
In Section 1.3.1. Risk Assessment, the following changes have been made:
No significant safety concerns were identified up to 30 days post Dose 2 in study RSV 
PED-001 with the ChAd155-RSV vaccine in healthy adults aged 18 to 45 years (refer 
to Section 1.1.6 and to the current IB). 
In Section 2.3. Tertiary objectives, the following changes have been made:

To further evaluate the CMI profile induced by two IM doses of three dose levels of 
the RSV investigational vaccine when administered according to a 0, 1-month 
schedule, up to Day 365 in RSV-seropositive infants aged 12 to 1723 months. 
 
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In Section 3. Study Design Overview, the following changes have been made:
Figure 1 Study design
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SE: safety evaluation solicited events;
¥ On Day 3 and Day 33, a visit may take place at the investigators clinical facility or the investigator/clinical staff may call the subjects’ parent(s)/LAR(s), as appropriate to 
the circumstances in the judgment of the investigator.
a Surveillance for RSV-RTI comprises monthly nasal swab collected to detect asymptomatic RSV infections during RSV season and active and passive surveillance contacts for RSV 
symptomatic RTI (see Section 9.2). Data about RSV–RTI incidence will be reviewed monthly by an IDMC.
Step 1 (N = 32) Ld (5x109 vp) 
ChAd155-RSV = 16
Placebo = 16
Step 2 (N = 32) Md (1.5x1010 vp)
ChAd155-RSV = 16
Placebo = 16
Step 3 (N = 32) Hd (5x1010 vp) 
ChAd155-RSV = 16
Placebo = 16
D0
D1
D7
D30
D31
D37
Dose 1
SE up to D6
Dose 2
SE up to D36
D60
D365
BSS
BSS
V1
V2 c
V4 c
V5
V6 c
V8 c
V9
V10
Visit
Day
= Blood sample for safety
BSS
Epoch 001
Epoch 002
Dose 1
SE up to D6
Dose 2
SE up to D36
Dose 1
SE up to D6
Dose 2
SE up to D36
BSS
SCR
D-29 to D0
Surveillance period for RSV RTI a
BSH
BSH
BSH
BSH
BSC
BSC
BSC
BSC
BSR
= Blood sample for humoral immunogenicity
BSH
= Blood sample for CMI
BSC
= Blood sample for RSV serostatus
BSR
iSRC/IDMC review of all accumulating reactogenicity and safetyb
Nasal swab, as applicable g
D730
V11 c
BSS
BSS
BSS
IDMC 
review
BSS
d
d
e
f
f
e
D3
V3¥
D33
V7¥
h
IDMC review of SAEb
i
i
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b Within each step, an iSRC will review accumulated all accumulating safety data three weeks after the start of vaccination and then about every three weeks (until the IDMC reviews
the data.) has reviewed all safety data up to 30 days after administration of Dose 2 in Step 3, i.e. Day 60). The IDMC will review all accumulating reactogenicity and safety 
data monthly throughout the period of vaccination (up to 30 days after administration of Dose 2 in Step 3, i.e. Day 60) and accumulating SAEs until Day 730. Refer to 
Sections 9.10.2 and. 9.10.3.
c Visit 2 (Day 1), Visit 3 (Day 3), Visit 4 (Day 7), Visit 6 (Day 31), Visit 7 (Day 33), Visit 8 (Day 37) and Visit 11 (Day 730) may take place in the subject’s home or at the investigators 
clinical facility as appropriate to the circumstances in the judgment of the investigator.
d Dose escalation will proceed after administration of the vaccine to all 32 subjects in the previous Step, and in the absence of a safety concern detected by the IDMC in 
the regular monitoring of accumulating safety data. It will be ensured that, as a minimum the IDMC will have reviewed safety data of at least 16 subjects for two doses 
and given their formal approval prior to enrolling subjects to the next dose level.
e Only for hematology.
f Day 7 hematology testing will be performed if any ≥ Grade 1 for platelet decrease is detected on Day 1 after vaccination; to ensure its resolution. Similarly, hematology 
testing on Day 37 will be performed if any ≥ Grade 1 for platelet decrease is detected on Day 31.
g Refer to Section 6.6.11.3.
h The IDMC will perform a review when all safety data up to 30 days after administration of Dose 2 in Step 3 (i.e. Day 60) are available.
i Blood samples for CMI and for humoral immunogenicity may be postponed until after the RSV serostatus is known and eligibility is confirmed up to or on Day 0 (but 
before vaccination).
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
End of Study: Last testing results released of samples collected at Visit 11 (Day 
730).*
* Up to Visit 11 (Day 730), there will be monthly nasal swab to detect 
asymptomatic RSV infections during the RSV season and if following active or a 
passive surveillance contacts, a subject presents symptoms of RTI, a nasal swab 
will be collected.

Sampling schedule:

Blood samples for biochemistry will be taken from all infants at Screening (up 
to 29 days before first vaccination to Day 0) and on Day 7, Day 30, Day 37, and 
Day 60 (refer to Table 11 for the list of parameters to be tested). Blood samples 
for hematology will be taken from all infants at Screening (up to 29 days before 
first vaccination to Day 0) and on Day 1, Day 7, Day 30, Day 31, Day 37, and 
Day 60 (refer to Table 11 for the list of parameters to be tested). Day 7 
hematology testing will be performed if any ≥ Grade 1 for platelet decrease is 
detected on Day 1 after vaccination, to ensure its resolution. Similarly, 
hematology testing on Day 37 will be performed if any ≥ Grade 1 for platelet 
decrease is detected on Day 31. A clinical history and examination with special 
attention given to detection of spontaneous bleeding or easy bruising and 
evidence of bruising or petechiae will be performed by the investigator/study 
staff on Day 1, Day 3 and Day 7 after each vaccination (i.e. Day 1, Day 3, Day 7, 
Day 31, Day 33, and Day 37). The visits on Day 3 and Day 33 may be replaced 
by a phone call by the investigator/study staff to inquire of the infants' general 
health and to solicit reports of a rash, spontaneous bleeding or easy bruising. 
On Day 1, Day 7, and Day 31, and Day 37, special attention will also be given to 
the detection of petechiae or evidence of petechiae induced by the tourniquet. 
This special attention to detection of petechiae or evidence of petechiae 
induced by the tourniquet will also be given on Day 7 and/or Day 37 in case 
hematology testing will be performed on that day. Further testing may be 
required to investigate a finding or guide subject management based on the 
investigators clinical judgment. Subjects’ parent(s)/LAR(s) will be instructed to 
contact the investigator/study staff if their child presents symptoms of 
spontaneous bleeding or easy bruising or if their child develops a rash in the 
month following vaccination, in order to detect any thrombocytopenic petechiae 
or purpura. The investigator will, based on his/her medical judgement, 
appropriately investigate infants with clinical suspicion of low platelets.

Blood samples for CMI are limited to those in investigational sites with a 
laboratory in proximity capable to perform WBS necessary for the CMI assay. 
In those sites, samples will be taken from all subjects at Screening (or 
alternatively during an additional visit before Day 0) and on Day 7, Day 30, 
Day 37, Day 60, and Day 365.
Note: Blood samples for CMI taken on Day 7 and Day 37 for subjects enrolled 
under protocol amendment 1 will still be assessed for CMI.
 
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
Blood samples for humoral immunogenicity will be taken from all subjects at 
Screening (or alternatively during an additional visit before Day 0) and on Day 
30, Day 60, and Day 365.

Study visits: Visit 1 (Day 0), Visit 5 (Day 30), Visit 9 (Day 60) and Visit 10 (Day 
365) must be performed at the investigators clinical facility. Visit 2 (Day 1), Visit 4 
(Day 7), Visit 6 (Day 31), Visit 8 (Day 37) and Visit 11 (Day 730) (no blood 
sampling for immune response and no vaccine administration) may take place in 
the subject’s home or at the investigators clinical facility as appropriate to the 
circumstances in the judgment of the investigator. Visit 3 (Day 3) and Visit 7 (Day 
33) may take place at the investigators clinical facility or the investigator/clinical 
staff may call the subjects’ parent(s)/LAR(s), as appropriate to the circumstances 
in the judgment of the investigator.
In Section 4.1 RTI case definitions, the following changes have been made:
During the analysis of the study, all cases identified during the surveillance of RSV-RTI 
will be definitively classified as either RTI, LRTI, and severe LRTI or very severe LRTI 
according to the standardized case definitions described in (see Table 4) based on the 
available World Health Organization (WHO) case definitions. The analysis may also be 
done using the available World Health Organization (WHO) case definitions for RTI, 
LRTI and severe LRTI.
Table 4 Case definitions for data analysis 
 
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RSV-RTI
RSV-LRTI*
severe RSV-LRTI*
RSV A or B 
positive by 
quantitative PCR 
AND
Runny nose, OR
Blocked nose, 
OR
Cough
RSV A or B positive by quantitative PCR AND
Infant with RTI AND
SpO2 < 95% (measured in room air by pulse 
oximetry), OR
RR increase:
> 40/minutes 12 - 30 months of age
RSV A or B positive by quantitative PCR AND
Infant with LRTI AND
SpO2 < 92% (measured in room air by pulse 
oximetry), OR
Difficulty breathing leading to:
Irritability/agitation, OR
Lethargy/sleepiness, OR
Lower chest wall indrawing, OR
Reduced/no vocalization, OR
Apnea > 20 seconds, OR
Cyanosis, OR
Stop feeding well/dehydration
All-cause RTI
All-cause LRTI
All-cause severe LRTI
Runny nose, OR
Blocked nose, 
OR
Cough
Infant with RTI AND
SpO2 < 95% (measured in room air by pulse 
oximetry), OR
RR increase:
> 40/minutes 12 - 30 months of age
Infant with LRTI AND
SpO2 < 92% (measured in room air by pulse 
oximetry), OR
Difficulty breathing leading to:
Irritability/agitation, OR
Lethargy/sleepiness, OR
Lower chest wall indrawing, OR
Reduced/no vocalization, OR
Apnea > 20 seconds, OR
Cyanosis, OR
Stop feeding well/dehydration
PCR: polymerase chain reaction; RR: respiratory rate; SpO2: blood oxygen saturation; RTI: respiratory tract infections; 
LRTI: lower respiratory tract infections
* Any infants meeting the RSV-LRTI case definition will be included in the RSV-RTI case definition and any infants 
meeting the severe RSV-LRTI case definition will be included in the RSV-LRTI and RSV-RTI case definitions.
 
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RSV-RTI
Runny nose OR blocked nose OR cough
AND 
Confirmed RSV infection 4
RSV-LRTI
History of cough OR difficulty breathing 1
AND 
SpO2 < 95% 2, OR RR increase 3
AND 
Confirmed RSV infection 4
RSV-severe LRTI
Meeting the case definition of RSV-LRTI
AND
SpO2 < 93% 2, OR lower chest wall in-drawing
RSV-very severe LRTI
Meeting the case definition of RSV-LRTI 
AND 
SpO2 < 90% 2, OR inability to feed, OR failure to respond / unconscious
RSV hospitalization
Confirmed RSV infection 5
AND
Hospitalized for acute medical condition 6
All-cause LRTI
History of cough OR difficulty breathing 1
AND 
SpO2 < 95% 2, OR RR increase 3
Definitions based on [Modjarrad, 2016]
LRTI = lower respiratory tract infections; RR = respiratory rate; RTI = respiratory tract infections; SpO2 = blood 
oxygen saturation.
1 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.
2 For blood oxygen saturation (SpO2), the lowest value monitored will be used.
3 RR increase defined as 40/minute (12 months of age or above).
4 RSV infection confirmed on nasal swab positive for RSV A or B by quantitative Reverse Transcription 
Polymerase Chain Reaction (qRT-PCR).
5 RSV sampling and testing is based on medical judgment of medical practitioner or driven by algorithm.
6 Hospitalization is defined as a medical decision that the infant requires admission for observation or 
treatment.
In Section 5.2. Inclusion criteria, the following changes have been made:

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.
 
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In Section 6.5. Outline of study procedures, the following changes have been made:
Table 5 List of study procedures 
Epoch
Epoch 001 
Epoch 002 
Age
12-1723
mth
24-2935
mth
36-41
47 mth
Type of contact
Screening Visit 
1 
Visit 
2#
Visit 
3##
Visit 
4#
Visit 
5
Visit 
6#
Visit 
7##
Visit 
8#
Visit 
9 
Visit 10 
Visit 
11#
Unscheduled 
visit for 
safety*
Contact for 
active/passive 
surveillance**
Surveillance 
for 
asymptomatic 
RSV-RTI*** 
Assessment 
of potential 
RSV-RTI****
Timepoints
D-29 to 
D0
D0
D1
D3
D7
D30 D31 D33 D37 D60
D365
D730
Monthly or 
Weekly
Monthly
Informed consent
●
Informed consent Addendum$
●
Check inclusion/exclusion criteria
●
O
Collect demographic data
●a
Medical history
●
Physical examinationb
●
O
O
O
O
O
O
O
O
O
O
O
O
O
●
Growth monitoringc
●
●
●
●
●
Check contraindications and warnings 
and precautions
O
O
Pre-vaccination body temperature
●
●
Randomization
O
Vaccine administration
●
●
Recording of administered treatment 
number
●
●
60 minutes post-vaccination 
observationd
●
●
Blood sampling for RSV serostatus 
(1.0 mL)
●
Blood sampling for assessment of 
mechanisms of illness (potential ERD; 
2.5 mL) 
●l
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Epoch
Epoch 001 
Epoch 002 
Age
12-1723
mth
24-2935
mth
36-41
47 mth
Type of contact
Screening Visit 
1 
Visit 
2#
Visit 
3##
Visit 
4#
Visit 
5
Visit 
6#
Visit 
7##
Visit 
8#
Visit 
9 
Visit 10 
Visit 
11#
Unscheduled 
visit for 
safety*
Contact for 
active/passive 
surveillance**
Surveillance 
for 
asymptomatic 
RSV-RTI*** 
Assessment 
of potential 
RSV-RTI****
Timepoints
D-29 to 
D0
D0
D1
D3
D7
D30 D31 D33 D37 D60
D365
D730
Monthly or 
Weekly
Monthly
Blood sampling for hematology (1.2 
mL)
●e
●f
●f,p
●f,g
●f
●f,p
●f
●f
Blood sampling for biochemistry (1.1 
mL)
●e
●f,
●f,g
●f,
●f
●f
Blood sampling for CMI response (2.0 
mL)o
●r
●
●g
●
●
●
Blood sampling for humoral response 
(2.5 mL) 
●r
●g
●
●
Detection of spontaneous bleeding or 
easy bruising and evidence of bruising 
or petechiae q
●
●
●
●
●
●
Examination of limb for petechiae 
induced by the tourniquet 
●
●
●
●
Surveillance for RSV-RTI, difficulty in 
breathing and wheezing
O
O
O
O
O
O
O
O
O
O
O
●
●
Documentation of symptoms and signs 
of RTIj
●
Nasal swab for central testings
●m
●h
Specimen for local testings 
●n
Distribution of RTI episode cardsk
O
Collection of completed RTI episode 
cardsk
O
O
O
O
O
O
O
O
O
O
O
O
O
Transcription of completed RTI 
episode cards
●
●
●
●
●
●
●
●
●
●
O
●
●
Record any concomitant 
medications/vaccinations
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Distribution of the subject card
O
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Epoch
Epoch 001 
Epoch 002 
Age
12-1723
mth
24-2935
mth
36-41
47 mth
Type of contact
Screening Visit 
1 
Visit 
2#
Visit 
3##
Visit 
4#
Visit 
5
Visit 
6#
Visit 
7##
Visit 
8#
Visit 
9 
Visit 10 
Visit 
11#
Unscheduled 
visit for 
safety*
Contact for 
active/passive 
surveillance**
Surveillance 
for 
asymptomatic 
RSV-RTI*** 
Assessment 
of potential 
RSV-RTI****
Timepoints
D-29 to 
D0
D0
D1
D3
D7
D30 D31 D33 D37 D60
D365
D730
Monthly or 
Weekly
Monthly
Distribution of diary card
O
O
Return of diary card
O
O
O
O
Diary card transcription by investigator
●
●
●
●
Recording of solicited AEs (Day 0-6)
●
●
●
●
●
●
●
●
●i
Recording of unsolicited AEs (Day 0-
29)
●
●
●
●
●
●
●
●
●
●i
Recording of AE leading to study 
withdrawal 
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Recording of AE of specific interest 
(RSV-LRTI) 
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Recording of AE of specific interest 
(spontaneous or excessive bleeding)
●
●
●
●
●
●
●
●
●
●
●
●
●
Recording of SAEs 
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
Screening conclusion
●
Study conclusion
● 
Study conclusion for GSK data 
management Signing of investigator 
signature form by investigator after 
Screening and before each analysis
●
●
●
●
* This visit is applicable for infants with hematological/biochemical values out of normal range or for further evaluation of clinical suspicion of low platelet count.
** Active contacts for surveillance of RSV-RTI will take place weekly during the RSV season and every month outside the RSV season (refer to Section 9.2). Passive phone contacts 
from the carers subjects’ parent(s)/LAR(s) to the investigator will take place when symptoms occur.
# Visit 2 (Day 1), Visit 3 (Day 3),Visit 4 (Day 7), Visit 6 (Day 31), Visit 7 (Day 33), Visit 8 (Day 37) and Visit 11 (Day 730) may take place in the subject’s home or at the investigators 
clinical facility as appropriate to the circumstances in the judgment of the investigator.
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## On Day 3 and Day 33, a visit may take place at the investigators clinical facility or the investigator /clinical staff may call the subjects’ parent(s)/LAR(s), as appropriate to 
the circumstances in the judgment of the investigator.
$ This is only applicable for subject’s parent(s)/LAR(s) who have previously signed the Version 12 of the model ICF
b At Screening, pPerform a complete physical examination, including assessment of vital signs (body temperature, heart rate [HR], and RR). At subsequent study visits, perform a 
physical examination only if the subject’s parent(s)/LAR(s) indicate(s) during questioning that there might be some underlying pathology(ies) or if deemed necessary.
e At Screening, for infants with hematological/biochemical values out of normal range which are expected to be temporary, a re-screening visit may be scheduled during which blood 
sample collection for hematology/biochemistry will be repeated (maximum one re-screening visit per infant is allowed; blood for CMI response and humoral response will not be re-
sampled at the re-screening visit), if already done before.
f If any Grade 1 abnormality with potential clinical relevance (according to investigators judgment) or any ≥ Grade 2 abnormality is detected, or for further evaluation of clinical 
suspicion of low platelet count, refer to Section 6.6.11.2 and Figure 2 for re-test.
hIf during passive or active surveillance contact, the investigator/study staff assesses that an infant presents a potential RSV-RTI (refer to Table 4 for definition), the potential RSV 
infection will be assessed by quantitative RT-PCR.
m Nasal swab collected at the monthly surveillance for asymptomatic RSV-RTI will be tested by quantitative RT-PCR.
o In investigational sites with a laboratory in proximity capable to perform WBS necessary for the CMI assay.
p Day 7 hematology testing will be performed if any ≥ Grade 1 for platelet decrease is detected on Day 1 after vaccination. Similarly, hematology testing on Day 37 will be 
performed if any ≥ Grade 1 for platelet decrease is detected on Day 31
q A clinical examination with special attention given to detection of spontaneous bleeding or easy bruising and evidence of bruising or petechiae will be performed by the 
investigator/study staff on Day 1, Day 3 and Day 7 after each vaccination (i.e. Day 1, Day 3, Day 7, Day 31, Day 33 and Day 37). The visits on Day 3 and Day 33 may be 
replaced by a phone call by the investigator/study staff to inquire of the infants' general health and to solicit reports of a rash, spontaneous bleeding or easy bruising. 
Subjects’ parent(s)/LAR(s) will be instructed to contact the investigator/study staff if their child presents symptoms of spontaneous bleeding or easy bruising or if their 
child develops a rash in the month following vaccination, in order to detect any thrombocytopenic petechiae or purpura.
r Blood samples for CMI and for humoral immunogenicity may be postponed until after the RSV serostatus is known and eligibility is confirmed up to or on Day 0 (but 
before vaccination).
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Table 6 Intervals between study visits 
Interval
Optimal length of interval
Allowed interval
Visit 1 (Day 0) Visit 4 (Day 7)
7 days
7 - 910 days2
Visit 5 (Day 30) Visit 8 (Day 37)
7 days
7 - 910 days2
1 Visit 1 should take place no longer than 30 days after the Screening visit. When applicable, a re-screening visit may 
be scheduled at any time (but only once to assess eligibility; blood for CMI response and humoral response will not be 
re-sampled if already done before). All screening procedures need to be performed within 30 days of Visit 1.
2 Immunogenicity data from blood samples collected outside this interval will not be eligible for inclusion in the 
according-to-protocol (ATP) cohort for analysis of immunogenicity.
In Section 6.6.5. Physical examination, the following changes have been made:
At screening, Pperform a physical examination of the subject, including assessment of 
vital signs preferably when the infant is calm. Vital signs are body temperature, heart rate 
(HR) and RR. Collected information needs to be recorded in the eCRF.
In Section 6.6.11.1. Blood sampling for RSV serostatus, humoral immunity, and cell-
mediated immunity, the following changes have been made:

A volume of 2.0 mL of whole blood should be drawn from all infants for analysis of 
CMI response at each pre-defined timepoint, in investigational sites with a 
laboratory in proximity capable to perform WBS necessary for the CMI assay.
Refer to the SPM for more details on sample storage conditions.

Blood sampling for CMI and humoral response will not be repeated in case of 
insufficient volume, at any timepoint.
In Section 6.6.11.2. Blood sampling for hematology and biochemistry, the following 
changes have been made:
Day 7 hematology testing will be performed if any ≥ Grade 1 for platelet decrease
is detected on Day 1 after vaccination. Similarly, hematology testing on Day 37 will 
be performed if any ≥ Grade 1 for platelet decrease is detected on Day 31 (refer to 
Figure 2 and Appendix C).
If any Grade 1 abnormality with potential clinical relevance (according to 
investigators judgment, refer to the glossary of terms) or any ≥Grade 2 abnormality 
is detected (refer to Figure 2 and Appendix C):

at Day 7, the relevant hematology/biochemistry parameter(s) must be re-tested 
before administration of vaccine Dose 2, either during an unscheduled visit or at 
the Dose 2 vaccination visit itself (provided results are obtained before 
vaccination). Only if the concerned parameter(s) is/are within the acceptable 
range (i.e. within normal range or Grade 1 without clinical relevance), vaccine 
Dose 2 can be administered. If the concerned parameter(s) is/are not within the 
acceptable range by Day 35 (which is the maximum within the allowed interval 
for the second dosing visit, Visit 5), the infant will not receive Dose 2 but should 
still continue the study for safety follow-up (up to Day 730).

at Days 1, 30, 31, 37 and 60 the relevant hematology/biochemistry parameter(s) 
may be re-tested as per the opinion of the investigator.
 
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Note: For safety reasons and specifically for further investigation of an AE of specific 
interest (suspected bleeding or low platelet count), blood can be re-sampled for 
hematology and biochemistry assessment.
 
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Figure 2 Schematic overview of required additional hematology and biochemistry testing during the study
Re-testing at screening
Grade 1 abnormality with 
potential clinical 
relevance  or ≥ Grade 2 
abnormality, expected to 
be temporary 
Subject may be 
enrolled in the study 
Testing may be repeated at 
any time (but only once to 
assess eligibility). 
To be performed within 
screening visit window
Grade 1 with potential clinical 
relevance  or ≥ Grade 2
Values within normal range or 
Grade 1 without clinical 
relevance
Subject not 
eligible
Grade 1 abnormality with 
potential clinical 
relevance or ≥ Grade 2 
abnormality
Re-testing during the study
If at Day 7: 
Mandatory re-testing of 
concerned parameter(s) prior to 
Dose 2 administration.
To be performed within the  visit 
window
If at any other study visit: 
Optional re-testing of 
concerned parameter(s) at the 
discretion of the investigator
Within normal range or Grade 
1 without clinical relevance 
prior to Dose 2 administration
Not within normal range or 
Grade 1 with potential clinical 
relevance or ≥ Grade 2 by 
Day 35 
Proceed with 
Dose 2 
administration
Withdraw subject 
from Dose 2  
Vaccination
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Note: For safety reasons and specifically for further investigation of an AE of specific interest (suspected bleeding or low platelet count), blood can be re-sampled for 
hematology and biochemistry assessment.
Re-testing at screening
Grade 1 abnormality with 
potential clinical 
relevance  or ≥ Grade 2 
abnormality, expected to 
be temporary 
Subject may be 
enrolled in the study 
Testing may be repeated at 
any time (but only once to 
assess eligibility). 
To be performed within 
screening visit window
Grade 1 with potential clinical 
relevance  or ≥ Grade 2
Values within normal range or 
Grade 1 without clinical 
relevance
Subject not 
eligible
Grade 1 abnormality with 
potential clinical 
relevance or ≥ Grade 2 
abnormality
Re-testing during the study
Grade 1 abnormality 
with potential clinical 
relevance or ≥ Grade 
2 abnormality
at Day 7: 
Mandatory re-testing
of concerned 
parameter(s) prior to 
Dose 2 administration.
To be performed within 
the  visit window
If at any other study 
visit: 
Optional re-testing of 
concerned parameter(s) 
at the discretion of the 
investigator
Within normal range or Grade 
1 without clinical relevance 
prior to Dose 2 administration
Not within normal range or 
Grade 1 with potential clinical 
relevance or ≥ Grade 2 by 
Day 35 
Proceed with 
Dose 2 
administration
Withdraw subject 
from Dose 2  
Vaccination
If at Day 1: 
Mandatory re-testing
of concerned 
parameter(s) at Day 7
≥ Grade 1 abnormality of 
platelets
If at Day 31: 
Mandatory re-testing of 
concerned parameter(s) 
at Day 37
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In Section 6.6.11.3. Nasal swab and other specimen for local assay, the following 
changes have been made:
Nasal swab and other specimen for local assay collected during assessment visit
If during passive or active surveillance contact, the investigator/study staff assesses that 
an infant presents a potential RSV-RTI (refer to 9.2), a nasal swab and another specimen 
for local assay will be collected during an assessment visit:

The nasal swab will allow assessing the potential RSV infection by quantitative RT-
PCR at sponsor laboratory.

The specimen for local assay will allow assessing the potential RSV infection and 
RVP at a local routine laboratory, where available. The specimen type will depend 
on the assay run locally.
Nasal swab collected to detect asymptomatic RSV infections
During RSV season, there will be monthly nasal swabs to detect asymptomatic RSV 
infections. These nasal swabs will allow assessing the potential RSV infection by 
quantitative RT-PCR at sponsor laboratory.
Cells and secretions from the nasal septum will be collected using sterile swabs. Refer to 
the SPM for more details about nasal swab.
In Section 6.6.12. Detection of spontaneous bleeding or easy bruising and evidence 
of bruising or petechiae, the following changes have been made:
Subjects’ parent(s)/LAR(s) will be instructed to contact the investigator/study staff if 
their child presents symptoms of spontaneous bleeding or easy bruising or if their child 
develops a rash in the month following vaccination, in order to detect any 
thrombocytopenic petechiae or purpura. Refer to Sections 9.1.5 and 9.4.3 for reporting 
of adverse events of specific interest (spontaneous or excessive bleeding).
At Visit 2 (Day 1), Visit 3 (Day 3)*, Visit 4 (Day 7), Visit 6 (Day 31), Visit 7 (Day 33)*, 
and Visit 8 (Day 37), the investigator will perform a clinical examination with special 
attention given to detection of spontaneous bleeding or easy bruising and evidence of 
bruising or petechiae. Episodes of spontaneous bleeding or easy bruising and evidence of 
bruising or petechiae will be recorded in the eCRF.
* The visits on Day 3 and Day 33 may be replaced by a phone call by the 
investigator/study staff to inquire of the infants' general health and to solicit reports of 
a rash, spontaneous bleeding or easy bruising.
In Section 6.6.13. Detection of petechiae or evidence of petechiae induced by the 
tourniquet, the following changes have been made:
At Visit 2 (Day 1), Visit 4 (Day 7), Visit 6 (Day 31), and Visit 8 (Day 37), the 
investigator will perform an examination of the limb where the tourniquet for blood 
sample has been placed in order to detect petechiae or evidence of petechiae induced by 
 
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the tourniquet. This special attention to detection of petechiae or evidence of petechiae 
induced by the tourniquet will also be given at Visit 4 (Day 7) and/or Visit 8 (Day 37) in 
case hematology testing will be performed on that day. Episodes of petechiae will be 
recorded in the eCRF. 
In Section 6.6.14. Surveillance for RSV-RTI and wheezing, the following changes 
have been made:
At the first vaccination visit (Visit 1 [Day 0]), RTI episode cards will be provided to the 
subject's parent(s)/LAR(s). At subsequent study visits, new RTI episode card(s) will be 
distributed as needed.
In Section 6.6.18. Signing of investigator signature form by investigator, the 
following changes have been made:
At the end of the screening visit, Visit 9 (Day 60), Visit 10 (Day 365) and Visit 11 (Day 
730), the investigator will sign the investigator signature form in the eCRF.
 
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In Section 6.7.2. Biological samples, the following changes have been made:
Table 7 Biological samples 
Sample Timepoint
Type of sample †
Subject
Number of 
subjects
Quantity
Blood
Screening
Blood sample for RSV serostatus
All infants
96
1.0 mL
Blood sample for hematology 
All infants
96
1.2 mL
Blood sample for biochemistry 
All infants
96
1.1 mL
Blood sample for cell-mediated immunogenicity 
response 
All infants††
or96
††,¥
2.0 mL
Blood sample for humoral response 
All infants
96¥
2.5 mL
Total volume of blood collected for each subject††
7.8 mL
Visit 2 (Day 
1)
Blood sample for hematology 
All infants
96
1.2 mL
Total volume of blood collected for each subject
1.2 mL
Visit 4 (Day 
7)
Blood sample for hematology 
All infants‡
96‡
1.2 mL
Blood sample for biochemistry 
All infants
96
1.1 mL
Blood sample for cell-mediated immunogenicity 
response 
All infants
96
2.0 mL
Total volume of blood collected for each subject‡
4.3 1.2 
mL
Visit 5 (Day 
30)
Blood sample for hematology 
All infants
96
1.2 mL
Blood sample for biochemistry 
All infants
96
1.1 mL
Blood sample for cell-mediated immunogenicity 
response 
All infants††
96††
2.0 mL
Blood sample for humoral response 
All infants
96
2.5 mL
Total volume of blood collected for each subject††
6.8 mL
Visit 6 (Day 
31)
Blood sample for hematology 
All infants
96
1.2 mL
Total volume of blood collected for each subject
1.2 mL
Visit 8 (Day 
37)
Blood sample for hematology 
All infants‡
96‡
1.2 mL
Blood sample for biochemistry 
All infants
96‡
1.1 mL
Blood sample for cell-mediated immunogenicity 
response 
All infants
96
2.0 mL
Total volume of blood collected for each subject‡
4.3 1.2
mL
Visit 9 (Day 
60)
Blood sample for hematology 
All infants
96
1.2 mL
Blood sample for biochemistry 
All infants
96
1.1 mL
Blood sample for cell-mediated immunogenicity 
response 
All infants††
96††
2.0 mL
Blood sample for humoral response 
All infants
96
2.5 mL
Total volume of blood collected for each subject††
6.8 mL
Total volume of blood collected for each subject††,‡ from Screening to Visit 9 (Day 60)*
32.4
26.2 mL
Visit 10 (Day 
365)
Blood sample for cell-mediated immunogenicity 
response 
All infants††
96††
2.0 mL
Blood sample for humoral response 
All infants
96
2.5 mL
Total volume of blood collected for each subject††
4.5 mL
Assessment 
of potential 
RSV-RTI 
Blood sample for assessment of mechanism of illness 
(potential ERD)
Hospitalization 
for RSV-LRTI
Hospitalization 
for RSV-LRTI
2.5 mL
Unscheduled 
visit for safety 
Blood sample for hematology 
Event-driven
Event-driven
1.2 mL
Blood sample for biochemistry 
Event-driven
Event-driven
1.1 mL
Total volume of blood collected for each subject††,‡ from Screening to Visit 11 (Day 730)*
36.9
30.7 mL
 
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Sample Timepoint
Type of sample †
Subject
Number of 
subjects
Quantity
Nasal 
swab 
Assessment 
of potential 
RSV-RTI 
Nasal swab**
Event-driven
Event-driven
-
Surveillance 
for 
asymptomatic 
RSV-RTI 
Nasal swab***
All infants
96
-
** If during passive or active surveillance contact, the investigator/study staff assesses that an infant presents a 
potential RSV-RTI (refer to Table 4 for definition), the potential RSV infection will be assessed by quantitative RT-PCR 
of nasal swab specimens taken at an assessment visit.
*** During RSV season, there will be monthly nasal swabs to detect asymptomatic RSV infections. These swabs will be 
tested by quantitative RT-PCR at sponsor laboratory.
¥ Blood samples for CMI and for humoral immunogenicity may be postponed until after the RSV serostatus is 
known and eligibility is confirmed up to or on Day 0 (but before vaccination).
† The priority ranking in blood sampling is hematology > biochemistry > humoral response > CMI response. 
Venipuncture will not be repeated for CMI and humoral response in case of insufficient volume, at any 
timepoint.
†† In investigational sites with a laboratory in proximity capable to perform WBS necessary for the CMI assay.
‡ Day 7 hematology testing will be performed if any ≥ Grade 1 for platelet decrease is detected on Day 1 after 
vaccination. Similarly, hematology testing on Day 37 will be performed if any ≥ Grade 1 for platelet decrease is 
detected on Day 31.
In Section 6.7.3. Laboratory assays, the following changes have been made:
The following laboratory assays are planned:

Frequency of interleukin 2, 13, and 17 (IL-2, IL-13 and IL-17), cluster of 
differentiation 40 ligand (CD40L), 41BB, tumor necrosis factor alpha (TNF-), and 
IFN-secreting CD3+/CD4+ and CD3+/CD8+ T-cells will be determined by 
intracellular staining (ICS) assay on whole blood samples (Table 8).

RTI will be assessed by:

Quantitative RT-PCR that is able to discriminate RSV-A and RSV-B subtypes 
(Table 10).

Qualitative multiplex PCR for detection of a panel of 17 viruses (Table 10).
Table 8
Cell-Mediated Immunity (CMI)
System
Component
Challenge
Method
Unit
Laboratory
Whole 
blood
IL-2, CD40L, 41BB,
TNF-, IFN-, IL-13, IL-
17 secreting 
CD3+/CD4+ and 
CD3+/CD8+ T-cells
Peptide pools covering 
the proteins F, N & M2-1
ICS
Events/10E6 cells 
GSK Biologicals1 or 
designated laboratory
 
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Table 10
Molecular Biology (PCR tests)
System
Component
Kit / 
Manufacturer
Method
Unit
Laboratory
Nasal 
swab
RSV A RNA 
RSV B RNA 
In-house
Quantitative
real-time RT
PCR 
Copies/ml 
GSK Biologicals1 
or designated 
laboratory
Nasal 
swab
RSV
Influenza A, including subtypes H1 and H3
Influenza A H1N1 2009
Influenza B
Parainfluenza virus type 1, 2, 3, and 4
Human Metapneumovirus
Enterovirus/Rhinovirus
Adenovirus
Bocavirus
Coronavirus - 229E, OC43, NL63, HKU1
Influenza A virus (Flu A)
Influenza B virus (Flu B)
Human respiratory syncytial virus A 
(RSV A)
Human respiratory syncytial virus B 
(RSV B)
Human Influenza A virus subtype H1 
(Flu A-H1)
Human Influenza A virus subtype H3 
(Flu A-H3)
Human Influenza A virus subtype 
H1pdm09 (Flu A-H1pdm09)
Human adenovirus (AdV)
Human metapneumovirus (MPV)
Human enterovirus (HEV)
Human parainfluenza virus 1 (PIV1)
Human parainfluenza virus 2 (PIV2)
Human parainfluenza virus 3 (PIV3)
Human parainfluenza virus 4 (PIV4)
Human bocavirus 1/2/3/4 (HBoV)
Human rhinovirus A/B/C (HRV)
Human coronavirus 229E (229E)
Human coronavirus NL63 (NL63)
Human coronavirus OC43 (OC43) 2
xTAG Respiratory
Viral Panel Fast
Allplex
Respiratory 
Panel or 
equivalent 2
Multiplex 
PCR
Qualitative 
assay 
(positive/ 
negative)
GSK Biologicals1 
or designated 
laboratory
RT: Reverse Transcription; 
2 The list of components might be subject to change in case equivalent kit is used for multiplex RVP testing.
Table 11
Hematology and biochemistry tests
System
Discipline
Component
Timepoint
Method
Scale
Laboratory
Whole blood Hematology
Hemoglobin 
Screening, Day 1, 
Day 7*, Day 30, 
Day 31, Day 37*, 
Day 60
As per local 
practice
Quantitative
Local 
laboratory
Leukocytes (White Blood 
Cells) 
Platelets 
Serum
Biochemistry
Alanine Aminotransferase 
Screening, Day 7*, 
Day 30, Day 37*,
Day 60
As per local 
practice
Quantitative
Aspartate Aminotransferase 
Creatinine 
* Day 7 hematology testing will be performed if any ≥ Grade 1 for platelet decrease is detected on Day 1 after 
vaccination. Similarly, hematology testing on Day 37 will be performed if any ≥ Grade 1 for platelet decrease is 
detected on Day 31.
 
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In Section 6.7.4.1. Immunological read-outs, the following changes have been made:
Table 12
Immunological read-outs
Blood sampling timepoint
No. 
subjects
Component
Components 
priority rank
Type of contact 
and timepoint
Sampling timepoint
System
Screening (Day -
29 to Day 0)
Pre-Vaccination
Whole blood
96*,¥
IL-2, CD40L, 41BB, TNF-, IFN-, IL-
13, IL-17 secreting T-cells
1
Serum
96
Respiratory Syncytial virus Ab.IgG 
(RSV F or G antibody)
1
96¥
Anti-RSV A Neutralizing Antibody 
2
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody ) 
3
Respiratory Syncytial Virus F protein 
Ab.IgG (Palivizumab competing Ab) 
4
Visit 4 (Day 7)
Post-Vaccination 1 Whole blood
~96
IL-2, CD40L, 41BB, TNF-, IFN-, IL-
13, IL-17 secreting T-cells
1
Visit 5 (Day 30)
Post-Vaccination 1
Whole blood
96*
IL-2, CD40L, 41BB, TNF-, IFN-, IL-
13, IL-17 secreting T-cells
1
Serum
~96
Anti-RSV A Neutralizing Antibody 
1
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody )
2
Respiratory Syncytial Virus F protein 
Ab.IgG (Palivizumab competing Ab) 
3
Visit 8 (Day 37)
Post-Vaccination 2 Whole blood
~96
IL-2, CD40L, 41BB, TNF-, IFN-, IL-
13, IL-17 secreting T-cells
1
Visit 9 (Day 60)
Post-Vaccination 2
Whole blood
96*
IL-2, CD40L, 41BB, TNF-, IFN-, IL-
13, IL-17 secreting T-cells
1
Serum
~96
Anti-RSV A Neutralizing Antibody 
1
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody ) 
2
Respiratory Syncytial Virus F protein 
Ab.IgG (Palivizumab competing Ab) 
3
Visit 10 (Day 365)
Post-Vaccination 2
Whole blood
96*
IL-2, CD40L, 41BB, TNF-, IFN-, IL-
13, IL-17 secreting T-cells
1
Serum
~96
Anti-RSV A Neutralizing Antibody 
1
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody ) 
2
* Only in investigational sites with a laboratory in proximity capable to perform WBS necessary for the CMI 
assay.
† Blood samples for CMI taken on Day 7 and Day 37 for subjects enrolled under protocol amendment 1 will still 
be assessed for CMI.
¥ Blood samples for CMI and for humoral immunogenicity may be postponed until after the RSV serostatus is 
known and eligibility is confirmed up to or on Day 0 (but before vaccination).
 
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Table 13
Molecular biology for nasal swab and specimen analysis 
Blood sampling timepoint
No. 
subjects
Component
Components 
priority rank
Type of contact 
and timepoint
Sampling 
timepoint
System
Surveillance for 
asymptomatic 
RSV-RTI 
Monthly contact 
during the RSV 
season
Nasal swab
~96
Quantitative real-time RT-PCR
(RSV A RNA and RSV B RNA)
Not applicable
Assessment of 
potential RSV-
RTI
All subjects 
attending 
assessment visit
Nasal swab
Event-
driven
Quantitative real-time RT-PCR
(RSV A RNA and RSV B RNA)
Not applicable
Assessment of 
potential RSV-
RTI
All subjects 
attending 
assessment visit 
with positive 
Quantitative RSV 
A/B RT-PCR results
Nasal swab
Event-
driven
Qualitative multiplex PCR** (RSV; 
Influenza A [including subtypes H1 and 
H3]; Influenza A H1N1 2009; Influenza 
B; Parainfluenza virus type 1, 2, 3, and 
4; Human Metapneumovirus; 
Enterovirus/Rhinovirus; Adenovirus; 
Bocavirus; Coronavirus - 229E, OC43, 
NL63, HKU1 Influenza A virus (Flu A)
Influenza B virus (Flu B)
Human respiratory syncytial virus A 
(RSV A)
Human respiratory syncytial virus B 
(RSV B)
Human Influenza A virus subtype H1 
(Flu A-H1)
Human Influenza A virus subtype H3 
(Flu A-H3)
Human Influenza A virus subtype 
H1pdm09 (Flu A-H1pdm09)
Human adenovirus (AdV)
Human metapneumovirus (MPV)
Human enterovirus (HEV)
Human parainfluenza virus 1 (PIV1)
Human parainfluenza virus 2 (PIV2)
Human parainfluenza virus 3 (PIV3)
Human parainfluenza virus 4 (PIV4)
Human bocavirus 1/2/3/4 (HBoV)
Human rhinovirus A/B/C (HRV)
Human coronavirus 229E (229E)
Human coronavirus NL63 (NL63)
Human coronavirus OC43 (OC43))
Not applicable
Assessment of 
potential RSV-
RTI
All subjects 
presenting 
confirmed LRTI* 
(with negative 
Quantitative RSV A 
and B RT-PCR 
results)
Nasal swab
Event-
driven
Qualitative multiplex PCR** (RSV; 
Influenza A [including subtypes H1 and 
H3]; Influenza A H1N1 2009; Influenza 
B; Parainfluenza virus type 1, 2, 3, and 
4; Human Metapneumovirus; 
Enterovirus/Rhinovirus; Adenovirus; 
Bocavirus; Coronavirus - 229E, OC43, 
NL63, HKU1 Influenza A virus (Flu A)
Influenza B virus (Flu B)
Human respiratory syncytial virus A 
(RSV A)
Human respiratory syncytial virus B 
(RSV B)
Human Influenza A virus subtype H1 
(Flu A-H1)
Not applicable
 
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Blood sampling timepoint
No. 
subjects
Component
Components 
priority rank
Type of contact 
and timepoint
Sampling 
timepoint
System
Human Influenza A virus subtype H3 
(Flu A-H3)
Human Influenza A virus subtype 
H1pdm09 (Flu A-H1pdm09)
Human adenovirus (AdV)
Human metapneumovirus (MPV)
Human enterovirus (HEV)
Human parainfluenza virus 1 (PIV1)
Human parainfluenza virus 2 (PIV2)
Human parainfluenza virus 3 (PIV3)
Human parainfluenza virus 4 (PIV4)
Human bocavirus 1/2/3/4 (HBoV)
Human rhinovirus A/B/C (HRV)
Human coronavirus 229E (229E)
Human coronavirus NL63 (NL63)
Human coronavirus OC43 (OC43))
** The list of components might be subject to change in case equivalent kit is used for multiplex RVP testing.
In Section 7.2. Storage and handling of study vaccines, the following changes have 
been made:
For the placebo any temperature excursion outside the range of 0.0 to +8.0C (for +2 to 
+8°C/+36 to +46°F label storage condition) and for the ChAd155-RSV vaccine any 
temperature excursion above -60°C (for -60°C/-76°F label storage condition) or 
below -90°C must be reported in the appropriate (electronic) temperature excursion 
decision form ([e]TDF).
In Section 7.5. Contraindications to subsequent vaccination, the following changes 
have been made:

Any Grade 1 abnormality with potential clinical relevance or any Grade 2 
abnormality in hematological/biochemical parameters detected in the Day 7 blood 
sample (refer to Section 6.6.11.2, Figure 2 and Appendix C).
In Section 9.2.1. Passive surveillance, the following changes have been made:
All subjects’ parent(s)/LAR(s) will be instructed to contact investigator/study staff in 
case of any new RTI symptoms (cough, runny nose or blocked nose) or in case of any 
new difficulty in breathing or wheezing. They will be also reminded to record the start 
date and the end date of RTI symptoms on the RTI episode card.

If there is any new difficulty in breathing, wheezing or parental concern, the 
investigator/study staff will schedule an assessment visit as soon as possible (refer to 
Section 9.2.4), but no later than 24 hours after the phone contact to ensure prompt 
assessment of the need for medical care.

If there is no suspicion of difficulty in breathing, nor wheezing, nor parental 
concern, but there are any new symptoms of an RTI (cough, runny nose or blocked 
nose), the investigator/study staff will schedule an assessment visit as soon as 
possible (refer to Section 9.2.4), but no later than 72 hours after the phone contact. 
 
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In Section 9.2.3. Active surveillance, the following changes have been made:
If there has not been a contact through a clinic visit/home visit/phone call (i.e. Visits 1, 2, 
3, 4, 5, 6, 7, 8, 9, 10, 11), a passive surveillance contact (refer to Section 9.2.1), an 
assessment visit (refer to Section 9.2.4) or a surveillance for asymptomatic RSV infection 
(refer to Section 9.2.2), then the investigator/study staff will contact the subject’s 
parent(s)/LAR(s).

Confirm with the subjects’ parent(s)/LAR(s), if the subject has developed new RTI 
symptoms (cough, runny nose or blocked nose) and if he/she has developed any 
symptoms of difficulty in breathing or wheezing (during and between contacts).

If there is any new or ongoing difficulty in breathing, wheezing or parental 
concern, the investigator/study staff will schedule an assessment visit as soon as 
possible (refer to Section 9.2.4), but no later than 24 hours after the contact to 
ensure prompt assessment of the need for medical care. 

If there is no suspicion of difficulty in breathing, nor wheezing, nor parental 
concern but any new symptoms of an RTI (cough, runny nose or blocked nose) 
are present, the investigator/study staff will schedule an assessment visit as soon 
as possible (refer to Section 9.2.4), but no later than 72 hours after the contact. 
 
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In Section 9.3.1. Time period for detecting and recording adverse events, adverse events of specific interest and serious adverse 
events, the following changes have been made:
Table 18 Reporting periods for collecting safety information 
Visit
SCR
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
Days
-29 to 0
0
1
3
6
7
29
30
31
33
36
37
59
60
365
730
Clinical examination with special attention 
given to the detection of episodes of 
spontaneous bleeding or easy bruising and 
evidence of bruising or petechiae*
Examination of limb for petechiae induced by 
the tourniquet**
SCR: Screening
* Clinical examination with special attention given to the detection of spontaneous bleeding or easy bruising and evidence of bruising or petechiae will be performed by the 
investigator/study staff on Day 1, Day 3, and Day 7 after each vaccination. The visits on Day 3 and Day 33 may be replaced by a phone call by the investigator/study staff to 
inquire of the infants' general health and to solicit reports of a rash, spontaneous bleeding or easy bruising. Subjects’ parent(s)/LAR(s) will be instructed to contact the 
investigator/study staff if their child presents symptoms of spontaneous bleeding or easy bruising or if their child develops a rash in the month following vaccination, in order to 
detect any thrombocytopenic petechiae or purpura.
**On Day 7 and/or Day 37, special attention to detection of petechiae or evidence of petechiae induced by the tourniquet will be given in case hematology testing will be 
performed on that day.
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In Section 9.4.2. Contact information for reporting serious adverse events and 
adverse events of specific interest, the following changes have been made:
Back-up Study Contact for Reporting SAEs and AEs of specific interest
24/24 hour and 7/7 day availability:
GSK Biologicals Clinical Safety & Pharmacovigilance
Outside US & Canada sites:
Fax: 
 or 
Email address: 
US sites only:
Fax: 
, Tel: 
Canadian sites only:
Fax: 
In Section 9.10.2. Internal safety review committee (iSRC) oversight, the following 
changes have been made:
The iSRC will review all accumulating accumulated safety data three weeks after the 
start of vaccination and then about every three weeks (until the IDMC reviews the data
has reviewed all safety data up to 30 days after administration of Dose 2 in Step 3 (i.e. 
Day 60).
In Section 9.10.3. Independent Data Monitoring Committee (IDMC) oversight, the 
following changes have been made:
!
The IDMC will receive the following safety data at the end of Steps 1, 2, and 3
monthly throughout the period of vaccination (up to 30 days after administration 
of Dose 2 in Step 3, i.e. Day 60):
!
The IDMC will receive the following safety data approximately monthly from 
beginning of the first RSV season and the frequency will be adapted based on the 
instruction of the IDMC:
∀
Cumulative reports of the incidence of RSV-RTI, RSV-LRTI, and RSV-severe 
LRTI and RSV-RTI leading to hospitalization.
In Section 9.10.4. Dose-escalation and safety evaluations by iSRC and IDMC, the 
following changes have been made:
The study will be conducted in a staggered manner to ensure maximum safety of the
participating infants progressing sequentially through the 3 dose levels (Figure 1):
!
Step 1: vaccination of 32 infants (approximately 16 infants in the RSV-Ld group and 
approximately 16 infants in the placebo-Ld group). An iSRC will review all 
accumulating accumulated safety data three weeks after the start of vaccination in 
Step 1 and then about every three weeks (until the IDMC reviews has reviewed all 
safety data up to 30 days after administration of Dose 2 in Step 3 (i.e. Day 60).the 
data). As soon as safety data up to 7 days after administration of Dose 2 for all 

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infants in Step 1 are available, the entire set of safety data will be reviewed by the 
IDMC. If there is a favorable outcome of the safety evaluation, enrolment and 
vaccination (Dose 1) of the infants in Step 2 can start. The IDMC will review all 
accumulating reactogenicity and safety data monthly throughout the period of 
vaccination (up to 30 days after administration of Dose 2 in Step 3, i.e. Day 60). 
Dose escalation will proceed after administration of the vaccine to all 32 subjects 
in the previous Step, and in the absence of a safety concern detected by the IDMC 
in the regular monitoring of accumulating safety data. It will be ensured that, as a 
minimum the IDMC will have reviewed safety data of at least 16 subjects for two 
doses (in Step 1) and given their formal approval prior to enrolling subjects to the 
next dose level (Step 2).

Step 2: vaccination of 32 infants (approximately 16 infants in the RSV-Md group 
and approximately 16 infants in the placebo-Md group). An iSRC will review all 
accumulating accumulated safety data three weeks after the start of vaccination in 
Step 2 and then about every three weeks (until the IDMC reviews has reviewed all 
safety data up to 30 days after administration of Dose 2 in Step 3 (i.e. Day 60).the 
data). As soon as safety data up to 7 days after administration of Dose 2 for all 
infants in Step 2 are available, the entire set of safety data will be reviewed by the 
IDMC. If there is a favorable outcome of the safety evaluation, enrolment and 
vaccination (Dose 1) of the infants in Step 3 can start. The IDMC will review 
accumulating reactogenicity and safety data monthly throughout the period of 
vaccination (up to 30 days after administration of Dose 2 in Step 3, i.e. Day 60). 
Dose escalation will proceed after administration of the vaccine to all 32 subjects 
in the previous Step, and in the absence of a safety concern detected by the IDMC 
in the regular monitoring of accumulating safety data. It will be ensured that, as a 
minimum the IDMC will have reviewed safety data of at least 16 subjects for two 
doses (in Step 2) and given their formal approval prior to enrolling subjects to the 
next dose level (Step 3).

Step 3: vaccination of 32 infants (approximately 16 infants in the RSV-Hd group 
and approximately 16 infants in the placebo-Hd group). An iSRC will review all 
accumulating accumulated safety data three weeks after the start of vaccination in 
Step 3 and then about every three weeks (until the IDMC reviews has reviewed all 
safety data up to 30 days after administration of Dose 2 in Step 3 (i.e. Day 60). A 
review of the entire set of safety data from Steps 1, 2 and 3 will be performed by the 
IDMC after availability of safety data up to 30 days after administration of Dose 2 in 
Step 3 (i.e. Day 60).
In Section 11.1. Primary endpoint, the following changes have been made:

Occurrence of AEs from first vaccination (Day 0) up to Day 60, in all infants.

Occurrence of episode of spontaneous or excessive bleeding (AE of specific 
interest), during a 30-day follow-up period after each vaccination, in all subjects.

Occurrence of any biochemical (alanine aminotransferase, aspartate 
aminotransferase and creatinine) laboratory abnormalities at Screening, Day 7, 
Day 30, Day 37, and Day 60. 
 
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In Section 11.2. Secondary endpoints, the following changes have been made:

Occurrence of SAEs from study start (Day 0) up to study conclusion (Day 730) in all 
subjects.

Occurrence of RSV-LRTI (AE of specific interest) as from Dose 1 administration up 
to study conclusion (Day 730) in all subjects.

Occurrence of RSV-RTI, RSV-LRTI, severe RSV-LRTI (according to standardized
case definitions) as from Dose 1 administration up to study conclusion (Day 730) in 
all subjects.

Magnitude of the CMI response to the investigational RSV vaccine, pre-vaccination 
(Screening), post-Dose 1 (Day 7 and Day 30) and post-Dose 2 (Day 37, Day 60 and 
Day 365), in all subjects.

CD3+/CD4+ and CD3+/CD8+ T-cells expressing at least one marker at least two 
markers among CD40L, IL-2, TNF-α, and IFN-γ upon stimulation with F, N 
and M2-1 peptide pools.

Humoral response to the investigational RSV vaccine, pre-vaccination (Screening), 
post-Dose 1 (Day 30) and post-Dose 2 (Day 60 and Day 365), in all subjects: 

Neutralizing antibody titers against RSV-A.

RSV F antibody concentrations.

Humoral response to the investigational RSV vaccine, pre-vaccination (Screening), 
post-Dose 1 (Day 30) and post-Dose 2 (Day 60), in all subjects:

Palivizumab-competing antibody concentrations.
In Section 11.3. Tertiary endpoints, the following changes have been made:

CMI response profile (Th1, Th2, Th17) to the investigational RSV vaccine, pre-
vaccination (Screening), post-Dose 1 (Day 7 and Day 30) and post-Dose 2 (Day 37, 
Day 60 and Day 365), in all subjects.

CD3+/CD4+ and/or CD3+/CD8+ T-cells expressing any marker or a 
combination of markers, for determination of Th profile at least one or any 
combination of immune marker(s) among CD40L, 41BB, IL-2, TNF-α, IFN-γ, 
IL-13 and IL-17 upon stimulation with F, N and M2-1 peptide pools.

Any further exploratory immunology to detect disease–related or vaccine-related 
immune responses, such as but not limited to:

Anti-vector immunity: neutralization.
In Section 11.6.4. RTI and LRTI, the following changes have been made:
For the analysis of RTI and LRTI, all cases will be definitively classified as either RTI, 
LRTI or severe LRTI according to the standardized case definitions presented in (see 
Table 4) based on the available WHO case definitions, and the association to RSV 
infection will be assessed by quantitative PCR as primary analysis. The analysis may also 
be done using the available WHO case definitions for RTI, LRTI and severe LRTI.
 
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In Section 11.9.1.1. Analysis of secondary objectives, the following changes have been 
made:
The following parameters will be summarized by group using descriptive statistics, at 
each timepoint during which blood samples are collected for CMI in investigational sites 
with a laboratory in proximity capable to perform WBS necessary for the CMI assay:

Frequency of CD8+ T-cells and T-helper cell profile (Th1, Th2, Th17) based on IL-
2, CD40L, 41BB, TNF-, IFN-, IL-13, and IL-17 secreting CD3+/CD4+ and 
CD3+/CD8+ T-cells.

Frequency of CD3+/CD4+ T-cells expressing at least two markers among CD40L, 
IL-2, TNF-α, and IFN-γ upon stimulation with F, N and M2-1 peptide pools.
In Section 11.9.1.2. Analysis of tertiary objectives, the following changes have been 
made:
The cellular immune response will be further characterized using descriptive analysis 
of the frequency of CD3+/CD8+ T-cells and CD3+/CD4+ T-helper cell profile (Th1, 
Th2, Th17) expressing at least one or any combination of marker(s) among IL-2, 
CD40L, 41BB, TNF-, IFN-, IL-13, and IL-17. 
In Section 11.10. Analysis of RTI and LRTI, the following changes have been made:
As primary analysis, the assessment of RSV infection will be performed using the 
quantitative RT-PCR according to standardized case definitions presented in (see Table 
4) based on the available WHO case definitions. The analysis may also be done using 
the available WHO case definitions for RTI, LRTI and severe LRTI.
Descriptive analyses (mean, median, min, max) of viral load assessed by the quantitative 
RT-PCR (RSV-A/B) of RSV-RTI, RSV-associated LRTI and severe LRTI cases will be 
tabulated. This analysis will also be done by study group.
The incidence rate of asymptomatic RSV infections (with 95% CI) detected by the 
quantitative PCR (RSV-A/B) will be tabulated by group. Descriptive analyses (mean, 
median, min, max) of viral load assessed by the quantitative RT-PCR (RSV-A/B) of 
those asymptomatic RSV infections will also be done by group.
In Section 14. References, the following changes have been made:
Modjarrad K, Giersing B, Kaslow DC, Smith PG, Moorthy VS; WHO RSV Vaccine 
Consultation Expert Group. WHO consultation on Respiratory Syncytial Virus 
Vaccine Development Report from a World Health Organization Meeting held on 23-
24 March 2015. Vaccine. 2016;34(2):190-7.
Zent O, Arras-Reiter C, Broeker M et al. Immediate allergic reactions after vaccinations-
a post-marketing surveillance review. Eur J Pediatr. 2002; 161: 21-5.
 
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In Appendix A Laboratory assays, the following changes have been made:
Assay descriptions could be subjects to change, due to assay re-development and/or 
qualification.
Intracellular staining (ICS)
The results are expressed as the frequency of CD4+ or CD8+ T-cells expressing, per 
million of CD4+ or CD8+ T-cells:

CD3+/CD4+ T-cells expressing at least two markers among CD40L, IL-2, TNF-α, 
and IFN-γ (poly-functional CD4+ T-cells). At least one immune marker (to detect 
and measure the CD4 or CD8 T-cell response).

CD3+/CD4+ and/or CD3+/CD8+ T-cells expressing at least one or any 
combination of immune marker(s) among CD40L, 41BB, IL-2, TNF-α, IFN-γ, IL-
13 and IL-17 (for determination of Th profile). Any Th specific immune marker (to 
determine the Th profile of the CD4 response).
PCR

Qualitative multiplex PCR for detection of a panel of viruses.
A qualitative PCR multiplex assay is used for the detection and identification of 
multiple respiratory virus nucleic acids in nasal swabs from individuals suspected 
of respiratory tract infections. The following virus types and subtypes can be 
identified in the assay:

Influenza A virus (Flu A)

Influenza B virus (Flu B)

Human Influenza A virus subtype H1 (Flu A-H1)

Human Influenza A virus subtype H3 (Flu A-H3)

Human Influenza A virus subtype H1pdm09 (Flu A-H1pdm09)

Human respiratory syncytial virus A (RSV A)

Human respiratory syncytial virus B (RSV B)

Human adenovirus (AdV)

Human metapneumovirus (MPV)

Human enterovirus (HEV)

Human parainfluenza virus 1 (PIV1)

Human parainfluenza virus 2 (PIV2)

Human parainfluenza virus 3 (PIV3)

Human parainfluenza virus 4 (PIV4)

Human bocavirus 1/2/3/4 (HBoV)
 
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
Human rhinovirus A/B/C (HRV)

Human coronavirus 229E (229E)

Human coronavirus NL63 (NL63)

Human coronavirus OC43 (OC43)
Following total nucleic acids extraction, viruses are detected by multiplex real-time 
RT-PCR assays targeting the above mentioned viruses. A comparative analysis of 
the fluorescence intensities of each target is performed to detect the viruses present 
in the sample.

17 viruses: xTAG™ RVP FAST assay:
After extraction of nucleic acids from the sample, a single multiplex RT-PCR is 
performed using random primers. Then, each complementary deoxyribonucleic acid 
is detected by virus-specific primers, each primer containing a unique tag sequence. 
A deoxyribonucleic acid polymerase extends the primer when there is a perfect 
match on the 3’ end of the virus specific primer. Biotin-dCTP is incorporated into the 
extending chain if extension occurs. 
Tagged amplified deoxyribonucleic acid is mixed with Luminex beads. These beads 
are coated with anti-tag oligonucleotides complementary to the tag sequences 
included in the virus-specific primers. These beads are colored making them 
spectrally distinguishable from each other. Each tagged primer hybridizes only to its 
unique anti-tag complement; therefore, each bead color represents a specific virus 
through the bead/anti-tag/tagged primer association. 
Revelation is performed by using a fluorescent reporter molecule (streptavidin-
phycoerythrin) that binds to the Biotin-dCTP included in the extended sequences. 
The beads are then analyzed by the Luminex® 200 instrument which corresponds to a 
flow-cytometer containing two lasers: one laser allows identification of the color-
coded bead associated to each virus and one laser allows identification of the 
presence or absence of extended primer through the reporter molecule. The data 
generated by the Luminex® 200 system are expressed in Median Fluorescence 
Intensity units per bead, which are translated in a positive or negative status for each 
target.
 
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GlaxoSmithKline Biologicals SA
Vaccines R &D
Protocol Amendment 3
eTrack study number and 
Abbreviated Title:
204838 (RSV PED-002) 
IND number:
16999
EudraCT number:
2016-000117-76 
Amendment number:
Amendment 3
Amendment date:
12 September 2017
Co-ordinating authors:
!
 (Scientific Writer, Keyrus Biopharma 
contractor for GSK Biologicals)
!
, Scientific Writer
Rationale/background for changes:
!
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 in Section 5.2 will be 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 (Table 5) in Section 6.5 and described 
in Section 6.6.3. This procedure will be applicable to all participating countries and 
will permit the identification of pre-term infants recruited in the study.
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
On the protocol cover page, the following change has been made:
Co-ordinating authors
!
, Scientific Writer
In Section 5.2. Inclusion criteria, the following change has been made:
!
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. (Required for Spain)
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In Section 6.5. Outline of study procedures, the following change has been made:
Table 5 List of study procedures
Epoch
Epoch 001
Epoch 002
Age
12-23 mth
24-35 
mth
36-47 
mth
Type of contact
Screening Visit 
1
Visit 
2#
Visit 
3##
Visit 
4#
Visit 
5
Visit 
6#
Visit 
7##
Visit 
8#
Visit 
9
Visit 10
Visit 
11#
Unscheduled 
visit for 
safety*
Contact for 
active/passive 
surveillance**
Surveillance 
for 
asymptomatic 
RSV-RTI*** 
Assessment 
of potential 
RSV-RTI****
Timepoints
D-29 to 
D0 
D0
D1
D3
D7
D30 D31 D33 D37 D60
D365
D730
Monthly or 
Weekly
Monthly
Collect birth weight and gestation at 
birth in weeks
●
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In Section 6.6.3. Collect demographic data, the following change has been made:
Record demographic data such as date of birth (day, month and year), gender, geographic 
ancestry, and ethnicity in the subject’s eCRF. Collect and record the birth weight and 
gestation at birth (in weeks) in the eCRF.
 
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GlaxoSmithKline Biologicals SA
Vaccines R &D
Protocol Amendment 4
eTrack study number and 
Abbreviated Title:
204838 (RSV PED-002) 
IND number:
16999
EudraCT number:
2016-000117-76 
Amendment number:
Amendment 4
Amendment date:
10 December 2017
Co-ordinating authors:
!
, Scientific Writer
Rationale/background for changes:
!
An Independent Data Monitoring Committee (IDMC) is reviewing all accumulating
unblinded safety and reactogenicity data on a monthly basis for this study to ensure 
that there is a timely identification of any safety signal. As safety data accumulates, 
it may be that there is 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 will apply both Frequentist and Bayesian 
approaches to the existing data, as described in Section 11.4 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 may 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. These amendment 
changes were implemented in the Synopsis and Synopsis Table 1, as well as Sections 
1.2.4.1, 1.2.4.2, 1.3, Figure 1 in Section 3, Table 1 in Section 3, Sections 5.1, 
6.2.2.2.1, Table 7 in 6.7.2, Table 11 in Section 6.7.3, Table 12 and Table 13 in 
Section 6.7.4.1, and in Sections 9.10.4 and 11.4.
!
A footnote was added to indicate the requirement to record the white blood cell 
differential including absolute neutrophil and lymphocyte counts in the eCRF to 
Table 11 in Section 6.7.3 and the toxicity grading scales for the absolute neutrophil 
and lymphocyte counts were indicated in Table 25 of Appendix C.
!
In addition, some typographical errors have been corrected throughout the protocol.
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
On the protocol cover page, the following changes were made:
Contributing authors
!
 (Project Statistician)
!
, (Clinical Trial Supply Manager)
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!
 (Central Safety Physician)
!
 (Safety Scientist)
In the Synopsis, the following changes have been made:
Rationale for the 
study and study 
design
Rationale for the study design
!
Study blinding: Given the different appearance and storage 
conditions of the investigational RSV vaccine and placebo, 
double blinding is not possible and the study will be 
conducted in an observer-blind manner.
The investigational ChAd155-RSV vaccine will be 
administered to up to 48 subjects in total. As a control, up 
to 48 subjects will be vaccinated with placebo across the 
three steps.
∀
In Step 1, 32between a maximum of 32 to a minimum 
of 16 RSV-seropositive infants will receive two doses 
of either low dose ChAd155-RSV vaccine (5 x 109 vp 
[RSV-Ld]; 0.5 mL) or placebo (0.5 mL), according to 
their random assignment.
∀
In Step 2, between a maximum of 32 to a minimum of 
16 RSV-seropositive infants will receive two doses of 
either middle dose ChAd155-RSV vaccine (1.5 x 1010
vp [RSV-Md]; 0.15 mL) or placebo (0.15 mL), 
according to their random assignment.
The iSRC and IDMC will determine whether any of the 
predefined study holding rules are met. If this is the case, 
vaccination in the study will be immediately put on hold. 
At any time, the IDMC may recommend to the sponsor to 
suspend the enrolment to the study and/or vaccination 
based on the safety data regularly arising in this study.
Dose escalation will proceed after administration of the 
vaccine to all 32 subjects in the previous Step, and in the 
absence of a step if no significant safety concern is 
detected by the IDMC in thetheir regular monitoringreview 
of accumulating safety data. It will be ensured that, as a 
minimum, theThe IDMC will have reviewedmay 
recommend for dose escalation to proceed in the absence 
of a concern based on safety data review on a minimum 
of at least 16 subjects for two doses and given their formal 
approval prior to enrolling subjects completing dose 2. The
IDMC may recommend that based on the evolving safety 
profile, sufficient information has been accumulated to 
allow safe progression to the next sequential dose level.
Thus, the number of subjects enrolled to the low and mid 
dose is between 16 and 32 subjects but the number of 
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subjects enrolled to the high dose remains fixed at 32 
subjects.
In the Synopsis Table 1 Study groups and epochs foreseen in the study a footnote
was added as follows:
*The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the time of first 
vaccination (unless the dose escalation IDMC decision can be made based on the evaluation of 
accumulating safety data on fewer subjects) to ensure that at least 64 infants receive two doses of study 
vaccine (ChAd155-RSV or Placebo). Then the number of subjects at each step will be at least 16 
(approximately 8 subjects per group) at steps 1 and 2 and 32 (approximately 16 subjects per group) at step 3.
Number of subjects
The target will be to enroll approximately up to 96 RSV-
seropositive infants (32 infants per step) aged 12 to 23 months 
at the time of first vaccination (unless the dose escalation 
IDMC decision can be made based on the evaluation of 
accumulating safety data on fewer subjects) to ensure that 96at 
least 64 infants receive at least one dose two doses of study 
vaccine. (ChAd155-RSV or Placebo).
LIST OF ABBREVIATIONS
mm³
cubic millimeter
In Section 1.2.4. Rationale for safety monitoring plan, the following changes have
been made:
The Section 1.2.4.1. Rationale for earlier dose escalation decision making, was added.
Under Amendment 4 of the protocol, the IDMC may on reviewing of the accumulating 
safety data recommend that dose escalation can safely proceed based on the experience 
of a minimum of 16 subjects.
Taking the a priori safety concern of thrombocytopenia, both Frequentist and 
Bayesian approaches are applied to provide complementary assurance on the 
possibility to exclude a signal based on the accumulated safety data. The Frequentist 
approach examines the statistical power to rule out a significant decrease in platelet 
counts due to vaccination that would suggest a four-fold or greater increase in the risk 
of a Grade 3 or higher thrombocytopenia with 16 subjects per dose cohort. The 
Bayesian approach calculates the posterior predictive probability of not observing any 
subject with a Grade 3 or higher thrombocytopenia among the future 16 subjects by 
basing it on what we have observed in the first 16 subjects (see Section 11.4).
 
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In Section 1.2.4.2 Staggered design with 3 steps, the following changes have been 
made:
The target will be to enroll approximately up to 96 RSV-seropositive infants aged 12 to 
23 months at the time of first vaccination (unless the dose escalation IDMC decision 
can be made based on the evaluation of accumulating safety data on fewer subjects) to 
ensure that 96at least 64 infants receive at least one dose two doses of study vaccine. The 
(ChAd155-RSV vaccine will be administered to 48 subjects in total. As a control, 48 
subjects will be administered with placebo across the three steps.or Placebo).

In Step 1, 32between a maximum of 32 to a minimum of 16 RSV-seropositive 
infants will receive two doses of either low dose ChAd155-RSV vaccine (5 x 109 vp 
[RSV-Ld]; 0.5 mL) or placebo (0.5 mL), according to their random assignment.

In Step 2, between a maximum of 32 to a minimum of 16 RSV-seropositive infants 
will receive two doses of either middle dose ChAd155-RSV vaccine (1.5 x 1010 vp 
[RSV-Md]; 0.15 mL) or placebo (0.15 mL), according to their random assignment.

In Step 3, 32 RSV-seropositive infants will receive two doses of either high dose 
ChAd155-RSV vaccine (5 x 1010 vp [RSV-Hd]; 0.5 mL) or placebo (0.5 mL), 
according to their random assignment.
Dose escalation will proceed after administration of two doses of the vaccine to all 32 
subjects in the previous Step, and . However, in the absence of a significant safety 
concern detected in the regular monitoring of accumulating safety data on at least 16 
subjects, the IDMC may allow for dose escalation to proceed without the requirement 
of enrolling and evaluating the full group size of 32 subjects. A subsequent dose 
escalation will proceed after administration of two doses of the vaccine to between a 
maximum of 32 to a minimum of 16 subjects in in the absence of a significant safety 
concern detected by the IDMC in the regular monitoring of accumulating safety data.
Thus, upon review of the accumulating safety data on a minimum of 16 subjects after 
administration of two doses of the vaccine, the IDMC may decide that based on the 
evolving safety profile, sufficient information has been accumulated to allow safe 
progression to the next sequential dose level. It will be ensured that, as a minimum the 
IDMC will have reviewed safety data of at least 16 subjects for two doses and given their 
formal approval prior to enrolling subjects to the next dose level.
In Section 1.2.5. Rationale for study blinding, the following change has been made:
Given the different appearance and storage conditions of the investigational RSV vaccine 
and placebo, double blinding is not possible and the study will be conducted in an 
observer-blind manner.
In Section 1.3. Benefit : Risk Assessment, the following change has been made:
Approximately Hhalf of the infants (between 32 and 48) in this study will be exposed to 
the ChAd155-RSV vaccine, whereas the other infants will receive a placebo.
 
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In Section 3. STUDY DESIGN OVERVIEW, the following change has been made:
In the Figure 1 Study Design, footnote d has been modified as follows:
d Dose escalation will proceed after administration of two doses of the vaccine to all 32 subjects in the previous Step, 
and 1. However, in the absence of a significant safety concern detected in the regular monitoring of accumulating 
safety data on at least 16 subjects, the IDMC may allow for dose escalation to proceed without the 
requirement of enrolling and evaluating the full group size of 32 subjects. A subsequent dose escalation 
(from Step 2 to Step 3) will proceed after administration of two doses of the vaccine to between a maximum
of 32 to a minimum of 16 subjects in the absence of a significant safety concern detected by the IDMC in the 
regular monitoring of accumulating safety data. Thus, upon review of the accumulating safety data on a 
minimum of 16 subjects after administration of two doses of the vaccine, the IDMC may decide that based on 
the evolving safety profile, sufficient information has been accumulated to allow safe progression to the next 
sequential dose level. It will be ensured that, as a minimum the IDMC will have reviewed safety data of at least 16 
subjects for two doses and given their formal approval prior to enrolling subjects to the next dose level.
In the Table 1 Study groups and epochs foreseen in the study a footnote was added as 
follows:
*The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the time of first 
vaccination (unless the dose escalation IDMC decision can be made based on the evaluation of accumulating 
safety data on fewer subjects) to ensure that at least 64 infants receive two doses of study vaccine (ChAd155-
RSV or Placebo) (see Section 5.1). Then the number of subjects at each step will be at least 16 (approximately 
8 subjects per group) at steps 1 and 2 and 32 (approximately 16 subjects per group at step 3).
In Section 5.1. Number of subjects, the following change has been made:
The target will be to enroll approximately up to 96 RSV-seropositive infants (32 infants 
per step) aged 12 to 23 months at the time of first vaccination (unless the dose escalation 
IDMC decision can be made based on the evaluation of accumulating safety data on
fewer subjects to ensure that 96at least 64 infants receive at least one dose two doses of 
study vaccine (ChAd155-RSV or Placebo). Refer to Section 11.4 for the determination of 
sample size.
In Section 6.2.2.2.1. Study group and treatment number allocation, the following 
changes have been made:
The target will be to enroll approximately up to 96 RSV-seropositive infants (32 infants 
per step)aged 12 to 23 months at the time of first vaccination (unless the dose escalation 
IDMC decision can be made based on the evaluation of accumulating safety data on
fewer subjects to ensure that 96at least 64 infants receive at least one dose two doses of 
study vaccine (ChAd155-RSV or Placebo) (see Section 5.1). Infants will be randomly 
assigned to two study groups per step in a (1:1) ratio (approximately 16 subjects in each 
group).

In Step 1, between approximately 8 and 16 RSV-seropositive infants will be 
randomly assigned to receive low dose ChAd155-RSV vaccine (5 x 109 vp [RSV-
Ld]; 0.5 mL) and between approximately 8 and 16 RSV-seropositive infants will be 
randomly assigned to receive placebo (0.5 mL).

In Step 2, between approximately 8 and 16 RSV-seropositive infants will be 
randomly assigned to receive middle dose ChAd155-RSV vaccine (1.5 x 1010 vp 
 
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[RSV-Md]; 0.15 mL) and between approximately 8 and 16 RSV-seropositive infants
will be randomly assigned to receive placebo (0.15 mL).

In Step 3, approximately 16 RSV-seropositive infants will be randomly assigned to 
receive high dose ChAd155-RSV vaccine (5 x 1010 vp [RSV-Hd]; 0.5 mL) and 
approximately 16 RSV-seropositive infants will be randomly assigned to receive 
placebo (0.5 mL).
In Section 6.6.8. Assess pre-vaccination body temperature, the following change has
been made:
The axillary, rectal, oral, or tympanic body temperature of all subjects needs to be 
measured prior to any study vaccines administration.
In Section 6.7.2. Biological samples, the following changes have been made:
In the Table 7 Biological samples, a footnote was added as follows:
Sample Timepoint
Type of sample†
Subject Number of 
subjects§
Quantity
§ The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the time of first 
vaccination (unless the dose escalation IDMC decision can be made based on the evaluation of accumulating 
safety data on fewer subjects) to ensure that at least 64 infants receive two doses of study vaccine (ChAd155-
RSV or Placebo) (see Section 5.1).
In Section 6.7.3. Laboratory assays, the following changes have been made:
In the Table 11 Hematology and biochemistry tests, a footnote was added as follows:
System
Discipline
Component
Timepoint
Method
Scale
Laboratory
Whole blood Hematology
Hemoglobin
Screening, Day 1, 
Day 7*, Day 30, 
Day 31, Day 37*, 
Day 60
As per local 
practice
Quantitative
Local 
laboratory
Leukocytes (White Blood 
Cells)**
Platelets
Serum
Biochemistry
Alanine Aminotransferase
Screening, Day 
30, Day 60
As per local 
practice
Quantitative
Aspartate Aminotransferase
Creatinine
** White Blood Cell differential including absolute neutrophil and lymphocyte counts must be recorded in the 
eCRF.
In Section 6.7.4.1. Immunological read-outs, the following changes have been made:
In the Table 12 Immunological read-outs, a footnote was added as follows:
 
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Blood sampling timepoint
No. 
subjects†
Component
Components 
priority rank
Type of contact 
and timepoint*
Sampling timepoint
System
Screening (Day -
29 to Day 0)
Pre-Vaccination
Whole blood
96*,¥‡,¥
IL-2, CD40L, 41BB, TNF-, IFN-, 
IL-13, IL-17 secreting T-cells
1
Serum
96
Respiratory Syncytial virus Ab.IgG
(RSV F or G antibody)
1
96¥
Anti-RSV A Neutralizing Antibody
2
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody ) 
3
Respiratory Syncytial Virus F protein 
Ab.IgG (Palivizumab competing Ab) 
4
Visit 5 (Day 30)
Post-Vaccination 1
Whole blood
96*‡
IL-2, CD40L, 41BB, TNF-, IFN-, 
IL-13, IL-17 secreting T-cells
1
Serum
~96
Anti-RSV A Neutralizing Antibody
1
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody )
2
Respiratory Syncytial Virus F protein 
Ab.IgG (Palivizumab competing Ab) 
3
Visit 9 (Day 60)
Post-Vaccination 2
Whole blood
96*‡
IL-2, CD40L, 41BB, TNF-, IFN-, 
IL-13, IL-17 secreting T-cells
1
Serum
~96
Anti-RSV A Neutralizing Antibody
1
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody ) 
2
Respiratory Syncytial Virus F protein 
Ab.IgG (Palivizumab competing Ab) 
3
Visit 10 (Day 365)
Post-Vaccination 2
Whole blood
96*‡
IL-2, CD40L, 41BB, TNF-, IFN-, 
IL-13, IL-17 secreting T-cells
1
Serum
~96
Anti-RSV A Neutralizing Antibody
1
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody ) 
2
CD40L: cluster of differentiation 40 ligand; IFN-: interferon gamma; IgG: immunoglobulin G; IL (IL-2; IL-13; IL-17): 
interleukin; TNF-: tumor necrosis factor alpha; RSV: respiratory syncytial virus.
* Only in investigational sites with a laboratory in proximity capable to perform WBS necessary for the CMI assay.
†* Blood samples for CMI taken on Day 7 and Day 37 for subjects enrolled under protocol amendment 1 will still be 
assessed for CMI.
† The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the time of first 
vaccination (unless the dose escalation IDMC decision can be made based on the evaluation of accumulating 
safety data on fewer subjects) to ensure that at least 64 infants receive two doses of study vaccine (ChAd155-
RSV or Placebo) (see Section 5.1).
‡Only in investigational sites with a laboratory in proximity capable to perform WBS necessary for the CMI assay.
¥ Blood samples for CMI and for humoral immunogenicity may be postponed until after the RSV serostatus is known 
and eligibility is confirmed up to or on Day 0(but before vaccination).
In the Table 13 Molecular biology for nasal swab and specimen analysis, a footnote 
was added as follows:
Blood sampling timepoint
No. 
subjects†
Component
Components 
priority rank
Type of contact 
and timepoint
Sampling 
timepoint
System
† The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the time of first 
vaccination (unless the dose escalation IDMC decision can be made based on the evaluation of accumulating 
safety data on fewer subjects) to ensure that at least 64 infants receive two doses of study vaccine (ChAd155-
RSV or Placebo) (see Section 5.1).
 
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In Section 9.10.4. Dose-escalation and safety evaluations by iSRC and IDMC, the 
following changes have been made:

Step 1: vaccination of a maximum of 32 infants (approximately 16 infants in the 
RSV-Ld group and approximately 16 infants in the placebo-Ld group). An iSRC will 
review all accumulating safety data three weeks after the start of vaccination in Step 
1 and then about every three weeks (until the IDMC has reviewed all safety data up 
to 30 days after administration of Dose 2 in Step 3 (i.e. Day 60). The IDMC will 
review all accumulating reactogenicity and safety data monthly throughout the 
period of vaccination (up to 30 days after administration of Dose 2 in Step 3, i.e. Day 
60). Dose escalation to Step 2 will proceed after administrationcompletion of the 
vaccine to allvaccination for 32 subjects in the previous step, and in the absence of a 
significant safety concern detected by the IDMC in the regular monitoring of 
accumulating safety data. However, in the absence of a significant safety concern 
detected in the regular monitoring of accumulating safety data on at least 16 
subjects, the IDMC may recommend for dose escalation to proceed without the 
requirement of enrolling and evaluating the full group size of 32 subjects. A 
subsequent dose escalation will proceed after administration of two doses of the 
vaccine to between a maximum of 32 to a minimum of 16 subjects in the absence 
of a significant safety concern detected by the IDMC in the regular monitoring of 
accumulating safety data. It will be ensured that, as a minimum the IDMC will have 
reviewed safety data of at least 16 subjects for two doses (in Step 1) and given their 
formal approval prior to enrolling subjects to the next dose level (Step 2).

Step 2: vaccination of a maximum of 32 infants (approximately 16 infants in the 
RSV-Md group and approximately 16 infants in the placebo-Md group). An iSRC 
will review all accumulating safety data three weeks after the start of vaccination in 
Step 2 and then about every three weeks (until the IDMC has reviewed all safety data 
up to 30 days after administration of Dose 2 in Step 3 (i.e. Day 60). The IDMC will 
review accumulating reactogenicity and safety data monthly throughout the period of 
vaccination (up to 30 days after administration of Dose 2 in Step 3, i.e. Day 60). 
Dose escalation to Step 3 will proceed after administration of two doses of the 
vaccine to all 32 subjects in the previous step, and in the absence of a significant 
safety concern detected by the IDMC in the regular monitoring of accumulating 
safety data. However, as for the dose escalation from Step 1 to Step 2, in the 
absence of a significant safety concern detected in the regular monitoring of 
accumulating safety data on at least 16 subjects, the IDMC may again allow for 
dose escalation to proceed without the requirement of enrolling and evaluating the 
full group size of 32 subjects. A subsequent dose escalation will proceed after 
administration of two doses of the vaccine to between a maximum of 32 to a 
minimum of 16 subjects in the absence of a significant safety concern detected by 
the IDMC in the regular monitoring of accumulating safety data. It will be ensured 
that, as a minimum the IDMC will have reviewed safety data of at least 16 subjects 
for two doses (in Step 2) and given their formal approval prior to enrolling subjects 
to the next dose level (Step 3).
 
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In Section 9.10.5. Holding rules, the following change has been made:
Figure 4
Evaluations based on 16 subjects - Risk assessment curve for one 
formulation based on the proposed safety holding rules
The above figure illustrates that, with a maximum of 16 subjects per study group:
In Section 11.4. Determination of sample size, the following changes have been made:
No hypothesis driven sample size calculation was conducted due to the nature of 
descriptive summary of the study objectives. The sample size of 32 subjects per dose 
cohort/Step, randomized 1:1 to vaccine or placebo, was based on conventional study 
designs for Phase 1/2 trials. Specifically, if no adverse event was observed among 16 
RSV vaccinated subjects, the exact, two-sided 95% confidence interval (CI) would rule 
out an AE rate of 20% or more; if the incidence rate of AEs is more than 10%, there 
will still be more than an 80% chance of observing at least one subject with this AE. 
Combining all RSV vaccinees across all dose levels, there will be more than a 99% 
chance of observing at least one subject with this AE.
Furthermore, with 16 RSV vaccinees, the maximum width of a 95% CI for the 
proportion of subjects with adverse events among 16 vaccinees is about 50% (see 
Figure 5).
Considering the sample size of 16 subjects in each study group, Figure 5 illustrates the 
precision on the percentage of subjects with symptoms following vaccination.
 
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Figure 5
Exact 95% confidence interval on the percentage of subjects with 
adverse events following vaccination for 16 subjects per group
Taking the a priori safety concern of thrombocytopenia, both Frequentist and 
Bayesian approaches will be applied here to provide complementary assurance on the 
possibility to exclude a signal based on the accumulated safety data. The Frequentist 
approach examines the statistical power to rule out a significant decrease in platelet 
counts due to vaccination that would suggest a four-fold or greater increase in the risk 
of a Grade 3 or higher thrombocytopenia with 16 subjects per dose cohort. The 
Bayesian approach calculates the posterior predictive probability of not observing any 
subject with a Grade 3 or higher thrombocytopenia among the future 16 subjects by 
basing it on what we have observed in the first 16 subjects.
If we assume platelet counts in healthy infants between 12 and 23 months follow a 
normal distribution with a mean of 300,000 platelets/mm³ and a standard deviation of 
75,000 platelets/mm³, then we would expect 0.04% of unvaccinated infants to have a 
count below 50000 platelets/mm³, which is the cut-off for a Grade 3 thrombocytopenia. 
To rule out a four-fold or greater increase, we would need to show that the mean 
platelet count does not fall below 190,000 platelets/mm³ with a standard deviation of 
47,500. The sample size needed to rule out a 110,000 platelets/mm³ decrease due to 
vaccination with 84% power when vaccination has no effect on platelet count is 16 
infants per dose cohort (8 per group). Sample size is based on a one-sided 0.025 test of
non-inferiority using the Mann-Whitney statistic (PASS 12, Non-inferiority Tests for 
Two Means using Differences).
The Bayesian approach to predict the probability of no Grade 3 or higher 
thrombocytopenia in the future 16 subjects per dose cohort will be conducted by 
treating the mean of platelet counts µ as a random variable with a normal prior 
distribution N(µ0, σ0
2), where µ0 and σ0 will be determined by using laboratory normal 
 
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range. For this analysis the range of 150,000 to 450,000 platelets/mm³ will be the 
focus. Based on this laboratory range, µ0 would be 300,000, a mean of the range, and 
σ0 would be 75000, an approximate of a standard deviation of data sampled from this 
normal range. After 16 infants complete the two-dose vaccination schedule, a posterior 
distribution of µ will be calculated based on the prior of µ and the observed platelet 
counts from Day 31. The posterior predictive probability of no Grade 3 or higher 
thrombocytopenia in the future 16 subjects per dose cohort will be calculated, and 
sensitivity on the prior will be assessed.
After the first 16 infants of a dose cohort have completed the two-dose vaccination 
schedule, the 95% CI for the difference in mean platelets at Day 31 between vaccinees 
and placebo recipients will be calculated along with the posterior predictive probability 
of no Grade 3 or higher thrombocytopenia in the future 16 infants. If the lower 
boundary of the 95% CI is above 110,000 platelets/mm³ and the predictive probability is 
sufficiently high (e.g., 80% or more), the IDMC may recommend enrolling infants into 
the next dose cohort without completing enrolment in the current cohort. However, if a 
Grade 3 or higher thrombocytopenia occurs in a vaccinated infant at any time point or 
if there is a significant safety concern with another laboratory parameter such as 
hemoglobin or neutrophils, the IDMC may recommend continuing enrolment into the 
lower dose cohort.
In Section 11.8.1. Within groups assessment, the following change was made:
The percentage of subjects with at least one local AE (solicited and unsolicited), with at 
least one general AE (solicited and unsolicited) and with any AE during the 7-day or 
30-day follow-up period will be tabulated with exact 95% confidence interval (CI) after 
each vaccine dose and overall.
In Section APPENDIX A LABORATORY ASSAYS, the following changes have been 
made:
ELISA

Anti-RSV protein F ELISA
The anti-F protein IgG ELISA is an indirect ELISA allowing the detection and the 
quantitation of specific IgG antibodies directed against the RSV F protein in human 
serum samples.
First, F protein antigens purified from CHO expression system are coated onto 96-
well microplates. Then, after a washing and a blocking step, serial two-fold dilutions 
of test sera, controls, and reference standard are incubated to allow specific binding 
of antibodies directed against the F protein antigens. Bound IgG are detected by 
addition of a goat anti-human IgG antibody conjugated to horseradish peroxidase. 
After a washing step, the horseradish peroxidase substrate solution (TMB/H2O2) is 
added and a colored product develops proportionally to the amount of anti-F protein 
IgG antibodies present in the test serum. The color is quantified by reading the 
optical densities at 450-620 nm using a spectrophotometer. Antibody concentrations 
of individual serum and control samples are determined after interpolation from the 
 
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reference standard curve using a four-parameter equation and are expressed in 
arbitrary ELISA units (EU)/mL.
In APPENDIX C TOXICITY GRADING FOR HEMATOLOGY AND 
BIOCHEMISTRY PARAMETERS, the following changes have been made:
In the Table 25 Toxicity grading scales for hematology and biochemistry parameters 
applicable for this study, two grading scales were added as follows:
Component
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin (g/dL)
9.0 to < 10.5
8.0 to < 9.0
7.0 to < 8.0
< 7.0
Leukocytes decreased 
(cell/mm3)
2500 to < 3500
1500 to < 2500
1000 to < 1500
< 1000
Absolute neutrophil count 
decreased (cell/mm³)
1000 to < 1300
750 to < 1000
500 to < 750
< 500
Absolute lymphocyte count 
decreased (cell/mm³)
600 to < 650
500 to < 600
350 to < 500
< 350
Platelets decreased (cell///mm3) 75000 to < 150000
50000 to < 75000
25000 to < 50000
< 25000
Alanine Aminotransferase
(increase by factor)
1.1 to < 2.0 xULN
2.0 to < 3.0 xULN
3.00 to ≤8.0 xULN
> 8.0 xULN
Aspartate Aminotransferase
(increase by factor)
1.1 to < 2.0 xULN
2.0 to < 3.0 xULN
3.00 to ≤8.0 xULN
> 8.0 xULN
Creatinine (mg/dL) 
0.6 to < 0.9
0.9 to < 1.2
1.2 to ≤1.5
> 1.5
Grading scale adapted from [Division of AIDS, 2003], [Division of AIDS, 2004] and [Division of AIDS, 2007].
ULN: upper limit of normal
 
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SAP_001.pdf: 
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Statistical Analysis Plan Final
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Page 1 of 104
Statistical Analysis Plan
Detailed Title:
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
eTrack study number and 
Abbreviated Title
204838 (RSV PED-002)
Scope:
All data pertaining to the above study.
Date of Statistical Analysis 
Plan
Final: 28-Mar-2018
Co-ordinating author:
 (Study Statistician)
Reviewed by:
(Clinical and Epidemiology 
Project Lead)
(Clinical Research and Development 
Lead)
(Lead statistician) 
(Lead statistical analyst)
 (Scientific writer)
 (Regulatory Affairs) 
 (SERM physician)
Mandatory (Public disclosure representative)
 (Head CLS)
 (Senior Manager, Immuno Lab 
Platform3)
 (Expert Scientist, Biology Molecular)
 (Lead ADaM CEO Head)
Approved by:
(Clinical and Epidemiology 
Project Lead), 
 (Clinical Research 
and Development Lead, 
 (Lead statistician),
 (Lead Scientific writer) 
 
(Lead stat Analyst)
APP 9000058193 Statistical Analysis Plan Template (Effective date: 14 April 2017)
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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TABLE OF CONTENTS
PAGE
LIST OF ABBREVIATIONS...........................................................................................10
1.
DOCUMENT HISTORY..........................................................................................12
2.
STUDY DESIGN ....................................................................................................12
3.
OBJECTIVES.........................................................................................................16
3.1.
Primary objective ........................................................................................16
3.2.
Secondary objectives..................................................................................16
3.3.
Tertiary objectives.......................................................................................16
4.
ENDPOINTS ..........................................................................................................16
4.1.
Primary endpoints.......................................................................................16
4.2.
Secondary endpoints ..................................................................................17
4.3.
Tertiary endpoints.......................................................................................18
5.
ANALYSIS SETS ...................................................................................................18
5.1.
Definition.....................................................................................................18
5.1.1.
Total vaccinated cohort................................................................18
5.1.2.
According-to-protocol cohort for analysis of 
immunogenicity............................................................................18
5.2.
Criteria for eliminating data from Analysis Sets...........................................19
5.2.1.
Elimination from Exposed Set (ES)..............................................19
5.2.2.
Elimination from Per-protocol analysis Set (PPS) ........................20
5.2.2.1.
Excluded subjects ......................................................20
5.2.2.2.
Right censored Data...................................................20
5.2.2.3.
Visit-specific censored Data .......................................21
5.3.
Important protocol deviation not leading to elimination from per-
protocol analysis set ...................................................................................22
6.
STATISTICAL ANALYSES.....................................................................................23
6.1.
Demography...............................................................................................23
6.1.1.
Analysis of demographics/baseline characteristics planned 
in the protocol..............................................................................23
6.2.
Immunogenicity...........................................................................................23
6.2.1.
Analysis of immunogenicity planned in the protocol.....................23
6.2.1.1.
CMI analysis...............................................................24
6.2.1.2.
Humoral immune response.........................................25
6.3.
Analysis of RSV incidence ..........................................................................26
6.4.
Analysis of safety........................................................................................27
6.4.1.
Analysis of safety planned in the protocol ....................................27
6.4.1.1.
Within groups assessment..........................................27
6.4.1.2.
Between groups assessment......................................28
6.4.2.
Additional considerations.............................................................29
6.4.2.1.
Additional safety analysis ...........................................29
6.4.2.2.
Exclusion of implausible solicited Adverse 
Event..........................................................................29


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6.4.2.3.
Combined Solicited and Unsolicited Adverse 
Events ........................................................................29
7.
ANALYSIS INTERPRETATION..............................................................................30
8.
CONDUCT OF ANALYSES....................................................................................30
8.1.
Sequence of analyses.................................................................................30
8.2.
Statistical considerations for interim analyses.............................................31
9.
CHANGES FROM PLANNED ANALYSES.............................................................31
10. LIST OF FINAL REPORT TABLES, LISTINGS AND FIGURES .............................32
11. ANNEX 1 STANDARD DATA DERIVATION RULE AND STATISTICAL 
METHODS .............................................................................................................33
11.1.
cDISC specification.....................................................................................33
11.2.
Statistical Method References ....................................................................33
11.3.
Standard data derivation.............................................................................33
11.3.1.
Date derivation ............................................................................33
11.3.2.
Dose number...............................................................................34
11.3.3.
Demography................................................................................34
11.3.4.
Immunogenicity............................................................................35
11.3.5.
Safety ..........................................................................................37
11.3.6.
RTI and LRTI...............................................................................39
11.3.7.
Number of decimals displayed.....................................................40
12. ANNEX 2: RELEVANT PREFERRED TERMS FOR DETECTION OF AESI ..........41
13. ANNEX 3: STUDY SPECIFIC MOCK TFL..............................................................46
13.1.
List of individual data listing ........................................................................47
13.2.
Template of Tables and Figures .................................................................48


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LIST OF TABLES
PAGE
Table 1
Study groups and epochs foreseen in the study.....................................14
Table 2
Implausible Solicited Adverse Events.....................................................29
Table 3
Endpoints assessed at different analysis time points..............................31
Table 4
Toxicity grading scales for hematology and biochemistry 
parameters applicable for this study.......................................................38
Table 5
Case definition of RSV- RTI/LRTI...........................................................39


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LIST OF FIGURES
PAGE
Figure 1
Study design ..........................................................................................12
Figure 2
Individuals results of hemoglobin levels in < group> <Exposed 
Set> .......................................................................................................70
Figure 3
Reverse cumulative distribution curves for anti-RSV-A 
neutralising antibody titres in each group at baseline and 
<D60/D365> <PPS for analysis of immunogenicity at Day X>................86
Figure 4
Individual results of anti-RSV-A neutralising antibody titre at Day 
<60/365> versus pre-vaccination in <each group> and Control 
group> <PPS for analysis of immunogenicity at Day X>.........................87
Figure 5
Boxplots of individual data for CD4+ T-cells expressing at least 
two markers among CD40L, IL-2, TNF-α, and IFN-γ upon 
stimulation with <RSV F/ N /M2-1/combined> peptide pool <from 
pre-vaccination to Day 61/Day 366> <PPS for analysis of 
immunogenicity at Day X>......................................................................89
Figure 6
Co-expression profile of the RSV <F/N/M2-1> specific <CD4+> 
T-cells expressing at least two markers among CD40L, IL-2, 
TNF-α, and IFN-γ in <RSV-Ld group> <PPS for analysis of 
immunogenicity at Day X>......................................................................90


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LIST OF TEMPLATES
PAGE
Template 1
Number of subjects by country and center <Exposed Set> ....................48
Template 2
Number of subjects vaccinated, completed and withdrawn with 
reason for withdrawal – up to Day X <Exposed set> ..............................48
Template 3
Visit attendance <Exposed set>.............................................................49
Template 4
Number of subjects enrolled into the study as well as the number 
of subjects excluded from the PPS analysis of immunogenicity at 
Day X with reasons for exclusion ...........................................................49
Template 5
Summary of demographic characteristics <Exposed set> ......................50
Template 6
Summary of vital signs characteristics <Exposed set> ...........................51
Template 7
Distribution of weight for age Z-score (WAZ) at vaccination 
<Exposed Set> ......................................................................................52
Template 8
Distribution of height for age Z-score (HAZ) at vaccination 
<Exposed Set> ......................................................................................52
Template 9
Deviations from specifications for age and intervals between 
study visits up to Day X <Exposed Set>.................................................53
Template 10
Study Population....................................................................................53
Template 11
Number of enrolled subjects by country .................................................54
Template 12
Number of enrolled subjects by age category.........................................54
Template 13
Minimum and maximum activity dates <Exposed set> ...........................54
Template 14
Exposure to study vaccines <Exposed Set>...........................................55
Template 15
Compliance in completing solicited symptoms information 
<Exposed Set> ......................................................................................55
Template 16
Incidence and nature of symptoms (solicited and unsolicited) 
reported during the 7-day post-vaccination period (Days 1-7) 
following each dose and overall <Exposed Set> ....................................56
Template 17
Incidence of solicited local symptoms reported during the 7-day 
(Days 1-7) post-vaccination period following each dose and 
overall <Exposed Set> ...........................................................................57
Template 18
Incidence of solicited local symptoms reported during the 7-day 
(Days 1-7) post-vaccination period following each dose and 
overall by maximum grading <Exposed Set> .........................................58


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Template 19
Incidence of solicited general symptoms reported during the 7-
day (Days 1-7) post-vaccination period following each dose and 
overall <Exposed Set> ...........................................................................60
Template 20
Incidence of solicited general symptoms reported during the 7-
day (Days 1-7) post-vaccination period following each dose and 
overall by maximum grading <Exposed Set> .........................................62
Template 21
Maximum Temperature reported during the 7-day (Days 1-7) 
post-vaccination period – dose X <Exposed Set> ..................................65
Template 22
Percentage of subjects reporting the occurrence of unsolicited 
symptoms classified by MedDRA Primary System Organ Class 
and Preferred Term within the 30-day (Days 1-30) post-
vaccination period <Exposed Set> .........................................................65
Template 23
Number and percentage of subjects taking a concomitant 
medication during the 7- day (Days 1-7) post -vaccination period 
<Exposed Set> ......................................................................................66
Template 24
Distribution of change from baseline in hematology and 
biochemistry with respect to normal laboratory ranges <Exposed 
Set> .......................................................................................................67
Template 25
Summary of hematology and biochemistry results by maximum 
grade from VISIT X (DX) up to VISIT Y (DY) – post dose 1 of 
vaccination versus baseline <Exposed Set> ..........................................68
Template 26
Descriptive statistics table on eosinophils, basophils, and 
monocytes counts for subjects <Exposed Set>......................................69
Template 27
Exploratory comparisons between groups in terms of percentage 
of subjects reported any Grade 2/3 AE and/or any fever >38.5°C 
and/or any vaccine-related SAE during the 7-day (Days 1-7) 
post-vaccination period <Exposed Set> .................................................71
Template 28
Percentage of subjects reporting episode of spontaneous or 
excessive bleeding (AE of specific interest) classified by
MedDRA Primary System Organ Class and Preferred Term 
within the 30-day (Days 1-30) post-vaccination period <Exposed 
Set> .......................................................................................................72
Template 29
Solicited and unsolicited symptoms classified by MedDRA 
Primary System Organ Class and Preferred Term within the 30-
day (Days 1-30) post-vaccination period including number of 
events - SAE excluded <Exposed Set>..................................................73
Template 30
Number (%) of subjects with serious adverse events from 
vaccination dose 1 up to Day X/Study end including number of 
events reported <Exposed Set>.............................................................74
Template 31
Listing of unscheduled safety visit from vaccination dose 1 up to 
Day X/study end <Exposed Set>............................................................75


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Template 32
Listing of SAEs reported from vaccination dose 1 up to Day X 
visit /study end <Exposed Set> ..............................................................76
Template 33
Listing of AEs related to LRTI and association to RSV infection 
from vaccination dose 1 up to Day X visit/study end <Exposed 
Set> .......................................................................................................77
Template 34
Listing of RSV-RTI cases identified according to WHO case 
definitions and RSV-LRTI reported as AESI from vaccination 
dose 1 up to Day X visit /study end <Exposed Set> ...............................78
Template 35
Listing of AEs related to spontaneous or excessive bleeding 
together with hemoglobin and platelet count results from 
vaccination dose 1 up to Day 60 visit <Exposed Set> ............................79
Template 36
Listing of adverse events, SAEs and solicited symptoms leading 
to withdrawal from the study or treatment from vaccination dose 
1 up to Day X visit/study end <Exposed Set>.........................................80
Template 37
Number and percentage of subjects with anti-RSV-A neutralising 
antibody titre equal to or above <cut-off> and GMTs <PPS for 
analysis of immunogenicity at Day X>....................................................81
Template 38
Vaccine response for anti-RSV-A neutralising antibody titre at 
each post-vaccination timepoint <PPS for analysis of 
immunogenicity at Day X>......................................................................82
Template 39
Distribution of anti-RSV-A neutralising antibody titer <PPS for 
analysis of immunogenicity at Day X>....................................................83
Template 40
Distribution of fold of anti-RSV-A neutralising antibody titer by 
pre-vaccination titer category <PPS for analysis of 
immunogenicity at Day X>......................................................................84
Template 41
Geometric mean of the individual ratio of anti-RSV-A neutralising 
antibody titers at each post-vaccination timepoint compared to 
pre-vaccination with 95% CI <PPS for analysis of 
immunogenicity at Day X>......................................................................85
Template 42
Descriptive statistics on the frequency of CD4+ T-cells 
expressing at least two markers among CD40L, IL-2, TNF-α, and 
IFN-γ upon stimulation with <RSV F/ N /M2-1/combined> peptide
pool <PPS for analysis of immunogenicity at Day X>.............................88
Template 43
Number and percentage of subjects with at least one RSV 
infection, RSV-RTI, RSV-LRTI, RSV-severe LRTI, RSV-very 
severe LRTI, All-cause LRTI and RSV hospitalization from 
vaccination dose 1 up to D366/D731 visit <Exposed Set>......................91
Template 44
Number and percentage of subjects reporting the RSV infection 
of different severity by number of events experienced between 
vaccination dose 1 up to D366/D731 visit <Exposed Set>......................92


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Template 45
Number and percentage of RSV infections and associated 
disease severity between vaccination dose 1 up to D366/D731 
visit <Exposed Set> ...............................................................................93
Template 46
Number and percentage of RSV infections requiring 
hospitalization between vaccination dose 1 up to D366/D731 
<Exposed Set> ......................................................................................94
Template 47
Descriptive statistics of viral load calculated on all qRT-PCR 
confirmed RSV infection episodes with varying disease severity 
from vaccination dose 1 up to D366/D731 <Exposed Set>.....................95
Template 48
Descriptive statistics of maximum viral load per subjects based 
on qRT-PCR confirmed episode with varying disease severity 
form vaccination dose 1 up to D366/D731 <Exposed Set>.....................96
Template 49
Frequency of multiple respiratory pathogen for qRT-PCR 
confirmed RSV-RTI episodes from vaccination dose 1 up to 
D366/D731 visit <Exposed Set>.............................................................97
Template 50
Frequency of multiple respiratory pathogen for confirmed LRTI 
episodes from vaccination dose 1 up to D366/D731 visit 
<Exposed Set> ......................................................................................98
Template 51
Listing of RSV-RTI cases identified according to case definitions 
<Exposed Set> ......................................................................................99
Template 52
Listing of RSV-RTI requiring hospitalization and type of inpatient 
facility required <Exposed Set>............................................................100
Template 53
Number and percentage of subjects with highest associated 
severity of RSV infection from vaccination dose 1 up to 
D366/D731 visit <Exposed Set>...........................................................101
Template 54
Number and percentage of subjects reporting the RSV infection 
of maximum severity by number of events experienced between 
vaccination dose 1 up to D366/D731 visit <Exposed Set>....................102
Template 55
Number (%) of subjects reported solicited local symptoms during 
the 7-day (Days 1-7) post-vaccination period following each dose 
and across doses <Exposed Set>........................................................103
Template 56
Number (%) of subjects reported solicited general symptoms 
during the 7-day (Days 1-7) post-vaccination period following 
each dose and across dose <Exposed Set> ........................................104


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LIST OF ABBREVIATIONS
AE
Adverse event
AESI
Adverse Events of Special Interest
ChAd155-
RSV
Investigational recombinant chimpanzee adenovirus Type 155-
vectored RSV vaccine
CI
Confidence Interval
CMI
Cell-mediated immunity
CTRS
Clinical Trial Registry Summary
ERD
Enhanced RSV disease
ES
Exposed Set
GMC
Geometric mean antibody concentration
GMT
Geometric mean antibody titer
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee
iSRC
Internal Safety Review Committee
LL
Lower Limit of the confidence interval
LLOQ
Lower Limit of Quantification
LRTI
Lower respiratory tract infection
MedDRA
Medical Dictionary for Regulatory Activities
N.A.
Not Applicable
PCA
Palivizumab Competing Antibodies
PPS
Per Protocol Set
RR
Respiratory rate
RSV
Respiratory syncytial virus
RSV-Hd
High dose ChAd155-RSV vaccine (5 x 1010 vp)
RSV-Ld
Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md
Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-RTI
Respiratory tract infection associated with RSV infection
RTI
Respiratory tract infection
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SD
Standard Deviation
SHS
Study Headline Summary


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SR
Study Report
TFL
Tables Figures and Listings 
TOC
Table of Content
UL
Upper Limit of the confidence interval


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1.
DOCUMENT HISTORY
Date
Description
Protocol Version
28-MAR-2018
Final version
Amendment 4 - 10-DEC-2017
2.
STUDY DESIGN
Figure 1
Study design 
Please note that for the analysis for D61, D366 and D731, the study will be converted 
in cDISC standard. To avoid confusion between analysis planned and table template, 
all the text and figures have been changed into cDISC, i.e, Day ‘DX’ is changed to Day 
‘DX+1’.
Hd: High dose; IDMC: Independent Data Monitoring Committee; iSRC: Internal Safety Review Committee; Ld: low 
dose; Md: middle dose; RSV: respiratory syncytial virus; SCR: Screening; SE: solicited events; vp: viral particles.
¥ On Day 4 and Day 34, a visit may take place at the investigators clinical facility or the investigator/clinical staff may 
call the subjects’ parent(s)/LAR(s), as appropriate to the circumstances in the judgment of the investigator.
a Surveillance for RSV-RTI comprises monthly nasal swab collected to detect asymptomatic RSV infections during 
RSV season and active and passive surveillance contacts for RSV symptomatic RTI (see Section 9.2 of the 
protocol). Data about RSV–RTI incidence will be reviewed monthly by an IDMC.
b Within each step, an iSRC will review all accumulating safety data three weeks after the start of vaccination and then 
about every three weeks (until the IDMC has reviewed all safety data up to 30 days after administration of Dose 2 in 
Step 3 i.e. Day 61). The IDMC will review all accumulating reactogenicity and safety data monthly throughout the 
period of vaccination (up to 30 days after administration of Dose 2 in Step 3, i.e. Day 61) and accumulating SAEs 
until Day 731. Refer to Sections 9.10.2 and 9.10.3 of the protocol.


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c Visit 2 (Day 2), Visit 4 (Day 8), Visit 6 (Day 32), Visit 8 (Day 38) and Visit 11 (Day 731) may take place in the 
subject’s home or at the investigators clinical facility as appropriate to the circumstances in the judgment of the 
investigator.
d Dose escalation will proceed after administration of two doses of the vaccine to 32 subjects in Step 1. However, in 
the absence of a significant safety concern detected in the regular monitoring of accumulating safety data on at least 
16 subjects, the IDMC may allow for dose escalation to proceed without the requirement of enrolling and evaluating 
the full group size of 32 subjects. A subsequent dose escalation (from Step 2 to Step 3) will proceed after 
administration of two doses of the vaccine to between a maximum of 32 to a minimum of 16 subjects in the absence 
of a significant safety concern detected by the IDMC in the regular monitoring of accumulating safety data. Thus, 
upon review of the accumulating safety data on a minimum of 16 subjects after administration of two doses of the 
vaccine, the IDMC may decide that based on the evolving safety profile, sufficient information has been accumulated 
to allow safe progression to the next sequential dose level. It will be ensured that, as a minimum the IDMC will have 
reviewed safety data of at least 16 subjects for two doses and given their formal approval prior to enrolling subjects 
to the next dose level.
e Only for hematology.
f Day 8 hematology testing will be performed if any ≥ Grade 1 for platelet decrease is detected on Day 1 after 
vaccination; to ensure its resolution. Similarly, hematology testing on Day 38 will be performed if any ≥ Grade 1 for 
platelet decrease is detected on Day 32.
g Refer to Section 6.6.11.3 of the protocol
h The IDMC will perform a review when all safety data up to 30 days after administration of Dose 2 in Step 3 (i.e. Day 
61) are available. 
i Blood samples for CMI and for humoral immunogenicity may be postponed until after the RSV serostatus is known 
and eligibility is confirmed up to or on Day 1 (but before vaccination).

Experimental design:  Phase I/II, observer-blind, randomized, placebo-controlled, 
multi-centric, study with two parallel groups per step in a 3-step staggered design

Duration of the study: approximately 24 months:

Epoch 001: primary starting at the Screening visit and ending at Visit 9 (Day 61)

Epoch 002: follow-up starting at Visit 10 (Day 366) and ending at Visit 11 (Day 
731)
Any safety, immunogenicity and disease surveillance data collected beyond Visit 9
(Day 61) will be collected in Epoch 002

Primary completion Date: Visit 9 (Day 61).

End of Study: Last testing results released of samples collected at Visit 11 (Day 
731). *
* Up to Visit 11 (Day 731), there will be monthly nasal swab to detect asymptomatic 
RSV infections during the RSV season and if following active or a passive 
surveillance contacts, subject presents symptoms of RTI, a nasal swab will be 
collected.

Study groups: Throughout the three steps, infants will be randomized in two groups 
to receive either ChAd155-RSV vaccine or placebo.


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Table 1
Study groups and epochs foreseen in the study
Step
Study 
groups
Number of 
subjects*
Age (Min/Max)
Epochs
Epoch 001 
Epoch 002 
1
RSV-Ld 
16 
12 months - 23 months 
X
x
Placebo-Ld 
16 
12 months - 23 months 
X
x
2
RSV-Md 
16 
12 months - 23 months 
X
x
Placebo-Md 
16 
12 months - 23 months 
X
x
3
RSV-Hd 
16 
12 months - 23 months 
X
x
Placebo-Hd 
16 
12 months - 23 months 
X
x
RSV-Ld: low dose ChAd155-RSV vaccine (5 x 109 vp); RSV-Md: middle dose ChAd155-RSV vaccine (1.5 x 1010 vp); 
RSV-Hd: high dose ChAd155-RSV vaccine (5 x 1010 vp).
*The target will be to enroll up to 96 RSV-seropositive infants aged 12 to 23 months at the time of first vaccination 
(unless the dose escalation IDMC decision can be made based on the evaluation of accumulating safety data on 
fewer subjects) to ensure that at least 64 infants receive two doses of study vaccine (ChAd155-RSV or Placebo) 
(see Section Error! Reference source not found.). Then the number of subjects at each step will be at least 16 
(approximately 8 subjects per group) at steps 1 and 2 and 32 (approximately 16 subjects per group at step 3)

Vaccination schedule: two IM vaccine doses administered according to a 0, 1-
month schedule (i.e. at Day 1 and Day 31)

Treatment allocation: infants will be randomized using a randomization system on 
internet (SBIR) at first vaccination

Blinding: observer-blind in Epoch 001 and single-blind in Epoch 002

Sampling schedule: 
Blood samples for biochemistry will be taken from all infants at Screening (up to 29 
days before first vaccination to Day 1) and on Day 31, and Day 61 (refer to Table 11
of the protocol for the list of parameters to be tested). Blood samples for hematology 
will be taken from all infants at Screening (up to 29 days before first vaccination to 
Day 1) and on Day 1, Day 31, Day 32, and Day 61 (refer to Table 11of the protocol
for the list of parameters to be tested). Day 8 hematology testing will be performed if 
any ≥ Grade 1 for platelet decrease is detected on Day 2 after vaccination, to ensure 
its resolution. Similarly, hematology testing on Day 38 will be performed if any ≥ 
Grade 1 for platelet decrease is detected on Day 32. A clinical examination with 
special attention given to detection of spontaneous bleeding or easy bruising and 
evidence of bruising or petechiae will be performed by the investigator/study staff on 
Day 2, Day 4 and Day 8 after each vaccination (i.e. Day 2, Day 4, Day 8, Day 32, 
Day 34, and Day 38. The visits on Day 4 and Day 34 may be replaced by a phone 
call by the investigator/study staff to inquire of the infants' general health and to 
solicit reports of a rash, spontaneous bleeding or easy bruising. On Day 2, and Day 
32, special attention will also be given to the detection of petechiae or evidence of 
petechiae induced by the tourniquet. This special attention to detection of petechiae 
or evidence of petechiae induced by the tourniquet will also be given on Day 8
and/or Day 38 in case hematology testing will be performed on that day. Further 
testing may be required to investigate a finding or guide subject management based 
on the investigators clinical judgment. Subjects’ parent(s)/LAR(s) will be instructed 
to contact the investigator/study staff if their child presents symptoms of spontaneous 
bleeding or easy bruising or if their child develops a rash in the month following 
vaccination, in order to detect any thrombocytopenic petechiae or purpura. The 


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investigator will, based on his/her medical judgement, appropriately investigate 
infants with clinical suspicion of low platelets

Blood sample for RSV serostatus will be taken from all infants at Screening.

Blood samples for CMI are limited to those in investigational sites with a 
laboratory in proximity capable to perform WBS necessary for the CMI assay. 
In those sites, samples will be taken from all subjects at Screening and on Day 
31, Day 61, and Day 366.
Note: Blood samples for CMI taken on Day 8 and Day 38 for subjects enrolled 
under protocol amendment 1 will still be assessed for CMI.

Blood samples for humoral immunogenicity will be taken from all subjects at 
Screening and on Day 31, Day 61, and Day 366.

Blood sample for assessment of mechanism of illness (potential ERD) will be 
taken from subjects hospitalized for LRTI (only for RSV-positive subjects using 
a locally available RSV test).

Nasal swab: there will be monthly nasal swab to detect asymptomatic RSV 
infections during the RSV season and if following active or a passive 
surveillance contacts, a subject present symptom of RTI, a nasal swab will be 
collected.

Study visits: Visit 1 (Day 1), Visit 5 (Day 31), Visit 9 (Day 61) and Visit 10 (Day 
366) must be performed at the investigators clinical facility. Visit 2 (Day 2), Visit 4 
(Day 8), Visit 6 (Day 32), Visit 8 (Day 38) and Visit 11 (Day 731) (no blood 
sampling for immune response and no vaccine administration) may take place in the 
subject’s home or at the investigators clinical facility as appropriate to the 
circumstances in the judgment of the investigator. Visit 3 (Day 4) and Visit 7 (Day 
34) may take place at the investigators clinical facility or the investigator/clinical 
staff may call the subjects’ parent(s)/LAR(s), as appropriate to the circumstances in 
the judgment of the investigator. 

Surveillance for RSV-RTI, difficulty in breathing and wheezing episodes.
Surveillance period will be carried out from Visit 1 (after Dose 1) until Visit 11 (Day 
731). In order to detect asymptomatic RSV-RTI, monthly nasal swabs for analysis at 
sponsor laboratory will be performed for all subjects during the RSV season. In order 
to timely detect RSV-RTI and to ensure cases are timely captured by the study sites, 
both active and passive surveillance will be conducted:

Passive surveillance: Parent(s)/LAR(s) are instructed to contact the 
investigator/study staff as soon as the subject experiences new RTI symptoms 
(cough, runny nose or blocked nose) or worsening of RTI symptoms, or in case 
of difficulty in breathing or wheezing.

Active surveillance: parent(s)/LAR(s) of all the subjects will be contacted by 
the investigator/study staff on a regular basis (weekly during the RSV season 
and every month outside the RSV season) to identify any potential RSV-RTI 
and to remind the parent(s)/LAR(s) of the subjects to report any new occurrence 
of RTI symptoms (cough, runny nose, blocked nose) or worsening of RTI 
symptoms, or in case of difficulty in breathing or wheezing as soon as possible.


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3.
OBJECTIVES
3.1.
Primary objective

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
3.2.
Secondary objectives

To evaluate the safety of two IM doses of three dose levels of the RSV 
investigational vaccine when administered according to a 0, 1-month schedule from 
study start (Day 1) up to study conclusion (Day 731) in RSV-seropositive infants 
aged 12 to 23 months

To evaluate the occurrence of RSV respiratory tract infections in RSV-seropositive 
infants from Visit 1 (Day 1, after Dose 1) up to study conclusion (Day 731)

To evaluate the magnitude of the CMI induced by two IM doses of three dose levels 
of the RSV investigational vaccine when administered according to a 0, 1-month 
schedule, up to Day 366 in RSV-seropositive infants aged 12 to 23 months.

To evaluate the humoral immunogenicity induced by two IM doses of three dose 
levels of the RSV investigational vaccine when administered according to a 0, 1-
month schedule, up to Day 366 in RSV-seropositive infants aged 12 to 23 months
3.3.
Tertiary objectives

To further evaluate the CMI profile induced by two IM doses of three dose levels of 
the RSV investigational vaccine when administered according to a 0, 1-month 
schedule, up to Day 366 in RSV-seropositive infants aged 12 to 23 months

If deemed necessary, to further characterize the immune response of the RSV 
investigational vaccine when two IM doses are administered according to a 0, 1-
month schedule in RSV-seropositive infants.
4.
ENDPOINTS
4.1.
Primary endpoints 

Occurrence of AEs from first vaccination (Day 1) up to Day 61. 

Occurrence of each solicited local and general AE, during a 7-day follow-up 
period after each vaccination (i.e. the day of vaccination and 6 subsequent days). 

Occurrence of any unsolicited AE, during a 30-day follow-up period after each 
vaccination (i.e. the day of vaccination and 29 subsequent days). 


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
Occurrence of any SAE from Day 1 up to Day 61. 

Occurrence of episode of spontaneous or excessive bleeding (AE of specific 
interest), during a 30-day follow-up period after each vaccination. 

Occurrence of any hematological (hemoglobin level, white blood cells and 
platelets) laboratory abnormalities at Screening, Day 1, Day 8, Day 31, Day 32, 
Day 38, and Day 61. 

Occurrence of any biochemical (alanine aminotransferase, aspartate 
aminotransferase and creatinine) laboratory abnormalities at Screening, Day 31, 
and Day 61
4.2.
Secondary endpoints

Occurrence of SAEs from study start (Day 1) up to Day 366. 

Occurrence of RSV-LRTI (AE of specific interest) as from Dose 1 administration up 
to Day 366. 

Occurrence of RSV-RTI, RSV-LRTI, severe RSV-LRTI (according to standardized 
case definitions) as from Dose 1 administration up to Day 366. 

Occurrence of SAEs from study start (Day 1) up to study conclusion (Day 731). 

Occurrence of RSV-LRTI (AE of specific interest) as from Dose 1 administration up 
to study conclusion (Day 731). 

Occurrence of RSV-RTI, RSV-LRTI, severe RSV-LRTI (according to standardized 
case definitions) as from Dose 1 administration up to study conclusion (Day 731). 

Magnitude of the CMI response to the investigational RSV vaccine, pre-vaccination 
(Screening), post-Dose 1 (Day 31) and post-Dose 2 (Day 61 and Day 366).

CD3+/CD4+ T-cells expressing at least two markers among CD40L, IL-2, TNF-
α, and IFN-γ upon stimulation with F, N and M2-1 peptide pools. 

Humoral response to the investigational RSV vaccine, pre-vaccination (Screening), 
post-Dose 1 (Day 31) and post-Dose 2 (Day 61 and Day 366): 

Neutralizing antibody titers against RSV-A. 

RSV F antibody concentrations. 

Humoral response to the investigational RSV vaccine, pre-vaccination (Screening), 
post-Dose 1 (Day 31) and post-Dose 2 (Day 61): 

Palivizumab-competing antibody concentrations.


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4.3.
Tertiary endpoints

CMI response profile (Th1, Th2, Th17) to the investigational RSV vaccine, pre-
vaccination (Screening), post-Dose 1 (Day 31) and post-Dose 2 (Day 61 and Day 
366). 

CD3+/CD4+ and/or CD3+/CD8+ T-cells expressing at least one or any 
combination of immune marker(s) among CD40L, 41BB, IL-2, TNF-α, IFN-γ, 
IL-13 and IL-17 upon stimulation with F, N and M2-1 peptide pools. 

Any further exploratory immunology to detect disease-related or vaccine-related 
immune responses, such as but not limited to: 

Anti-vector immunity: neutralization. (Analysis for this endpoint will be 
described in another SAP/AAR).
5.
ANALYSIS SETS
5.1.
Definition
5.1.1.
Total vaccinated cohort
The total vaccinated cohort (TVC) will include all subjects with at least one study 
vaccine administration documented.

A safety analysis based on the TVC will include all vaccinated subjects.

An immunogenicity analysis based on the TVC will include all vaccinated subjects 
for whom immunogenicity data are available.
The TVC analysis will be performed per treatment actually administered at Dose 1.
5.1.2.
According-to-protocol cohort for analysis of immunogenicity
The ATP cohort for analysis of immunogenicity will be defined by timepoint and will 
consist of all subjects from the TVC who complied with eligibility criteria, study 
procedures up to the end of the study and had immunogenicity results in the epoch as 
described below.
More specifically, the ATP cohort for analysis of immunogenicity up to Visit 9 (Day 
61)/at Visit 10 (Day 366) will include all evaluable subjects:

Who met all eligibility criteria (i.e. no protocol violation linked to the 
inclusion/exclusion criteria, including age).

Who received two dose of study vaccine.

For whom the administration route and site of the vaccine was as according to 
protocol.


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
Who received the vaccine according to protocol procedures.

Who complied with the vaccination schedule, as specified in Table 5 of the protocol.

Who did not receive a concomitant medication/product leading to exclusion from an 
ATP analysis, as described in Section 7.6.2 of the protocol, up to Visit 9 (Day 61)/up 
to Visit 10 (Day 366).

Who complied with the timings of the post vaccination blood sampling for immune 
response evaluation, up to Visit 9 (Day 61) /at Visit 10 (Day 366), as specified in
Table 5 of the protocol.

For whom post-vaccination immunogenicity results are available for at least one 
assay up to Visit 9 (Day 61) /at Visit 10 (Day 366).
Note that in order to align to ICH and cDISC terminology the Total Vaccinated Cohort 
and the According to Protocol cohort have been renamed Exposed Set (ES) and Per-
Protocol Set (PPS) respectively.
5.2.
Criteria for eliminating data from Analysis Sets
Elimination codes are used to identify subjects to be eliminated from analysis.  Detail is 
provided below for each set.  
5.2.1.
Elimination from Exposed Set (ES)
Code 1030 (Study vaccine not administered at all) and code 900 (invalid informed 
consent or fraud data) will be used for identifying subjects eliminated from ES 


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5.2.2.
Elimination from Per-protocol analysis Set (PPS)
5.2.2.1.
Excluded subjects
A subject will be excluded from the PPS for analysis of immunogenicity at Day 61 and 
Day 366 under the following conditions 
Code
Condition under which the code is used
900
Invalid informed consent or fraud data (Subjects receiving a code 900 should 
not receive any other elimination codes)
1030
Study vaccine not administered at all (Subjects receiving a code 1030 should 
not receive any other elimination codes)
1050
Randomization failure
1070$
Subjects got vaccinated with the correct vaccine but containing a lower volume
1070$
Administration not according to protocol for reason specified by the 
investigator, other than side, site and route
1070$
Site or route of study vaccine administration wrong or unknown
1070$
Wrong replacement or study vaccine administered (not compatible with the 
vaccine regimen associated to the treatment number)
1070$
Administered study vaccine reported as being the correct one but is not 
compatible with the vaccine regimen associated to the treatment number
1080
Vaccine temperature deviation
1090
Expired vaccine administered
1500$
Subjects who have received only one dose of vaccination 
2010
Protocol violation (inclusion/exclusion criteria)
2080
Subjects did not comply with vaccination schedule
(DOSE 1 to DOSE 2 = 23-36 (days)
$Attribution of code to a subject requires CRDL confirmation
Please note that all the elimcode has to be checked for the subject under schedule 1.
5.2.2.2.
Right censored Data
Data from visit X and subsequent visit will be censored for the PPS analysis under the 
following conditions. The code ****.Vx will be used to identify subjects whose 
immunogenicity data should be eliminated from a specific visit onwards. Vx will be V9 
and V10 with respect to PPS defined up to Visit 9 and Visit 10, respectively.
Code
Decode Condition under which the code is used
1040*.Vx
Administration of concomitant vaccine(s) forbidden in the protocol
A vaccine not foreseen by the study protocol administered from dose 
1and ending 30 days after the last dose of vaccines administration

Applicable visits

For Day 61 PP, to check from Dose 1 up to Day 61

For Day 366 PP, to check from Dose 1 up to Day 366
1060
Randomization code was broken
* Attribution of these elimcodes are responsibility of CRDL following review of individual data listings
Please note that all the elimcode has to be checked for the subject under schedule 1 who have received vaccination.


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5.2.2.3.
Visit-specific censored Data
Data at visit X will be censored for the PPS analysis under the following conditions.  The 
code ****.Vx will also be used to identify study withdrawal at visit X. Vx will be V9 and 
V10 with respect to PPS defined up to Visit 9 and Visit 10, respectively.
Code
Decode Condition under which the code is used
2040*.Vx

Administration of any medication forbidden by the protocol

Any investigational or non-registered product (drug or vaccine) 
other than the study vaccines used during the study period.

Immunosuppressants or other immune-modifying drugs 
administered chronically (i.e., more than 14 days) during the study 
period.

Immunoglobulins and/or any blood products administered during 
the study period

Administration of long-acting immune-modifying drugs during the 
study period.

Applicable visits

For Day 61 PP (V9), check from Dose 1 up to Day 61 BS

For Day 366 PP (V10), check from Dose 1 up to Day 366 BS
2050*.Vx

Underlying medical condition forbidden by the protocol

Applicable visits

For Day 61 PP, to check from Dose 1 up to Day 61

For Day 366 PP, to check from Dose 1 up to Day 366
2060*.Vx
Concomitant infection related to the vaccine which may influence immune 
response

Applicable visits

For Day 61 PP (V9), to check from Dose 1 up to Day 61

For Day 366 PP (V10), to check from Dose 1 up to Day 366
2070*.Vx
Concomitant infection not related to the vaccine which may influence 
immune response

Applicable visits

For Day 61 PP, to check from Dose 1 up to Day 61

For Day 366 PP, to check from Dose 1 up to Day 366
2090.Vx
Subjects did not comply with immunological blood sample schedule 
Applicable visits

For Day 61 PP, to check for Dose 1 to Visit 5 BS = 23-36 days and 
Dose 2 to Visit 9 BS = 28-35 days]

For Day 366 PP, to check for Dose 1 to Visit 10 BS = 335-395 
days]


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Code
Decode Condition under which the code is used
2100.Vx
Serological results not available post-vaccinationNo immunological 
result at all for the specific blood sample collection timepoint

Applicable visits

For Day 61 PP, check for availability of atleast one assay [CMI 
(ICS), Neutra, RSV F IgG or PCA result] at Day 31 and Day 61

For Day 366 PP, check for availability of atleast one assay [CMI 
(ICS), Neutra, RSV F IgG or PCA result] at Day 366
2120!@.Vx
Obvious incoherence or abnormality or error in data Incoherence 
between CRF and results, wrong sample labelling, Central/internal/external 
lab deviations; incorrect spinning/processing of sample including processing 
within the time required by protocol; temperature deviations from range 
defined in protocol and/or SPM - room temperature/refrigerator/freezer; an 
assessment was completed, but was not completed according to protocol or 
SPM.

Applicable visits 

For Day 61 PP, check on Day 31 and Day 61 CMI (ICS), Neutra, 
RSV F IgG or PCA result

For Day 366 PP, check on Day 366 CMI (ICS), Neutra, RSV F IgG 
or PCA result
* Attribution of these elimcodes are responsibility of CRDL following review of individual data listings
Please note that all the elimcode has to be checked for the subject under schedule 1 who is vaccinated.
@this code need confirmation from lab expert of particular test performed
! Attribution of code to a subject requires CRDL confirmation
5.3.
Important protocol deviation not leading to elimination from 
per-protocol analysis set 
The following important protocol deviations will be reported by groups:

Forced randomization: In case of supplies shortage for the next assigned vaccine 
according to the randomization schedule at the clinical site, the randomization 
system will use the forced randomization procedure in order to continue to enrol and 
vaccinate subjects. The system moves seamlessly to the next 
treatment/randomization number for which vaccine supplies are available. The site 
will not be aware of the forced randomization event. 

Short follow-up: subjects who completed the last study contact before the minimum 
length of follow-up requirement

In case unexpected vaccinations at study start were granted due to regulatory
recommendation or medical need, the subjects who had such vaccination could be
mentioned.   


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6.
STATISTICAL ANALYSES
Note that standard data derivation rule and stat methods are described in annex 1 and will 
not be repeated below.
6.1.
Demography
6.1.1.
Analysis of demographics/baseline characteristics planned in the 
protocol
The analysis of demographics will be performed on the Exposed Set and on the PPS for
analysis of immunogenicity at Day 61 and Day 366 analysis. The analysis of demography 
will be performed on Exposed Set at Day 731. 
Demographic characteristics (age at first vaccination in months, gender, race, country), 
weight, height or length, and vital signs, and cohort description will be summarized by 
group using descriptive statistics:

Frequency tables will be generated for categorical variable such as race.

Mean, median, standard error and range will be provided for continuous data such as 
age.
The above analysis will also be done at Day 366 and Day 731 with age at the visit in 
months. 
The weight for age Z score (WAZ) and height or length for age Z score (HAZ) at first 
vaccination, Day 366 and Day 731 will be calculated on ES. The distribution of subjects 
will be tabulated as a whole and per group.
Withdrawal status will be summarized by group using descriptive statistics. 

The numbers of withdrawn subjects will be tabulated according to the reason for 
withdrawal on ES.

The number of subjects enrolled into the study as well as the number of subjects 
excluded from PPS analyses will be tabulated.
6.2.
Immunogenicity
6.2.1.
Analysis of immunogenicity planned in the protocol
The primary analysis will be performed on the PPS for analysis of immunogenicity and a 
complementary analysis will be performed on Exposed Set. All the immune analysis is 
within group only.


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6.2.1.1.
CMI analysis 
The analysis will be performed on each group separately, pooled placebo group and 
pooled RSV group. All the CMI analysis will be performed for each peptide pool (F, N, 
M2-1) separately and taking all the peptide pool together for subjects who has data 
available for the three peptide pools.
With respect to secondary objectives, the following parameters will be summarized by 
group using descriptive statistics (N, geometric mean [GM], minimum [min], 1st quartile 
[Q1], median, third quartile [Q3], maximum [max]), at each timepoint during which 
blood samples are collected for CMI in investigational sites with a laboratory in 
proximity capable to perform WBS necessary for the CMI assay:

Frequency of CD4+ T-cells expressing at least two markers among CD40L, IL-2, 
TNF-α, and IFN-γ upon stimulation with F, N and M2-1.

Box plot with individual data for CD4+ T-cells expressing at least two markers 
among CD40L, IL-2, TNF-α, and IFN-γ upon stimulation with F, N and M2-1 and 
combined peptide pool will be presented.
With respect to tertiary objectives, the cellular immune response will be further 
characterized using descriptive analysis of the frequency of CD8+ T-cells and CD4+ T-
helper cell profile (Th1, Th2, Th17) expressing at least one or any combination of 
marker(s) among CD40L, 41BB, IL-2, TNF-, IFN-, IL-13, and IL-17. 
The following parameters will be summarized by group using description statistics (N, 
GM, min, Q1, median, Q3, max), at each timepoint during which blood samples are 
collected for CMI:

Frequency of CD4+ and CD8+ T-cells expressing at least one or any combination of 
immune marker(s) among CD40L, 41BB, IL-2, TNF-α, IFN-γ, IL-13 and IL-17 upon 
stimulation with F, N and M2-1 peptide pools.

Tabular presentation of T-helper cell ‘Th1’ profile - Frequency of CD4+ T-cells 
expressing at least IFN-γ but no IL-13 upon stimulation with F, N and M2-1 peptide 
pools.

Tabular presentation of T-helper cell ‘Th2’ profile: Frequency of CD4+ T-cells 
expressing at least IL-13 but no IFN-γ upon stimulation with F, N and M2-1 peptide 
pools.

Tabular presentation of T-helper cell ‘Th17’ profile - Frequency of CD4+ T-cell 
expressing atleast IL17 upon stimulation with F, N and M2-1 peptide pools.

Calculation of ‘Th2/Th1 ratio’ = Frequency of Th2 T-cells / frequency of Th1 T-
cells. 

Separate box plot with individual data for CD4+ and CD8+ T-cells expressing at 
least one marker among CD40L, 41BB, IL-2, TNF-α, IFN-γ, IL-13 and IL-17 upon 
stimulation with F, N and M2-1 and combined peptide pools will be presented.


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
Separate box plot with individual data for CD4+ T-cells expressing at least IFN-γ but 
no IL-13 (Th1 profile) upon stimulation with F, N and M2-1 and combined peptide 
pools will be presented.

Separate box plot with individual data for CD4+ T-cells expressing at least IL-13 but 
no IFN-γ (Th2 profile) upon stimulation with F, N and M2-1 and combined peptide 
pools will be presented.

Separate box plot with individual data for CD4+ T-cells expressing at least 
IL17(Th17 profile) upon stimulation with F, N and M2-1 and combined peptide 
pools will be presented.
The need to generate co-expression profile graph for any combination for CD4+ and 
CD8+ will be evaluated after looking at the descriptive tables.
6.2.1.2.
Humoral immune response 
For each group, at each timepoint that blood samples are collected for humoral immune 
response against the investigational RSV vaccine (neutralizing antibody titers against 
RSV-A, RSV F antibody concentrations, and palivizumab-competing antibody 
concentrations):

GMTs/GMCs will be tabulated with 95% CI and represented graphically.

Percentage of subjects above the seropositivity threshold will be tabulated with exact 
95% CI.

Antibody titers/concentrations will be displayed using reverse cumulative curves.

The distributions of neutralizing antibody titers/concentrations will be tabulated (< 
128, 128-256, > 256-512, > 512-1024, > 1024-2048, > 2048-4096, > 4096)

Percentage of responders in terms of RSV-A neutralizing antibody titers will be 
tabulated with exact 95% CI.

Individual post-vaccination versus pre-vaccination results will be plotted using 
scatter plots. Results of the Placebo groups will be used as a reference.

Geometric mean of ratios of antibody titers/concentrations at each post-vaccination 
timepoint over pre-vaccination will be tabulated with 95% CI.

Distribution of the fold increase of the neutralizing antibody titers will be tabulated 
by pre-vaccination titer category (percentage of subjects with a fold increase equal to 
or above 1, 2, 2.5, 3, 4, 6, 8 10, 11 and 12 by pre-vaccination titre category: (< 128, 
128-256, > 256-512, > 512-1024, > 1024-2048, > 2048-4096,  > 4096, and by 
cumulative category: <128, ≥128, ≥256, ≥512, ≥1024, ≥2048, ≥4096.).

The kinetics of individual antibody titer/antibody concentration results will be 
plotted as a function of time for subjects with results available at all timepoints.
If available, any further exploratory immunology results (including, but not limited to 
anti-vector immunity) will be reported by group and timepoint using descriptive 
summary statistics will be described separately in Additional analysis request (AAR). 


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6.3.
Analysis of RSV incidence
The assessment of RSV analysis incidence and severity will be performed on the 
Exposed Set on RSV groups, placebo groups, pooled RSV and pooled Placebo groups 
separately for first RSV season (Day 1-366) and second RSV season (Days 367-731) and 
overall (Days 1-731).
The analysis will be performed according to all case definitions presented in Table 5.
The proportion of subjects with at least one RSV infection and number of infections
experienced by subjects meeting each of the case definition in Table 5 (with 95 % CI) 
will be calculated by group.
The number of RSV infections within each group and the maximum disease severity of 
the event will be tabulated.  The number of RSV infections within each group and 
frequency of hospitalization will be tabulated.  The number of infections in each group 
and descriptive analysis of the viral load associated with the maximum disease severity of 
the event will be tabulated (mean, median, min, max). Descriptive analysis on maximum 
viral load per subject based on qRT-PCR confirmed RSV infection of maximum severity 
will be performed.
The viruses identified in the Respiratory Viral Panel will be tabulated to those events 
where RSV-RTI was identified to describe frequency of co-infections and responsible 
viruses. These tables will be repeated limited to RVP results of cases of confirmed LRTI 
and RSV-LRTI.
After looking at the frequency of coinfection of all confirmed LRTI and RSV-LRTI, if 
there will be more than 10% coinfections (RSV infection with identification of another 
viral pathogen on RVP), tables will be reproduced including those RSV episodes where 
co-infection was present and those where no other respiratory viral pathogen was 
identified. The descriptive analysis on viral load table will not be repeated on subject 
with at least one episode with maximum viral load.
Listing will be presented for all cases of RSV infection until Day 731 with the details of 
gender, age at episode, country, site, day of event (i.e days since first visit), classification 
according to maximum severity of episode as RSV RTI/RSV LRTI/ RSV severe LRTI 
and RSV very severe LRTI, RSV hospitalization ‘Yes/No’, SpO2 value, respiratory rate, 
result of RSV qRT-PCR and RVP result will be presented.
Listings will be generated at Day 731 for all hospitalized cases with gender, age at 
episode, classification according to maximum severity of episode as (RSV RTI/RSV 
LRTI/ RSV severe LRTI and RSV very severe LRTI), RVP result, total number of 
calendar days on which the child was hospitalized, days requiring monitoring/nursing 
observation, days requiring nasogastric or intravenous fluids, days requiring 
supplemental oxygen, days requiring respiratory support excluding mechanical 
ventilation, days requiring mechanical ventilation and days requiring pediatric intensive 
care unit management. 


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6.4.
Analysis of safety
6.4.1.
Analysis of safety planned in the protocol
6.4.1.1.
Within groups assessment
The analysis will be based on the ES on each treatment groups separately.
The percentage of subjects with at least one local AE (solicited and unsolicited), with at 
least one general AE (solicited and unsolicited) and with any AE during the 7-day or 
30-day follow-up period will be tabulated with exact 95% confidence interval (CI) after 
each vaccine dose and overall. The percentage of doses followed by at least one local AE 
(solicited and unsolicited), by at least one general AE (solicited and unsolicited) and by 
any AE during the 7-day or 30-day follow-up period will be tabulated, overall 
vaccination course, with exact 95% CI. The same computations will be done for Grade 3 
AEs, for any AEs considered related to vaccination and for any Grade 3 AEs considered 
related to vaccination.
The percentage of subjects reporting each individual solicited local AE (any grade, Grade 
2, Grade 3, resulting in a medically attended visit) and solicited general AE (any grade, 
Grade 2, Grade 3, any related, Grade 2 related, Grade 3 related, resulting in medically 
attended visit) during the 7-day follow-up period (Day 1-7) will be tabulated for each 
group after each vaccine dose and overall. Similarly, the percentage of doses followed by 
each individual solicited local and general AE and their sub-categories, will be tabulated, 
overall vaccination course, with exact 95% CI.
For fever, the number and percentage of subjects reporting fever by half degree (°C) 
cumulative increments during the 7-day follow-up period (Day 0-6) will be tabulated for 
each group after each vaccine dose and overall. Similar tabulations will be performed for 
any fever with a causal relationship to vaccination, Grade 3 (> 39.5°C) causally related 
fever and for any fever resulting in a medically attended visit. In addition, the prevalence 
of any and Grade 3 fever will be presented graphically over time after vaccination.
The percentage of subjects with unsolicited AEs within 30 days (Day 1-30) after each 
vaccine dose (overall doses) with its exact 95% CI will be tabulated by group and by 
MedDRA preferred term. Similar tabulation will be done for Grade 3 unsolicited AEs, for 
any causally related unsolicited AEs, for Grade 3 causally related unsolicited AEs and for 
unsolicited AEs resulting in a medically attended visit. The verbatim reports of 
unsolicited AEs will be reviewed by a physician and the signs and AEs will be coded 
according to the MedDRA Dictionary Version 20 for Adverse Reaction Terminology. 
Every verbatim term will be matched with the appropriate Preferred Term.
The percentage of subject with episode of spontaneous or excessive bleeding (AE of 
specific interest), during a 30-day follow-up period after each vaccination will be 
tabulated by group according to associated PT code presented in Section 12. The 
percentage of subjects with RSV-LRTI (AE of specific interest) from Dose 1 up to Day 
365 and from Dose 1 up to study conclusion (Day 730) will be tabulated by group 
according to associated PT code presented in Section 12.


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The percentage of subjects with SAE within 30 days (Day 1-30) after each vaccine dose 
with its exact 95% CI will be tabulated by group and by MedDRA preferred term. Similar 
table will be generated for SAE from Dose 1 up to Day 61, from Dose 1 up to Day 366
and from Dose 1 up to Day 731. 
SAEs reported throughout the study and AE of specific interest will be described in 
detail.
The percentage of subjects using concomitant medication (any medication, any 
antipyretic/ analgesic and any antipyretic taken prophylactically, respectively) during the 
7-day follow-up period (Day 1-7) and during the 30-day follow-up period (Day 1-30) will 
be summarized by group after each vaccine dose and overall.
For each group and for each hematology and biochemistry parameter:

The percentage of subjects having hematology and biochemistry results 
below/above/within the local laboratory normal ranges will be tabulated by 
timepoint and toxicity grading scale.

The maximum grading from Screening up to Visit 9 (Day 61) will be tabulated 
by grading the safety laboratory values according to toxicity criteria Grading 
scale adapted from [Division of AIDS, 2003], [Division of AIDS, 2004] and 
[Division of AIDS, 2007].

For eosinophils, basophils, and monocytes, summary statistics (min, max, 
standard deviation, mean and median) will be presented as there is no grading 
provided for these parameters.
6.4.1.2.
Between groups assessment
Exploratory comparisons between the investigational RSV groups and the Placebo groups 
will be done in terms of the percentage of subjects, overall doses, reporting any Grade 2/3 
AE during the 7-day follow-up period (Day 1-7) after vaccination, and/ or any fever 
>38.5°C during the 7-day follow-up period (Day 1-7) after vaccination, and/ or any 
vaccine-related SAE during the 7-day follow-up period (Day 1-7) after vaccination.
The standardized asymptotic 95% CI for the following differences will be computed: 

RSV_Ld minus Placebo_Ld

RSV_Md minus Placebo_Md

RSV_Hd minus Placebo_Hd


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6.4.2.
Additional considerations
6.4.2.1.
Additional safety analysis
For the analysis of safety, the percentage of subjects reporting each individual solicited 
local AE (any, each grade, resulting in medically attended visit) during the 7-day follow-
up period after vaccination will be tabulated based on maximum intensity per subject for 
each study vaccine for each group. The percentage of subjects reporting each individual 
solicited general AE (any, each grade, any related, any Grade 2 related, any Grade 3 
related, resulting in medically attended visit) during the 7-day follow-up period after 
vaccination will be based on maximum intensity per subject for each study vaccine for 
each group. 
6.4.2.2.
Exclusion of implausible solicited Adverse Event
Some local and systemic adverse events will be directly measured by the subject and will 
not be subject to a reconciliation process, even if they are biologically implausible. 
Therefore, these implausible measurements will be removed from the analysis but 
included in listings. Implausible measurements are summarized in the table below:
Table 2
Implausible Solicited Adverse Events
Parameter
Implausible measurements
Body temperature
≤ 33°C or ≥ 42°C
Swelling
For subjects < 6 years: Measurements < 0 mm
6.4.2.3.
Combined Solicited and Unsolicited Adverse Events
A summary of subjects with all combined solicited (regardless of their duration) and 
unsolicited adverse events will be provided. Solicited adverse events will be coded by 
MedDRA as per the following codes
Solicited symptom
Lower level term name
Lower level term code
Corresponding Primary Term code
Pain
Pain
10033371
10033371
Redness
Erythema
10015150
10015150
Swelling
Swelling
10042674
10042674
Drowsiness
Drowsiness
10013649
10013649
Fever
Fever
10016558
10016558
Irritability/Fussiness
Irritability
10022998
10022998
Loss of appetite 
Appetite lost 
10003028
10003028
For clintrial.gov and EudraCT posting purposes, a summary of combined solicited and unsolicited 
non-serious adverse events will be produced by System Organ Class and preferred terms and 
according to occurrence of each event. 


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7.
ANALYSIS INTERPRETATION
All analyses are descriptive. Comparative analyses will be descriptive with the aim to 
characterize the difference in safety/reactogenicity between groups and should be 
interpreted with caution considering that there is no adjustment for multiplicity and that 
group sizes are small for these comparisons.
8.
CONDUCT OF ANALYSES
8.1.
Sequence of analyses
The statistical analyses will be performed in 3 steps:
A first analysis will be performed when all data (safety and immunogenicity) up to Day
61 (i.e. data that are as clean as possible) are available. Additional safety data available at 
the time of this analysis will be described. At this point, the statistician will be unblinded 
(i.e. individual subject treatment assignments will be available) and the study will be 
conducted in a single-blind manner, with patients remaining blinded up to study end (Day 
731). Summary results may unblind some specific subjects but no individual listings will 
be provided and the investigators will not have access to the treatment allocation up to 
study end (Day 731), except in case of emergency unblinding (see Section 9.8 of the 
protocol).
An analysis will be performed when all data (safety and immunogenicity) up to Visit 10 
(Day 366; i.e. data that are as clean as possible) are available. No individual listings will 
be provided.
The final analysis will be performed when all data up to study conclusion (Day 731) are 
available. An integrated clinical study report containing all data will be written and made 
available to the investigators at that time.
If the data for tertiary endpoints (additional exploratory analyses) become available at a 
later stage, (an) additional analysis/ analyses will be performed. These data will be 
documented in amendments to the study report and will be made available to the 
investigators at that time.
Description
Analysis ID 
Disclosure 
Purpose
(CTRS=public 
posting, 
SR=study report, 
internal)
Dry run 
review 
needed 
(Y/N)
Study Headline Summary 
(SHS)requiring expedited 
communication to upper 
management (Yes/No)
Reference for 
TFL 
Final Analysis
E1_01
SR
N
Yes
Analysis of 
epoch 1
E1_0X
CTRS
Y
Yes
Up to D366
E1_0X+1
N
No
All tables from 
TFL dated 
xxxxxx 


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Table 3
Endpoints assessed at different analysis time points
Analysis
Analysis ID
Safety
Immuno
RSV/RTI
Epoch 1 
(Day 60)
Solicited AE, Unsolicited 
AE, haematology and 
biochemistry, 
AESI(bleeding), SAE 
from D1-Day 61
All CMI and Humoral 
readout from D1-D61
Up to D366
SAE, AESI –
D1-D366
All CMI and Humoral 
response at D366
RSV analysis for 1st season 
– D1-D366
Final (Day 
731)
SAE, AESI –
D1-D731
None 
RSV 2nd season – D367-
D731; Overall (D1-D731)
8.2.
Statistical considerations for interim analyses
No interim analysis is planned.
9.
CHANGES FROM PLANNED ANALYSES
Following are the changes in the planned analysis:-

The naming of the cohort has been changed per cDISC standards. 

Per cDISC standard, the day of first vaccination is now changed from Day 0 to 
Day 1. 

The study design diagram has been adapted as per cDISC format

In secondary endpoints, specific safety endpoints for Day 1 up to D366 has been 
added as follows: -

Occurrence of SAEs from study start (Day 1) up to Day 366. 

Occurrence of RSV-LRTI (AE of specific interest) as from Dose 1 
administration up to Day 366. 

Occurrence of RSV-RTI, RSV-LRTI, severe RSV-LRTI (according to 
standardized case definitions) as from Dose 1 administration up to Day 366. 

For the immunogenicity analysis, the analysis will be performed on both PPS 
and ES without any condition on percentage of subjects excluded

For inclusion of subjects in PPS for analysis of immunogenicity, subjects should 
have received both the doses and not atleast one dose.


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10.
LIST OF FINAL REPORT TABLES, LISTINGS AND
FIGURES
The TFL TOC provides the list of tables/listings and figures needed for the study report. 
It also identifies the tables eligible for each analyses and their role (synopsis, in-text, 
post-text, SHS, CTRS,…).  Note that all TFL aimed to be included as post-text are noted 
as post-text even if these are tabulation of individual data such as listing of SAE.  The 
post-text material contains all source material for the study report and accordingly a post-
text table may be redundant with an in-text table.
The mock tables referred under column named ‘layout’ can be found in legacy-GSK 
SDD dedicated folder for standard tables and in Section 12 (Annex 2) for study specific 
mock table/figure/listing. The latter table/figure/listing are identified by the prefix SS_ in 
the TFL Toc.
The following group names and pooled group names will be used in the TFLs, to be in 
line with the T-domains:
Group 
order in 
tables
Group label 
in tables
Group definition for 
footnote
Pooled 
Groups 
label in 
tables
Pooled definition for footnote
1
RSV-Ld
Low dose ChAd155-RSV 
vaccine (5 x 109 vp)
RSV
ChAd155-RSV vaccine (low/ middle/high 
dose pooled groups)
2
RSV-Md
Middle dose ChAd155-RSV 
vaccine (1.5 x 1010 vp)
RSV
ChAd155-RSV vaccine (low/ middle/high 
dose pooled groups)
3
RSV-Hd
High dose ChAd155-RSV 
vaccine (5 x 1010 vp)
RSV
ChAd155-RSV vaccine (low/ middle/high 
dose pooled groups)
4
Placebo-Ld
Non-active control (0.5 ml)
Placebo
Non active control (0.15/0.5 ml pooled 
groups)
5
Placebo-Md
Non-active control (0.15 ml)
Placebo
Non active control (0.15/0.5 ml pooled 
groups)
6
Placebo-Hd
Non-active control (0.5 ml)
Placebo
Non active control (0.15/0.5 ml pooled 
groups)
7^
Pooled
Pooled RSV + Placebo 
Pooled
Pooled RSV + Placebo 
^The pooled group is not in the treatment dataset but will be created for generating some tables during D366 analysis.


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11.
ANNEX 1 STANDARD DATA DERIVATION RULE AND 
STATISTICAL METHODS
11.1.
cDISC specification
The analysis planned at D61, D366 and D731 is planned in cDISC format. In cDISC 
format, the day of vaccination is mentioned as Day 1 rather than Day 0 per protocol. 
Accordingly, all the timepoint will be mentioned as Day X +1. The analysis will be 
performed adjusting for it so that correct interval will be selected.
11.2.
Statistical Method References
The exact two-sided 95% CIs for a proportion within a group will be the Clopper-Pearson 
exact CI [Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in 
the case of binomial. Biometrika. 1934; 26:404-413].
The standardised asymptotic two-sided 95% CI for the group difference in proportions is 
based on the method described in the following paper: Robert G. Newcombe, interval 
estimation for the difference between independent proportions: comparison of eleven 
methods, Statist Med. 1998; 17, 873-890]. The standardised asymptotic method used is 
the method six.
11.3.
Standard data derivation
11.3.1.
Date derivation

SAS date derived from a character date: In case day is missing, 15 is used. In 
case day & month are missing, 30June is used.

Onset day for an event (ae, medication, vaccination, …): The onset day is the 
number of days between the last study vaccination & the onset/start date of the 
event. This is 1 for an event starting on the same day as a vaccination. See SAS 
date derived in case the start date of the event is incomplete.

Duration: Duration of an event is expressed in days. It is the number of days 
between the start & the stop dates + 1. Therefore, duration is 1 day for an event 
starting & ending on the same day.

Association of an event to the primary epoch: An adverse event belongs to the 
primary epoch, if the onset date is before and including Visit 9 (Day 60). Any 
safety data collected beyond Visit 9 (Day 60) will be collected in Epoch 002.


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11.3.2.
Dose number

The study dose number is defined in reference to the number of study visits at 
which vaccination occurred.  More specifically dose 1 refers to all vaccines 
administered at the first vaccination visit while dose 2 corresponds to all 
vaccinations administered at the second vaccination visit even if this is the first 
time a product is administered to the subject. 

Relative dose: the relative dose for an event (AE, medication, vaccination) is the 
most recent study dose given before an event. In case the event takes place on 
the day a study dose is given, the related dose will be that of the study dose, 
even if the event actually took place before vaccination. For instance, if an 
adverse event begins on the day of the study vaccination but prior to 
administration of the vaccine, it will be assigned to this dose.   In case a study 
dose is not administered and an event occurs after the subsequent study dose (eg 
2nd study dose), the relative dose of the event will be study dose associated to the 
subsequent study dose (eg dose 2).

The number of doses for a product is the number of times the product was 
administered to a subject. 

The incidence per dose is the number of vaccination visits at which an event was 
reported among all vaccination visits. 
11.3.3.
Demography

Age: Age at the reference activity, computed as the number of units between the 
date of birth and the reference activity. Note that due to incomplete date, the 
derived age may be incorrect by 1 month when month is missing from the 
birthdate.  This may lead to apparent inconsistency between the derived age and 
the eligibility criteria/the age category used for randomization. 

Conversion of weight to kg: The following conversion rule is used:  
Weight in Kilogramm= weight in Pounds / 2.2
Weight in Kilogramm =weight in oncs / 35.27
The result is rounded to 2 decimals.

Conversion of height to cm: The following conversion rule is used:  
Height in Centimetres = Height in Feet * 30.48
Height in Centimetres = Height in Inch * 2.54
The result is rounded to the unit (ie no decimal).

Conversion of temperature to °C: The following conversion rule is used:  
Temperature in °Celsius  = ((Temperature in °Fahrenheit -32) *5)/9
The result is rounded to 1 decimal.


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
Calculation of weight for age Z-score (WAZ) for each subject (rounded to 2 
decimal): 
WAZ = (Weight of subject -median weight)/Standard deviation for weight

Calculation of height for age Z-score (HAZ) for each subject (rounded to 2 
decimal): 
HAZ = (Height of subject -median height)/Standard deviation for height
11.3.4.
Immunogenicity

For a given subject and given immunogenicity measurement, missing or non-
evaluable measurements will not be replaced. Therefore, an analysis will 
exclude subjects with missing or non-evaluable measurements. Kinetics will be 
plotted on subjects with results available at all timepoints.

The Geometric Mean Concentrations/Titres (GMC/Ts) calculations are 
performed by taking the anti-log of the mean of the log titre transformations. 
Antibody titres below the cut-off of the assay will be given an arbitrary value of 
half the cut-off of the assay for the purpose of GMT calculation. 

The 95% CI for the mean of log-transformed titer will be first obtained 
assuming that log-transformed values were normally distributed with unknown 
variance. The 95% CI for the GMTs/GMCs will be then obtained by 
exponential-transformation of the 95% CI for the mean of log-transformed titer.

A seronegative subject is a subject whose antibody titre is below the cut-off 
value of the assay. A seropositive subject is a subject whose antibody titre is 
greater than or equal to the cut-off value of the assay.

An exploratory definition of vaccine response to the RSV neutralising antibodies 
will be as:

At least a 4-fold increase from pre-vaccination if pre-vaccination 
neutralising antibody titre <128.

At least a 3-fold increase from pre-vaccination if pre-vaccination 
neutralising antibody titre in [128-256.

At least a 2.5-fold increase from pre-vaccination if pre-vaccination 
neutralising antibody titre in 256-1024.

At least 1-fold from pre-vaccination if pre-vaccination neutralising antibody 
titre >1024
Please note that other definition of vaccine response will be also be explored but 
interest might be limited considering this is not target population.

Assay cut-off for the humoral immunity will be per the following table
Component
Method
Unit
Cut-off
Respiratory Syncytial Virus A Ab
NEUTRALIZATION 
ED60
8
Respiratory Syncytial Virus F protein 
Ab.IgG (Anti-RSV PreF antibody) 
ELISA 
EU/ml
10 
Respiratory Syncytial Virus F protein 
Ab.IgG (Palivizumab competing Ab) 
ELISA 
µg/ml
9.6


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
Considering the cut-off for the neutralising antibody against RSV-A is below the 
assay’s LLOQ [32], the following rules will be applied for derivation of 
seropostivity status and GMT:
Assay
Raw result
Derivation for 
seropositivity 
status
Derivation for 
GMT 
calculation
Derivation for fold-
increase between Post and 
Pre-vaccination titres
RSV-A 
neutralising 
Antibody
<cut-off
NEG
Cut-off/2
LLOQ/2
[cut-off-LLOQ [
POS
Cut-Off
LLOQ/2
≥LLOQ
POS
Exact value
Exact value

The cut-off for the PCA assay is set at the level of the assay LLOQ (9.60 
µg/mL). For results below the cut-off (LLOQ), an arbitrary value of half of the 
cut-off will be considered for calculation of GMC and fold increase.

All CI computed will be two-sided 95% CI.

CMI: CD4+ and/or CD8+ T-cells, by ICS using WBS

All results available in the database (events/per million of cells) will be 
dividing by 10000 in order to express the results in percentage (%).

The derived variable that will be used for the analysis will be:

the frequency of RSV F/N/M2-1 specific and combined (RSV F/N/M2-
1) CD4+ T-cells expressing at least two marker among CD40L, IL-2, 
TNF-α, and IFN-γ;

the frequency of CD4+ and CD8+ T-cells expressing at least one or any 
combination of immune marker(s) among CD40L, 41BB, IL-2, TNF-α, 
IFN-γ, IL-13 and IL-17 upon stimulation with F, N and M2-1 peptide 
pools and combined peptide pools.

Those derived variables will be obtained as follows: sum of all specific 
responses of interest minus the sum of corresponding background 
responses. All values less or equal to zero will be set to 1 for the purpose of 
GM calculation.

Co-expression profile: for each CD4+/CD8+ any combination of markers, 
the RSV F/N/M2-1 specific response will be obtained by subtracting the 
background value to the RSV value (stimulation with RSV F/N/M2-1 
peptides), and by setting to 1 all values less than or equal to zero for the 
purpose of GM calculation and graphical representation. 

The log-transformation of the percentage of RSV F/N/M2-1specific 
CD4+/CD8+ T-cells will be applied, and the GM calculations will be 
performed by taking the anti-log of the mean of the log transformations.

For calculation of Th2/Th1 ratio has to be done by taking average of Th2 
and Th1 profile at the individual level after adjusting on background.


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 37 of 104
11.3.5.
Safety 

For a given subject and the analysis of solicited symptoms during the 7 day 
follow-up period after vaccination, missing or non-evaluable measurements will 
not be replaced. Therefore, the analysis of the solicited symptoms based on the 
ES will include only vaccinated subjects with documented safety data (i.e., 
symptom screen completed). More specifically the following rules will be used: 

Subjects who documented the absence of a solicited symptom after one 
dose will be considered not having that symptom after that dose.

Subjects who documented the presence of a solicited symptom and 
fully or partially recorded daily measurement over the solicited period 
will be included in the summaries at that dose and classified according 
to their maximum observed daily recording over the solicited period.

Subjects who documented the presence of a solicited symptom after 
one dose without having recorded any daily measurement will be 
considered as having symptom and will be considered in subjects who 
experiences the symptom but will not be considered in the specific 
information by grade. 

Doses without symptom sheets documented will be excluded.

For analysis of unsolicited AEs, SAEs and for the analysis of concomitant 
medications, all vaccinated subjects will be considered. Subjects who did not 
report an event or concomitant medication will be considered as subjects 
without the event or the concomitant medication respectively.

Related dose: The related dose for an event (e.g., AE, medication, 
vaccination…) is the study dose given before an event. In case the event takes 
place on a day a study dose is given, the related dose will be that of the study 
dose even if the event actually took place before. For instance, for a conc. 
medication started on the day of study dose 2 but before dose 2 administrations, 
the related dose will be dose 2.

The maximum intensity of local injection site redness and swelling will be scored at 
GSK Biologicals as follows:
0 : None
1 : < 5 mm
2 : 5 to 20 mm
3 : > 20 mm

Fever is defined as temperature 37.5°C / 99.5°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 will be axillary. For the analysis, temperatures will be 
coded as follows:
Grade
Temperature (oral, axillary 
or tympanic route)
Temperature (rectal route)
0
< 37.5C
< 38C
1
37.5C - 38.5C
38C - 39C
2
> 38.5C - 39.5C
> 39C - 40C
3
> 39.5C
> 40C


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 38 of 104

Conversion of temperature to °C

Temperature in °Celsius  = ((Temperature in °Fahrenheit -32) *5)/9. 

The result is rounded to 1 decimal.

Note that for all tables described in this section, the way the percentage of 
subjects will be derived will depend on the event analysed (see table below for 
details). As a result, the N value will differ from one table to another.
Event
N used for deriving % per subject 
for Vaccination phase
N used for deriving % per dose for 
Vaccination phase
Concomitant 
vaccination
All subjects with study vaccine 
administered
All study visits with study vaccine 
administered
Solicited 
general 
symptom
All subjects with at least one solicited 
general symptom documented as 
either present or absent (i.e., 
symptom screen completed)
All study visits with study vaccine 
administered and with at least one solicited 
general symptom documented as either 
present or absent (i.e., symptom screen 
completed)
Solicited local 
symptom
All subjects with at least one solicited 
local symptom documented as either 
present or absent (i.e., symptom 
screen completed)
All study visits with study vaccine 
administered and with at least one solicited 
local symptom documented as either present 
or absent (i.e., symptom screen completed)
Unsolicited 
symptom
All subjects with study vaccine 
administered 
All study visits with study vaccine 
administered
Concomitant 
medication
All subjects with study vaccine 
administered 
All study visits with study vaccine 
administered

All CI computed will be two-sided 95% CI.

Grading of haematological and biochemical parameters will be assessed as per 
the following tables: -
Table 4
Toxicity grading scales for hematology and biochemistry 
parameters applicable for this study
Component
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin (g/dL)
9.0 to < 10.5
8.0 to < 9.0
7.0 to < 8.0
< 7.0
Leukocytes decreased (cell/mm3)
2500 to < 3500
1500 to < 2500
1000 to < 1500
< 1000
Platelets decreased (cell//mm3) 
75000 to < 150000
50000 to < 75000
25000 to < 50000
< 25000
Alanine Aminotransferase
(increase by factor)
1.1 to < 2.0 xULN
2.0 to < 3.0 xULN
3.00 to ≤8.0 xULN
> 8.0 xULN
Aspartate Aminotransferase
(increase by factor)
1.1 to < 2.0 xULN
2.0 to < 3.0 xULN
3.00 to ≤8.0 xULN
> 8.0 xULN
Creatinine (mg/dL) 
0.6 to < 0.9
0.9 to < 1.2
1.2 to ≤ 1.5
> 1.5
Absolute neutrophil count decreased 
(cell/mm³)
1000 to < 1300
750 to < 1000
500 to < 750
< 500
Absolute lymphocyte count 
decreased (cell/mm³)
600 to < 650
500 to < 600
350 to < 500
< 350
Eosinophil
N.A
N.A
N.A
N.A
Basophil
N.A
N.A
N.A
N.A
Monocyte
N.A
N.A
N.A
N.A
Grading scale adapted from [Error! Reference source not found., 2003], [Error! Reference source not found., 
2004] and [Error! Reference source not found., 2007].
ULN: upper limit of normal


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 39 of 104
11.3.6.
RTI and LRTI 

For the analysis of RTI and LRTI, all cases will be definitively classified as 
either RSV-RTI, RSV-LRTI, RSV-severe LRTI or RSV-very severe LRTI 
according to standardized case definitions (see table below) based on the 
available WHO case definitions, and the association to RSV infection will be 
assessed by quantitative PCR as primary analysis. 
Table 5
Case definition of RSV- RTI/LRTI
RSV infection 
Symptomatic and/or asymptomatic RSV infection
RSV-RTI
Runny nose OR blocked nose OR cough
AND 
Confirmed RSV infection 4
RSV-LRTI
History of cough OR difficulty breathing 1
AND 
SpO2 < 95% 2, OR RR increase 3
AND 
Confirmed RSV infection 4
RSV-severe LRTI
Meeting the case definition of RSV-LRTI
AND
SpO2 < 93% 2, OR lower chest wall in-drawing
RSV-very severe LRTI
Meeting the case definition of RSV-LRTI 
AND 
SpO2 < 90% 2, OR inability to feed, OR failure to respond / unconscious
RSV hospitalization
Confirmed RSV infection 5
AND
Hospitalized for acute medical condition 6
All-cause LRTI
History of cough OR difficulty breathing 1
AND 
SpO2 < 95% 2, OR RR increase 3
Definition based on [Modjarrad, 2016]
LRTI = lower respiratory tract infections; RR = respiratory rate; RTI = respiratory tract infections; 
SpO2 = blood oxygen saturatin
1 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
2 For blood oxygen saturation (SpO2), the lowest value monitored will be used 
3 RR increase defined as 40/minute (12 months of age or above)
4 RSV infection confirmed on nasal swab positive for RSV A or B by quantitative Reverse Transcription Polymerase 
Chain Reaction (qRT-PCR)
5 RSV sampling and testing is based on medical judgment of medical practitioner or driven by algorithm
6 Hospitalization is defined as a medical decision that the infant requires admission for observation or treatment

For the analysis of RSV-RTI episode, the start date of an RTI episode will be 
defined as the first day of any occurrence of cough, runny nose, blocked nose, 
and a new case requires an interval of at least 7 symptom free days since the last 
episode of RTI that was diagnosed. 

For the analysis of RSV-LRTI or severe or very severe LRTI the start date of the 
LRTI episode is defined as the point at which the first symptoms of cough, or 
difficulty breathing were observed and a new case requires an interval of at least 
7 symptom free days since the last episode of LRTI that was diagnosed.


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 40 of 104

End date of the RTI episode is defined as the point at which the child is 
considered symptom-free of cough, runny nose, blocked nose, wheezing, and 
difficulty breathing.

For molecular biology (qRT-PCR test), the following cut-off will be applied: -
System
Component
Method
Unit
Cut-off
Nasal swab
RSV-A RNA
Quantitative real-time PCR (qRT-PCR)
Copies/ml
1123
Nasal swab
RSV-B RNA
Quantitative real-time PCR (qRT-PCR)
Copies/ml
1467

For calculation of viral load for RSV-A/B, all reported values will be included. 
Subject infected by either RSV-A or RSV-B or both will be included for 
calculation. Total viral load = Viral load for RSV-A + Viral load for RSV-B. 
LOD for RSV-A and RSV-B are 1123 and 1467 copies/ml, respectively. 
Following rule will be applied: -
Raw result
Derivation for positivity
Derivation for viral 
load calculation
<LOD
NEG
LOD/2
≥LOD
POS
Exact value
11.3.7.
Number of decimals displayed
The following decimal description from the decision rules will be used for the 
demography, immunogenicity and safety/reactogenicity.
Display Table
Parameters
Number of decimal digits
Demographic characteristics
Mean, median age
1
Demographic characteristics
SD (age)
1
Reactogenicity
Mean, Min, Q1, Median, Q3, Max for duration
1
All summaries
% of count, including LL & UL of CI
1
All summaries
% of difference, including LL & UL of CI
2


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 41 of 104
12.
ANNEX 2: RELEVANT PREFERRED TERMS FOR 
DETECTION OF AESI
Any of the below listed preferred term reported as an Expedited Adverse Event must be 
immediately escalated to the CRDL or Central Safety Physician to assess or confirm the 
need for an urgent IDMC review.
The list of preferred terms and associated PT codes is given below:
HAEMATOMA
Preferred term
PT code
abdominal wall haematoma
10067383
administration site haematoma
10075100
adrenal haematoma
10059194
aortic intramural haematoma
10067975
application site haematoma
10068317
arterial intramural haematoma
10074971
auricular haematoma
10003797
basal ganglia haematoma
10077031
brain stem haematoma
10073230
breast haematoma
10064753
broad ligament haematoma
10006375
bursal haematoma
10077818
catheter site haematoma
10055662
cephalhaematoma
10008014
cerebellar haematoma
10061038
cerebral haematoma
10053942
cervix haematoma uterine
10050020
chest wall haematoma
10076597
colonic haematoma
10009996
deep dissecting haematoma
10074718
extradural haematoma
10015769
eyelid haematoma
10064976
haematoma
10018852
haematoma evacuation
10060733
haematoma infection
10051564
hepatic haematoma
10019676
incision site haematoma
10059241
infusion site haematoma
10065463
injection site haematoma
10022066
instillation site haematoma
10073609
intestinal haematoma
10069829
intra-abdominal haematoma
10056457
intracerebral haematoma evacuation
10062025


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 42 of 104
intracranial haematoma
10059491
intraocular haematoma
10071934
laryngeal haematoma
10070885
lip haematoma
10066304
mediastinal haematoma
10049941
medical device site haematoma
10075577
mesenteric haematoma
10071557
nasal septum haematoma
10075027
oesophageal intramural haematoma
10077486
oral mucosa haematoma
10074779
ovarian haematoma
10033263
paranasal sinus haematoma
10069702
pelvic haematoma
10054974
penile haematoma
10070656
perineal haematoma
10034520
periorbital haematoma
10034544
periosteal haematoma
10077341
perirenal haematoma
10049450
peritoneal haematoma
10058095
pharyngeal haematoma
10068121
post procedural haematoma
10063188
pulmonary haematoma
10054991
renal haematoma
10038459
retroperitoneal haematoma
10058360
scrotal haematoma
10039749
spinal cord haematoma
10076051
spinal epidural haematoma
10050162
spinal subdural haematoma
10050164
splenic haematoma
10041646
spontaneous haematoma
10065304
subarachnoid haematoma
10076701
subcutaneous haematoma
10042345
subdural haematoma
10042361
subgaleal haematoma
10069510
subretinal haematoma
10071935
tongue haematoma
10043959
uterine haematoma
10063875
vaccination site haematoma
10069472
vaginal haematoma
10046909
vitreous haematoma
10071936
vulval haematoma
10047756


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 43 of 104
HAEMORRHAGE
Preferred term
PT code
abdominal wall haemorrhage
10067788
acute haemorrhagic conjunctivitis
10067817
administration site haemorrhage
10075101
adrenal haemorrhage
10001361
anal haemorrhage
10049555
anastomotic haemorrhage
10056346
angina bullosa haemorrhagica
10064223
application site haemorrhage
10072694
arterial haemorrhage
10060964
basal ganglia haemorrhage
10067057
bone marrow haemorrhage
10073581
brain stem haemorrhage
10006145
brain stem microhaemorrhage
10071205
breast haemorrhage
10006254
bronchial haemorrhage
10065739
catheter site haemorrhage
10051099
central nervous system haemorrhage
10072043
cerebellar haemorrhage
10008030
cerebellar microhaemorrhage
10071206
cerebral haemorrhage
10008111
cerebral microhaemorrhage
10067277
cervix haemorrhage uterine
10050022
ciliary body haemorrhage
10057417
conjunctival haemorrhage
10010719
diverticulitis intestinal haemorrhagic
10013541
diverticulum intestinal haemorrhagic
10013560
duodenitis haemorrhagic
10013865
ear haemorrhage
10014009
encephalitis haemorrhagic
10014589
gastric haemorrhage
10017788
gastroduodenal haemorrhage
10053768
gastrointestinal haemorrhage
10017955
genital haemorrhage
10061178
haemarthrosis
10018829
haematemesis
10018830
haematochezia
10018836
haematotympanum
10063013
haematuria
10018867
haemorrhage
10055798
haemorrhage coronary artery
10055803


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 44 of 104
haemorrhage intracranial
10018985
haemorrhage subcutaneous
10018999
haemorrhage subepidermal
10019001
haemorrhage urinary tract
10055847
haemorrhagic anaemia
10052293
haemorrhagic diathesis
10062713
haemorrhagic disorder
10019009
haemorrhagic infarction
10019013
haemorrhagic ovarian cyst
10060781
haemorrhagic pneumonia
10077933
haemorrhagic thyroid cyst
10072256
haemorrhagic urticaria
10059499
injection site haemorrhage
10022067
internal haemorrhage
10075192
intestinal haemorrhage
10059175
intra-abdominal haemorrhage
10061249
intraventricular haemorrhage
10022840
iris haemorrhage
10057418
joint microhaemorrhage
10077666
lacrimal haemorrhage
10069930
large intestinal haemorrhage
10052534
laryngeal haemorrhage
10065740
lip haemorrhage
10049297
lower gastrointestinal haemorrhage
10050953
lymph node haemorrhage
10074270
mediastinal haemorrhage
10056343
mesenteric haemorrhage
10060717
mouth haemorrhage
10028024
mucocutaneous haemorrhage
10076048
mucosal haemorrhage
10061298
muscle haemorrhage
10028309
myocardial haemorrhage
10048849
naevus haemorrhage
10062955
ocular retrobulbar haemorrhage
10057571
oesophageal haemorrhage
10030172
optic disc haemorrhage
10030919
optic nerve sheath haemorrhage
10030941
ovarian haemorrhage
10065741
pancreatic haemorrhage
10033625
papillary muscle haemorrhage
10059164
parathyroid haemorrhage
10059051
parotid gland haemorrhage
10051166


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 45 of 104
pelvic haemorrhage
10063678
penile haemorrhage
10034305
pericardial haemorrhage
10034476
periorbital haemorrhage
10071697
peritoneal haemorrhage
10034666
petechiae
10034754
pharyngeal haemorrhage
10034827
pituitary haemorrhage
10049760
post procedural haemorrhage
10051077
procedural haemorrhage
10071229
prostatic haemorrhage
10036960
pulmonary alveolar haemorrhage
10037313
pulmonary haemorrhage
10037394
putamen haemorrhage
10058940
rectal haemorrhage
10038063
renal haemorrhage
10038460
respiratory tract haemorrhage
10038727
retinal haemorrhage
10038867
retroperitoneal haemorrhage
10038980
scleral haemorrhage
10050508
skin haemorrhage
10064265
small intestinal haemorrhage
10052535
soft tissue haemorrhage
10051297
spermatic cord haemorrhage
10065742
spinal cord haemorrhage
10048992
spinal epidural haemorrhage
10049236
spinal subarachnoid haemorrhage
10073564
spinal subdural haemorrhage
10073563
splenic haemorrhage
10041647
spontaneous haemorrhage
10074557
subarachnoid haemorrhage
10042316
subdural haemorrhage
10042364
testicular haemorrhage
10051877
thalamus haemorrhage
10058939
thoracic haemorrhage
10062744
thyroid haemorrhage
10064224
tongue haemorrhage
10049870
tracheal haemorrhage
10062543
upper gastrointestinal haemorrhage
10046274
ureteric haemorrhage
10065743
urethral haemorrhage
10049710
urinary bladder haemorrhage
10046528


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 46 of 104
urogenital haemorrhage
10050058
uterine haemorrhage
10046788
vaccination site haemorrhage
10069475
vaginal haemorrhage
10046910
venous haemorrhage
10065441
vitreous haemorrhage
10047655
vulval haemorrhage
10063816
THROMBOCYTOPENIA
Preferred term
PT code
bleeding time abnormal
10049227
bleeding time prolonged
10005140
coagulation test abnormal
10063557
platelet count abnormal
10035526
platelet count decreased
10035528
platelet disorder
10035532
platelet dysfunction
10073391
thrombocytopenia
10043554
thrombocytopenic purpura
10043561
LOWER RESPIRATORY TRACT INFECTION
Preferred term
PT code
atypical pneumonia
10003757
bronchitis
10006451
bronchitis viral
10053160
haemorrhagic pneumonia
10077933
lower respiratory tract infection
10024968
lower respiratory tract infection viral
10065188
lung infection
10061229
pneumonia
10035664
pneumonia respiratory syncytial viral
10035732
pulmonary sepsis
10051739
respiratory syncytial virus bronchiolitis
10038718
respiratory syncytial virus bronchitis
10069811
respiratory tract infection
10062352
respiratory tract infection viral
10062106
13.
ANNEX 3: STUDY SPECIFIC MOCK TFL
The data display, title and footnote is for illustration purpose and will be adapted to the 
study specificity as indicated in the TFL TOC.   Note that there may be few changes 
between the study specific SAP mock TFL and the final TFLs as editorial/minor changes
do not require a SAP amendment.  


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 47 of 104
13.1.
List of individual data listing 
Following individual data listing will be generated
Appendix Table I.A - Elimination codes
Appendix Table I.B – Demography
Appendix Table IBii - Physical examination/vital signs
Appendix Table I.Ci - Dates of birth, Informed consent, Vaccination and blood sampling, 
Contact
Appendix Table I.Cii - Reason for visit not done
Appendix Table I.D - General medical history - Physical examination
Appendix Table I.Ei – Study Conclusion 
Appendix Table I.Eii – Screening conclusion
Appendix Table I.F – Notes (this appendix is provided for info only and should not be 
used for the clinical report)
Appendix Table I.G / I.H - Vaccination procedure
Appendix Table I.I - Reason for not administration of vaccine
Appendix Table I.J - Reason for non-eligibility
Appendix Table I.Ki – Previous history of vaccination
Appendix Table I.Kii – Previous history of disease 
Appendix Table II.Ai - Solicited local adverse events
Appendix Table II.B - Solicited general adverse events
Appendix Table II.Ci - Unsolicited adverse events within (30) days post-vaccination
Appendix Table II.Cii - Unsolicited adverse events after (30) days post-vaccination
Appendix Table II.Di - Concomitant medications
Appendix Table II.Dii - Concomitant vaccinations
Appendix Table III.A – Immunogenicity - HI
Appendix Table III.B – Immunogenicity- CMI 
Appendix Table IV.A – Haematology and Biochemistry
Appendix Table IIIA – Altitude of the site
Appendix Table IIE –Detection of Episodes and Limb Examination
Appendix Table IIF - Surveillance Contact 
Appendix Table IIG - Assessment of RTI Episode
Appendix Table IIH - RTI Symptoms
Appendix Table IIJ - Signs and Symptoms of RSV-LRTI
Appendix Table IIK - Chest X-Ray Observations
Appendix Table IIL- Inpatient Care
Appendix Table IIIA – Local RSV Result
Appendix Table IIIB – Nasal Swab (qRT-PCR Result)
Appendix IIIC – Blood culture result
Appendix IIID- Re-screening


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 48 of 104
13.2.
Template of Tables and Figures
Template 1
Number of subjects by country and center <Exposed Set>
<Each group>
N=XXXX
<Each group>
N=XXXX
Total
N=XXXX
Country
Center
n
%
n
%
n
%
<each country>
<each center >
XXX
XX.X
XXX
XX.X
XXX
XX.X
All
XXX
XX.X
XXX
XX.X
XXX
XX.X
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
n = number of subjects in a given center or country
N = total number of subjects
% = n/N x 100
Center = GSK Biologicals assigned center number
Template 2
Number of subjects vaccinated, completed and withdrawn with 
reason for withdrawal – up to Day X <Exposed set>
<Each group>
N=XXXX
<Each group>
N=XXXX
Total
N=XXXX
n
n
n
Number of subjects vaccinated
xxx
xxx
xxx
End of study status
 [EACH CATEGORY]
xxx
xxx
xxx
Reasons for withdrawal:
 [REASONS]
xxx
xxx
xxx
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
Vaccinated = number of subjects who were vaccinated in the study
Completed  = number of subjects who completed last study visit
Withdrawn = number of subjects who did not come for the last study visit


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 49 of 104
Template 3
Visit attendance <Exposed set>
<Each group>
N=XXX
Visit
Status
n
%
INFORMED CONSENT 
Completed
RANDOMIZATION
Completed
<EACH VISIT>
Attended 
Not attended yet
Permanent discontinuation prior to this visit
Not attended
CONCLUSION
Completed
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = Number of subjects in each group or in total
Conclusion = date of last visit or withdrawal
Template 4
Number of subjects enrolled into the study as well as the number of 
subjects excluded from the PPS analysis of immunogenicity at Day 
X with reasons for exclusion 
Total
<each group>
Title
n
s
%
n
s
Enrolled Set
Invalid informed consent or fraudulent data (code 900)
Study vaccine dose not administered but subject number allocated (code 1030)
Exposed set
<Reason for elimination & elimination code>
<Reason for elimination & elimination code>
PPS for analysis of immunogenicity at Day X
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
Note: Subjects may have more than one elimination code assigned
n = number of subjects with the elimination code assigned excluding subjects who have been assigned a lower 
elimination code number
s = number of subjects with the elimination code assigned
% = percentage of subjects in the considered PPS relative to the Exposed set


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
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Template 5
Summary of demographic characteristics <Exposed set>
<Each group>
N=XXXX
<Each group>
N=XXXX
Total
N=XXXX
Value or n
%
Value or n
%
Value or n
%
Age in months at <timepoint>
 N with data
xxx
xxx
xxx
 Mean
xxx.x
xxx.x
xxx.x
 SD
xxx.x
xxx.x
xxx.x
 Median
xxx.x
xxx.x
xxx.x
 Minimum
xxx
xxx
xxx
 Maximum
xxx
xxx
xxx
Gender
 <EACH GENDER>
xxx
xx.x
xxx
xx.x
xxx
xx.x
 …
xxx
xx.x
xxx
xx.x
xxx
xx.x
Ethnicity
 <EACH ETHNICITY>
xxx
xx.x
xxx
xx.x
xxx
xx.x
 …
xxx
xx.x
xxx
xx.x
xxx
xx.x
Geographic Ancestry
 <EACH GEOGRAPHIC ANCESTRY>
xxx
xx.x
xxx
xx.x
xxx
xx.x
 …
xxx
xx.x
xxx
xx.x
xxx
xx.x
Country
 <EACH COUNTRY>
xxx
xx.x
xxx
xx.x
xxx
xx.x
 …
xxx
xx.x
xxx
xx.x
xxx
xx.x
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = total number of subjects
n/% = number / percentage of subjects in a given category
Value = value of the considered parameter
N with data = number of subjects with documentation of the corresponding data
SD = standard deviation


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
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Template 6
Summary of vital signs characteristics <Exposed set>
<each group>
N = 
Total
N = 
Visit
Characteristics
Parameters
Value
Value
<Each visit>
Height (Cm)
N with data
Mean
SD
Median
Minimum
Maximum
Weight (Kg)
N with data
Mean
SD
Median
Minimum
Maximum
Heart rate (Beats per minute)
N with data
Mean
SD
Median
Minimum
Maximum
Respiratory rate (Breadth per minute)
N with data
Mean
SD
Median
Minimum
Maximum
Temperature/(Axillary) (°C)
N with data
Mean
SD
Median
Minimum
Maximum
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = total number of subjects
N with data = number of subjects with documentation of the corresponding data 
Value = value of the considered parameter
SD = standard deviation


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 52 of 104
Template 7
Distribution of weight for age Z-score (WAZ) at vaccination 
<Exposed Set>
Each group 
N =
Total 
N =
Visit
Characteristics
n
%
n
%
Day 1 
Normal (-1 < WAZ < 0)
Mildly underweight (-2<WAZ<-1)
Moderately underweight (-3<WAZ<-2)
Severely underweight (WAZ<-3)
Day 366 
Normal (-1 < WAZ < 0)
Mildly underweight (-2<WAZ<-1)
Moderately underweight (-3<WAZ<-2)
Severely underweight (WAZ<-3)
<group>
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = Total number of subjects
n = number of subjects in each category
% = n / Number of subjects with available results x 100
For weight for age Z score calculation of each subject, median = XX and SD = YY
Template 8
Distribution of height for age Z-score (HAZ) at vaccination <Exposed 
Set>
Each group 
N = 
Total 
N = 
Visit
Characteristics
n
%
n
%
Day 1
Normal (-1 < HAZ < 0  )
Mildly stunted (-2<HAZ<-1)
Moderately stunted (-3<HAZ<-2)
Severely stunted (HAZ<-3)
Day 366
Normal (-1 < HAZ < 0  )
Mildly stunted (-2<HAZ<-1)
Moderately stunted (-3<HAZ<-2)
Severely stunted (HAZ<-3)
<group>
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = Total number of subjects
n = number of subjects in each category
% = n / Number of subjects with available results x 100
For height for age Z score calculation of each subject, median = XX and SD = YY


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
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Template 9
Deviations from specifications for age and intervals between study 
visits up to Day X <Exposed Set>
Age
SCR-
Dose:1
Dose:1-
VISIT3 
(D4)
Dose:1-
VISIT4 
(D8)
Dose:1-
Dose:2
Dose:2-
VISIT7 
(D34)
Dose:2-
VISIT8 
(D38)
Dose:2-
VISIT9 
(D61)
Dose:1-
VISIT10 
(D366)
Dose:1-
VISIT11 
(D731)
Group
Protocol Protocol Protocol Protocol Protocol Protocol Protocol Protocol
Protocol Protocol
from 12 
to 23 
months
from 1 to 
30 days
from 3 to 
4 days
from 7 to 
10 days
from 23 
to 36 
days
from 3 to 
4 days
from 7 to 
10 days
from 28 to 
35 days
from 335 
to 395 
days
from 700 
to 760 
days
<each 
group>
N
n
%
range
<each group (pooled groups)>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = total number of subjects with available results
n/% = number / percentage of subjects with results outside of the interval
range = minimum-maximum for age and intervals
Please note - On Day 3 and Day 33, a visit may take place at the investigators clinical facility or the investigator/clinical 
staff may call the subjects’ parent(s)/LAR(s), as appropriate to the circumstances in the judgment of the 
investigator
Template 10 Study Population 
<Each group>
N=XXXX
<Each group>
N=XXXX
Total
N=XXXX
Number of subjects
Planned, N
xxx
xxx
xxx
Randomised, N <cohort name>
xxx
xxx
xxx
Completed, n (%)
xxx (xx.x)
xxx (xx.x)
xxx (xx.x)
<Unknown>
xxx 
xxx 
xxx 
Demographics
N <cohort name>
xxx
xxx
xxx
Females:Males
xxx:xxx
xxx:xxx
xxx:xxx
Mean Age, <unit> (SD)
xxx.x (xxx.x)
xxx.x (xxx.x)
xxx.x (xxx.x)
Median Age, <unit> (minimum, maximum)
xxx (xxx,xxx)
xxx (xxx,xxx)
xxx (xxx,xxx)
<MOST FREQUENT CATEGORY OF RACE>
xxx (xx.x)
xxx (xx.x)
xxx (xx.x)
<SECOND MOST FREQUENT CATEGORY OF RACE>
xxx (xx.x)
xxx (xx.x)
xxx (xx.x)
<THIRD MOST FREQUENT CATEGORY OF RACE>
xxx (xx.x)
xxx (xx.x)
xxx (xx.x)
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = Total number of subjects
SD = Standard deviation


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 54 of 104
Template 11 Number of enrolled subjects by country 
<each group>
N =
Total
N =
Characteristics
n
n
Country
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = Number of enrolled subjects
n= number of enrolled subjects included in each group or in total for a given country or for all countries
Template 12 Number of enrolled subjects by age category 
<each group>
N =
Total
N =
Characteristics
Categories
n
n
Age category
1=Infants and toddlers (28 days-23 month)
Missing
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = Number of enrolled subjects
n= number of enrolled subjects included in each group or in total for a given age category or for all age categories
Missing = age at dose 1 unknown
Template 13 Minimum and maximum activity dates <Exposed set>
<each group>
<each group>
Overall
Visit Description Parameter
Date
Date
Date
<each inform 
consent>
Minimum
Maximum
[Randomisation]
Minimum
Maximum
<each visit>
Minimum
Maximum
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 55 of 104
Template 14 Exposure to study vaccines <Exposed Set>
<Each group>
N=XXXX
<Each group>
N=XXXX
Total
N=XXXX
Number of subjects receiving
n
%
n
%
n
%
Exactly 1 Dose
Exactly 2 Doses
…
At least 1 Dose
Total number of doses administered during the study
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = number of subjects in each group or in total included in the considered cohort
n = number of subjects/doses in the given category
% = percentage of subjects in the given category
Template 15 Compliance in completing solicited symptoms information
<Exposed Set>  
<each group>
<each group>
DOSE
Symptom 
information
N
n
Compliance 
(%)
N
n
Compliance 
(%)
DOSE <each dose 
number>
General SS
Local SS
TOTAL
General SS
Local SS
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N=Number of administered doses
n = number of doses with SS returned
General SS = Symptom screens used for the collection of general solicited AEs
Local SS = Symptom screens used for the collection of local solicited AEs
Compliance (%) = (n / N) X 100


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 56 of 104
Template 16 Incidence and nature of symptoms (solicited and unsolicited) 
reported during the 7-day post-vaccination period (Days 1-7) 
following each dose and overall <Exposed Set>
<Each group>
<Each group>
Local symptoms
95% CI
95% CI
95% CI
Dose
Symptoms
N n %
LL
UL
N n % LL
UL
N
n
%
LL
UL
Dose 1
Any symptom
General symptoms
Local symptoms
Dose 2
Any symptom
General symptoms
Local symptoms
Overall/dose
Any symptom
General symptoms
Local symptoms
Overall/subject
Any symptom
General symptoms
Local symptoms
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
For each dose:
N = number of subjects with the corresponding documented dose
n/% = number/percentage of subjects presenting at least one type of symptom following the corresponding dose 
For overall/dose:
N = number of documented dose
n/% = number/percentage of doses followed by at least one type of symptom 
For overall/subject:
N = number of documented dose
n/% = number/percentage of subjects presenting at least one type of symptom 
95% CI = exact 95% confidence interval, LL = Lower Limit, UL = Upper Limit


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 57 of 104
Template 17 Incidence of solicited local symptoms reported during the 7-day 
(Days 1-7) post-vaccination period following each dose and overall 
<Exposed Set>
<each group>
95 % CI
Dose
Symptom
Type
N
n
%
LL
UL
DOSE 1
Pain
All
Grade 2
Grade 3
Medical advice
Redness (mm)
All
5
>20
Medical advice
Swelling (mm)
All
5
>20
Medical advice
DOSE 2
Pain
…
Redness (mm)
…
Swelling (mm)
…
OVERALL/DOSE
Pain
…
Redness (mm)
…
Swelling (mm)
…
OVERALL/SUBJECT
Pain
…
Redness (mm)
…
Swelling (mm)
…
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
For each dose:
N = number of subjects with the corresponding documented dose
n/% = number/percentage of subjects reporting the type of symptom at least once following the corresponding dose 
For Overall/dose:
N = number of documented dose
n/% = number/percentage of doses followed by at least one type of symptom
For Overall/subject:
N = number of subjects with at least one documented dose
n/% = number/percentage of subjects reporting the type of symptom at least once 
95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit
The maximum intensity of local injection site redness/swelling was coded as follows:
1: > 0.1 mm to < 5 mm
2: ≥ 5 mm to ≤ 20 mm
3: > 20 mm


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 58 of 104
Template 18 Incidence of solicited local symptoms reported during the 7-day 
(Days 1-7) post-vaccination period following each dose and overall 
by maximum grading <Exposed Set>
<each group>
95 % CI
Dose 
Symptom
Type
N n
%
LL
UL
DOSE 1
Pain
All
Grade 1
Grade 2
Grade 3
Medical advice
Redness (mm)
All
≥0.1 - <5.0
≥5.0 - ≤20.0
>20
Medical advice
Swelling (mm)
All
≥0.1 - <5.0
≥5.0 - ≤20.0
>20
Medical advice
DOSE 2
Pain
All
Grade 1
Grade 2
Grade 3
Medical advice
Redness (mm)
All
≥0.1 - <5.0
≥5.0 - ≤20.0
>20
Medical advice
Swelling (mm)
All
≥0.1 - <5.0
≥5.0 - ≤20.0
>20
Medical advice
OVERALL/DOSE
Pain
All
Grade 1
Grade 2
Grade 3
Medical advice
Redness (mm)
All
≥0.1 - <5.0
≥5.0 - ≤20.0
>20
Medical advice
Swelling (mm)
All
≥0.1 - <5.0
≥5.0 - ≤20.0
>20
Medical advice


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 59 of 104
<each group>
95 % CI
Dose 
Symptom
Type
N n
%
LL
UL
OVERALL/SUBJECT
Pain
All
Grade 1
Grade 2
Grade 3
Medical advice
Redness (mm)
All
≥0.1 - <5.0
≥5.0 - ≤20.0
>20
Medical advice
Swelling (mm)
All
≥0.1 - <5.0
≥5.0 - ≤20.0
>20
Medical advice
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
For each dose:
N = number of subjects with the corresponding documented dose
n/% = number/percentage of subjects reporting the type of symptoms as maximum intensity during the follow-up 
period
For Overall/dose:
N = number of documented dose
n/% = number/percentage of doses followed by the type of symptom as maximum intensity during the follow-up period
For Overall/subject:
N = number of documented dose
n/% = number/percentage of subjects reporting the type of symptom as maximum intensity during the follow-up period
CI = Exact 95% confidence interval; LL = lower limit, UL = upper limit
The maximum intensity of local injection site redness/swelling was coded as follows:
1: > 0.1 mm to < 5 mm
2: ≥ 5 mm to ≤ 20 mm
3: > 20 mm


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 60 of 104
Template 19 Incidence of solicited general symptoms reported during the 7-day 
(Days 1-7) post-vaccination period following each dose and overall 
<Exposed Set>
<each group>
95 % CI
Dose 
Symptom
Type
N
n
%
LL
UL
DOSE 1
Drowsiness
All
Grade 2
Grade 3
Related
Grade 2*Related
Grade 3*Related
Medical advice
Irritability/Fussiness
All
Grade 2
Grade 3
Related
Grade 2*Related
Grade 3*Related
Medical advice
Loss of appetite
All
Grade 2
Grade 3
Related
Grade 2*Related
Grade 3*Related
Medical advice
Fever (Axillary) (°C)
All (≥37.5)
>37.5
>38.0
>38.5
>39.0
>39.5
Related
>38.5*Related
>39.5*Related
Medical advice
DOSE 2
Drowsiness
…
Irritability/Fussiness
…
Loss of appetite
…
Fever (Axillary) (°C)
…
OVERALL/DOSE 
Drowsiness
…
Irritability/Fussiness
…
Loss of appetite
…
Fever (Axillary) (°C)
…
OVERALL/SUBJECT
Drowsiness
…
Irritability/Fussiness
…
Loss of appetite
…
Fever (Axillary) (°C)
…
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 61 of 104
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
For each dose:
N = number of subjects with the corresponding documented dose
n/% = number/percentage of subjects reporting the symptom at least once following the corresponding dose 
For Overall/dose:
N = number of documented dose
n/% = number/percentage of doses followed by at least one type of symptom
For Overall/subject:
N = number of subjects with at least one documented dose
n/% = number/percentage of subjects reporting the type of symptom at least once 
95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit
Temperatures were coded as follows:
1: ≥ 37.5 °C to ≤ 38.5 °C
2: > 38.5 °C to ≤ 39.5°C
3: > 39.5°C


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 62 of 104
Template 20 Incidence of solicited general symptoms reported during the 7-day 
(Days 1-7) post-vaccination period following each dose and overall 
by maximum grading <Exposed Set>
Each group
95 % CI
Dose
Symptom
Type
N n % LL
UL
DOSE 1 
Drowsiness
All
Grade 1
Grade 2
Grade 3
Related
Grade 2 Related
Grade 3 Related
Medical advice
Irritability / Fussiness
All
Grade 1
Grade 2
Grade 3
Related
Grade 2 Related
Grade 3 Related
Medical advice
Loss Of Appetite
All
Grade 1
Grade 2
Grade 3
Related
Grade 2 Related
Grade 3 Related
Medical advice
Temperature/(Axillary) (°C)
All
≥37.5 - ≤38.5
>38.5 - ≤39.5
>39.5
Related
>38.5 - ≤39.5*Related
>39.5*Related
Medical advice
DOSE 2
Drowsiness
All
Grade 1
Grade 2
Grade 3
Related
Grade 2 Related
Grade 3 Related
Medical advice
Irritability / Fussiness
All
Grade 1
Grade 2
Grade 3
Related
Grade 2 Related
Grade 3 Related
Medical advice


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 63 of 104
Each group
95 % CI
Dose
Symptom
Type
N n % LL
UL
Loss Of Appetite
All
Grade 1
Grade 2
Grade 3
Related
Grade 2 Related
Grade 3 Related
Medical advice
Temperature/(Axillary) (°C)
All
≥37.5 - ≤38.5
>38.5 - ≤39.5
>39.5
Related
>38.5 - ≤39.5*Related
>39.5*Related
Medical advice
OVERALL/DOSE 
Drowsiness
All
Grade 1
Grade 2
Grade 3
Related
Grade 2 Related
Grade 3 Related
Medical advice
Irritability / Fussiness
All
Grade 1
Grade 2
Grade 3
Related
Grade 2 Related
Grade 3 Related
Medical advice
Loss Of Appetite
All
Grade 1
Grade 2
Grade 3
Related
Grade 2 Related
Grade 3 Related
Medical advice
Temperature/(Axillary) (°C)
All
≥37.5 - ≤38.5
>38.5 - ≤39.5
>39.5
Related
>38.5 - ≤39.5*Related
>39.5*Related
Medical advice
OVERALL/SUBJECT
Drowsiness
All
Grade 1
Grade 2
Grade 3
Related


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
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Each group
95 % CI
Dose
Symptom
Type
N n % LL
UL
Grade 2 Related
Grade 3 Related
Medical advice
Irritability / Fussiness
All
Grade 1
Grade 2
Grade 3
Related
Grade 2 Related
Grade 3 Related
Medical advice
Loss Of Appetite
All
Grade 1
Grade 2
Grade 3
Related
Grade 2 Related
Grade 3 Related
Medical advice
Temperature/(Axillary) (°C)
All
≥37.5 - ≤38.5
>38.5 - ≤39.5
>39.5
Related
>38.5 - ≤39.5*Related
>39.5*Related
Medical advice
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
For each dose:
N = number of subjects with the corresponding documented dose
n/% = number/percentage of subjects reporting the type of symptom as maximum intensity during the follow-up period
For Overall/dose:
N = number of documented dose
n/% = number/percentage of doses followed by the type of symptoms as maximum intensity during the follow-up period
For Overall/subject:
N = number of subjects with at least one documented dose
n/% = number/percentage of subjects reporting the type of symptoms as maximum intensity during the follow-up period
95%CI = Exact 95% confidence interval; LL = lower limit, UL = upper limit
Temperatures were coded as follows:
1: ≥ 37.5 °C to ≤ 38.5 °C
2: > 38.5 °C to ≤ 39.5°C
3: > 39.5°C


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 65 of 104
Template 21 Maximum Temperature reported during the 7-day (Days 1-7) post-
vaccination period – dose X <Exposed Set>
Each group 
N = 
Total
N = 
95% CI
95% CI
Characteristics
Categories
n
%
LL
UL
n
%
LL
UL
Maximum temperature
No fever
Unknown temperature
[37.5-37.9]
[38.0-38.4]
[38.5-38.9]
[39.0-39.4]
[39.5-39.9]
[40.0-….
N = number of subjects with documented dose
n/% = number/percentage of subjects in a given category
95%CI = Exact 95% confidence interval; LL = lower limit, UL = upper limit
Template 22 Percentage of subjects reporting the occurrence of unsolicited 
symptoms classified by MedDRA Primary System Organ Class and 
Preferred Term within the 30-day (Days 1-30) post-vaccination 
period <Exposed Set>
Each group
N = 
95% 
CI
Primary System Organ Class (CODE)
Preferred Term (CODE)
n % LL UL
At least one symptom
Gastrointestinal disorders (10017947)
Diarrhoea (10012735)
Teething (10043183)
Vomiting (10047700)
General disorders and administration site conditions 
(10018065)
Pyrexia (10037660)
Immune system disorders (10021428)
Seasonal allergy (10048908)
Infections and infestations (10021881)
Conjunctivitis (10010741)
Otitis media (10033078)
Paronychia (10034016)
Tonsillitis (10044008)
Tonsillitis streptococcal (10044013)
Viral upper respiratory tract infection 
(10047482)
Injury, poisoning and procedural complications (10022117) Arthropod bite (10003399)
Face injury (10050392)
Head injury (10019196)
Skin and subcutaneous tissue disorders (10040785)
Miliaria (10027627)
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
At least one symptom = at least one symptom experienced (regardless of the MedDRA Preferred Term)
N = number of subjects included in the considered cohort in each group
n/% = number/percentage of subjects reporting the symptom at least once
95% CI = exact 95% confidence interval; LL = Lower Limit, UL = Upper Limit


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 66 of 104
Template 23 Number and percentage of subjects taking a concomitant 
medication during the 7- day (Days 1-7) post -vaccination period 
<Exposed Set>
<each group>
95% CI
Dose
Type 
N
n
%
LL
UL
DOSE 1
Any
Any antipyretics
Prophylactic antipyretics
DOSE 2
Any
Any antipyretics
Prophylactic antipyretics
OVERALL/DOSE 
Any
Any antipyretics
Prophylactic antipyretics
OVERALL/SUBJECT
Any
Any antipyretics
Prophylactic antipyretics
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
For each dose:
N = total number of subjects with the corresponding administered dose
n/% = number/percentage of subjects took the specified type of concomitant medication at least once during the 
considered period
For Overall/dose:
N = number of administered doses
n/% = number/percentage of doses after which the specified type of concomitant medication was taken at least once 
during the considered period 
For Overall/subject:
N = total number of subjects with at least one administered dose
n/% = number/percentage of subjects who took the specified type of concomitant medication at least once during the 
considered period
95%CI = Exact 95% confidence interval; LL = lower limit, UL = upper limit


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 67 of 104
Template 24 Distribution of change from baseline in hematology and 
biochemistry with respect to normal laboratory ranges <Exposed 
Set>
<each group >
Laboratory parameter
Timing
Range indicator at 
Baseline (SCR)
Range indicator at 
timing
N
n
%
Alanine Aminotransferase
PI(D2)
Unknown
Unknown
Below
Within
Above
Below
Unknown
Below
Within
Above
Within
Unknown
Below
Within
Above
Above
Unknown
Below
Within
Above
PI (D8)
…
PI (D31)
PII (D32)
…
PII (D38)
…
PII (D61)
…
UNSCH1
UNSCH2
…
…
Aspartate Aminotransferase
…
…
Creatinine
…
…
Hemoglobin
Leukocytes (White Blood Cells)
…
…
Neutrophil 
Platelets
…
…
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = number of subjects with available results for the specified laboratory parameter and timing in a given baseline 
category
n/% = number/percentage of subjects in the specified category
Below = below the normal laboratory range defined for the specified laboratory parameter 
Within = within the normal laboratory range defined for the specified laboratory parameter
Above = above the normal laboratory range defined for the specified laboratory parameter
SCR= Screening
PI (D2): Post-vaccination dose 1 at Day 2
PI (D8): Post-vaccination dose 1 at Day 8
PI (D31): Post-vaccination dose 1 at Day 31
PII (D32): Post-vaccination dose 2 at Day 32
PII (D38): Post-vaccination dose 2 at Day 38


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
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PII (D61): Post-vaccination dose 2 at Day 61
UNSCH: Unscheduled visit for safety
Template 25 Summary of hematology and biochemistry results by maximum 
grade from VISIT X (DX) up to VISIT Y (DY) – post dose 1 of 
vaccination versus baseline <Exposed Set>
<each group >
Laboratory parameter
Baseline 
(SCR)
Visit 2 to Visit X
N
n
%
Hemoglobin (decrease)
Unknown
Unknown
Grade 0
Grade 1
Grade 2
Grade 3
Grade 4
Grade 0
Grade 1
Grade 2
Total
Leukocytes (White Blood Cells) (decrease)
…
Neutrophil (decrease)
Platelets
Alanine Aminotransferase
Aspartate Aminotransferase
Creatinine
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = number of subjects with at least one available result for the specified laboratory parameter and follow-up period
n/% = number/percentage of subjects reporting at least once the laboratory event when the maximum grading over the 
follow-up period is considered
SCR=Screening


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 69 of 104
Template 26 Descriptive statistics table on eosinophils, basophils, and
monocytes counts for subjects <Exposed Set>
Each Group
N=
95% CI
Parameters
Timing
Parameter
Value
LL
UL
Eosinophils
SCR
n
Mean
95% CI
Q1
Median
Q3
Min/Max
PI(D2)
PI (D8)
PI (D31)
PII (D32)
PII (D38)
Basophils
Monocytes
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = number of subjects in each group
n= Number of subjects with result available 
SD=Standard Deviation
Q1, Q2 and Q3 = 1st , 2nd (median) and 3rd quantiles
Min/Max = Minimum/Maximum
95% CI = exact 95% confidence interval, LL = Lower Limit, UL = Upper Limit


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
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Figure 2
Individuals results of hemoglobin levels in < group> <Exposed Set>
Note: This figure is shown as an example.
PPD
PPD


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 71 of 104
Template 27 Exploratory comparisons between groups in terms of percentage of 
subjects reported any Grade 2/3 AE and/or any fever >38.5°C and/or
any vaccine-related SAE during the 7-day (Days 1-7) post-
vaccination period <Exposed Set>
Difference in percentage
(Group 1 minus Group 2)
95 % CI
Group 1
N
n
%
Group 2
N
n
%
Difference
%
LL
UL
RSV_Ld
Placebo_Ld
RSV_Ld – Placebo_Ld
RSV_Md
Placebo_Md
RSV_Md – Placebo_Md
RSV_Hd
Placebo_Hd
RSV_Hd – Placebo_Hd
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = Number of subjects with the administered dose
n/% = number/percentage of subjects reporting a specified symptom
95% CI = Standardized asymptotic 95% confidence interval, LL = Lower Limit, UL = Upper Limit


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 72 of 104
Template 28 Percentage of subjects reporting episode of spontaneous or 
excessive bleeding (AE of specific interest) classified by MedDRA 
Primary System Organ Class and Preferred Term within the 30-day 
(Days 1-30) post-vaccination period <Exposed Set>
Each group
N = 
95% CI
Primary System Organ Class (CODE)
Preferred Term (CODE)
n* n % LL UL
At least one symptom
Gastrointestinal disorders (10017947)
Diarrhoea (10012735)
Teething (10043183)
Vomiting (10047700)
General disorders and administration site conditions 
(10018065)
Pyrexia (10037660)
Immune system disorders (10021428)
Seasonal allergy (10048908)
Infections and infestations (10021881)
Conjunctivitis (10010741)
Otitis media (10033078)
Paronychia (10034016)
Tonsillitis (10044008)
Tonsillitis streptococcal (10044013)
Viral upper respiratory tract infection 
(10047482)
Injury, poisoning and procedural complications (10022117)
Arthropod bite (10003399)
Face injury (10050392)
Head injury (10019196)
Skin and subcutaneous tissue disorders (10040785)
Miliaria (10027627)
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
At least one symptom = at least one symptom experienced (regardless of the MedDRA Preferred Term)
N = number of subjects with at least one administered dose
n* = number of events reported 
n/% = number/percentage of subjects reporting the symptom at least once
95% CI = exact 95% confidence interval; LL = Lower Limit, UL = Upper Limit


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 73 of 104
Template 29 Solicited and unsolicited symptoms classified by MedDRA Primary 
System Organ Class and Preferred Term within the 30-day (Days 1-
30) post-vaccination period including number of events - SAE 
excluded <Exposed Set>
<each group>
N = 
Primary System Organ Class (CODE)
Preferred Term (CODE)
n*
n
%
At least one symptom
<each SOC>
<each PT term>
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
At least one symptom = at least one symptom experienced (regardless of the MedDRA Preferred Term)
N = number of subjects with the administered dose
n* = number of events reported 
n/% = number/percentage of subjects reporting the symptom at least once


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 74 of 104
Template 30 Number (%) of subjects with serious adverse events from 
vaccination dose 1 up to Day X/Study end including number of 
events reported <Exposed Set>
<each group>
N =
Type of Event
Primary System Organ Class
Preferred Term (CODE)
n*
n
%
SAE
At least one symptom
<each SOC>
<each PT term>
Related SAE
At least one symptom
<each SOC>
<each PT term>
Fatal SAE
At least one symptom
<each SOC>
<each PT term>
Related fatal SAE
At least one symptom
<each SOC>
<each PT term>
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = number of subjects with the administered dose
n* = number of events reported
n/% = number/percentage of subjects reporting the symptom at least once


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 75 of 104
Template 31 Listing of unscheduled safety visit from vaccination dose 1 up to Day X/study end <Exposed Set>
Group
Sub.
No.
Gender
Country
Race
Age at
visit
(Month)
Date of 
sample
Date of previous 
safety sample
Timing
Laboratory parameter
Result
Unit
Grade
<timepoint previous to 
unsched safety>
Hemoglobin
Platelet count
UNSCHED SAFETY 1
Hemoglobin
Platelet count
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
Please note the listing will be generated on group blinded at D61 and D366 analysis


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 76 of 104
Template 32 Listing of SAEs reported from vaccination dose 1 up to Day X visit /study end <Exposed Set>
Group Sub.
No.
Sex
Country Race
Age at
onset
(Month)
Verbatim Preferred 
term
Primary 
System 
Organ 
Class
MED
type
Dose
Day of 
onset
Duration Intensity Causality Outcome Seriousness 
criteria 
Potential 
AESI 
(preferred 
term)
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
Potential AESI: AEs potentially related to spontaneous or excessive bleeding or LRTI will be identified based on the list of preferred terms described in section 11 –Annex
Please note the listing will be generated on group blinded at D61 and D366 analysis


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 77 of 104
Template 33 Listing of AEs related to LRTI and association to RSV infection from vaccination dose 1 up to Day X visit/study 
end <Exposed Set>
Group Sub.
No.
Age at
onset
(month)
Verbatim Preferred 
term
MED 
type
Previous 
Dose
Day 
of
onset
Start 
date
End 
date
Duration Intensity Causality Outcome
Local 
RSV test 
result
Date of 
sample 
for local 
testing
Central 
test 
RSV A
Central 
test 
RSV B
Date of 
sample 
for 
central 
testing
AESI
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
AESI: AEs of Special Interest - LRTI identified by the Investigator
*AEs related to LRTI will be identified based on the list of preferred terms described in in section 12 –Annex 2


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 78 of 104
Template 34 Listing of RSV-RTI cases identified according to WHO case definitions and RSV-LRTI reported as AESI from 
vaccination dose 1 up to Day X visit /study end <Exposed Set>
Group Sub.
No.
Episode 
nb
Surveillance 
type
Start 
date of 
episode
End 
date of 
episode
SpO2 Respiratory 
rate
Local 
RSV 
test
Date of 
sample 
for 
local 
testing
Central 
test 
RSV A
Central 
test 
RSV B
Date of 
sample 
for 
central 
testing
RSV-
RTI
RSV-
LRTI
RSV-
severe 
LRTI
RSV-
very 
severe 
LRTI
All-
cause 
LRTI
AESI
Hospitalization
Yes/No Yes/No Yes/No Yes/NoYes/NO Yes/No Yes/No
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
Placebo-Ld = Non-active control (0.5 ml)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
Placebo-Md = Non-active control (0.15 ml)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Hd = Non-active control (0.5 ml)
AESI: AEs of Special Interest - LRTI identified by the Investigator


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 79 of 104
Template 35 Listing of AEs related to spontaneous or excessive bleeding together with hemoglobin and platelet count results 
from vaccination dose 1 up to Day 60 visit <Exposed Set>
Group
Sub. No.
Age at 
onset 
(month)
Verbatim
Preferred term*
Previous
Dose
Day
of
onset
Duration
Intensity
Start date
End date
AESI
Date of 
sample
Laboratory 
parameter
Raw 
result
Unit
xx
xx
xx
xx
xx
xx
xx
xx
xx
Hemoglobin
Platelet 
count
xx
Hemoglobin
Platelet 
count
…
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
*AEs related to spontaneous or excessive bleeding will be identified based on the list of preferred terms described in section 12 –Annex
AESI: AEs of Special Interest – Spontaneous or excessive bleeding identified by the Investigator


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 80 of 104
Template 36 Listing of adverse events, SAEs and solicited symptoms leading to withdrawal from the study or treatment from 
vaccination dose 1 up to Day X visit/study end <Exposed Set>
Group
Subject No.
Country
Gender
Race
AE Description
SAE
Causality
Outcome
Type of discontinuation
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)


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Statistical Analysis Plan Final
28-MAR-2018
Page 81 of 104
Template 37 Number and percentage of subjects with anti-RSV-A neutralising 
antibody titre equal to or above <cut-off> and GMTs <PPS for 
analysis of immunogenicity at Day X>
≥cut-off unit
GMT
95% CI
95% CI
Antibody
Group
Timing
N
n
%
LL
UL
value
LL
UL
Min Max
Anti-RSV-A 
Neutralizing 
Antibody
<each 
group>
PRE
PI(D31)
PII(D61)
PII(D366)
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
GMT = geometric mean antibody titre calculated on all subjects
N = Number of subjects with available results 
95% CI = 95% confidence interval; LL = lower limit, UL = upper limit
n/% = number/percentage of subjects with titer equal to or above specified value
MIN/MAX = Minimum/Maximum
PRE= Pre-vaccination at Day 1
PI(D31) = Post-vaccination dose 1 at Day 31
PII(D61) = Post-vaccination dose 2 at Day 61
PII(D366) = Post-vaccination dose 2 at Day 366


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204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 82 of 104
Template 38 Vaccine response for anti-RSV-A neutralising antibody titre at each 
post-vaccination timepoint <PPS for analysis of immunogenicity at 
Day X>
<Each Group>
95% CI
Antibody
Timing
Pre-vaccination status
N
n
%
LL
UL
<each antibody>
PII(D61)
<128
≥128 - ≤256
>256-≤1024
>1024
Total
PII(D366)
<128
≥128 - ≤256
>256-≤1024
>1024
Total
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
Total = all subjects with pre-and post- vaccination result available
Vaccine response defined as :
For subjects with pre-vaccination titer <128: antibody titer at post-vaccination>= 4 fold the pre-vaccination antibody titer
For subjects with pre-vaccination titer in ≥128 - ≤256: antibody titer at post-vaccination >= 3 fold the pre-vaccination 
antibody titer
For subjects with pre-vaccination titer in >256-≤1024: antibody titer at post-vaccination>= 2.5 fold the pre-vaccination 
antibody titer
For subjects with pre-vaccination titer >1024: antibody titer at post-vaccination >= 1 fold the pre-vaccination antibody 
titer
N = number of subjects with both pre- and post-vaccination results available
n/% = number/percentage of responders
95% CI = exact 95% confidence interval, LL = Lower Limit, UL = Upper Limit
PII(D61) = Post-vaccination dose 2 at Day 61
PII(D366) = Post-vaccination dose 2 at Day 366


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 83 of 104
Template 39 Distribution of anti-RSV-A neutralising antibody titer <PPS for 
analysis of immunogenicity at Day X>
Each group
Antibody
Timing
Titre
N
n
%
Anti-RSV A Neutralizing Antibody
PRE
<128
≥128
≥256
≥512
≥1024
≥2048
≥4098
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = number of subjects with available results
n/% = number/percentage of subjects with titre within the specified criterion
PRE = Pre-vaccination at Day 1
PI(D31) = Post-vaccination dose 1 at Day 31
PII(D61) = Post-vaccination dose 2 at Day 61
PII(D366) = Post-vaccination dose 2 at Day 366


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 84 of 104
Template 40 Distribution of fold of anti-RSV-A neutralising antibody titer by pre-
vaccination titer category <PPS for analysis of immunogenicity at 
Day X>
Each group
Antibody
Fold change
Pre-vaccination status
Timing
N
n
%
Anti-RSV A Neutralizing 
Antibody
<1
<128
PI(D31)
PII(D61)
PII(D366)
≥128-≤256
>256-≤512
>1024-≤2048
>2048-≤4096
>4096
Total
≥1
≥2
≥2.5
≥3
≥4
≥6
≥8
≥10
≥11
≥12
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = number of subjects with pre and corresponding post-vaccination results available
n/% = number/percentage of subjects with titre fold change meeting the specified criterion
PI(D31) = Post-vaccination dose 1 at Day 31
PII(D61) = Post-vaccination dose 2 at Day 61
PII(D366) = Post-vaccination dose 2 at Day 366


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 85 of 104
Template 41 Geometric mean of the individual ratio of anti-RSV-A neutralising 
antibody titers at each post-vaccination timepoint compared to pre-
vaccination with 95% CI <PPS for analysis of immunogenicity at Day 
X>
GMT ratio
95% CI
Group
N
Time point 
description
GMT
Time point 
description
GMT
Ratio order
Value
LL
UL
<each group>
PI(D31)
PRE
PI(D31) / PRE
PII(D61)
PRE
PII(D61) / PRE
PII(D366)
PRE
PII(D366) / PRE
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
GMT = geometric mean antibody titer
N = Number of subjects with available results at the two considered time points
95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit
PRE= Pre-vaccination at Day 1
PI(D31) = Post-vaccination dose 1 at Day 31
PII(D61) = Post-vaccination dose 2 at Day 61
PII(D366) = Post-vaccination dose 2 at Day 366


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 86 of 104
Figure 3
Reverse cumulative distribution curves for anti-RSV-A neutralising 
antibody titres in each group at baseline and <D60/D365> <PPS for 
analysis of immunogenicity at Day X>
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
Note: This graph is provided as an example. The same graph will be provided in colour for each time point and each 
assay comparing the values of the groups


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 87 of 104
Figure 4
Individual results of anti-RSV-A neutralising antibody titre at Day 
<60/365> versus pre-vaccination in <each group> and Control
group> <PPS for analysis of immunogenicity at Day X>
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
Note: This graph is provided as an example. The same graph will be generated for each assay and each timepoint 
separately (Days 61, 366): 


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 88 of 104
Template 42 Descriptive statistics on the frequency of CD4+ T-cells expressing at 
least two markers among CD40L, IL-2, TNF-α, and IFN-γ upon 
stimulation with <RSV F/ N /M2-1/combined> peptide pool <PPS for 
analysis of immunogenicity at Day X>  
<each group>
Stimulation
Group
Timing
Paramter
Value
LL
UL
IFNg protein – RSV F pool 15/11 Ag
PRE
n
NMiss
GM
Mean
SD
Min
Q1
Median
Q3
Max
PI(D31)
PII(D61)
PII(D366)
IFNg protein – RSV N pool 15/11 Ag
PRE
PI(D31)
PII(D61)
PII(D366)
IFNg protein – RSV M2-1 pool 15/11 Ag
PRE
PI(D31)
PII(D61)
PII(D366)
Combined (F,N and M2-1)
PRE
PI(D31)
PII(D61)
PII(D366)
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
N = number of subjects with available results; 
Nmiss = number of subjects with missing results
GM= Geometric Mean
SD = Standard Deviation
Q1,Q3 = First and third quartiles
Min/Max = Minimum/Maximum
PRE = Pre-vaccination at Day 1
PI(D31) = Post-vaccination dose 1 at Day 31
PII(D61) = Post-vaccination dose 2 at Day 61
PII(D366) = Post-vaccination dose 2 at Day 366
Please note that for combined peptide pool, we will only consider subjects who has data available for the three peptide 
pools


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 89 of 104
Figure 5
Boxplots of individual data for CD4+ T-cells expressing at least two 
markers among CD40L, IL-2, TNF-α, and IFN-γ upon stimulation with 
<RSV F/ N /M2-1/combined> peptide pool <from pre-vaccination to 
Day 61/Day 366> <PPS for analysis of immunogenicity at Day X>
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
PRE= Pre-vaccination at Day 1
PI(D31) = Post-vaccination dose 1 at Day 31
PII(D61) = Post-vaccination dose 2 at Day 61
PII(D366) = Post-vaccination dose 2 at Day 366
Note: This graph is provided as an example. Template will be adapted to display the 3 RSV or 3Control groups
together and the 4 timepoints: PRE, PI(D31), PII(D61) and PII(D366). 
Please note – To present the information on pooled RSV and pooled Placebo after looking at the data of Day 61 
analysis.


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 90 of 104
Figure 6
Co-expression profile of the RSV <F/N/M2-1> specific <CD4+> T-cells 
expressing at least two markers among CD40L, IL-2, TNF-α, and IFN-
γ in <RSV-Ld group> <PPS for analysis of immunogenicity at Day X>
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
Note: This graph is given as an example. Template will be adapted to display Q1-Median-Q3 for each combination of 
atleast 2 markers out of (CD40L, IL-2, TNF-α, and IFN-γ 11   combinations) for each timepoint: PRE, PI(D31), 
PII(D61) and PII(D366). It will be generated for each vaccine group and each RSV pool of peptides (RSV F/N/M2-1).
% F4co_c-specific CD4+ T-cells
0.0
0.1
0.2
0.3
CD40L
IL2
TNFa
IFNg
1 Marker
2 Markers
3 Markers
4 Markers
F4co_3
PRE
PII(W6)
PII(W28)
PIII(W30)
PIII(W48)


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 91 of 104
Template 43 Number and percentage of subjects with at least one RSV infection, 
RSV-RTI, RSV-LRTI, RSV-severe LRTI, RSV-very severe LRTI, All-
cause LRTI and RSV hospitalization from vaccination dose 1 up to 
D366/D731 visit <Exposed Set>
Group
N =
Total 
N = 
95% CI
95% CI
Categories
n** n % LL UL
n**
n % LL UL
No Infection
RSV infection - symptomatic or asymptomatic*
RSV-RTI
RSV-LRTI
RSV-severe LRTI
RSV-very severe LRTI
All-cause LRTI
RSV hospitalization$
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
RSV = ChAd155-RSV vaccine (low/ middle/high dose pooled groups)
Placebo = Non-active control (0.5/0.15/0.5 ml pooled groups)
* Association to RSV based on central testing only for asymptomatic visit (no local test available)
$Confirmed RSV infection and hospitalized for acute medical condition
N = number of subjects in each group
n** = number of cases in each category
n/%= number/percentage of subjects reporting at least once the case
95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit
Please note – Single episode can be considered in multiple category depending on the symptom experienced


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 92 of 104
Template 44 Number and percentage of subjects reporting the RSV infection of 
different severity by number of events experienced between 
vaccination dose 1 up to D366/D731 visit <Exposed Set>
<Each group>
N=xx
95% CI
Characteristics
Categories
n
%
LL
UL
RSV infection-symptomatic or asymptomatic*
0
1
2
RSV-RTI
0
1
RSV-LRTI
0
1
2
RSV-Severe LRTI
0
1
RSV-very severe LRTI
0
1
All cause LRTI
0
1
2
3
RSV hospitalization$
0
1
2
3
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
RSV = ChAd155-RSV vaccine (low/ middle/high dose pooled groups)
Placebo = Non-active control (0.5/0.15/0.5 ml pooled groups)
N = number of subjects in each group
n = number of subjects in a given category
% =100*n/N
LL, UL for percentage = Exact 95% Lower and Upper confidence limits
Please note – Single episode can be considered in multiple category depending on the symptom experienced
* Association to RSV based on central testing only for asymptomatic visit (no local test available)
$Confirmed RSV infection and hospitalized for acute medical condition


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 93 of 104
Template 45 Number and percentage of RSV infections and associated disease 
severity between vaccination dose 1 up to D366/D731 visit <Exposed 
Set>
Group
N = 
Total 
N = 
95% CI
95% CI
Categories
n % LL UL
n
%
LL UL
RSV asymptomatic (Excluding RSV-RTI, LRTI, RSV-severe LRTI or RSV-
very severe LRTI)
RSV RTI (Excluding LRTI, RSV-severe or very severe LRTI)
RSV LRTI (Excluding RSV-severe or very severe LRTI)
RSV-severe LRTI (Excluding RSV-very severe LRTI)
RSV-very severe LRTI
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
RSV = ChAd155-RSV vaccine (low/ middle/high dose pooled groups)
Placebo = Non-active control (0.5/0.15/0.5 ml pooled groups)
* Association to RSV based on central testing only for asymptomatic visit (no local test available)
N = number of RSV positive samples in each group
n** = number of cases in each category
n/%= number/percentage of cases in each category
95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit
Please note – Single episode is considered in single category of highest severity based on the symptom experienced


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 94 of 104
Template 46 Number and percentage of RSV infections requiring hospitalization 
between vaccination dose 1 up to D366/D731 <Exposed Set>
Group
N =
Total 
N = 
95% CI
95% CI
Categories
n** n % LL UL
n**
N % LL
UL
RSV RTI*(Excluding LRTI, severe or very severe LRTI)
RSV LRTI (Excluding severe or very severe LRTI)
RSV-severe LRTI (Excluding very severe LRTI)
RSV-very severe LRTI
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
RSV = ChAd155-RSV vaccine (low/ middle/high dose pooled groups)
Placebo = Non-active control (0.5/0.15/0.5 ml pooled groups)
N = number of RSV infections in each group
n** = number of cases in each category
n/%= number/percentage of subjects reporting at least once the case
95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 95 of 104
Template 47 Descriptive statistics of viral load calculated on all qRT-PCR 
confirmed RSV infection episodes with varying disease severity 
from vaccination dose 1 up to D366/D731 <Exposed Set>
Group
N=
Symptoms
Parameters
Value
LL
UL
RSV asymptomatic* (Excluding RSV-RTI, RSV-LRTI, RSV-severe 
LRTI or RSV-very severe LRTI)
n
GM
95% CI
SD
Q1
Median 
Q3
Min/Max
RSV RTI (Excluding RSV-LRTI, RSV-severe LRTI or RSV-very 
severe LRTI)
RSV LRTI (Excluding RSV-severe or RSV-very severe LRTI)
RSV-severe LRTI (Excluding RSV-very severe LRTI)
RSV-very severe LRTI
RSV hospitalization$
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
RSV = ChAd155-RSV vaccine (low/ middle/high dose pooled groups)
Placebo = Non-active control (0.5/0.15/0.5 ml pooled groups)
N = number of RSV infections episodes in each group
n= Number of events in each category
SD=Standard Deviation
Q1 and Q3 = 1st and 3rd quantiles
Min/Max = Minimum/Maximum
GM = Geometric mean 
LL, UL for GM = Exact 95% Lower and Upper confidence limits
Total RSV viral load computed as RSV A Viral load + RSV B Viral load
* Association to RSV based on central testing only for asymptomatic visit (no local test available)
$Confirmed RSV infection and hospitalized for acute medical condition
Please note: each episode for a subject is considered to be independent. We may have multiple swab for one episode. 
We have considered the swab with maximum viral load from one episode for the table
Please note – Except for RSV hospitalization, single episode is considered in single category of highest severity based 
on the symptom experienced
Please check:- To check for cases where asymptomatic swab has been taken but the subject hasve symptoms of RTI 
or LRTI. In this case, asymptomatic is also considered as RSV RTI/LRTI and maximum viral load of all the episode 
should be considered.


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 96 of 104
Template 48 Descriptive statistics of maximum viral load per subjects based on 
qRT-PCR confirmed episode with varying disease severity form 
vaccination dose 1 up to D366/D731 <Exposed Set>
Each Group
N=
95% CI
Symptoms
Parameters
Value
LL
UL
RSV asymptomatic* (Excluding RSV-RTI, RSV-LRTI, RSV-severe LRTI 
or RSV-very severe LRTI)
n
GM
95% CI
SD
Q1
Median 
Q3
Min/Max
RSV RTI (Excluding RSV-LRTI, RSV-severe or RSV-very severe LRTI)
…
RSV LRTI (Excluding RSV-severe or RSV-very severe LRTI)
…
RSV-severe LRTI (Excluding RSV-very severe LRTI)
…
RSV-very severe LRTI
…
RSV hospitalization$
…
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
RSV = ChAd155-RSV vaccine (low/ middle/high dose pooled groups)
Placebo = Non-active control (0.5/0.15/0.5 ml pooled groups)
N = number of RSV positive subjects in each group
n= Number of subjects in each category
SD=Standard Deviation
Q1 and Q3 = 1st and 3rd quantiles
Min/Max = Minimum/Maximum
GM = Geometric mean 
LL, UL for GM = Exact 95% Lower and Upper confidence limits
Total RSV viral load computed as RSV A Viral load + RSV B Viral load
Please note: Except of RSV hospitalization, the subject has been considered only once in one of the category based 
on the maximum severity of event experienced 
* Association to RSV based on central testing only for asymptomatic visit (no local test available)
$Confirmed RSV infection and hospitalized for acute medical condition


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 97 of 104
Template 49 Frequency of multiple respiratory pathogen for qRT-PCR confirmed 
RSV-RTI episodes from vaccination dose 1 up to D366/D731 visit
<Exposed Set>
Group
N =
Total 
N = 
95% CI
95% CI
Categories
n % LL UL
n
%
LL UL
Influenza Virus A/California/7/2009(H1N1)
Adenovirus
Human Coronavirus OC43
Human Coronavirus 229E
Human Coronavirus NL63
Human Coronavirus HKU1
Enterovirus + Rhinovirus
Influenza Virus A
Influenza Virus B
Influenza Virus A (H1N1)
Influenza Virus A (H3N2)
Human bocavirus
Human metapneumovirus
Parainfluenza virus 1
Parainfluenza virus 2
Parainfluenza virus 3
Parainfluenza virus 4
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
RSV = ChAd155-RSV vaccine (low/ middle/high dose pooled groups)
Placebo = Non-active control (0.5/0.15/0.5 ml pooled groups)
N = number of qRT-PCR confirmed RSV-RTI infection episodes in each group
n = number of episodes in a given category
% =100*n/N
LL, UL for percentage = Exact 95% Lower and Upper confidence limits


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 98 of 104
Template 50 Frequency of multiple respiratory pathogen for confirmed LRTI 
episodes from vaccination dose 1 up to D366/D731 visit <Exposed 
Set>
Group
N =
Total 
N = 
95% CI
95% CI
Categories
n % LL UL
n
%
LL UL
Respiratory syncytial virus
Influenza Virus A/California/7/2009(H1N1)
Adenovirus
Human Coronavirus OC43
Human Coronavirus 229E
Human Coronavirus NL63
Human Coronavirus HKU1
Enterovirus + Rhinovirus
Influenza Virus A
Influenza Virus B
Influenza Virus A (H1N1)
Influenza Virus A (H3N2)
Human bocavirus
Human metapneumovirus
Parainfluenza virus 1
Parainfluenza virus 2
Parainfluenza virus 3
Parainfluenza virus 4
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
RSV = ChAd155-RSV vaccine (low/ middle/high dose pooled groups)
Placebo = Non-active control (0.5/0.15/0.5 ml pooled groups)
N = number of confirmed LRTI infection episodes in each group
n = number of episodes in a given category
% =100*n/N
LL, UL for percentage = Exact 95% Lower and Upper confidence limits


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 99 of 104
Template 51 Listing of RSV-RTI cases identified according to case definitions <Exposed Set>
Group Sub.
No. Sex Age at 
episode(month)CountrySite
Surveillance 
type
Episode 
nb
Dose Dose 
nb.
Onset 
day
SpO2 Respiratory 
rate
Central 
test 
RSV A
Central 
test 
RSV B
RSV-
RTI
RSV-
LRTI
Severe 
RSV-
LRTI
RSV-
very 
severe 
LRTI
HospitalizationRVP 
result
Yes/No Yes/No Yes/No Yes/NoYes/No
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
Placebo-Ld = Non-active control (0.5 ml)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
Placebo-Md = Non-active control (0.15 ml)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Hd = Non-active control (0.5 ml)
RSV-LM=ChAd155-RSV vaccine (low/ middle dose pooled groups)
Placebo-LM= Non-active control (0.5/0.15 ml pooled groups)
RSV = ChAd155-RSV vaccine (low/ middle/high dose pooled groups)
Placebo = Non-active control (0.5/0.15/0.5 ml pooled groups)


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 100 of 104
Template 52 Listing of RSV-RTI requiring hospitalization and type of inpatient facility required <Exposed Set>
Group
Sub.
No.
Sex
Age at 
episode(month)Country
Classification 
of episode 
per WHO*
Total days 
hospitalized
No. of 
days of 
monitoring 
or nursing 
No. of days 
of 
nasogastric 
or 
intravenous 
fluids given 
No. of days 
oxygen 
administered
No. of 
days 
respiratory 
support 
given 
No. of days 
mechanical 
ventilation 
given
No. of 
days child 
kept in 
paediatrics 
intensive 
care unit 
RVP 
result
Pathogen 
identified 
in RVP
Yes/No
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
Placebo-Ld = Non-active control (0.5 ml)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
Placebo-Md = Non-active control (0.15 ml)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Hd = Non-active control (0.5 ml)
RSV-LM=ChAd155-RSV vaccine (low/ middle dose pooled groups)
Placebo-LM= Non-active control (0.5/0.15 ml pooled groups)
RSV = ChAd155-RSV vaccine (low/ middle/high dose pooled groups)
Placebo = Non-active control (0.5/0.15/0.5 ml pooled groups)
*subject will be classified per maximum severity experienced


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 101 of 104
Template 53 Number and percentage of subjects with highest associated severity 
of RSV infection from vaccination dose 1 up to D366/D731 visit
<Exposed Set>
Group
N =
Total 
N = 
95% CI
95% CI
Categories
n** n % LL UL
n**
n % LL
UL
No Infection
RSV asymptomatic (Excluding RSV-RTI, RSV-LRTI, RSV-severe LRTI 
or RSV-very severe LRTI)
RSV RTI (Excluding RSV-LRTI, RSV-severe or very severe LRTI)
RSV LRTI (Excluding RSV-severe or very severe LRTI)
RSV-severe LRTI (Excluding RSV-very severe LRTI)
RSV-very severe LRTI
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
RSV = ChAd155-RSV vaccine (low/ middle/high dose pooled groups)
Placebo = Non-active control (0.5/0.15/0.5 ml pooled groups)
N = number of subjects in each group
n** = number of cases in each category
n/%= number/percentage of subjects reporting at least once the case
95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit
Please note – Single episode can be considered in single category depending on the highest severity symptom 
experienced


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 102 of 104
Template 54 Number and percentage of subjects reporting the RSV infection of 
maximum severity by number of events experienced between 
vaccination dose 1 up to D366/D731 visit <Exposed Set>
Total
95% CI
Characteristics
Categories
N n % LL UL
RSV asymptomatic (Excluding RSV-RTI, RSV-LRTI, RSV-
severe LRTI or RSV-very severe LRTI)
0
1
2
RSV-RTI (Excluding RSV-LRTI, RSV severe or very severe 
LRTI)
0
1
RSV-LRTI (Excluding RSV severe or very severe LRTI)
0
1
RSV-Severe LRTI Excluding RSV very severe LRTI)
0
1
RSV-very severe LRTI
0
1
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
RSV = ChAd155-RSV vaccine (low/ middle/high dose pooled groups)
Placebo = Non-active control (0.5/0.15/0.5 ml pooled groups)
N = number of subjects in each group
n = number of subjects in a given category
% =100*n/N
LL, UL for percentage = Exact 95% Lower and Upper confidence limits
Please note – Single episode will be considered in single category depending on the maximum severity experienced


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 103 of 104
Template 55 Number (%) of subjects reported solicited local symptoms during 
the 7-day (Days 1-7) post-vaccination period following each dose 
and across doses <Exposed Set>
<each group>
95 % CI
Dose
Symptom
Type
N
n
%
LL
UL
DOSE 1
Pain
All
Grade 3
Redness (mm)
All
>20
Swelling (mm)
All
>20
DOSE 2
Pain
…
Redness (mm)
…
Swelling (mm)
…
ACROSS DOSEs
Pain
…
Redness (mm)
…
Swelling (mm)
…
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
For each dose:
N = number of subjects with the corresponding documented dose
n/% = number/percentage of subjects reporting the type of symptom at least once following the corresponding dose 
For Across dose:
N = number of documented doses
n/% = number/percentage of doses followed by at least one type of symptom
95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit
The maximum intensity of local injection site redness/swelling was coded as follows:
1: > 0.1 mm to < 5 mm
2: ≥ 5 mm to ≤ 20 mm
3: > 20 mm


CONFIDENTIAL
204838 (RSV PED-002)
Statistical Analysis Plan Final
28-MAR-2018
Page 104 of 104
Template 56 Number (%) of subjects reported solicited general symptoms during 
the 7-day (Days 1-7) post-vaccination period following each dose 
and across dose <Exposed Set>
<each group>
95 % CI
Dose 
Symptom
Type
N
n
%
LL
UL
DOSE 1
Drowsiness
All
Grade 3
Related
Irritability/Fussiness
All
Grade 3
Related
Loss of appetite
All
Grade 3
Related
Fever (Axillary) (°C)
All (≥37.5)
>39.5
Related
DOSE 2
Drowsiness
…
Irritability/Fussiness
…
Loss of appetite
…
Fever (Axillary) (°C)
…
ACROSS DOSE 
Drowsiness
…
Irritability/Fussiness
…
Loss of appetite
…
Fever (Axillary) (°C)
…
<each group>:
RSV-Ld = Low dose ChAd155-RSV vaccine (5 x 109 vp)
RSV-Md = Middle dose ChAd155-RSV vaccine (1.5 x 1010 vp)
RSV-Hd = High dose ChAd155-RSV vaccine (5 x 1010 vp)
Placebo-Ld = Non-active control (0.5 ml)
Placebo-Md = Non-active control (0.15 ml)
Placebo-Hd = Non-active control (0.5 ml)
For each dose:
N = number of subjects with the corresponding documented dose
n/% = number/percentage of subjects reporting the symptom at least once following the corresponding dose 
For Across dose:
N = number of documented doses
n/% = number/percentage of doses followed by at least one type of symptom
95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit
Temperatures were coded as follows:
1: ≥ 37.5 °C to ≤ 38.5 °C
2: > 38.5 °C to ≤ 39.5°C
3: > 39.5°C