Safety and Immunogenicity Study of GSK Biologicals' Investigational Recombinant Chimpanzee Adenovirus Type 3-vectored Ebola Zaire Vaccine (GSK3390107A) in Children in Africa
Phase: PHASE2
Conditions: Virus Diseases
Sponsor: GlaxoSmithKline

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R u e d e l’i n stit ut 8 9,
1 3 3 0 Ri x e n s art, B el gi u m
Pri m ar y St u d y v acc i ne a n d 
n u m ber
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Gla x o S mit h Kli ne ( G S K) Bi ol o gicals’ 
i n vesti gati o nal rec o m bi na nt c hi m pa nzee 
a de n o vir us T y pe 3 -vect ore d E b ola Zaire vacci ne 
( C h A d 3-E B O -Z) ( G S K 3 3 9 0 1 0 7 A)
O t her St u d y v acci ne
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G S K Bi ol o gicals’ me ni n g oc occal ser o gr o u ps A, 
C, W -1 3 5, Y teta n us t o x oi d c o nj u gate 
( Me n A C W Y-T T) vacci ne ( G S K 1 3 4 6 1 2 A)
e Tr ac k st u d y n u m ber a n d 
A b bre vi ate d Title
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E u dr a C T n u m ber
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D ate of pr ot oc ol
Fi nal Versi o n 1 : 0 9 Dece m ber 2 0 1 4
D ate of pr ot oc ol
a me n d me nt
A me n d me nt 1 Fi nal: 2 9  Dece m ber 2 0 1 4
A me n d me nt 2 Fi nal : 0 6 Ma y 2 0 1 5
Title
Safet y  a n d i m m u n o ge nicit y st u d y of G S K Bi ol o gicals’ 
i n vesti gati o nal rec o m bi na nt c hi m pa nzee a de n o vir us 
T y pe 3- vect ore d E b ola Zaire vacci ne (G S K 3 3 9 0 1 0 7 A) 
i n c hil dre n i n Africa.
Det aile d Title
A P hase 2, ra n d o mise d, o bser ver -bli n d, c o ntr olle d, 
m ulti -c o u ntr y st u d y t o assess t he safety a n d 
i m m u n o ge nicity of a si n gle i ntra m usc ular d ose of 
G S K Bi ol o gicals’ i n vesti gati o nal rec o m bi na nt 
c hi m pa nzee a de n o vir us T ype 3 -vect ore d E b ola Zaire 
v acci ne ( C h A d 3 -E B O -Z) ( G S K 3 3 9 0 1 0 7 A), i n c hil dre n 
1 t o 1 7 y ears of a ge i n Africa.
C o -or di n ati n g a ut h or
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e Tr ac k st u d y n u m ber a n d 
A b bre vi ate d Title
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(I N D) n u m ber
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E u dr a C T n u m ber
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Title
Safet y a n d i m m u n o ge nicit y st u d y of G S K Bi ol o gicals’ 
i n vesti gati o nal rec o m bi na nt c hi m pa nzee a de n o vir us 
T y pe 3- vect ore d E b ola Zaire vacci ne ( G S K 3 3 9 0 1 0 7 A) i n 
c hil dre n i n Africa.
Det aile d Title
A P hase 2, ra n d o mise d, o bser ver - bli n d, c o ntr olle d, 
m ulti -c o u ntr y st u d y t o assess t he safet y a n d 
i m m u n o ge nicit y of a si n gle i ntra m usc ular d ose of G S K 
Bi ol o gicals’ i n vesti gati o nal rec o m bi na nt c hi m pa nzee 
a de n o vir us T y pe 3 -vect ore d E b ola Zaire v acci ne 
( C h A d 3-E B O -Z) ( G S K 3 3 9 0 1 0 7 A), i n c hil dre n 
1 t o 1 7 years of a ge i n Africa.
C o ntri b uti n g a ut h ors
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Cli nical Researc h a n d De vel o p me nt Lea ds
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, Q ui ntiles Me dical E x pert
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, Vice Presi de nt, Cli nical Researc h a n d 
Tra nslati o nal Scie nce
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, Pr oject Statisticia n
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, Lea d Statisticia n
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 a n d 
, Safet y 
Re prese ntati ves
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, Pr oject Deli ver y Lea d
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Bi ol o gicals) a n d L a ure nt Gles ner ( C R O M S o urce f or 
G S K Bi ol o gic als) , Vacci ne S u p pl y C o or di nat or
( A me n de d 0 6 M ay 2 0 1 5.)
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St u d y Data Ma na ger
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 a n d 
( B usi ness & 
Decisi o n Life Scie nces f or G S K Bi ol o gicals), G V C L 
St u d y Ma na ger
( A me n de d 0 6 M ay 2 0 1 5.)
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, Gl o bal Re g ulat or y Re prese ntati ve
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 a n d 
 ( X P E P har ma & 
Scie nce f or G S K Bi ol o gicals), Scie ntific Writer
( A me n de d 0 6 M ay 2 0 1 5.)
G S K Bi ol o gic als’ Pr ot oc ol D S v 1 4. 1
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U n a ut h orise d c o p yi n g or use of t his i nf or m ati o n is pr o hi bite d.
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CONFIDENTIAL
202090 (EBOLA Z CHAD3-004)
Protocol Amendment 2 Final
06-May-15
4
Protocol Amendment 2 Rationale
Amendment number
Amendment 2
Rationale/ background for changes: 

In the on-going Phase 1 studies with the investigational ChAd3-EBO-Z vaccine in 
the United States (US), United Kingdom (UK), Switzerland and Mali, transient 
decreases in thrombocyte counts were 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 as per protocol 
criteria for thrombocytopenia (thrombocyte count of < 150x103/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 bleed were 
reported in any of the subjects. Please refer to the Investigator’s Brochure (IB) for 
more information.
In the current study, a more vulnerable population (children) will be enrolled and 
the acceptable limit for the thrombocyte count for study eligibility (thrombocyte 
count of 100x103/µL is acceptable) will be lower as compared to the Phase 1 
studies. In addition, in order to ensure enhanced vigilance from the Investigators, 
clinical bleeding events (according to the Standardised Medical Dictionary for 
Regulatory Activities [MedDRA] Query clinical haemorrhage) within 7 days after 
vaccination at Day 0 will be recorded and reported as adverse events (AEs) of 
specific interest (clinical symptoms of thrombocytopenia).

Based on safety and immunogenicity data from the on-going Phase 1 studies, the 
1x1011 viral particles (vp) dose was selected for further assessment in Phase 2 and 
Phase 3 clinical studies in adults. This dose was determined using a high 
performance liquid chromatography (HPLC) analytical method for the vaccine lots 
used in the Phase 1 studies. The same dose will also be used in this paediatric 
study. However, depending on the recommendation of the independent data 
monitoring committee (IDMC), a lower dose may be selected based on safety and 
reactogenicity data accrued during the age de-escalation process for children in 
younger age strata. In addition, because a different analytical method was used to 
determine the vp concentration for the lots used in this study (quantitative 
polymerase chain reaction [qPCR]) as compared to the lots used in the Phase 1 
studies (HPLC), a dose of 2x1011 vp, as determined by qPCR, will be used in this 
study, to administer the equivalent of the 1x1011 vp dose, that was determined by 
HPLC and shown to be optimal in Phase 1 studies. This information was added in 
the protocol.

Demographic data collection was updated to allow the full date of birth in the 
subject’s eSource, but only month and year of the date of birth will be exported to 
GlaxoSmithKline’s (GSK’s) clinical database to guarantee subject confidentiality. 
The age as calculated in eSource will be used for analysis purposes as the full date 
of birth will not be exported.

The IDMC highlighted that the study is conducted in Malaria endemic countries
and that the presence of malarial infection may adversely affect the safety and 

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202090 (EBOLA Z CHAD3-004)
Protocol Amendment 2 Final
06-May-15
5
immunogenicity evaluations of the investigational ChAd3-EBO-Z vaccine. In 
order to prevent subjects with Malaria from entering the study, all subjects who 
provide informed consent for study participation will be tested for Malaria 
infection at the time of Screening, using a rapid diagnostic test (RDT) procedure. 
Subjects who are diagnosed with Malaria, will receive antimalarial treatment 
according to local/ national standards during the Screening period (e.g., a 3-day 
treatment course of artemisinin-based combination therapy). Hence, only subjects 
for whom the RDT was negative, or for whom the RDT was positive and who 
received a complete course of antimalarial treatment during the Screening period 
can be considered for study participation. Procedures for Malaria Screening and 
treatment, as well as eligibility criteria specific for these procedures were adapted 
in the protocol.

The scope of re-screening subjects has been clarified during the investigator’s 
meeting, i.e., re-screening of subjects must be avoided and redrawing blood from 
the subject is only permitted during the Screening period if, for technical reasons, 
test results are not available or if they are non-interpretable. To comply with this 
recommendation and avoid the risk of inadequate re-screening, footnote 11 under 
Table 5 (List of study procedures) has been removed. 

After consultation with the Principal Investigators and the IDMC, the exclusion 
criterion “Maternal death” was removed. Instead the following exclusion criterion 
was included:
Any condition that in the Investigator’s opinion may potentially compromise 
subject safety or interfere with subject assessment or compliance.
This will allow the investigator also to consider, on a case by case basis, whether 
the family circumstances of the child may allow participation to the study in 
compliance with local regulations, when applicable.

Blood sample volumes for haematology and biochemistry testing were corrected.

Some minor editorial updates were made.

CONFIDENTIAL
202090 (EBOLA Z CHAD3-004)
Protocol Amendment 2 Final
06-May-15
6
Protocol Amendment 2 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 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/ thumb 
printed informed consent of the subject and/or the subject’s legally acceptable 
representative (LAR). 

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, 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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202090 (EBOLA Z CHAD3-004)
Protocol Amendment 2 Final
06-May-15
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eTrack study number and 
Abbreviated Title
202090 (EBOLA Z CHAD3-004)
IND number
16300
EudraCT number
2014-004714-28
Date of protocol amendment
Amendment 2 Final: 06 May 2015
Detailed Title
A Phase 2, randomised, observer-blind, controlled, 
multi-country study to assess the safety and 
immunogenicity of a single intramuscular dose of 
GSK Biologicals’ investigational recombinant 
chimpanzee adenovirus Type 3-vectored Ebola Zaire 
vaccine (ChAd3-EBO-Z) (GSK3390107A), in 
children 1 to 17 years of age in Africa.
Investigator name
Signature
Date

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202090 (EBOLA Z CHAD3-004)
Protocol Amendment 2 Final
06-May-15
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Sponsor Information
Sponsor
GlaxoSmithKline Biologicals
Rue de l’institut 89,
1330 Rixensart, Belgium

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C o ntr a ct e d R e s e ar c h Or g a ni s ati o n ( Q ui ntil e s) I nf or m ati o n
1.
Me dic al E x pert f or t he St u d y
, M D
Se ni or Me dical Direct or
Aller gy, Res pir at ory, I nfecti o us Dise ases & V acci nes
Me dic al Str ate gy & Scie nce
T her a pe utic Scie nce & Str ate gy U nit
( A me n de d 0 6 M ay 2 0 1 5.)
2.
St u d y C o nt act f or Re p orti n g of a Seri o us A d verse E ve nt
Pri mar y  met h o d of re p orti n g is via e S o urce. If e S o urce is n ot a vaila ble, please refer t o 
S A E / Pre g na nc y  bac k- u p re p orti n g i nstr ucti o ns i n t he In vesti gat or bi n der.
B ac k - u p St u d y C o nt act f or Re p orti n g S A Es a n d pre g n a ncies:
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P h o ne: 
Fa x: 
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202090 (EBOLA Z CHAD3-004)
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SYNOPSIS
Detailed Title
A Phase 2, randomised, observer-blind, controlled, 
multi-country study to assess the safety and immunogenicity 
of a single intramuscular dose of GSK Biologicals’ 
investigational recombinant chimpanzee adenovirus 
Type 3-vectored Ebola Zaire vaccine (ChAd3-EBO-Z) 
(GSK3390107A), in children 1 to 17 years of age in Africa.
Indication
Primary immunisation against Ebolavirus Zaire (EBOV):
The investigational recombinant chimpanzee adenovirus 
type 3-vectored EBOV vaccine (ChAd3-EBO-Z) is developed 
for prevention of Zaire Ebola virus disease (EVD).
Rationale for the 
study and study 
design

Rationale for the study
On 7 August 2014, the World Health Organisation 
(WHO) requested that GlaxoSmithKline (GSK) “fully 
engages in WHO-coordinated efforts to test, license 
and make available safe and effective Ebola 
interventions” to assist in the control of the outbreak 
in Western Africa. Given the severity of the situation, 
time to vaccine deployment was an important aspect 
of the WHO request. In response to this call, an 
accelerated Phase 1, dose-finding vaccine 
development effort was initiated mid-August that 
involved WHO, GSK, Vaccine Research Center of 
the National Institute of Allergy and Infectious 
Diseases (VRC/NIAID), the University of Oxford, the 
University of Maryland and the University of 
Lausanne and the Centre for Vaccine Development in 
Mali.  
Although health care workers will be priority 
vaccination targets, mass vaccination strategies may 
be developed as one of the ways to protect 
populations and contain the epidemics. In this 
context, children will need to be vaccinated too. The 
present Phase 2, randomised, controlled trial will aim 
at collecting safety and immunogenicity data 
following a single intramuscular dose of the 
investigational ChAd3-EBO-Z vaccine. In parallel 
with the current study, the safety and immunogenicity 
of the investigational ChAd3-EBO-Z vaccine will be 
assessed in healthy adults living in countries adjacent 
to the current Ebola outbreak (study EBOLA Z 
CHAD3-005). Study EBOLA Z CHAD3-005 will 
start before the current study as to collect safety and 

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202090 (EBOLA Z CHAD3-004)
Protocol Amendment 2 Final
06-May-15
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reactogenicity data in 100 adults, after 1 week of 
follow-up, living in countries adjacent to the current 
Ebola outbreak before proceeding to vaccination of 
children.

Rationale for the study design

Investigational ChAd3-EBO-Z vaccine dose
Dose selection for paediatric use was based on 
information derived from dose-range studies 
conducted with the ChAd3-EBO-Z vaccine candidate 
in adults and on past experience with other 
recombinant adenovirus-based candidate vaccines.
(Amended 06 May 2015.)
While investigational ChAd3-based candidate 
vaccines have not been administered to children 
before, other recombinant adenovirus-based candidate 
vaccines have been administered to children without 
safety concerns. A recombinant chimpanzee 
adenovirus Type 63 vaccine expressing the 
Plasmodium falciparum pre-erythrocytic antigen 
ME-TRAP (multiple epitope string with 
thrombospondin-related adhesion protein) 
(ChAd63 ME-TRAP) malaria candidate vaccine has 
been safely administered to healthy adults in United 
Kingdom (UK) and Kenya, and to healthy infants and 
children in The Gambia and Burkina Faso. The 
intramuscular (IM) dose of 5x1010 viral particles (vp)
was determined to be optimal in both adults and 
children Afolabi, 2012; Ogwang, 2013; 
O’Hara, 2012; ClinicalTrials.gov NCT01635647; 
ClinicalTrials.gov NCT02083887; A. Hill, personal 
communication]. In the tuberculosis vaccine research 
field, up to two dose of 1x1011 vp of AERAS-402, a 
recombinant, replication-defective adenovirus type 35 
expressing tuberculosis antigens, the highest dose 
evaluated, showed favourable safety in infants 
6 to 9 months old Kagina, 2014]. This dose is also 
used in adults ClinicalTrials.gov NCT01683773].
Importantly, dose ranging in terms of vp is classically 
done on a logarithmic scale while arithmetic scales 
are usually used to describe weight differences 
between adults and children. In other words, the 
variability in weight between adults and children is 
small as compared to classical dose ranging in terms 
of number of vp, and inherent imprecision/variability 
in number of vp. 

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202090 (EBOLA Z CHAD3-004)
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Four different investigational vaccine doses are 
currently being evaluated for safety, reactogenicity 
and immunogenicity in adults in Phase 1 studies. 
Based on data from these studies, the 1x1011 vp dose 
was selected for further assessment in Phase 2 and 
Phase 3 clinical studies in adults. This dose was 
determined using a high performance liquid 
chromatography (HPLC) analytical method for the 
vaccine lots used in the Phase 1 studies. The same 
dose will be used in this paediatric study. However, 
depending on the recommendation of the 
independent data monitoring committee (IDMC), a 
lower dose may be selected based on safety and 
reactogenicity data accrued during the age 
de-escalation process for children in younger age 
strata. It should be noted that the analytical 
method (quantitative polymerase chain reaction 
[qPCR]) that measures the concentration of virus 
particles per mL (vp/mL) present in the 
ChAd3-EBO-Z vials used in the current paediatric 
study is different from the analytical method 
(HPLC) used for the Phase 1 studies. As a result, a 
dose of 2x1011 vp will be used in this study, to 
administer the equivalent of the 1x1011 vp dose that 
was shown to be optimal in Phase 1 studies. As for 
other recombinant adenovirus-based vaccine 
candidates which showed adequate safety upon the 
use of adult doses in children as explained above, it is 
currently proposed that the same vaccine dose will be 
assessed in children 1 to 17 years of age in this study. 
However, a lower vaccine dose may be selected for 
children of younger age groups based on the safety 
and reactogenicity data accrued during the age 
de-escalation process. (Amended 06 May 2015.)

Administration of the investigational ChAd3-EBO-Z 
vaccine
Considering the risk of exposure to Ebola and the 
potential (based on animal data) for the 
investigational ChAd3-EBO-Z vaccine to afford at 
least partial protection, all children in the study will 
receive the investigational ChAd3 EBO-Z vaccine. 
The children in the Group EBO-Z/ MENACWY-TT
will receive the investigational ChAd3-EBO-Z 
vaccine at Day 0 of the study, whereas the children in 
the Group MENACWY-TT/ EBO-Z will receive 
Nimenrix at Day 0 (as a control). At Month 6, the 
children in the Group MENACWY-TT/ EBO-Z will 

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202090 (EBOLA Z CHAD3-004)
Protocol Amendment 2 Final
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receive the investigational ChAd3-EBO-Z vaccine 
(provided that no safety concerns are raised), whereas 
the children in the Group EBO-Z/ MENACWY-TT
will receive Nimenrix.
In case the geographic range of EBOV transmission 
expands to encompass any of the regions where this 
trial is conducted, earlier administration of the 
investigational ChAd3-EBO-Z vaccine to the children 
in the Group MENACWY-TT/ EBO-Z will be 
considered in that region.

Control vaccine
GSK Biologicals’ meningococcal serogroups A, C, 
W-135, Y tetanus toxoid conjugate (MenACWY-TT) 
vaccine (Nimenrix) will be used as control. 
Nimenrix is indicated for the active immunisation 
against invasive meningococcal diseases caused by 
Neisseria meningitidis (meningococcus) serogroups 
A, C, W-135 and Y. Invasive meningococcal disease, 
including meningitis and meningococcal septicaemia, 
often follows invasive infection by 
Neisseria meningitidis and is a major cause of death 
and morbidity throughout the world. 
Neisseria meningitidis serogroups A, B, C, W-135 
and Y are the most common causes of invasive 
meningococcal disease worldwide: serogroup A is 
most common in Africa and Asia, while serogroups B 
and C account for more than 90% of the cases in 
Europe and Latin America [Anderson, 1998; 
Connolly, 1999; Harrison, 2009; Peltola, 1998]. 
Nimenrix is licensed in 50 countries (first approval in 
April 2012) and is currently available in at least 23 
countries.
Using Nimenrix as a control vaccine in this study will 
provide a theoretical benefit to the children in the 
study and adequately support safety comparison.

Stratification for age and staggered vaccination
In order to ensure equal distribution of the population, 
enrolment will be stratified by age so that an equal 
number of children are enrolled in each age stratum 
(1 to 5 years, 6 to 12 years and 13 to 17 years of age). 
In order to ensure maximum safety for the subjects in 
this study, vaccination at Day 0 will be done in a 
staggered manner, starting with vaccination of the 
children in the oldest age stratum. For each age 

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202090 (EBOLA Z CHAD3-004)
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stratum, an IDMC will conduct a review of all 
available safety data once data is available up to at 
least 7 days after vaccination of at least 50 subject 
(25/ group) in that age stratum. The start of 
vaccination in the younger age stratum, possibly with 
a lower vaccine dose, depends on the outcome of this 
IDMC review.

Human immunodeficiency virus testing
There will be no routine testing for human 
immunodeficiency virus (HIV) in this trial. Tests will 
be performed when clinically indicated to guide 
subject management. Voluntary counselling and 
testing, highly active anti-retroviral therapy (HAART) 
and prevention of mother to child transmission 
(PMTCT) will be available at all study centres 
according to national policies.

Malaria Screening and treatment
As this study is conducted in Malaria endemic regions 
and the presence of malaria infection may adversely 
affect the safety and immunogenicity evaluations of the 
investigational ChAd3-EBO-Z vaccine, all subjects will 
be tested for Malaria infection using a rapid diagnostic 
test (RDT) procedure during Screening and all subjects 
diagnosed with Malaria will receive antimalarial 
treatment according to local/ national standards (e.g., a 
3-day treatment course of artemisinin-based 
combination therapy), during the Screening period. 
Hence, only subjects for whom the RDT was negative, 
or for whom the RDT was positive and who received a 
complete course of antimalarial treatment during the 
Screening period can be considered for study 
participation.
(Amended 06 May 2015.)
Objectives
Primary

To assess the safety and reactogenicity of a single IM
dose of the ChAd3-EBO-Z vaccine, overall and in 
children aged 1 to 5, 6 to 12, and 13 to 17 years 
separately.

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Secondary

To assess the humoral immunogenicity of a single IM
dose of the ChAd3-EBO-Z vaccine, in terms of 
anti-glycoprotein (GP) EBOV antibody responses, overall 
and in children aged 1 to 5, 6 to 12, and 13 to 17 years 
separately. 
Tertiary

To assess the persistence of the humoral immune 
response induced by a single IM dose of the ChAd3-
EBO-Z vaccine, in terms of anti-GP EBOV antibody 
responses, overall and in children aged 1 to 5, 6 to 12, 
and 13 to 17 years separately.

To assess EBOV-specific cell-mediated immunity (CMI) 
of a single IM dose of the ChAd3-EBO-Z vaccine, overall 
and in children aged 1 to 5, 6 to 12, and 13 to 17 years 
separately.

To assess the pre-existing immunity to the ChAd3 virus 
vaccine vector prior vaccination, ChAd3-specific immune 
responses after vaccination and explore its potential 
impact on Ebola-specific immune responses, overall and 
in children aged 1 to 5, 6 to 12, and 13 to 17 years 
separately.

If deemed necessary, to further characterise the immune 
response to/ the safety profile of the investigational 
ChAd3-EBO-Z vaccine.
Study design

Experimental design: Phase 2, randomised, 
observer-blind, controlled, multi-country study with 
2 groups and 3 age strata.

Duration of the study: for each subject enrolled will be 
approximately 12 months from the Day 0 visit.

Epoch 001: Primary starting at Screening and ending 
at the Month 12 visit.

Study groups:

Group EBO-Z/ MENACWY-TT: approximately 
300 children in total; approximately 100 children per 
age stratum (1 to 5 years, 6 to 12 years, and 13 to 
17 years of age).

Group MENACWY-TT/ EBO-Z: approximately 
300 children in total; approximately 100 children per 
age stratum (1 to 5 years, 6 to 12 years, and 13 to 

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17 years of age).
Synopsis Table 1
Study groups and epochs foreseen in the study
Study group
Number of
subjects
Age
Epochs
Epoch 001
EBO-Z/ 
MENACWY-TT
~300
~100 children per age stratum: 13 to 17, 6 to 12, 
1 to 5 years
x
MENACWY-TT/ 
EBO-Z
~300
~100 children per age stratum: 13 to 17, 6 to 12, 
1 to 5 years
x
= approximately
Synopsis Table 2
Treatments foreseen in the study
Treatment name
Vaccine/Product 
name
Study Groups
EBO-Z/ MENACWY-TT
MENACWY-TT/ EBO-Z
ChAd3-EBO-Z
ChAd3-EBO-Z
x (Day 0)
x (Month 6)
Nimenrix
MenACWY-TT
x (Month 6)
x (Day 0)
NaCl
ChAd3-EBO-Z = investigational recombinant chimpanzee adenovirus type 3-vectored Ebola virus Zaire (EBOV)
vaccine; MenACWY-TT = meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate vaccine; NaCl = sodium 
chloride

Control: Active control (Nimenrix).

Vaccination schedule: All subjects will receive 
2 vaccinations, 1 at the Day 0 visit and 1 at the Month 6 
visit. All subjects will receive 1 dose of the 
investigational ChAd3-EBO Z vaccine and 1 dose of 
Nimenrix:

Subjects in Group EBO-Z/ MENACWY-TT will
receive the investigational ChAd3-EBO-Z vaccine at 
the Day 0 visit and Nimenrix at the Month 6 visit.

Subjects in Group MENACWY-TT/ EBO-Z will 
receive Nimenrix at the Day 0 visit and the 
investigational ChAd3-EBO-Z vaccine at the Month 6 
visit.

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
Treatment allocation: Subjects will be randomised (1:1) 
at Day 0. In order to ensure equal distribution of the 
population, enrolment will be stratified by age so that an 
equal number of children are enrolled in each age stratum 
(1 to 5 years, 6 to 12 years, and 13 to 17 years of age). In 
addition, the randomisation will use a minimisation 
procedure accounting for gender and centre.

Staggered vaccination: Vaccination at Day 0 will be 
done in a staggered manner, starting with vaccination of 
the children in the oldest age stratum (13 to 17 years of 
age). In order to proceed to vaccination of the subjects in 
the younger age stratum (6 to 12 years of age), possibly 
with a lower vaccine dose, a favourable outcome of the 
IDMC review of safety data up to at least 7 days after 
vaccination from at least 50 subjects (25/ group) in the 
oldest age stratum needs to be obtained. The same will be 
done for moving from the 6 to 12 years of age stratum to 
vaccination of the youngest children (1 to 5 years of age).

Blinding:

Observer-blind from study start until the interim 
analysis that will be conducted when safety, 
reactogenicity and immunogenicity (including at least 
anti-GP EBOV data at Day 30) data is available from 
all subjects up to 30 days after vaccination at Day 0.

Single-blind as of the interim analysis at Day 30.
(Amended 06 May 2015.)

Sampling schedule:

A blood sample (fingerprick) will be taken at 
Screening for Malaria RDT.
(Amended 06 May 2015.)

Blood samples for haematology/ biochemistry
assessment will be taken from all subjects at 
Screening, at the Day 3, Day 6, the Day 30, the 
Month 6, the Month 6 + 6 days, the 
Month 6 + 30 days, and the Month 12 visits.

Blood samples for humoral immunity will be taken 
from all subjects at the Day 0, the Day 30, the 
Month 6, the Month 6 + 30 days, and the Month 12 
visits.

Blood samples for CMI will be taken from a sub-
cohort of 90 subjects per group (30 children per age 
stratum per group) at the Day 0, the Day 30, the 

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Month 6, the Month 6 + 30 days, and the Month 12 
visits.

Safety monitoring: An IDMC will be appointed to 
monitor the safety and tolerability of the investigational 
ChAd3-EBO-Z vaccine. The IDMC will consist of 
clinical experts and a statistician who are not involved in 
the conduct of the study.
Number of subjects
The target is to enrol approximately 600 eligible children 
(approximately 300 per group and approximately 200 per age 
stratum).
Endpoints
Primary

Occurrence of each solicited local and general adverse 
event (AE), during a 7-day follow-up period after each 
vaccination (i.e., the day of vaccination and 6 subsequent 
days), in all subjects, in both groups.

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), in all subjects, in 
both groups.

Occurrence of haematological (complete blood count 
[CBC], including differential count and platelet count) 
and biochemical (alanine aminotransferase [ALT], 
creatinine) laboratory abnormalities at Screening, Day 3, 
Day 6, Day 30, Month 6, Month 6 + 6 days, Month 6 + 
30 days and Month 12 in all subjects in both groups.

Occurrence of clinical symptoms of thrombocytopenia 
(AE of specific interest), during a 7-day follow-up 
period after vaccination at Day 0 (i.e., Day 0 up to 
Day 6), in all subjects, in both groups. 
(Amended 06 May 2015.)

Occurrence of any serious adverse event (SAE), in all 
subjects, in both groups.
Secondary

Anti-GP EBOV antibody titres, as measured by 
enzyme-linked immunosorbent assay (ELISA):

At Day 0 and Day 30, in all subjects, in both groups.

At Month 6 and Month 6 + 30 days, in all subjects in 
the Group MENACWY-TT/ EBO-Z.
Tertiary

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
Anti-GP EBOV antibody titres, as measured by ELISA:

At Month 6 and Month 6 + 30 days, in all subjects, in 
the Group EBO-Z/ MENACWY-TT.

At Month 12, in all subjects, in both Group.

Magnitude, responder rate and cytokine co-expression 
profile of ChAd3-EBO-Z-specific CD4+ or CD8+ T-cell 
responses, as assessed by intracellular cytokine staining 
(ICS) after stimulation with EBOV GP antigens:

At Day 0, Day 30, Month 6, Month 6 + 30 days and 
Month 12, in a sub-cohort of 30 subjects per age 
stratum, per group.

ChAd3 neutralising antibody titres, as measured by a 
neutralisation assay:

At Day 0, Day 30, Month 6, and Month 6 + 30 days, 
in a subset of 30 subjects per age stratum, per group.

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TABLE OF CONTENTS
PAGE
SPONSOR INFORMATION ............................................................................................8
CONTRACTED RESEARCH ORGANISATION (QUINTILES) INFORMATION...............9
SYNOPSIS....................................................................................................................10
LIST OF ABBREVIATIONS (AMENDED 06 MAY 2015)................................................29
GLOSSARY OF TERMS ...............................................................................................33
TRADEMARKS .............................................................................................................37
1.
INTRODUCTION....................................................................................................38
1.1.
Background ................................................................................................38
1.1.1.
Ebola virus Zaire outbreak 2014 ..................................................38
1.1.2.
Ebola virus and Zaire Ebola virus disease ...................................38
1.1.3.
GlaxoSmithKline Biologicals’ investigational 
ChAd3-EBO-Z vaccine.................................................................39
1.2.
Rationale for the study and study design ....................................................39
1.2.1.
Rationale for the study.................................................................39
1.2.2.
Rationale for the study design......................................................40
1.2.2.1.
Investigational ChAd3-EBO-Z vaccine dose ...............40
1.2.2.2.
Administration of the investigational 
ChAd3-EBO-Z vaccine ...............................................41
1.2.2.3.
Control vaccine...........................................................41
1.2.2.4.
Stratification for age and staggered vaccination .........42
1.2.2.5.
Human immunodeficiency virus testing.......................42
1.3.
Benefit : Risk assessment...........................................................................42
1.3.1.
Risk Assessment .........................................................................43
1.3.2.
Benefit assessment .....................................................................44
1.3.3.
Overall Benefit : Risk conclusion..................................................45
2.
OBJECTIVES.........................................................................................................45
2.1.
Primary objective ........................................................................................45
2.2.
Secondary objective ...................................................................................45
2.3.
Tertiary objectives.......................................................................................45
3.
STUDY DESIGN OVERVIEW ................................................................................46
4.
STUDY COHORT...................................................................................................49
4.1.
Number of subjects/centres ........................................................................49
4.2.
Sub-cohort for cell-mediated immunity........................................................49
4.3.
Inclusion criteria for enrolment....................................................................49
4.4.
Exclusion criteria for enrolment...................................................................50
5.
CONDUCT OF THE STUDY ..................................................................................51
5.1.
Regulatory and ethical considerations, including the  informed 
consent process..........................................................................................51

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5.2.
Subject identification and randomisation of treatment .................................52
5.2.1.
Subject identification....................................................................52
5.2.2.
Randomisation of treatment.........................................................53
5.2.2.1.
Randomisation of supplies..........................................53
5.2.2.2.
Treatment allocation to the subject.............................53
5.2.2.2.1.
Study group and treatment name 
allocation at Day 0 ..................................53
5.2.2.2.2.
Treatment name allocation at 
Month 6 ..................................................54
5.2.3.
Allocation of subjects to assay subsets........................................54
5.3.
Method of blinding ......................................................................................54
5.4.
General study aspects ................................................................................55
5.5.
Outline of study procedures ........................................................................56
5.5.1.
List of study procedures...............................................................56
5.5.2.
Intervals between study visit ........................................................58
5.6.
Detailed description of study procedures ....................................................58
5.6.1.
Informed consent.........................................................................58
5.6.2.
Malaria Screening and treatment (Amended 06 May 2015) .........58
5.6.3.
Check inclusion and exclusion criteria .........................................60
5.6.4.
Collect demographic data ............................................................60
5.6.5.
Medical history.............................................................................60
5.6.6.
Physical examination ...................................................................60
5.6.7.
Pregnancy test.............................................................................61
5.6.8.
Check contraindications to vaccination ........................................61
5.6.9.
Assess pre-vaccination body temperature ...................................61
5.6.10.
Study group and treatment number allocation..............................61
5.6.11.
Sampling......................................................................................61
5.6.12.
Study vaccine administration .......................................................62
5.6.13.
Check and record concomitant medications/ products/ 
vaccinations.................................................................................62
5.6.14.
Recording of adverse events, serious adverse events, and  
pregnancies.................................................................................62
5.6.14.1.
Diary Card for follow-up adverse events 
occurring from day 0 to day 6  after vaccination..........63
5.6.14.2.
Unsolicited adverse events occurring from 
day 0 to day 29 after vaccination and serious 
adverse event data collection during the entire 
study duration.............................................................63
5.6.15.
Study conclusion..........................................................................64
5.7.
Biological sample handling and analysis.....................................................64
5.7.1.
Use of specified study materials ..................................................64
5.7.2.
Biological samples.......................................................................66
5.7.3.
Laboratory assays .......................................................................67
5.7.3.1.
Haematology/ biochemistry ........................................67
5.7.3.2.
Immune response against Ebola ................................67
5.7.3.3.
Immune response against ChAd3...............................67
5.7.4.
Biological samples evaluation......................................................68
5.7.4.1.
Immunological read-outs ............................................68
5.7.4.2.
Haematology/biochemistry .........................................68
5.7.5.
Immunological correlates of protection.........................................68

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6.
STUDY VACCINES/ PRODUCTS AND ADMINISTRATION (AMENDED 06 
MAY 2015.) ............................................................................................................68
6.1.
Malaria treatment (Amended 06 May 2015.)...............................................68
6.2.
Description of study vaccines......................................................................69
6.3.
Storage and handling of study vaccines......................................................69
6.4.
Dosage and administration of study vaccines .............................................70
6.5.
Replacement of unusable vaccine doses....................................................70
6.6.
Contraindications to vaccination .................................................................70
6.7.
Concomitant medications/products and concomitant  vaccinations.............71
6.7.1.
Recording of concomitant medications/products and 
concomitant vaccinations.............................................................71
6.7.2.
Concomitant medications/ products/ vaccines that may 
lead to the elimination of a subject from according-to-
protocol analyses.........................................................................71
6.8.
Intercurrent medical conditions that may lead to elimination  of a 
subject from according-to-protocol analyses ...............................................72
7.
OCCURRENCE OF SUSPECTED OR CONFIRMED EBOLA VIRUS 
DISEASE................................................................................................................72
8.
HEALTH ECONOMICS ..........................................................................................73
9.
SAFETY.................................................................................................................73
9.1.
Safety definitions ........................................................................................73
9.1.1.
Definition of an adverse event......................................................73
9.1.2.
Definition of a serious adverse event ...........................................74
9.1.3.
Solicited adverse events..............................................................75
9.1.3.1.
Solicited local (injection-site) adverse events..............75
9.1.3.2.
Solicited general adverse events................................75
9.1.4.
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events ............................................................................75
9.1.5.
Adverse events of specific interest...............................................76
9.1.5.1.
Clinical bleeding within 7 days post-vaccination 
at Day 0......................................................................76
9.2.
Events or outcomes not qualifying as adverse events or  serious 
adverse events (pregnancy)........................................................................76
9.3.
Detecting and recording adverse events, serious adverse  events 
and pregnancies .........................................................................................77
9.3.1.
Time period for detecting and recording adverse events, 
serious adverse events and pregnancies.....................................77
9.3.2.
Post-Study adverse events and serious adverse events..............78
9.3.3.
Evaluation of adverse events and serious adverse events...........79
9.3.3.1.
Active questioning to detect adverse events 
and serious adverse events........................................79
9.3.3.2.
Assessment of adverse events...................................80
9.3.3.2.1.
Assessment of intensity..........................80
9.3.3.2.2.
Assessment of causality .........................82
9.3.3.3.
Assessment of outcomes............................................83
9.3.3.4.
Medically attended visits.............................................84
9.4.
Reporting of serious adverse events, pregnancies, and  other 
events.........................................................................................................84

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9.4.1.
Prompt reporting of adverse events of specific interest 
(clinical symptoms of thrombocytopenia), serious adverse 
events, and pregnancies to the contracted research 
organisation (Quintiles) (Amended 06 May 2015) ........................84
9.4.2.
Contact information for reporting adverse events of 
specific interest (clinical symptoms of thrombocytopenia), 
serious adverse events, and pregnancies (Amended 06 
May 2015)....................................................................................85
9.4.3.
Reporting of adverse events of specific interest (clinical 
symptoms of thrombocytopenia) to the contract research 
organisation (Quintiles) (Amended 06 May 2015) ........................85
9.4.4.
Completion and transmission of serious adverse events 
reports to the contracted research organisation (Quintiles) ..........86
9.4.4.1.
Back-up system in case the electronic reporting 
system does not work.................................................86
9.4.5.
Completion and transmission of pregnancy reports to the 
contracted research organisation (Quintiles)................................87
9.4.6.
Updating of adverse events of specific interest (clinical 
symptoms of thrombocytopenia), serious adverse events,
and pregnancy information after removal of write access 
to the subject’s eSource (Amended 06 May 2015).......................87
9.4.7.
Regulatory reporting requirements for serious adverse 
events..........................................................................................87
9.5.
Follow-up of adverse events, serious adverse events, and  
pregnancies................................................................................................88
9.5.1.
Follow-up of adverse events and serious adverse events ............88
9.5.1.1.
Follow-up during the study..........................................88
9.5.1.2.
Follow-up after the subject is discharged from 
the study.....................................................................88
9.5.2.
Follow-up of pregnancies.............................................................88
9.6.
Treatment of adverse events ......................................................................89
9.7.
Unblinding...................................................................................................89
9.8.
Emergency unblinding ................................................................................89
9.9.
Subject card................................................................................................89
9.10.
Safety monitoring by the independent data monitoring  committee .............90
10. SUBJECT COMPLETION AND WITHDRAWAL.....................................................92
10.1.
Subject completion .....................................................................................92
10.2.
Subject withdrawal......................................................................................92
10.2.1.
Subject withdrawal from the study................................................92
10.3.
Extension study ..........................................................................................93
10.4.
Screen failures............................................................................................93
11. STATISTICAL METHODS......................................................................................93
11.1.
Primary endpoints.......................................................................................93
11.2.
Secondary endpoint....................................................................................94
11.3.
Tertiary endpoints.......................................................................................94
11.4.
Determination of sample size......................................................................94
11.5.
Cohorts for Analyses...................................................................................95
11.5.1.
Total vaccinated cohort................................................................95
11.5.2.
According-to-protocol cohort for analysis of 
immunogenicity............................................................................95

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11.6.
Derived and transformed data.....................................................................96
11.7.
Analysis of demographics ...........................................................................96
11.8.
Analysis of safety........................................................................................97
11.9.
Analysis of immunogenicity.........................................................................98
11.10. Interpretation of analyses............................................................................98
11.11. Conduct of analyses ...................................................................................99
11.11.1. Sequence of analyses..................................................................99
11.11.2. Statistical considerations for interim analyses..............................99
12. ADMINISTRATIVE MATTERS ...............................................................................99
12.1.
Electronic case report form instructions (eSource)......................................99
12.2.
Study monitoring by the contracted research organisation........................100
12.3.
Record retention .......................................................................................100
12.4.
Quality assurance.....................................................................................101
12.5.
Posting of information on publicly available clinical trial  registers 
and publication policy................................................................................101
12.6.
Provision of study results to Investigators .................................................101
13. COUNTRY SPECIFIC REQUIREMENTS.............................................................102
14. REFERENCES.....................................................................................................102

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LIST OF TABLES
PAGE
Table 1
Study groups and epochs foreseen in the study.....................................47
Table 2
Treatments foreseen in the study...........................................................47
Table 3
Sub-cohort for cell-mediated immunity ...................................................49
Table 4
Number of subjects required for enrolment.............................................53
Table 5
List of study procedures during visits to the vaccination centre 
(Amended 06 May 2015)........................................................................56
Table 6
Intervals between study visits.................................................................58
Table 7
Biological samples (Amended 06 May 2015.).........................................66
Table 8
Humoral immunity against Ebola (Amended 06 May 2015) ....................67
Table 9
Cell-mediated immunity against Ebola ...................................................67
Table 10
Humoral immunity against ChAd3 ..........................................................67
Table 11
Immunological read-outs (humoral immunity).........................................68
Table 13
Haematology/ biochemistry readouts .....................................................68
Table 14
Study vaccines (Amended 06 May 2015) ...............................................69
Table 15
Dosage and administration (Amended 06 May 2015).............................70
Table 16
Solicited local adverse events ................................................................75
Table 17
Solicited general adverse events (Amended 06 May 2015)....................75
Table 18
Reporting periods for collecting safety information (Amended 
06 May 2015).........................................................................................78
Table 19
Intensity scales for solicited symptoms in infants/toddlers and 
children less than 6 years of age (Amended 06 May 2015)....................80
Table 20
Intensity scales for solicited symptoms in children of 6 years of 
age or more (Amended 06 May 2015)....................................................81
Table 21
Timeframes for submitting adverse events of specific interest 
(clinical symptoms of thrombocytopenia), serious adverse 
events, and pregnancies to the contracted research organisation 
(Quintiles) (Amended 06 May 2015).......................................................85
Table 22
95% exact confidence intervals for the true AE rate at different 
possible observed AE rates within a group (300 subjects)......................95

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Table 23
True proportions associated with a 90% probability to observe a 
certain number of events........................................................................95
Table 24
Outsourced laboratories.......................................................................106
Table 25
Acceptable limits/normal ranges for eligibility determination 
(Amended 06 May 2015)......................................................................107
Table 26
Toxicity grading scales for hematology/ biochemistry parameters ........107
Table 27
Acceptable limits/normal ranges for eligibility determination.................108
Table 28
Toxicity grading scales for hematology/ biochemistry parameters ........108

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LIST OF FIGURES
PAGE
Figure 1
Study design overview ...........................................................................46
Figure 2
Screening procedures ............................................................................59
Figure 3
Overview of staggered design and independent data monitoring 
committee (IDMC) safety evaluations.....................................................91

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LIST OF APPENDICES
PAGE
APPENDIX A LABORATORY ASSAYS .....................................................................104
APPENDIX B CLINICAL LABORATORIES (Amended 06 May 2015).........................106
APPENDIX C ACCEPTABLE LIMITS FOR ELIGIBILITY AND TOXICITY 
GRADING SCALES FOR HAEMATOLOGY/ BIOCHEMISTRY 
PARAMETERS (Amended 06 May 2015).............................................107
APPENDIX D AMENDMENTS AND ADMINISTRATIVE CHANGES TO THE 
PROTOCOL.........................................................................................109

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LIST OF ABBREVIATIONS (Amended 06 May 2015)
AD5:
Adenovirus Type 5
AE:
Adverse Event
AIDS:
Acquired Immune Deficiency Syndrome
ALT:
Alanine Aminotransferase
ATP:
According-To-Protocol
BDBV:
Ebola Virus Bundibugyo
BNITM:
Bernhard Nocht Institute for Tropical Medicine
CBC:
Complete Blood Count
CDC:
Centers for Disease Control
ChAd3:
Chimpanzee Adenovirus Type 3
ChAd3-EBO-Z:
Investigational Recombinant Chimpanzee Adenovirus 
Type 3-vectored EBOV Vaccine
ChAd63 ME-TRAP:
Recombinant Chimpanzee Adenovirus Type 63 Vaccine 
Expressing the Plasmodium falciparum Pre-erythrocytic 
Antigen ME-TRAP (Multiple Epitope String with 
Thrombospondin-related Adhesion Protein)
CI:
Confidence Interval
CLIA:
Clinical Laboratory Improvement Amendments
CMI:
Cell-mediated Immunity
CRO:
Contract Research Organisation
EBOV:
Ebola Virus Zaire
EDD:
Estimated Date of Delivery
EENT:
Eyes/ Ears/ Nose/ Throat
EGA:
Estimated Gestational Age
ELISA:
Enzyme-linked Immunosorbent Assay
EU:
European Union

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EUA:
Emergency Use Authorization
EVD:
Ebola Virus Disease
FDA:
Food and Drug Administration
GCP:
Good Clinical Practice
GMT:
Geometric Mean Titre
GP:
Glycoprotein
GSK:
GlaxoSmithKline
HAART:
Highly Active Anti-retroviral Therapy
HIV:
Human Immunodeficiency Virus
HPLC:
High Performance Liquid Chromatography
IAF:
Informed Assent Form
IB:
Investigator Brochure
ICF:
Informed Consent Form
ICH:
International Conference on Harmonisation
ICS:
Intracellular Cytokine Staining
IDMC:
Independent Data Monitoring Committee
EC:
Independent Ethics Committee
IM:
Intramuscular
IND:
Investigational New Drug
IRB:
Institutional Review Board
IVRS:
Interactive Voice Response System
IWRS:
Interactive Web Response System
LAR:
Legally Acceptable Representative
LMP:
Last Menstrual Period
MACDP:
Metropolitan Atlanta Congenital Defects Program
MedDRA:
Medical Dictionary for Regulatory Activities

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MenACWY-TT:
Meningococcal Serogroups A, C, W-135, Y Tetanus 
Toxoid Conjugate vaccine
NA:
Not Applicable
NaCl:
Sodium Chloride
NVITAL:
NIAID Vaccine Immune T-cell and Antibody Laboratory 
(NIH)
PBMCs:
Peripheral Blood Mononuclear Cells
PSA:
Neisseria meningitidis Serogroup A Polysaccharide
PSC:
Neisseria meningitidis Serogroup C Polysaccharide
PSRI:
Periodic Safety Report Information
PSW:
Neisseria meningitidis Serogroup W-135 Polysaccharide
PsY:
Neisseria meningitidis Serogroup Y Polysaccharide
qPCR:
Quantitative Polymerase Chain Reaction
RDT:
Rapid Diagnostic Test
RESTV:
Ebola Virus Reston
RNA:
Ribonucleic Acid
SAE:
Serious Adverse Event
SmPC:
Summary of Product Characteristics
SOP:
Standard Operating Procedure
SUDV:
Ebola Virus Sudan 
TAFV:
Ebola Virus Taï Forest
TVC:
Total Vaccinated Cohort
US:
United States
UK:
United Kingdom
vp:
Viral Particles
VRC/NIAID:
Vaccine Research Center of the National Institute of 
Allergy and Infectious Diseases

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WHO:
World Health Organisation

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GLOSSARY OF TERMS
Adequate contraception:
Adequate contraception is defined as a contraceptive 
method with failure rate of less than 1% per year when 
used consistently and correctly and when applicable, in 
accordance with the product label for example: 

abstinence from penile-vaginal intercourse, when this 
is their preferred and usual lifestyle,

oral contraceptives, either combined or progestogen 
alone,

injectable progestogen,

implants of etenogestrel or levonorgestrel,

estrogenic vaginal ring,

percutaneous contraceptive patches,

intrauterine device or intrauterine system,

male partner sterilisation prior to the female subject’s 
entry into the study, and this male is the sole partner 
for that subject,
The information on the male sterility can come from 
the site personnel’s review of the subject’s medical 
records; or interview with the subject on her medical 
history.

male condom combined with a vaginal spermicide 
(foam, gel, film, cream or suppository),

male condom combined with a female diaphragm, 
either with or without a vaginal spermicide (foam, 
gel, film, cream, or suppository). 
Adequate contraception does not apply to subjects of 
childbearing potential with same sex partners, when this 
is their preferred and usual lifestyle.
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 unfavourable 
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 

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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. 
Observer-blind means that the subject and the vaccination 
centre and sponsor personnel involved in the clinical 
evaluation of the subjects are blinded while other study 
personnel may be aware of the treatment assignment. 
Single-blind means that vaccination centre and sponsor 
personnel are aware of the treatment assignment but the 
subject is not. 
Child in care:
A child who has been placed under the control or 
protection of an agency, organisation, 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.
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:
GlaxoSmithKline’s (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 6.7.2 and 11.5 for details on criteria for 
evaluability).

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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 authorisation 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. 
Menarche:
Menarche is the onset of menses for the first time in a 
young female and is preceded by several changes 
associated with puberty including breast development and 
pubic hair growth. Menarche usually occurs within 1 to 
2 years of breast development, thelarche. However, a 
young female can become pregnant before her first 
menses. Thus, a conservative definition of non-
childbearing potential in a pre-menarcheal female is a 
young female who has not yet entered puberty as 
evidenced by lack of breast development (palpable 
glandular breast tissue).
Protocol amendment:
The International Conference on Harmonisation (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. 
Randomisation:
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.
Solicited adverse event:
Adverse events 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.
Sub-cohort:
A group of subjects for whom specific study procedures 
are planned as compared to other subjects.
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 or as a control.

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Subject number:
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study.
Subset:
A subset is defined as a group of subjects for which 
additional assays are planned as compared to other 
subjects.
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 
randomisation or treatment allocation.
Treatment number:
A number identifying a treatment to a subject, according 
to the study randomisation or treatment allocation.
Unsolicited adverse 
event:
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 adverse 
event.

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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 vaccines will 
be written without the superscript symbol ® and in italics.
Trademarks of the GlaxoSmithKline 
group of companies
Generic description
Nimenrix®
Meningococcal A, C, W-135 & Y vaccine

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1.
INTRODUCTION
1.1.
Background
1.1.1.
Ebola virus Zaire outbreak 2014
The EVD outbreak in West Africa was first recognised on 22 March 2014 in Guinea. By 
02 December 2014, the epidemic had spread to Sierra Leone and Liberia, with a total of 
17 256 cases in those 3 countries (including 6 113 deaths). Travel-associated cases were 
observed in Mali, Senegal, Nigeria, Spain and United States (US), with localised 
transmission in Nigeria, Spain and US. The outbreaks of EVD in Senegal and Nigeria 
were declared over on 17 October and 19 October 2014, respectively. While children 
have been described as being less at risk of contracting of EVD McElroy, 2014], it has
been estimated that about 18% of cases in the current outbreak were people under 
15 years of age World Health Organisation (WHO) Ebola Response Team, 2014].
1.1.2.
Ebola virus and Zaire Ebola virus disease
The genus Ebola virus is one of 3 genera in the family Filoviridae, which along with the 
genera, Marburgvirus and Cuevavirus, are known to induce viral haemorrhagic fever. The 
5 distinct species included in the genus Ebola virus are Bundibugyo (BDBV), Reston 
(RESTV), Sudan (SUDV), Taï Forest (TAFV), and Zaire (EBOV).
Ebola virus is a large, negative-strand ribonucleic acid (RNA) virus composed of 7 genes 
encoding viral proteins, including a single glycoprotein (GP). The virus is responsible for 
causing EVD in humans. In particular, BDBV, EBOV, and SUDV have been associated 
with large outbreaks of EVD in Africa and reported case fatality ratios of up to 90% 
(WHO, 2014a). Transmission of Ebola virus to humans is not yet fully understood, but is 
likely due to incidental exposure to infected animals. EVD then spreads through 
human-to-human transmission, with infection resulting from direct contact with blood, 
secretions, organs or other bodily fluids of infected people, and indirect contact with 
environments contaminated by such fluids. 
EVD has an incubation period of 2 to 21 days (mean 4 to 10) which is followed by an 
abrupt onset of non-specific symptoms such as fever, chills, malaise, and myalgia. The 
subsequent signs and symptoms indicate multisystem involvement and include systemic 
(prostration), gastrointestinal (anorexia, nausea, vomiting, abdominal pain, diarrhoea), 
respiratory (chest pain, shortness of breath, cough, nasal discharge), vascular 
(conjunctival infection, postural hypotension, oedema), and neurological (headache, 
confusion, coma) manifestations. Haemorrhagic manifestations consistent with 
disseminated intravascular coagulation arise during the peak of the illness and include 
petechiae, ecchymoses, uncontrolled oozing from venepuncture sites, mucosal 
haemorrhages, and post-mortem evidence of visceral haemorrhagic effusions. A 
macropapular rash associated with varying severity of erythema and desquamate can 
often be noted by day 5 to 7 of the illness; this symptom is a valuable differential 
diagnostic feature and is usually followed by desquamation in survivors. Abdominal pain 
is sometimes associated with hyperamylasaemia and true pancreatitis. In later stages, 
shock, convulsions, severe metabolic disturbances, and, in more than half the cases, 

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diffuse coagulopathy supervene. Laboratory findings include low white blood cell and 
platelet counts and elevated liver enzymes. In general, the symptoms last for about 
7 to 14 days, after which recovery may occur. Death can occur 6 to 16 days after the 
onset of symptoms [Feldmann, 2011]. People are infectious as long as their blood and 
secretions contain the virus; the virus was isolated from semen 61 days after onset of 
illness in a man who was infected in a laboratory [WHO, 2014b].
1.1.3.
GlaxoSmithKline Biologicals’ investigational ChAd3-EBO-Z 
vaccine
The replication-defective investigational EBOV vaccine encoded by chimpanzee-derived 
adenovirus (ChAd3-EBO-Z) was developed by the Vaccine Research Center of the 
National Institute of Allergy and Infectious Diseases (VRC/NIAID) in the US using the 
ReiThera (formerly known as Okairos) adenovirus vaccine platform technology, which 
was acquired by GSK Biologicals in May 2013. The DNA fragment inserted in the 
chimpanzee adenovirus type 3 (ChAd3) vector encodes the EBOV GP, which is 
expressed on the virion surface and is critical for attachment to host cells and catalysis of 
membrane fusion. A single dose of 1010 viral particles (vp) of ChAd3-EBO-Z provided 
100% protection 4 to 5 weeks after vaccination in cynomolgous macaques 
[Stanley, 2014].
Serological studies showed a low seroprevalence in human sera for antibodies to ChAd3, 
and when present, antibody titres were low [Colloca, 2012]. Adenovirus type 5 (Ad5; a 
common adenovirus infection of humans) pre-existing immunity did not appear to 
cross-react with ChAd3 in mice [Peruzzi, 2009]. ChAd3-based vaccines were capable of 
inducing an immune response and protection comparable to human Ad5 vectored vaccine 
even in those with pre-existing immunity against Ad5.
Please refer to the current Investigator Brochure (IB) for information regarding the 
pre-clinical and clinical studies of ChAd3-EBO-Z.
1.2.
Rationale for the study and study design
1.2.1.
Rationale for the study
On 7 August 2014, the WHO requested that GSK “fully engages in WHO-coordinated 
efforts to test, license and make available safe and effective Ebola interventions” to assist 
in the control of the outbreak in Western Africa. Given the severity of the situation, time 
to vaccine deployment was an important aspect of the WHO request. In response to this 
call, an accelerated Phase 1, dose-finding vaccine development effort was initiated 
mid-August that involved WHO, GSK, VRC/NIAID, the University of Oxford, the 
University of Maryland and the University of Lausanne and the Centre for Vaccine 
Development in Mali. 
Although health care workers will be priority vaccination targets, mass vaccination 
strategies may be developed as one of the ways to protect populations and contain the 
epidemics. In this context, children will need to be vaccinated too. The present Phase 2, 
randomised, controlled trial will aim at collecting safety and immunogenicity data 
following a single intramuscular (IM) dose of the investigational ChAd3-EBO-Z vaccine.

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The study will be conducted in healthy children living in countries adjacent to the current 
Ebola outbreak zones. In parallel with the current study, the safety and immunogenicity 
of the investigational ChAd3-EBO-Z vaccine will be assessed in healthy adults living in 
countries adjacent to the current Ebola outbreak (study EBOLA Z CHAD3-005). Study 
EBOLA Z CHAD3-005 will start before the current study as to collect safety and 
reactogenicity data in 100 adults, after 1 week of follow-up, living in countries adjacent 
to the current Ebola outbreak before proceeding to vaccination of children.
1.2.2.
Rationale for the study design
1.2.2.1.
Investigational ChAd3-EBO-Z vaccine dose
Dose selection for paediatric use was based on information derived from dose-range 
studies conducted with the ChAd3-EBO-Z vaccine candidate in adults and on past
experience with other recombinant adenovirus-based candidate vaccines. (Amended 
06 May 2015.)
While investigational ChAd3-based candidate vaccines have not been administered to 
children before, other recombinant adenovirus-based candidate vaccines have been 
administered to children without safety concerns. A ChAd63 ME-TRAP malaria 
candidate vaccine has been safely administered to healthy adults in United Kingdom 
(UK) and Kenya, and to healthy infants and children in The Gambia and Burkina Faso. 
The IM dose of 5x1010 vp was determined to be optimal in both adults and children 
Afolabi, 2012; Ogwang, 2013; O’Hara, 2012; ClinicalTrials.gov NCT01635647; 
ClinicalTrials.gov NCT02083887; A. Hill, personal communication]. In the tuberculosis 
vaccine research field, up to two dose of 1x1011 vp of AERAS-402, a recombinant, 
replication-defective adenovirus type 35 expressing tuberculosis antigens, the highest 
dose evaluated, showed favourable safety in infants 6 to 9 months old Kagina, 2014]. 
This dose is also used in adults ClinicalTrials.gov NCT01683773].
Importantly, dose ranging in terms of vp is classically done on a logarithmic scale while 
arithmetic scales are usually used to describe weight differences between adults and 
children. In other words, the variability in weight between adults and children is small as 
compared to classical dose ranging in terms of number of vp, and inherent 
imprecision/ variability in number of vp. 
Four different investigational vaccine doses are currently being evaluated for safety, 
reactogenicity and immunogenicity in adults in Phase 1 studies. Based on data from 
these studies, the 1x1011 vp dose was selected for further assessment in Phase 2 and 
Phase 3 clinical studies in adults. This dose was determined using a high performance 
liquid chromatography (HPLC) analytical method for the vaccine lots used in the 
Phase 1 studies. The same dose will be used in this paediatric study. However, 
depending on the recommendation of the independent data monitoring 
committee (IDMC), a lower dose may be selected based on safety and reactogenicity 
data accrued during the age de-escalation process for children in younger age strata. It 
should be noted that the analytical method (quantitative polymerase chain 
reaction [qPCR]) that measures the concentration of virus particles per mL (vp/mL) 
present in the ChAd3-EBO-Z vials used in the current paediatric study is different 

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from the analytical method (HPLC) used for the Phase 1 studies. As a result, a dose of 
2x1011 vp will be used in this study, to administer the equivalent of the 1x1011 vp dose 
that was shown to be optimal in Phase 1 studies. As for other recombinant 
adenovirus-based vaccine candidates which showed adequate safety upon the use of adult 
doses in children as explained above, it is currently proposed that the same vaccine dose 
will be assessed in children 1 to 17 years of age in this study. However, a lower vaccine 
dose may be selected for children of younger age groups based on the safety and 
reactogenicity data accrued during the age de-escalation process. (Amended 
06 May 2015.)
As this study is conducted in Malaria endemic regions and the presence of Malaria 
infection may adversely affect the safety and immunogenicity evaluations of the 
investigational ChAd3-EBO-Z vaccine, all subjects will be tested for Malaria infection 
using a rapid diagnostic test (RDT) procedure during Screening. Subsequently, all 
subjects diagnosed with Malaria will receive antimalarial treatment according to 
local/ national standards (e.g., a 3-day treatment course of artemisinin-based 
combination therapy), during the Screening period. Hence, only subjects for whom the 
RDT was negative, or for whom the RDT was positive and who received a complete 
course of antimalarial treatment during the Screening period can be considered for 
study participation. (Amended 06 May 2015.)
1.2.2.2.
Administration of the investigational ChAd3-EBO-Z vaccine
Considering the risk of exposure to Ebola and the potential (based on animal data) for the 
investigational ChAd3-EBO-Z vaccine to afford at least partial protection, all children in 
the study will receive the investigational ChAd3 EBO-Z vaccine. The children in the 
Group EBO-Z/ MENACWY-TT will receive the investigational ChAd3-EBO-Z vaccine 
at Day 0 of the study, whereas the children in the Group MENACWY-TT/ EBO-Z will 
receive Nimenrix at Day 0 (as a control). At Month 6, the children in the 
Group MENACWY-TT/ EBO-Z will receive the investigational ChAd3-EBO-Z vaccine 
(provided that no safety concerns are raised. Refer to Section 9.10 for more information 
on the IDMC) whereas the children in the Group EBO-Z/ MENACWY-TT will receive 
Nimenrix.
In case the geographic range of EBOV transmission expands to encompass any of the 
regions where this trial is conducted, earlier administration of the investigational 
ChAd3-EBO-Z vaccine to the children in the Group MENACWY-TT/ EBO-Z will be 
considered in that region.
1.2.2.3.
Control vaccine
GSK Biologicals’ meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate 
(MenACWY-TT) vaccine (Nimenrix) will be used as control. 
Nimenrix is indicated for the active immunisation against invasive meningococcal 
diseases caused by Neisseria meningitidis (meningococcus) serogroups A, C, W-135 and 
Y. Invasive meningococcal disease, including meningitis and meningococcal septicaemia, 
often follows invasive infection by Neisseria meningitidis and is a major cause of death 
and morbidity throughout the world. Neisseria meningitidis serogroups A, B, C, W-135 

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and Y are the most common causes of invasive meningococcal disease worldwide: 
serogroup A is most common in Africa and Asia, while serogroups B and C account for 
more than 90% of the cases in Europe and Latin America [Anderson, 1998; Connolly, 
, 1999; Harrison, 2009; Peltola, 1998]. Nimenrix is licensed in 50 countries (first approval 
in April 2012) and is currently available in at least 23 countries.
Using Nimenrix as a control vaccine in this study will provide a theoretical benefit to the 
children in the study and adequately support safety comparison.
1.2.2.4.
Stratification for age and staggered vaccination
In order to ensure equal distribution of the population, enrolment will be stratified by age 
so that equal number of children are enrolled in each age stratum (1 to 5 years, 
6 to 12 years and 13 to 17 years of age). 
In order to ensure maximum safety for the subjects in this study, vaccination at Day 0 
will be done in a staggered manner, starting with vaccination of the children in the oldest 
age stratum. For each age stratum, an IDMC will conduct a review of all available safety 
data once data is available up to at least 7 days after vaccination of at least 50 subject 
(25/ group) in that age stratum. The start of vaccination in the younger age stratum, 
possibly with a lower vaccine dose, depends on the outcome of this IDMC review. For 
more detailed information on the staggered design of the study and on the safety 
monitoring, refer to Section 9.10.
1.2.2.5.
Human immunodeficiency virus testing
There will be no routine testing for human immunodeficiency virus (HIV) in this trial. 
Tests will be performed when clinically indicated to guide subject management. 
Voluntary counselling and testing, highly active anti-retroviral therapy (HAART) and 
prevention of mother to child transmission (PMTCT) will be available at all study centres 
according to national policies.
1.3.
Benefit : Risk assessment
All subjects in the study will receive a single dose of the investigational ChAd3-EBO-Z 
vaccine (either at Day 0 or at Month 6 of the study) and a single dose of Nimenrix (at 
Day 0 or at Month 6 of the study).
For general information on the risks and benefits of the investigational ChAd3-EBO-Z 
vaccine and Nimenrix, please refer to the current Investigator Brochure (IB), Periodic 
Safety Report Information (PSRI) and to the approved summary of product 
characteristics (SmPC)/ Prescribing Information/ package insert, as applicable.
The following section outlines the risk assessment and mitigation strategy for this study 
protocol.

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1.3.1.
Risk Assessment
Important Potential/Identified 
Risk
Data/Rationale for Risk
Mitigation Strategy
Both study vaccines
As with all injectable vaccines, 
allergic reactions to vaccination 
can occur.
Acute allergic reactions such as a 
rare case of anaphylactic event may 
occur with any vaccine 
administration. These are serious, but 
rare occurrences estimated in the 
range of 1 to 10 cases per million of 
vaccinations, depending on the 
vaccine studied [Rüggeberg, 2007]. 
No such event has been observed as 
of 14 November 2014 in the on-going 
Phase 1 trials with the investigational 
ChAd3-EBO-Z vaccine.
Warnings regarding allergic reactions. 
Anaphylaxis following vaccine 
administration is an exclusion 
criterion for study participation and a 
contraindication to vaccination. 
The onset of vaccine-related allergic 
symptoms is typically quite prompt. In 
order to treat subjects with a serious
allergic reaction to vaccination, all 
subjects will need to remain under 
observation (i.e., visibly followed; no 
specific procedure) at the vaccination 
centre for at least 30 minutes after 
vaccination.
Syncope
Syncope (fainting) can occur 
following, or even before, any 
vaccination especially in adolescents 
as a psychogenic response to the 
injection needle (also outlined in the 
Nimenrix Reference Safety 
Information). This can be 
accompanied by several neurological
signs such as transient visual 
disturbance, paraesthesia and tonic-
clonic limb movements during 
recovery.
It is important that procedures are in 
place to avoid injury from faints. All 
subjects will need to remain under 
observation (i.e., visibly followed; no 
specific procedure) at the vaccination 
centre for at least 30 minutes after 
vaccination.
Nimenrix
Extensive limb swelling
The active ingredients of Nimenrix
are conjugated to a tetanus toxoid 
carrier protein and exaggerated local 
(Arthus-like) reactions are 
occasionally reported following 
receipt of a diphtheria- or tetanus-
containing vaccine. These reactions 
present as extensive painful swelling, 
often from shoulder to elbow. They 
generally begin from 2 to 8 hours 
after vaccination and are reported 
most often in adults, particularly those 
who have received frequent doses of 
diphtheria or tetanus toxoid. 
Subjects’ parent(s)/ LAR(s) should 
report any untoward symptoms 
experienced by the child after 
receiving the vaccine immediately to 
the Investigator.
ChAd3-EBO-Z = investigational recombinant chimpanzee adenovirus type 3-vectored Ebola virus Zaire (EBOV)
vaccine; GSK = GlaxoSmithKline

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1.3.2.
Benefit assessment
Benefits linked to the investigational ChAd3-EBO-Z vaccine
The subjects in this study may not directly benefit from vaccination with the 
investigational ChAd3-EBO-Z vaccine as the vaccine has not been assessed in subjects 
exposed to EVD yet and it is hence not known whether it is effective in protecting against 
EVD. Moreover, this study will be conducted in countries adjacent to the current Ebola 
outbreak zone and the subjects in this study possibly may never come in contact with 
EBOV.
An indirect benefit is that the information obtained in this study will aid the development 
of a vaccine against EVD. 
Benefits linked to Nimenrix
Meningococcal disease continues to be endemic in both industrialised regions (such as 
North America and Europe) and developing regions and is associated with high case 
fatality even where adequate medical services and antibiotics are available. However, a 
significant decline in the incidence of confirmed meningococcal disease has been 
observed in those countries that include meningococcal vaccination in their routine 
immunisation schedule. Overall, clinical trial data and post-marketing experience 
continue to demonstrate the substantial benefit and acceptable safety profile of Nimenrix
vaccination.
Other benefits
All subjects who provide informed consent for study participation will be tested for 
Malaria infection using an RDT procedure at the time of Screening. Subjects who are 
diagnosed with Malaria will receive antimalarial treatment according to local/ national 
standards (e.g., a 3-day treatment course of artemisinin-based combination therapy), 
during the Screening period, to clear the infection prior to vaccination. (Amended 
06 May 2015.)
Another benefit for the subjects may include the gaining of information about their 
general health status through the medical evaluations/ assessments associated with this 
study (physical examination, blood testing [haematology and biochemistry data]). All 
subjects participating to the Screening Visit of this study will be medically examined 
including testing for haematological (complete blood count [CBC], including differential 
count and platelet count) and biochemical (alanine aminotransferase [ALT] and 
creatinine) parameters. Those subjects with clinically significant disease who are not 
eligible for study participation will be referred for medical care to local facilities. Those 
subjects who are eligible and participate in the study will receive medical follow-up
during the study.

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1.3.3.
Overall Benefit : Risk conclusion
The investigational ChAd3-EBO-Z vaccine is currently in an early stage of clinical 
development and no vaccine efficacy has been demonstrated. Measures are taken to 
minimise the risk to subjects participating in this study.
2.
OBJECTIVES
2.1.
Primary objective

To assess the safety and reactogenicity of a single IM dose of the ChAd3-EBO-Z 
vaccine, overall and in children aged 1 to 5, 6 to 12, and 13 to 17 years separately.
Refer to Section 11.1 for the definition of the primary endpoints.
2.2.
Secondary objective

To assess the humoral immunogenicity of a single IM dose of the ChAd3-EBO-Z
vaccine, in terms of anti-GP EBOV antibody responses, overall and in children aged 
1 to 5, 6 to 12, and 13 to 17 years separately.
Refer to Section 11.2 for the definition of the secondary endpoint.
2.3.
Tertiary objectives

To assess the persistence of the humoral immune response induced by a single IM
dose of the ChAd3-EBO-Z vaccine, in terms of anti-GP EBOV antibody responses, 
overall and in children aged 1 to 5, 6 to 12, and 13 to 17 years separately.

To assess EBOV specific cell-mediated immunity (CMI) of a single IM dose of the 
ChAd3-EBO-Z vaccine, overall and in children aged 1 to 5, 6 to 12, and 13 to 
17 years separately.

To assess the pre-existing immunity to the ChAd3 virus vaccine vector prior 
vaccination, ChAd3-specific immune responses after vaccination and explore its 
potential impact on Ebola-specific immune responses, overall and in children aged 
1 to 5, 6 to 12, and 13 to 17 years separately.

If deemed necessary, to further characterise the immune response to/ the safety 
profile of the investigational ChAd3-EBO-Z vaccine.
Refer to Section 11.3 for the definition of the tertiary endpoints.

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3.
STUDY DESIGN OVERVIEW
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 5.5), are essential and required for 
study conduct. 
Figure 1
Study design overview

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
Experimental design: Phase 2, randomised, observer-blind, controlled, multi-country
study with 2 groups and 3 age strata.

Duration of the study: For each subject enrolled it will be approximately 12 months 
from the Day 0 visit

Epoch 001: Primary starting at Screening and ending at the Month 12 visit.

Study groups:

Group EBO-Z/ MENACWY-TT: approximately 300 children in total; 
approximately 100 children per age stratum (1 to 5 years, 6 to 12 years, and 
13 to 17 years of age).

Group MENACWY-TT/ EBO-Z: approximately 300 children in total; 
approximately 100 children per age stratum (1 to 5 years, 6 to 12 years, and 
13 to 17 years of age).
Table 1
Study groups and epochs foreseen in the study
Study group
Number of 
subjects
Age
Epochs
Epoch 001
EBO-Z/ 
MENACWY-TT
~300
~100 children per age stratum: 13 to 17, 6 to 12, 1 to 
5 years
x
MENACWY-TT/ 
EBO-Z
~300
~100 children per age stratum: 13 to 17, 6 to 12, 1 to 
5 years
x
= approximately
Table 2
Treatments foreseen in the study
Treatment name
Vaccine/Product 
name
Study Groups
EBO-Z/ MENACWY-TT
MENACWY-TT/ EBO-Z
ChAd3-EBO-Z
ChAd3-EBO-Z
x (Day 0)
x (Month 6)
Nimenrix
MenACWY-TT
x (Month 6)
x (Day 0)
NaCl
ChAd3-EBO-Z = investigational recombinant chimpanzee adenovirus type 3-vectored Ebola virus Zaire (EBOV)
vaccine; NaCl = sodium chloride

Control: Active control (Nimenrix).

Vaccination schedule: All subjects will receive 2 vaccinations, 1 at the Day 0 visit 
and 1 at the Month 6 visit. All subjects will receive 1 dose of the investigational 
ChAd3-EBO Z vaccine and 1 dose of Nimenrix:

Subjects in Group EBO-Z/ MENACWY-TT will receive the investigational 
ChAd3-EBO-Z vaccine at the Day 0 visit and Nimenrix at the Month 6 visit.

Subjects in Group MENACWY-TT/ EBO-Z will receive Nimenrix at the Day 0 
visit and the investigational ChAd3-EBO-Z vaccine at the Month 6 visit.

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
Treatment allocation: Subjects will be randomised (1:1) at Day 0. In order to 
ensure equal distribution of the population, enrolment will be stratified by age so that 
an equal number of children are enrolled in each age stratum (1 to 5 years, 
6 to 12 years, and 13 to 17 years of age). In addition, the randomisation will use a 
minimisation procedure accounting for gender and centre.

Staggered vaccination: Vaccination at Day 0 will be done in a staggered manner, 
starting with vaccination of the children in the oldest age stratum (13 to 17 years of 
age). In order to proceed to vaccination of the subjects in the younger age stratum 
(6 to 12 years of age), possibly with a lower vaccine dose, a favourable outcome of 
the IDMC review of safety data up to at least 7 days after vaccination from at least 
50 subjects (25/ group) in the oldest age stratum needs to be obtained. The same will 
be done for moving from the 6 to 12 years of age stratum to vaccination of the 
youngest children (1 to 5 years of age). Refer to Section 9.10 for more information.

Blinding: 

Observer-blind from study start until the interim analysis that will be conducted 
when safety, reactogenicity and immunogenicity (including at least 
anti-GP EBOV data at Day 30) data is available from all subjects up to 30 days 
after vaccination at Day 0 (refer to Section 11.11.1 for more information on this 
interim analysis).

Single-blind as of the interim analysis at Day 30. (Amended 06 May 2015.)

Sampling schedule:

A blood sample (fingerprick) will be taken at Screening for Malaria RDT.
(Amended 06 May 2015.)

Blood samples for haematology/ biochemistry assessment will be taken from all 
subjects at Screening, at the Day 3, Day 6, the Day 30, the Month 6, the 
Month 6 + 6 days, the Month 6 + 30 days, and the Month 12 visits.

Blood samples for humoral immunity will be taken from all subjects at the 
Day 0, the Day 30, the Month 6, the Month 6 + 30 days, and the Month 12 visits.

Blood samples for CMI will be taken from a sub-cohort of 90 subjects per group 
(30 children per age stratum per group) at the Day 0, the Day 30, the Month 6, 
the Month 6 + 30 days, and the Month 12 visits.

Type of study: self-contained.

Data collection: eSource.

Safety monitoring: An IDMC will be appointed to monitor the safety and 
tolerability of the investigational ChAd3-EBO-Z vaccine. The IDMC will consist of 
clinical experts and a statistician who are not involved in the conduct of the study.
Refer to Section 9.10 for detailed description of the safety monitoring.

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4.
STUDY COHORT
4.1.
Number of subjects/centres
The target is to enrol approximately 600 eligible children (approximately 300 per group 
and approximately 200 per age stratum). Refer to Section 11.4 for a detailed description 
of the criteria used in the estimation of sample size. This study will be conducted in West 
and Central Africa.
4.2.
Sub-cohort for cell-mediated immunity
A sub-cohort is defined as a group of subjects for whom specific procedures are planned 
as compared to other subjects. For each group, the first approximately 30 children 
enrolled in each age stratum will be part of the sub-cohort for CMI (i.e., approximately 
90 children per group and approximately 180 children in total; possibly at selected 
vaccination centres only). A blood sample for assessment of CMI should be taken from 
these subjects at certain study visits.
Table 3
Sub-cohort for cell-mediated immunity
Sub-cohort name
Description
Estimated number of subjects
Sub-cohort for CMI
A blood sample for assessment of CMI will be 
taken from these subjects at certain study visits.
30 subjects per age stratum per group 
(90 subject per group and 
180 subjects in total)
= approximately; CMI = cell-mediated immunity
A subset is defined as a group of subjects for which additional assays are planned as 
compared to other subjects. Refer to Section 5.2.3 for the description of the subset for 
additional humoral immunogenicity assays.
4.3.
Inclusion criteria for enrolment
Deviations from inclusion criteria are not allowed because they can potentially jeopardise 
the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential.
All subjects must satisfy ALL the following criteria at study entry:

Subject’s parent(s)/ legally acceptable representative(s) (LAR[s]) who, in the opinion 
of the Investigator, can and will comply with the requirements of the protocol (e.g.,
availability for Diary Card completion, return for follow-up visits, availability for 
clinical follow-up throughout the study period). 

Written/ thumb printed informed consent obtained from the subject’ parent(s)/ 
LAR(s) prior to performing any study specific procedure. In addition, written/ thumb 
printed informed assent should be obtained if appropriate (from all subjects aged 
13 to 17 years and from younger subjects as per local requirements).

A male or female child aged 1 to 17 years inclusive at the time of Screening.
(Amended 06 May 2015.)

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
Subjects with a negative RDT test for Malaria within 30 days prior to 
randomisation into the study.
OR
Subjects with a positive RDT test for Malaria who completed antimalarial 
treatment at least 5 days prior to randomisation into the study.
(Amended 06 May 2015.)

Healthy subjects as per Investigator judgement, as established by medical history,
clinical examination and haematology/ biochemistry laboratory parameters screening
before entering into the study.

Female subjects of non-childbearing potential may be enrolled in the study. 

Non-childbearing potential is defined as pre-menarche or ovariectomy.
Please refer to the glossary of terms for the definition of menarche.

Female subjects of childbearing potential may be enrolled in the study, if the subject:

has practiced adequate contraception for 30 days prior to the Day 0 visit, and

has a negative pregnancy test at the Day 0 visit, and

has agreed to continue adequate contraception until 30 days after the Month 6
visit. 
Please refer to the glossary of terms for the definition of adequate contraception.
4.4.
Exclusion criteria for enrolment
Deviations from exclusion criteria are not allowed because they can potentially jeopardise 
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.
(Amended 06 May 2015.)

Use of any investigational or non-registered product (drug or vaccine) other than the 
study vaccine during the period starting 30 days before the Day 0 visit, or planned 
use during the study period.

Previous vaccination with an investigational EBOV or Marburg vaccine, or previous 
vaccination with a chimpanzee adenoviral vectored investigational vaccine.

Known prior EBOV or SUDV disease.

Travel to country affected by the EBOV epidemic or direct contact with person with 
EVD within 21 days prior to the Day 0 visit.

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
History of any reaction or hypersensitivity (such as anaphylaxis, urticaria [hives], 
respiratory difficulty, angioedema, or abdominal pain) likely to be exacerbated by 
any component of the study vaccine.

Planned administration/ administration of a vaccine not foreseen by the study 
protocol in the period starting 30 days before and ending 30 days after each 
vaccination visit.

Acute or chronic illness determined by medical history, clinical examination and 
laboratory screening tests including, but not limited to:

Clinically significant immunosuppressive or immunodeficient condition (e.g.,
clinical acquired immune deficiency syndrome [AIDS]).

Major congenital defects.

Malnutrition (defined as weight for age Z-score less than -3, or other clinical 
signs of malnutrition).

Any clinically significant haematological or biochemical laboratory abnormality
(see APPENDIX C for acceptable limits for eligibility determination).

Pregnant female.

Any condition that in the Investigator’s opinion may potentially compromise 
subject safety or interfere with subject assessment or compliance. 
(Amended 06 May 2015.)
5.
CONDUCT OF THE STUDY
5.1.
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 International Conference on 
Harmonisation (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 
Harmonised Tripartite Guideline for clinical investigation of medicinal products in the 
paediatric population (ICH E11) and all other applicable ethical guidelines.
GSK Biologicals/ the contracted research organisation (CRO) engaged to conduct the
study will obtain favourable opinion/ approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements, prior to a 
vaccination centre 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 
favourable opinion/approval of study protocol and any subsequent amendments.

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
Subject’s parent(s)/ LAR(s) informed consent and subject informed assent, as 
appropriate.

Investigator reporting requirements as stated in the protocol.
GSK/ the CRO 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 from each 
subject’s parent(s)/ LAR(s) and subject informed assent, as appropriate, must be obtained 
prior to participation in the study.
GSK Biologicals/ the CRO 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 judgement, local regulations and requirements should guide 
the final structure and content of the local version of the ICF. 
In accordance with the ICH Harmonised Tripartite Guidelines for Good Clinical Practice, 
subjects who can only be enrolled in the study with the consent of their parent(s)/ LAR(s) 
(e.g., minors), should be informed about the study to the extent compatible with the 
subject’s understanding and, if capable, the subject should sign and personally date a 
written informed assent form (IAF). It should be assessed whether an assent is required 
depending of the age of the study population and the local requirements. In this study, 
written/ thumb printed informed assent should be obtained from all subjects in the oldest 
age category (13 to 17 year olds) and from younger subjects as per local requirements in 
addition to the informed consent that is to be signed/ thumb printed by their parent(s)/ 
LAR(s).
GSK Biologicals strongly recommends that if a subject reaches the age of consent during 
the study, he/ she will be asked to provide consent at the next study visit (if applicable). 
This procedure should be applied according to local laws and regulations.
The Investigator has the final responsibility for the final presentation of the ICF and IAF, 
respecting the mandatory requirements of local regulations. The ICF and IAF generated 
by the Investigator with the assistance of the sponsor’s/ the CRO’s representative must be 
acceptable to GSK Biologicals and be approved (along with the protocol, and any other 
necessary documentation) by the IRB/ IEC.
5.2.
Subject identification and randomisation of treatment
5.2.1.
Subject identification
Subject identification numbers will be assigned sequentially to the subjects who have 
consented to participate in the study. The subject numbers will be assigned as a 
combination of the centre number and a sequential number.

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5.2.2.
Randomisation of treatment
5.2.2.1.
Randomisation of supplies
The ChAd3-EBO-Z vaccine and Nimenrix will be numbered sequentially and packed 
separately. 
To allow GSK Biologicals to take advantage of greater rates of recruitment than 
anticipated at individual centres in this multi-centre study and to thus reduce the overall 
study recruitment period, an over-packaging of supplies will be prepared.
5.2.2.2.
Treatment allocation to the subject
The treatment name will be allocated by dose to each subject.
5.2.2.2.1.
Study group and treatment name allocation at Day 0
The target will be to enrol approximately 600 eligible children who will be randomly 
assigned to 2 study groups in a (1: 1) ratio (approximately 300 per group and 
approximately 200 per age stratum).
The enrolment will be performed to ensure equal distribution of the population across the 
3 age strata (1 to 5 years, 6 to 12 years, and 13 to 17 years of age). Therefore the 
expected distribution of subjects is as shown in Table 4.
Table 4
Number of subjects required for enrolment
Age Stratum
Group
N
1 to 5 years
EBO-Z/ MENACWY-TT
100
MENACWY-TT/ EBO-Z
100
6 to 12 years
EBO-Z/ MENACWY-TT
100
MENACWY-TT/ EBO-Z
100
13 to 17 years
EBO-Z/ MENACWY-TT
100
MENACWY-TT/ EBO-Z
100
N = number of subjects to be enrolled
Allocation of the subject to a study group at the vaccination centre will be performed 
using a central Interactive Web Response System (IWRS). In addition to the IWRS, an 
Interactive Voice Response System (IVRS) will be available in case of possible 
connectivity issues with the IWRS. Within each age stratum (1 to 5 years, 6 to 12 years,
and 13 to 17 years of age), the randomisation algorithm will use a minimisation 
procedure accounting for gender and centre. The minimisation is a dynamic allocation 
method that will ensure that, within each age stratum, there is a good balance between 
groups in the number of subjects by gender and centre. Both minimisation factors will 
have equal weight in the minimisation algorithm.
After obtaining the signed/ thumb printed and dated ICF from the subject’s parent(s)/ 
LAR(s) and signed/ thumb printed and dated IAF from the subject (if applicable) and 
having checked the eligibility of the subject, the site staff in charge of the vaccine
administration will access IWRS/ IVRS. Upon providing the subject subject’s age (1 to 
5 years versus 6 to 12 years versus 13 to 17 years of age), gender, centre and the subject

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identification number, the randomisation system will determine the study group and will 
provide the treatment name to be administered. Access to the IVRS/ IWRS unblinded
treatment information will be limited to unblinded site staff. (Amended 06 May 2015.)
After vaccine administration, the treatment number of the vaccine administered (indicated 
on the label) should be recorded in IWRS/ IVRS, and for drug supply management 
purposes, by the unblinded study staff preparing and administering the vaccine. The 
applicable screen will only be available for unblinded staff in order to maintain the study 
blind.
When IWRS is not available, please refer to the relevant user guide for instructions for 
the use of the IVRS. 
Note that as soon as the target number of 200 subjects in a specific age group has been 
reached, the enrolment will be frozen for this age group.
5.2.2.2.2.
Treatment name allocation at Month 6
At Month 6, the study staff in charge of the vaccine administration will access 
IWRS/ IVRS, provide the subject identification number, and the system will provide a 
treatment name consistent with the allocated study group.
The number of the administered treatment should be recorded in the IWRS/IVRS by 
study staff preparing the vaccine.
5.2.3.
Allocation of subjects to assay subsets
A subset is defined as a group of subjects for which additional assays are planned as 
compared to other subjects. Approximately 90 subjects per group (approximately 
30 children per age stratum per group) will be part of the subset for additional humoral 
immunogenicity assays. These will be the same subjects as the subjects in the sub-cohort 
for CMI (refer to Section 4.2).
5.3.
Method of blinding 
The blinding level will change in the course of the study:

Observer-blind from study start until the interim analysis that will be conducted 
when safety, reactogenicity and immunogenicity (including at least anti-GP EBOV 
data at Day 30) data is available from all subjects up to 30 days after vaccination at 
Day 0 (refer to Section 11.11.1 for more information on this interim analysis). By 
observer-blind, it is meant that the vaccine recipient and those responsible for the 
evaluation of any study endpoint will all be unaware of which vaccine was 
administered. To do so, vaccine preparation and administration at Day 0 will be done 
by authorised medical personnel who will not participate in any of the study clinical 
evaluation assays.

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To ensure blinding of the site staff when preparing and administering the study 
vaccine details of vaccine management will be defined in a site vaccine 
management plan before site initiation.
(Amended 06 May 2015.)

Single-blind as of the interim analysis. At the time of the interim analysis, the study 
will become single-blind to ensure full data availability. By single-blind, it is meant 
that vaccination centre and sponsor personnel are aware of the treatment assignment 
but the subject is not. 
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.
5.4.
General study aspects
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying manuals. The manuals provide the Investigator and the site 
personnel with administrative and detailed technical information that does not impact the 
safety of the subjects.

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5.5.
Outline of study procedures
5.5.1.
List of study procedures
Table 5
List of study procedures during visits to the vaccination centre (Amended 06 May 2015)
Type of contact
Visit
Visit
Visit
Visit
Visit
Contact *
Visit
Visit 
Visit
Contact *
Visit
Timepoint
Screening 1 Day 0 1 Day 3 Day 6 Day 30
Month 3
Month 6
Month 6 + 
6 days 
Month 6 + 
30 days
Month 9
Month 12
Informed consent
●
Informed assent 10
●
RDT for Malaria
●
Malaria treatment 11
●
Inclusion/exclusion criteria 12
●
●
Demographic data
●
Medical history 12
●
●
Physical examination (including vital signs 2) 
●12
●3
O
O
O
●
O
O
O
Pregnancy test 4
●
● 5
● 
Pre-vaccination body temperature
●
● 
Check contraindications to vaccination
O
O
Study group and treatment name allocation 6
O
O 
Vaccination
●
● 
Recording of administered treatment number
O
O
30 minutes post-vaccination observation
O
O
Blood sampling:
  Blood for haematology/ biochemistry 
●12
●
●
●
●
●
●
●
  Blood for humoral immunity 
●
●
●
●
●
  Blood for CMI 7
●
●
●
●
●
Safety assessment:
  Record solicited AEs (day 0 to day 6)
●
●
●
● 
●
  Record unsolicited AEs (day 0 to day 29)
●
●
●
●
● 
●
●
Record AEs of specific interest (clinical symptoms of 
thrombocytopenia)
●
●
  Record SAEs
● 8
●
●
●
●
●
●
●
●
●
●
  Record pregnancies
●
●
●
●
●
●
●
●

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Type of contact
Visit
Visit
Visit
Visit
Visit
Contact *
Visit
Visit 
Visit
Contact *
Visit
Timepoint
Screening 1 Day 0 1 Day 3 Day 6 Day 30
Month 3
Month 6
Month 6 + 
6 days 
Month 6 + 
30 days
Month 9
Month 12
Record concomitant medications/ products/ vaccinations 9
●
●
●
●
●
●
●
●
●
●
Screening Conclusion
●
Study Conclusion
●
= approximately; AE = adverse event; CMI = cell-mediated immunity; CRO = Contract research organisation; EVD = Ebola virus disease; GSK = GlaxoSmithKline; RDT = Rapid 
Diagnostic Test; SAE = serious adverse event
● is used to indicate a study procedure that requires documentation in eSource.
O is used to indicate a study procedure that does not require automatic transfer of the study data fields from the source database into the study database at the CRO.
* Home visit by field worker or phone call.
1 The Screening visit and the Day 0 visit may take place on the same day (allowed interval 0 to 30 days).
2Refer to Section 5.6.6 for the specific assessments included in the physical examination. 
3Only if Visit 1 and Screening take place on a different day.
4 Only for women of childbearing potential.
5Only if Visit 1 takes place more than 1 week after the Screening Visit.
6Treatment name allocation with randomisation at Day 0; treatment name allocation without randomisation at Month 6.
7Only for subjects in the sub-cohort for cell-mediated immunity (CMI).
8From Screening to Day 0, only those SAEs that are considered related to study participation or to concurrent use of GlaxoSmithKline (GSK) medication/ vaccine need to be recorded.
9Concomitant medications/ products/ vaccinations as described in Section 6.7.1 and 6.7.2 need to be recorded in eSource.
10Only for subjects in the oldest age stratum (13 to 17 year olds) and younger subjects as per local requirements.
11 Subjects diagnosed with Malaria at Screening must receive antimalarial treatment according to local/ national standards (e.g., a 3-day treatment course of 
   artemisinin-based combination therapy), during the Screening period.
12 Study procedure must be performed at least 5 days after completion of Malaria treatment for all subjects diagnosed with Malaria at Screening.

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5.5.2.
Intervals between study visit
Table 6
Intervals between study visits
Interval
Allowed interval
Screening Visit Day 0
0 to 30 days
Visit Day 0 Visit Day 3
3 days
Visit Day 0 Visit Day 6
6 to 8 days
Visit Day 0 Visit Day 30
30 to 44 days 1
Visit Day 0 Contact Month 3
3 months ± 30 days
Visit Day 0 Visit Month 6
6 months ± 30 days 1
Visit Month 6 Visit Month 6 + 6 days
6 to 8 days
Visit Month 6 Visit Month 6 + 30 days
30 to 44 days 1
Visit Month 6 Contact Month 9
3 months ± 30 days
Visit Month 6 Visit Month 12
6 months ± 30 days 1
1 Subjects will not be eligible for inclusion in the according-to-protocol cohort for immunogenicity if they make the study 
visit outside this interval.
5.6.
Detailed description of study procedures
5.6.1.
Informed consent
The signed/witnessed/thumb printed informed consent of the subject’s parent(s)/ LAR(s)
must be obtained before study participation. For subjects in the oldest age stratum (13 to 
17 years) and for younger subjects as per local requirements, the signed informed assent 
of the subject should be obtained in addition to the signed informed consent by his/her 
parent(s)/ LAR(s). Refer to Section 5.1 for the requirements on how to obtain informed 
consent as appropriate.
5.6.2.
Malaria Screening and treatment (Amended 06 May 2015)
After obtaining the informed consent of the subject’s parent(s)/ LAR(s), all subjects 
should first be tested for Malaria infection using the WHO pre-qualified RDT. 
All subjects diagnosed with Malaria using the RDT must receive antimalarial 
treatment according to local/ national standards (e.g., a 3-day treatment course of 
artemisinin-based combination therapy), during the Screening period. In addition, a 
pregnancy test should be performed for women of childbearing potential in case the 
RDT is positive, so that an antimalarial treatment alternative to artemisinin-based 
combination therapy (e.g., quinine plus clindamycin) is proposed in case the pregnancy 
test is positive. For subjects whose RDT is positive, the following Screening procedures 
should be postponed until at least 5 days after completion of the Malaria treatment 
(Figure 2):

Blood sampling for haematology and biochemistry testing.

Physical examination.

Review of eligibility criteria.

Completion of the medical history.

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Figure 2
Screening procedures
ICF = Informed Consent Form; RDT = Rapid Diagnostic Test

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The outcome of the Malaria RDT and completion of Malaria treatment needs to be 
recorded in eSource. 
(Amended 06 May 2015.)
5.6.3.
Check inclusion and exclusion criteria
Check all inclusion and exclusion criteria as described in Sections 4.3 and 4.4 before 
enrolment. 
For subjects diagnosed with Malaria at Screening, a full eligibility check should be 
postponed until at least 5 days after completion of Malaria treatment.
(Amended 06 May 2015.)
5.6.4.
Collect demographic data
Record demographic data such as date of birth (full date of birth will be collected in 
eSource, but only month and year of the date of birth will be exported to GSK’s clinical 
database. The age as calculated in eSource will be used for analysis purposes as the 
full date of birth will not be exported), gender, geographic ancestry, and ethnicity, in the 
subject’s eSource.
(Amended 06 May 2015.)
5.6.5.
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 study vaccination in eSource. 
For subjects diagnosed with Malaria at Screening, completion of medical history 
should be postponed until at least 5 days after completion of Malaria treatment.
(Amended 06 May 2015.)
5.6.6.
Physical examination
Perform a complete physical examination of the subject at the Screening, the Day 0, and 
the Month 6 visit, including assessment of height, weight, body temperature and resting 
vital signs: heart rate, respiratory rate after at least 10 minutes of rest, and an assessment 
of the following systems: head/ neck/ thyroid; eyes/ ears/ nose/ throat (EENT); 
respiratory; cardiovascular; lymph nodes; abdomen; skin; musculoskeletal; and 
neurological. Breast, anorectal, and genital examinations will be performed when 
medically indicated. Collected information needs to be recorded in eSource (height only 
needs to be recorded at Screening).

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For subjects diagnosed with Malaria at Screening, physical examination should be 
postponed until at least 5 days after completion of Malaria treatment.
(Amended 06 May 2015.)
During all other study visits, perform a physical examination only if the subject indicates 
during questioning that there might be some underlying pathology(ies) or if deemed 
necessary by the Investigator or delegate.
(Amended 06 May 2015.)
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. 
5.6.7.
Pregnancy test 
Female subjects of childbearing potential are to have a pregnancy test prior to any study 
vaccine administration. The study vaccine may only be administered if the pregnancy test 
is negative. Note: The pregnancy test must be performed even if the subject is 
menstruating at the time of the study visit.
5.6.8.
Check contraindications to vaccination 
Contraindications to vaccination must be checked at the beginning of each vaccination 
visit. Refer to Sections 6.6 for more details. 
5.6.9.
Assess pre-vaccination body temperature
The axillary body temperature of all subjects needs to be measured prior to any study 
vaccine administration. If the subject has fever [fever is defined as temperature 
37.5°C/99.5°F on the day of vaccination, the vaccination visit will be rescheduled 
within the allowed interval for this visit (see Table 6).
5.6.10.
Study group and treatment number allocation
Study group and treatment name allocation will be performed as described in 
Section 5.2.2.
5.6.11.
Sampling
Refer to the Laboratory Manual for detailed instructions for the collection, handling and 
processing of the samples.
Blood samples will be taken during certain study visits as specified in Section 5.5 List of 
Study Procedures.

A blood sample (fingerprick) will be taken at Screening for Malaria RDT.
(Amended 06 May 2015.)

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
A volume of approximately 1 mL of whole blood (to provide at least 300 μL of
serum) should be drawn from the children in the youngest age stratum (1 to 5 years 
of age) and a volume of approximately 2.5 mL of whole blood (to provide at least 
800 μL of serum) should be drawn from the children in the other age strata (6 to 
17 years of age) for each analysis of humoral immune response at each pre-defined 
timepoint. Refer to the Laboratory Manual for more details on sample storage 
conditions.

Among the children in the sub-cohort for CMI, a volume of approximately 4 mL of
whole blood should be drawn from the children in the youngest age stratum (1 to 
5 years of age), a volume of approximately 6 mL of whole blood should be drawn 
from the children in the middle age stratum (6 to 12 years of age), and a volume of 
approximately 10 mL of whole blood should be drawn from the children in the oldest 
age stratum (13 to 17 years of age), at each pre-defined timepoint. Refer to the 
Laboratory Manual for more details on sample storage conditions.

A volume of approximately 0.5 to 1.5 mL (depending on the age of the child) of 
whole blood should be drawn from all subjects for each analysis of haematology and 
each analysis of biochemistry parameters at each pre-defined timepoint. 
(Amended 06 May 2015.)
5.6.12.
Study vaccine administration

After completing all prerequisite procedures prior to vaccination, one dose of study 
vaccine will be administered IM in the deltoid, or for small children, in the thigh
(refer to Section 6.4 for detailed description of the vaccine administration procedure). 
If the Investigator or delegate determines that the subject’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 for at least 30 minutes following the 
administration of the vaccine, with appropriate medical treatment readily available in 
case of anaphylaxis.
5.6.13.
Check and record concomitant medications/ products/ 
vaccinations
Concomitant medication/ products/ vaccinations must be checked and recorded in 
eSource as described in Section 6.7.
5.6.14.
Recording of adverse events, serious adverse events, and 
pregnancies 

Refer to Section 9.3 for procedures for the Investigator to record AEs, serious 
adverse events (SAEs), and pregnancies. Refer to Section 9.4 for guidelines and how 
to report AEs of specific interest (clinical symptoms of thrombocytopenia), SAEs,
and pregnancies to the CRO (Quintiles).
(Amended 06 May 2015.)

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
The subjects and/ or the subjects’ parent(s)/ LAR(s) will be instructed to contact the 
Investigator immediately should he/ she/ the subjects manifest any signs or 
symptoms they perceive as serious.
5.6.14.1.
Diary Card for follow-up adverse events occurring from day 0 to day 6 
after vaccination
Subjects will be followed up for AEs on a daily basis during the 7-day follow-up period 
after vaccination. During this period, AEs with the exception of AEs of specific interest 
(clinical symptoms of thrombocytopenia) will be recorded on a Diary Card, which will 
be managed/ completed by the Investigator (at study visits during the 7-day follow-up 
period), or by a field worker (at home visits during the 7-day follow-up period; on those 
days that no study visit is planned).
(Amended 06 May 2015.)
The home visits will be conducted by a trained field worker under the supervision of the 
Investigator. In the event that the field worker finds any Grade 3 AE, the child will be 
brought to the vaccination centre for examination by a study clinician. Any further 
clinical data, including treatment provided, will be documented on the paper Diary Card 
and on specific clinic forms and transcribed in eSource. If the physician finds that the 
child has experienced a SAE, the appropriate measures will be taken to report this (refer 
to Section 9.4 for instructions on reporting SAEs).
Diary Cards will be checked and verified by the Investigator or his/ her designate before 
transcription in eSource. The Investigator has a primary responsibility for the data 
transcribed in eSource. Unresolved AEs will be followed-up by field workers until 
resolution under the supervision of the Investigator and data will be entered in eSource. 
The procedures and frequency of visits will be outlined in an SOP at the vaccination 
centre. 
5.6.14.2.
Unsolicited adverse events occurring from day 0 to day 29 after 
vaccination and serious adverse event data collection during the entire 
study duration
Subjects will be advised to present when unwell. All unsolicited AEs will be captured by 
passive detection from day 0 up to day 29 after vaccination. All SAEs will be captured 
during the entire study duration. In order to maximise data completeness, occurrence of 
events will be discussed and reviewed during the planned study visits.

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5.6.15.
Study conclusion
The Investigator will:

review data collected to ensure accuracy and completeness

complete the Study Conclusion screen in eSource.
5.7.
Biological sample handling and analysis
Samples will not be labelled with information that directly identifies the subject but will 
be coded with the identification number for the subject.

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’ parent(s)/ LAR(s), 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 
parents/ LAR(s).
Refer also to the Amendment 2 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 5.7.4.1
may be changed.
Collected samples will be stored for a maximum of 15 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.
5.7.1.
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 

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materials in the appropriate manner. The use of other materials could result in the 
exclusion of the subject from the according-to-protocol (ATP) analysis (See Section 11.5
for the definition of cohorts to be analysed). The Investigator must ensure that his/her 
personnel and the 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 Pharmacy Manual.

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5.7.2.
Biological samples
Table 7
Biological samples (Amended 06 May 2015.)
Sample type
Quantity
Unit
Age strata
Timepoint
Sub-cohort *
Number of 
subjects
Blood for 
Malaria 
Screening
Fingerprick NA
1 to 17 years
Screening
All screened subjects
> 600
Blood for 
haematology
0.5 to 1.5
mL
1 to 17 years
Screening
All screened subjects
> 600
Day 3
All enrolled subjects
600
Day 6
Day 30
Month 6
Month 6 + 6 days
Month 6 + 30 days
Month 12
Blood for 
biochemistry
0.5 to 1.5
mL
1 to 17 years
Screening
All screened subjects
> 600
Day 3
All enrolled subjects
600
Day 6
Day 30
Month 6
Month 6 + 6 days
Month 6 + 30 days
Month 12
Blood for 
humoral 
immunity 
1
mL
1 to 5 years
Day 0
All enrolled subjects
600
2.5
mL
6 to 17 years
1
mL
1 to 5 years
Day 30
All enrolled subjects
600
2.5
mL
6 to 17 years
1
mL
1 to 5 years
Month 6
All enrolled subjects
600
2.5
mL
6 to 17 years
1
mL
1 to 5 years
Month 6 +30 days
All enrolled subjects
600
2.5
mL
6 to 17 years
1
mL
1 to 5 years
Month 12
All enrolled subjects
600
2.5
mL
6 to 17 years
Blood for CMI 
4
mL
1 to 5 years
Day 0
Sub-cohort for CMI
180
6
mL
6 to 12 years
10
mL
13 to 17 years
4
mL
1 to 5 years
Day 30
Sub-cohort for CMI
180
6
mL
6 to 12 years
10
mL
13 to 17 years
4
mL
1 to 5 years
Month 6
Sub-cohort for CMI
180
6
mL
6 to 12 years
10
mL
13 to 17 years
4
mL
1 to 5 years
Month 6 +30 days
Sub-cohort for CMI
180
6
mL
6 to 12 years
10
mL
13 to 17 years
4
mL
1 to 5 years
Month 12
Sub-cohort for CMI
180
6
mL
6 to 12 years
10
mL
13 to 17 years
= approximately; CMI = cell-mediated immunity; NA = not applicable
* Refer to Section 4.2 for the description of the sub-cohorts for CMIs.

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5.7.3.
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 used for 
sample analysis.
In addition to the assays described below, other tests to characterise the safety and/ or the 
immunogenicity of the investigational ChAd3-EBO-Z vaccine may be performed if 
deemed necessary for accurate interpretation of the data and/ or should such test(s) 
become available.
Screening for Malaria infection will be performed using the WHO pre-qualified RDT 
at the site. 
(Amended 06 May 2015.)
5.7.3.1.
Haematology/ biochemistry
Haematology (CBC, including differential count and platelet count) and biochemistry 
(ALT and creatinine) assessments will be performed at a local laboratory.
5.7.3.2.
Immune response against Ebola
Table 8
Humoral immunity against Ebola (Amended 06 May 2015)
System
Component
Method
Kit/ Manufacturer
Laboratory *
Serum
anti-GP EBOV
ELISA
In-house
Quest Diagnostics
EBOV = Ebola virus Zaire; ELISA = enzyme-linked immunosorbent assay; GP = glycoprotein; GSK = GlaxoSmithKline; 
* Refer to APPENDIX B for the laboratory addresses.
Table 9
Cell-mediated immunity against Ebola
System
Component
Challenge
Method
Kit/ Manufacturer
Laboratory *
PBMCs
ChAd3-EBO-Z-specific CD4+
or CD8+ T-cell responses
EBOV GP 
antigens
ICS
In-house
NVITAL
ChAd3-EBO-Z = investigational recombinant chimpanzee adenovirus type 3-vectored Ebolavirus Zaire (EBOV)
vaccine; EBOV = Ebola virus Zaire; ICS = intracellular cytokine staining; NVITAL = NIAID Vaccine Immune T-cell and 
Antibody Laboratory (NIH); PBMCs = peripheral blood mononuclear cells
* Refer to APPENDIX B for the laboratory addresses.
5.7.3.3.
Immune response against ChAd3
Table 10
Humoral immunity against ChAd3
System
Component
Method
Kit/ Manufacturer
Laboratory *
Serum
ChAd3 neutralising antibody
neutralisation
In-house
NVITAL
NVITAL = NIAID Vaccine Immune T-cell and Antibody Laboratory (NIH)
* Refer to APPENDIX B for the laboratory addresses.

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5.7.4.
Biological samples evaluation
5.7.4.1.
Immunological read-outs
Table 11
Immunological read-outs (humoral immunity)
Timepoints
Component
Subset/ Sub-cohort *
No. subjects
Priority 
rank
Day 0, Day 30, Month 6, 
Month 6 + 30 days, 
Anti-GP EBOV
All subjects
600
1
ChAd3 neutralising antibody
Subset for additional humoral 
immunogenicity assays
~180
2
Month 12
Anti-GP EBOV
All subjects
600
1
= approximately; EBOV = Ebolavirus Zaire; GP = glycoprotein
* Refer to Section 5.2.3 for the description of the subset for additional humoral immunogenicity assays.
In case of insufficient blood sample volume to perform assays for all antibodies, the 
samples will be analysed according to priority ranking provided in Table 11.    
Table 12 
Immunological read-outs (cell-mediated immunity)
Timepoints
Component
Subset/ Sub-cohort *
No. 
subjects
Day 0, Day 30, Month 6, 
Month 6 + 30 days, Month 12
ChAd3-EBO-Z-specific CD4+ or CD8+ T-cell 
responses
Sub-cohort for CMI
~180
= approximately; ChAd3-EBO-Z = investigational recombinant chimpanzee adenovirus type 3-vectored Ebolavirus 
Zaire (EBOV) vaccine; CMI = cell-mediated immunity
* Refer to Section 4.2 for the description of the sub-cohort for CMI.
5.7.4.2.
Haematology/biochemistry
Table 13
Haematology/ biochemistry readouts
Timepoints
Component
Subset/ Sub-cohort
No. 
subjects
Screening
CBC (including differential count and platelet 
count), ALT and creatinine
All screened subjects
> 600
Day 3, Day 6, Day 30, Month 6, 
Month 6 + 30 days, Month 12
CBC (including differential count and platelet 
count), ALT and creatinine
All enrolled subjects
600
= approximately; ALT = alanine aminotransferase; CBC = complete blood count
5.7.5.
Immunological correlates of protection
No generally accepted immunological correlate of protection has been demonstrated so 
far for the antigen used in the candidate vaccine, ChAd3-EBO-Z.
6.
STUDY VACCINES/ PRODUCTS AND ADMINISTRATION
(AMENDED 06 MAY 2015.)
6.1.
Malaria treatment (Amended 06 May 2015.)
All subjects diagnosed with Malaria during Screening will receive antimalarial 
treatment according to local/ national standards (e.g., a 3-day treatment course of 
artemisinin-based combination therapy), during the Screening period.

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6.2.
Description of study vaccines
The investigational ChAd3-EBO-Z vaccine has been developed by the VRC/NIAID 
using the ReiThera (formerly known as Okairos) adenovirus vaccine platform 
technology, which was acquired by GSK Biologicals in May 2013. 
The Quality Control Standards and Requirements for the investigational vaccines are 
described in separate Quality Assurance documents (i.e., release protocols, certificate of 
analysis) and the required approvals have been obtained. 
Commercial vaccines are assumed to comply with the specifications given in the 
manufacturer’s SmPC.
Table 14
Study vaccines (Amended 06 May 2015)
Treatment 
name
Vaccine/ 
Product name
Formulation
Presentation
Volume to be 
administered
Number 
of doses
ChAd3-EBO-Z
ChAd3-EBO-Z
ChAd3-EBO-Z= 
2*1011vp/mL*
Liquid in vial
0.25 mL to
1 mL **
1
Nimenrix
MenACWY-TT 
PSA=5 µg TT; 
PSC=5 µg TT; 
PSW₁₃₅=5 µg TT; 
PsY=5 µg TT; 
TT~=44 µg 
Powder in vial
0.5 mL ***
1
NaCl 
NaCl=150 mM 
Liquid in 
monodose, 
prefilled syringe
ChAd3-EBO-Z = investigational recombinant chimpanzee adenovirus type 3-vectored Ebolavirus Zaire (EBOV)
vaccine; MenACWY-TT = meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate; NaCl = sodium 
chloride; PSA = Neisseria meningitidis serogroup A polysaccharide; PSC = Neisseria meningitidis serogroup C 
polysaccharide; PSW = Neisseria meningitidis serogroup W-135 polysaccharide; PsY = Neisseria meningitidis
serogroup Y polysaccharide; TT = tetanus toxoid; vp = viral particles
* The dose used in this study, labelled 2*1011 vp corresponds to the dose, labelled 1*1011 vp, used in the 
Phase I studies that was selected for further clinical development. The difference in vp concentration on the 
labels of the lots used in this study and the Phase I studies is the result of a different analytical method that 
was used to determine the vp concentration. 
** The volume to be administered to children in younger age strata will depend on the recommendation of the 
independent data monitoring committee as a lower vaccine dose may be selected based on safety and 
reactogenicity data accrued during the age de-escalation process (Refer to Section 1.2.2.1).
*** Refer to the Pharmacy Manual for the volume to be injected after reconstitution.
6.3.
Storage and handling of study vaccines
The study vaccines 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 authorised 
study personnel. The storage conditions will be assessed during pre-study activities under 
the responsibility of the CRO study contact. The storage temperature should be 
continuously monitored with calibrated (if not validated) temperature monitoring 
device(s) and recorded. Refer to the Pharmacy Manual for more details on storage of the 
study vaccine(s).
Temperature excursions must be reported in degree Celsius.

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Refer to the Pharmacy Manual for details and instructions on the temperature excursion 
reporting and usage decision process, packaging and accountability of the study vaccine.
6.4.
Dosage and administration of study vaccines
Table 15
Dosage and administration (Amended 06 May 2015)
Type of contact 
and timepoint
Volume to be 
administered
Treatment name
Study group
Route
Site *
Visit Day 0
0.25 mL to 1 mL **
ChAd3-EBO-Z
Group EBO-Z/ MENACWY-TT
IM
Deltoid
0.5 mL
Nimenrix
Group MENACWY-TT/ EBO-Z
IM
Deltoid
Visit Month 6
0.5 mL
Nimenrix
Group EBO-Z/ MENACWY-TT
IM
Deltoid
0.25 mL to 1 mL **
ChAd3-EBO-Z
Group MENACWY-TT/ EBO-Z
IM
Deltoid
ChAd3-EBO-Z = investigational recombinant chimpanzee adenovirus type 3-vectored Ebolavirus Zaire (EBOV)
vaccine; IM = intramuscular; vp = viral particles
* For small children, the vaccine may be given in the thigh.
** The volume to be administered to children in younger age strata will depend on the recommendation of the 
independent data monitoring committee as a lower vaccine dose may be selected based on safety and 
reactogenicity data accrued during the age de-escalation process (Refer to Section 1.2.2.1).
6.5.
Replacement of unusable vaccine doses
In addition to the vaccine doses provided for the planned number of subjects (including 
over-randomisation when applicable), at least 20% additional vaccine doses will be 
supplied to replace those that are unusable. 
Staff responsible for preparing the vaccine will provide to the Investigator the next 
available vaccine vial for the relevant treatment as assigned by the IWRS/ IVRS in case 
of a replacement. Replacement vaccine vial numbers will be recorded in the IWRS/IVRS 
by the staff preparing the vaccine. In addition, the original unusable vaccine vial number 
will be reported in the IWRS/ IVRS as such.
6.6.
Contraindications to vaccination
The following event constitutes a contraindication to study vaccination at that point in 
time; if this event occurs at the time scheduled for vaccination, the subject may be 
vaccinated at a later date, within the allowed time window:

Acute disease and/ or fever at the time of vaccination. 

Fever is defined as temperature 37.5°C/99.5°F. Body temperature will be 
measured axillary.
The following events constitute absolute contraindications to subsequent vaccination. If 
any of these events are applicable at Month 6 the subject must not be vaccinated, but may 
continue other study procedures at the discretion of the Investigator:

Anaphylaxis following vaccine administration.

Clinically significant immunosuppressive or immunodeficient condition (e.g.,
AIDS).

Pregnancy (see Section 9.2).

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6.7.
Concomitant medications/products and concomitant 
vaccinations
At each study visit, the Investigator should question the subject and/ or the subject’s 
parents/ LAR(s) about any medications/ products taken and vaccinations received by the 
subject, with a focus on the medications listed in the Section 6.7.1 and 6.7.2, which need 
to be recorded in eSource.
6.7.1.
Recording of concomitant medications/products and 
concomitant vaccinations
The following concomitant medications/ products/ vaccinations must be recorded in 
eSource:

All concomitant medications/ products, except vitamins and dietary supplements,
administered as of study vaccination up to 29 days after (30-day follow-up period).

Any concomitant vaccination administered as of the Day 0 visit up to study
conclusion (Day 0 to Month 12).

Prophylactic medication (i.e., medication administered in the absence of ANY
symptom and in anticipation of a reaction to the vaccination).
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).

Any concomitant medications/products/vaccines relevant to an 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 electronic AE/ SAE form in eSource.

Any concomitant medications/products/vaccines listed in Section 6.7.2 during the 
period specified in that section.

Any antipyretic administered in the period starting 6 hours before vaccination and
ending 12 hours after vaccination.
6.7.2.
Concomitant medications/ products/ vaccines that may lead to 
the elimination of a subject from according-to-protocol analyses
The use of the following concomitant medications/ products/ vaccinations 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 analysed.

Any investigational or non-registered product (drug or vaccine) other than the study
vaccine used during the study period.

A vaccine* not foreseen by the study protocol administered within 30 days of each
vaccination visit.
*In case an emergency mass vaccination for an unforeseen public health threat (e.g.,
a pandemic) is organised by the public health authorities, outside the routine 

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immunisation programme, the time period described above can be reduced if 
necessary for that vaccine provided it is licensed and used according to its SmPC or 
Prescribing Information and according to the local governmental recommendations 
and provided a written approval of the sponsor is obtained.

Any immunosuppressive medication used during the study period.

Any immunoglobulins and/ or any blood products administered during the study 
period.
6.8.
Intercurrent medical conditions that may lead to elimination 
of a subject from according-to-protocol analyses
Subjects may be eliminated from the ATP cohort for immunogenicity if, during the study, 
they incur a condition that has the capability of altering their immune response or if they 
are diagnosed with an immunological disorder.
7.
OCCURRENCE OF SUSPECTED OR CONFIRMED 
EBOLA VIRUS DISEASE
This study is planned to be conducted in areas free of Ebola transmission. However, 
consideration has been given to the unlikely occurrence of a suspected EVD case. EVD 
will be considered in subjects who have travelled to a country affected by the EBOV 
epidemic, or have had direct contact with a person with EVD in the last 21 days, 
presenting with compatible symptoms.
In case of a suspected EVD, the following steps will be taken:

All precautions will be taken to preserve the safety of the subject and Investigator, 
and anybody with potential exposure to biohazard.

Public health authorities, regulatory authorities and IRBs/ IECs will be alerted.

Case details will be captured as part of SAE reporting. In the case of a confirmed 
negative result, the event may be downgraded to non-serious.
(Amended 06 May 2015.)

While sampling will be organised to support diagnostic confirmation (refer to the 
Laboratory Manual), all safety precautions will be taken to prevent any biohazard. 
Samples at risk already collected from the subject will be destroyed and no further 
samples will be taken in case of biohazard. 

If transmission in the community is suspected, the ability to preserve study integrity 
will be considered but if needed the study will be interrupted, with due consideration 
for investigational ChAd3-EBO-Z vaccination of all participants, considering 
potential risks and benefits upon review of available data. 

Care to infected subjects, and isolation of suspected/ confirmed cases will be 
organised according to best local medical standards in collaboration with 
organisations involved in outbreak control.

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8.
HEALTH ECONOMICS
Not applicable.
9.
SAFETY
The Investigator or vaccination centre 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 and/ or the subjects’ parent(s)/ LAR(s) will be instructed to contact the 
Investigator immediately should 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 unfavourable 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:

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 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 or a concurrent medication (overdose per se should not be 
reported as an AE/ SAE).

Signs, symptoms temporally associated with vaccine administration.

Pre- or post-treatment events that occur as a result of protocol-mandated procedures 
(e.g., invasive procedures, modification of subject’s previous therapeutic regimen).
AEs to be recorded as endpoints (solicited AEs) are described in Section 9.1.3. All other 
AEs will be recorded as UNSOLICITED AEs.

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Examples of an AE DO NOT include:

Medical or surgical procedures (i.e., endoscopy, appendectomy); the condition that 
leads to the procedure is an AE/ SAE.

Situations where an untoward medical occurrence did not occur (i.e., 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 study 
vaccination. These events will be recorded in the medical history section of eSource.
9.1.2.
Definition of a serious adverse event 
An 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 hospitalisation or prolongation of existing hospitalisation,
Note: In general, hospitalisation 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 hospitalisation are also considered AEs. If a complication prolongs 
hospitalisation or fulfils any other serious criteria, the event will also be considered 
serious. When in doubt as to whether ‘hospitalisation’ occurred or was necessary, the 
AE should be considered serious.
Hospitalisation 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, OR
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, diarrhoea, influenza like illness, and accidental trauma (i.e., sprained 
ankle) which may interfere or prevent everyday life functions but do not constitute a 
substantial disruption.
e.
Is a congenital anomaly/birth defect in the offspring of a study subject.
Medical or scientific judgement 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 hospitalisation but may jeopardise the 
subject or may require medical or surgical intervention to prevent one of the other 

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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 hospitalisation.
9.1.3.
Solicited adverse events
Solicited local and general AEs occurring during a 7-day follow-up period after 
vaccination (i.e., the day of vaccination and 6 subsequent days) will be recorded via paper 
Diary Cards, which will be completed by a trained field worker/ the Investigator (see 
Section 5.6.14.1).
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
Pain at injection site
Redness * at injection site
Swelling at injection site
* In case it is not possible to determine the extent of redness on darkly pigmented skin, it will be reported as 
uninterpretable on the Diary Card and in eSource.
9.1.3.2.
Solicited general adverse events
The following general AEs will be solicited:
Table 17
Solicited general adverse events (Amended 06 May 2015)
Infant/ Toddler/ Child (< 6 years)
Child/ Adult (6 years)
Drowsiness
Fatigue
Fever *
Fever *
Irritability/Fussiness
Gastrointestinal symptoms **
Loss of appetite
Headache
* Fever is defined as temperature 37.5°C / 99.5°F. Body temperature may be measured axillary (preferred), oral, 
tympanic, or rectal.
** Gastrointestinal symptoms include nausea, vomiting, diarrhoea and/ or abdominal pain.
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, 
haematology) or other abnormal assessments (e.g., vital signs measurements) 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 judgement in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant.

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9.1.5.
Adverse events of specific interest
9.1.5.1.
Clinical bleeding within 7 days post-vaccination at Day 0
In the Phase 1 studies with the investigational ChAd3-EBO-Z vaccine in healthy 
adults, transient decreases in thrombocyte counts were 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 as per 
protocol criteria for thrombocytopenia (thrombocyte count of < 150x103/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 bleed were reported 
in any of the subjects. Please refer to the IB for more information.
In the current study, a more vulnerable population (children) will be enrolled and the 
acceptable limit for the thrombocyte count for study eligibility (thrombocyte count of 
100x103/µL is acceptable) will be lower as compared to the Phase 1 studies. In 
addition, in order to ensure enhanced vigilance from the Investigators, clinical 
bleeding events (according to the Standardised MedDRA Query clinical haemorrhage) 
within 7 days after vaccination at Day 0 will be recorded and reported as AEs of 
specific interest (clinical symptoms of thrombocytopenia).
(Amended 06 May 2015.)
9.2.
Events or outcomes not qualifying as adverse events or 
serious adverse events (pregnancy)
Female subjects who become pregnant after completion of study vaccination may 
continue the study at the discretion of the Investigator.
Female subjects who are pregnant at the time of the vaccination at Month 6 must not be 
vaccinated, but may continue other study procedures at the discretion of the Investigator.
While pregnancy itself is not considered an AE or SAE, any adverse pregnancy outcome 
or complication or elective termination of a pregnancy for medical reasons will be 
recorded and reported as an AE or a SAE.
Note: The pregnancy itself should always be recorded on an electronic pregnancy form in 
eSource.
The following should always be considered as SAE:

Spontaneous pregnancy loss, including:

Spontaneous abortion, (spontaneous pregnancy loss before/at 22 weeks of 
gestation).

Ectopic and molar pregnancy.

Stillbirth (intrauterine death of foetus after 22 weeks of gestation).

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Note: the 22 weeks cut-off in gestational age is based on WHO-ICD 10 noted in the 
EMA Guideline on pregnancy exposure [EMA, 2006]. It is recognised that national 
regulations might be different.

Any early neonatal death (i.e., death of a live born infant occurring within the first 
7 days of life). 

Any congenital anomaly or birth defect (as per Centers for Disease Control and 
Prevention Metropolitan Atlanta Congenital Defects Program [CDC MACDP] 
guidelines) identified in the offspring of a study subject (either during pregnancy, at 
birth or later) regardless of whether the foetus is delivered dead or alive. This 
includes anomalies identified by prenatal ultrasound, amniocentesis or examination 
of the products of conception after elective or spontaneous abortion.
Furthermore, any SAE occurring as a result of a post-study pregnancy AND considered 
by the Investigator to be reasonably related to the investigational vaccine will be 
reported. While the Investigator is not obligated to actively seek this information from 
former study participants, he/ she may learn of a pregnancy through spontaneous 
reporting.
9.3.
Detecting and recording adverse events, serious adverse 
events and pregnancies
9.3.1.
Time period for detecting and recording adverse events, serious 
adverse events and pregnancies
An overview of the protocol-required reporting periods for AEs, SAEs and pregnancies is 
given in Table 18.
Adverse events
All AEs starting in the 30-day follow-up period following administration of each dose of 
study vaccine must be recorded into the appropriate section of eSource, irrespective of 
intensity or whether or not they are considered vaccination-related.
Adverse events of specific interest
All AEs of specific interest (clinical symptoms of thrombocytopenia) starting in the 
7-day follow-up period following vaccination at Day 0 must be recorded in the 
appropriate section of eSource.
(Amended 06 May 2015.)
Serious adverse events
The time period for collecting and recording SAEs will begin at study vaccination at 
Day 0 and will end at study conclusion for each subject. 
In addition to the above-mentioned reporting requirements and in order to fulfil 
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 

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time the subject’s parent(s)/ LAR(s) consents to participation of the subject in the study 
until she/he is discharged from the study.
See Section 9.4 for instruction on reporting SAEs.
Pregnancies
The time period for collecting and recording pregnancies will begin at study vaccination 
and will end at the Month 6 + 30 days visit. See Section 9.4 for instruction on reporting 
pregnancies.
Table 18
Reporting periods for collecting safety information (Amended 
06 May 2015)
Event
Scree-
ning*
Vacc end 7-day 
follow-up
end 30-day 
follow-up
Vacc end 7-day 
follow-up
end 30-day 
follow-up
Study 
Conclusion
Timepoint
D0
D6
D29
M6 M6 + 6 days
M6 + 29
days
M12
Solicited local and 
general AEs
Unsolicited AEs
AEs of specific 
interest (clinical 
symptoms of 
thrombocyto-
penia)
SAEs
SAEs related to study 
participation 
or concurrent GSK 
medication/vaccine
Pregnancies
AE = adverse event; D = Day, GSK = GlaxoSmithKline; M = Month; SAE = serious adverse event; Vacc = vaccination
* i.e., consent obtained.
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 

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event reasonably related to the investigational vaccine, 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 and/ or the subject’s 
parent(s)/ LAR(s) should be asked a non-leading question such as:
‘Have you felt different in any way since receiving the vaccine or since the previous 
visit?’‘Has your child acted differently or felt different in any way since receiving the 
vaccine 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 eSource. The Investigator is not allowed to send photocopies of the subject’s 
medical records instead of appropriately completing in eSource. 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.
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 below.
Table 19
Intensity scales for solicited symptoms in infants/toddlers and 
children less than 6 years of age (Amended 06 May 2015)
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
Behaviour 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
Behaviour 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
* In case it is not possible to determine the extent of redness on darkly pigmented skin, it will be reported as 
uninterpretable on the Diary Card and in eSource.
** Fever is defined as temperature 37.5°C / 99.5°F. Body temperature may be measured axillary (preferred), oral 
tympanic, or rectal.

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Table 20
Intensity scales for solicited symptoms in children of 6 years of age 
or more (Amended 06 May 2015)
Adverse Event
Intensity grade
Parameter
Pain at injection site
0
None
1
Mild: Any pain neither interfering with nor preventing 
normal every day activities.
2
Moderate: Painful when limb is moved and interferes with 
every day activities.
3
Severe: Significant pain at rest. Prevents normal every 
day activities.
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
Headache
0
Normal
1
Mild: Headache that is easily tolerated
2
Moderate: Headache that interferes with normal activity
3
Severe: Headache that prevents normal activity
Fatigue
0
Normal
1
Mild: Fatigue that is easily tolerated
2
Moderate: Fatigue that interferes with normal activity
3
Severe: Fatigue that prevents normal activity
Gastrointestinal symptoms
0
Normal
(nausea, vomiting, diarrhoea and/or 
abdominal pain)
1
Mild: Gastrointestinal symptoms that are easily tolerated
2
Moderate: Gastrointestinal symptoms that interfere with 
normal activity
3
Severe: Gastrointestinal symptoms that prevent normal 
activity
* In case it is not possible to determine the extent of redness on darkly pigmented skin, it will be reported as 
uninterpretable on the Diary Card and in eSource.
** Fever is defined as temperature 37.5°C / 99.5°F. Body temperature may be measured axillary (preferred), oral 
tympanic, or rectal.
The maximum intensity of local injection site redness/swelling will be scored as follows:
1.
Children 1 to 5 years of age:
0
:
None 
1
:
> 0 mm to ≤ 10 mm
2
:
> 10 mm to ≤ 30 mm
3
:
> 30 mm
2.
Children 6 to 12 years of age:
0
:
None
1
:
> 0 mm to ≤ 20 mm
2
:
> 20 mm to ≤ 50 mm
3
:
> 50 mm

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3.
Children 13 to 17 years of age:
0
:
≤ 20 mm
1
:
> 20 mm to ≤ 50 mm
2
:
> 50 mm to ≤ 100 mm
3
:
> 100 mm
The maximum intensity of fever will be scored as follows:
0
:
< 37.5 °C
1
:
≥ 37.5 °C to ≤ 38.5 °C
2
:
> 38.5 °C to ≤ 39.5°C
3
:
> 39.5°C
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 judgement.
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. In a 
young child, such an AE would, for example, prevent 
attendance at school/ kindergarten/ a day-care centre and 
would cause the parent(s)/ LAR(s) to seek medical advice. 
In an older child, such an AE would, for example, prevent 
attendance at work/school and would necessitate the 
administration of corrective therapy.
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 the study vaccination and 
the occurrence of each AE/ SAE. The Investigator will use clinical judgement 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 vaccine will be considered and investigated. 

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There may be situations when a SAE has occurred and the Investigator has minimal 
information to include in the initial report to the CRO (Quintiles). However, it is very 
important that the Investigator always makes an assessment of causality for every event 
prior to submission of the electronic AE/ SAE form (eSource) to the CRO (Quintiles). 
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, 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.
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 study vaccine?
YES
: There is a reasonable possibility that the study 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 vaccine, 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.

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
Recovering/resolving.

Not recovered/not resolved.

Recovered with sequelae/resolved with sequelae.

Fatal (SAEs only).
9.3.3.4.
Medically attended visits
For each solicited and unsolicited symptom the subject experiences, the subject/ subject’s 
parent(s)/ LAR(s) will be asked if he/she received medical attention defined as 
hospitalisation, or an otherwise unscheduled visit to or from medical personnel for any 
reason, including emergency room visits. This information will be recorded in eSource.
9.4.
Reporting of serious adverse events, pregnancies, and 
other events
9.4.1.
Prompt reporting of adverse events of specific interest (clinical 
symptoms of thrombocytopenia), serious adverse events, and 
pregnancies to the contracted research organisation (Quintiles)
(Amended 06 May 2015)
Adverse events of specific interest (clinical symptoms of thrombocytopenia) that occur 
in the time period defined in Section 9.3.1 will be reported promptly to the CRO
(Quintiles) within the timeframes described in Table 21, once the Investigator becomes 
aware of the event.
(Amended 06 May 2015.)
SAEs that occur in the time period defined in Section 9.3 will be reported promptly to the 
CRO (Quintiles) within the timeframes described in Table 21, once the Investigator 
determines that the event meets the protocol definition of a SAE.
Pregnancies that occur in the time period defined in Section 9.3 will be reported promptly 
to the CRO (Quintiles) within the timeframes described in Table 21, once the Investigator 
becomes aware of the pregnancy. 

C O N FI D E N TI A L
2 0 2 0 9 0 ( E B O L A Z C H A D 3 -0 0 4)
Pr ot o c ol A m e n d m e nt 2 Fi n al
0 6 -M a y -1 5
8 5
T a bl e 2 1
Ti m efr a m e s f or s u b mitti n g a d v er s e e v e nt s of s p e cifi c i nt er e st
( cli ni c al s y m pt o m s of t hr o m b o c yt o p e ni a), s eri o u s a d v er s e e v e nt s ,
a n d pr e g n a n ci e s t o t h e c o ntr a ct e d r e s e ar c h or g a ni s ati o n ( Q ui ntil e s)
( A m e n d e d 0 6 M a y 2 0 1 5 )
T y p e o f E v e nt
I niti al R e p ort s
F oll o w -u p of R el e v a nt I nf or m ati o n o n a 
Pr e vi o u s R e p ort
Ti m efr a m e
D o c u m e nt s
Ti m efr a m e
D o c u m e nt s
A E s of s p e cifi c 
i nt er e st ( cli ni c al 
s y m pt o m s of 
t hr o m b o c yt o p e ni a)
2 4 h o ur s*
el e ctr o ni c A E/ S A E f or m 
i n e S o ur c e
2 4 h o ur s*
el e ctr o ni c A E/ S A E f or m 
i n e S o ur c e
S A E s
2 4 h o ur s* , ‡
el ectr o nic A E/ S A E f or m 
i n e S o urc e
2 4 h o ur s*
el ectr o nic A E/ S A E f or m 
i n e S o urc e
Pr e g n a n ci e s 
2 w e e k s*
el ectr o nic pr e g n a ncy f or m 
i n e S o urc e
2 w e e k s*
el ectr o nic pr e g n a ncy f or m 
i n e S o urc e
A E = a dv ers e ev e nt; S A E = s eri o us a dv ers e ev e nt
* Ti m efr a m e all o w e d aft er r ec ei pt or a w ar e n ess of t h e i nf or m ati o n.
‡ T h e I nv esti g at or will al w a y s pr o vi d e a n a s s e s s m e nt of c a u s alit y wit hi n 2 4 h o urs of s u b missi o n of t h e S A E.
9. 4. 2.
C o nt a ct i nf or m ati o n f or r e p orti n g a d v er s e e v e nt s of s p e cifi c 
i nt er e st ( cli ni c al s y m pt o m s of t hr o m b o c yt o p e ni a), s eri o u s 
a d v er s e e v e nt s , a n d pr e g n a n ci e s ( A m e n d e d 0 6 M a y 2 0 1 5 )
St u d y C o nt act f or Re p orti n g A E s of s pecific i nterest, S A Es , a n d pre g n a ncies 
Pri mar y  met h o d of re p orti n g is via e S o urce.
If e S o urce is n ot a vaila ble, please refer t o S A E/ Pre g na nc y  bac k- u p re p orti n g 
i nstr ucti o ns i n t he In vesti gat or bi n der.
B ac k - u p St u d y C o nt act f or Re p orti n g A E s of s pecific i nterest, S A Es , a n d 
pre g n a ncies 
2 4/ 2 4 h o ur a n d 7/ 7 da y  a vaila bilit y:
Q ui ntiles L ifec ycle Safet y
E mail :
P h o ne : 
Fa x : 
9. 4. 3.
R e p orti n g of a d v er s e e v e nt s of s p e cifi c i nt er e st ( cli ni c al 
s y m pt o m s of t hr o m b o c yt o p e ni a) t o t h e c o ntr a ct r e s e ar c h 
or g a ni s ati o n ( Q ui ntil e s) ( A m e n d e d 0 6 M a y 2 0 1 5)
P P D
O nce a n I nvesti g at or bec o mes a w are t h at a n A E of s pecific i nterest (cli nic al sy m pt o ms 
of t hr o m b ocyt o pe ni a) h as occ urre d i n a st u dy s u bject, t he I nvesti g at or ( or desi g n ate) 
m ust c o m plete t he i nf or m ati o n i n t he electr o nic A E / S A E f or m i n e S o urce WI T HI N 
2 4 H O U R S. T he A E a n d S A E f or m i n e S o urce is t he s a me f o r m. W he n a n A E of 
s pecific i nterest (cli nic al sy m pt o ms of t hr o m b ocyt o pe ni a) is i n dic ate d o n t he electr o nic 
A E/ S A E f or m, a d diti o n al f oll o w- u p q uesti o ns will bec o me av ail a ble, f or c o m pleti o n by 
t he I nvesti g at or ( or desi g nee). T he re p ort will al w ays be c o m plete d as t h or o u g hly as 
P P D
P P D

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possible with all available details of the event. Even if the Investigator does not have all 
information regarding an AE of specific interest (clinical symptoms of 
thrombocytopenia), 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.
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 serious adverse events reports 
to the contracted research organisation (Quintiles)
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 AE/ SAE form 
in eSource WITHIN 24 HOURS. The AE and the SAE form in eSource is the same form. 
When the user indicates that an AE meets the definition of ‘serious’, the rest of the form 
related to SAE information unlocks and the user is required to enter the SAE information. 
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.
The Investigator will always provide an assessment of causality within 24 hours of 
submission of the SAE.
(Amended 06 May 2015.)
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 AE of specific interest (clinical symptoms of 
thrombocytopenia)/ SAE form and fax it to the Back-up Study Contact for Reporting 
SAEs 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 AE/ AE of specific 
interest (clinical symptoms of thrombocytopenia)/ SAE form in eSource within 24 hours. 
The final valid information for regulatory reporting will be the information reported 
through the electronic AE of specific interest (clinical symptoms of thrombocytopenia)/
SAE reporting system.
(Amended 06 May 2015.)

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9.4.5.
Completion and transmission of pregnancy reports to the 
contracted research organisation (Quintiles)
Once the Investigator becomes aware that a subject is pregnant, the Investigator (or 
designate) must complete the required information onto the electronic pregnancy form in 
eSource WITHIN 2 WEEKS.
Note: Conventionally, the estimated gestational age (EGA) of a pregnancy is dated from 
the first day of the last menstrual period (LMP) of the cycle in which a woman conceives. 
If the LMP is uncertain or unknown, dating of EGA and the estimated date of delivery 
(EDD) should be estimated by ultrasound examination and recorded in the pregnancy 
report.
9.4.6.
Updating of adverse events of specific interest (clinical 
symptoms of thrombocytopenia), serious adverse events, and 
pregnancy information after removal of write access to the 
subject’s eSource (Amended 06 May 2015)
When additional AE of specific interest (clinical symptoms of thrombocytopenia), SAE,
or pregnancy information is received after removal of the write access to the subject’s 
eSource, 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 Back-up Study Contact for Reporting AE of specific interest (clinical symptoms of 
thrombocytopenia), SAEs, and pregnancy information within the designated reporting 
time frames specified in Table 21.
(Amended 06 May 2015.)
9.4.7.
Regulatory reporting requirements for serious adverse events
The Investigator will promptly report all SAEs to the CRO (Quintiles) in accordance with 
the procedures detailed in Section 9.4.1. The sponsor (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/ Back-up 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 CRO’s (Quintiles) policy and are 
forwarded to Investigators as necessary. An Investigator safety report is prepared for an 
SAE that is both attributable to the Investigational vaccine and unexpected. The purpose 
of the report is to fulfil 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 
pregnancies
9.5.1.
Follow-up of adverse events and serious adverse events 
9.5.1.1.
Follow-up during the study
After the initial AE/ AE of specific interest (clinical symptoms of thrombocytopenia)/ 
SAE report, the Investigator is required to proactively follow each subject and provide 
additional relevant information on the subject’s condition to the CRO (Quintiles) (within 
24 hours for AEs of specific interest (clinical symptoms of thrombocytopenia) and 
SAEs; refer to Table 21).
All AEs of specific interest (clinical symptoms of thrombocytopenia) 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 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.
(Amended 06 May 2015.)
9.5.1.2.
Follow-up after the subject is discharged from the study
The Investigator will follow subjects with AEs of specific interest (clinical symptoms of 
thrombocytopenia) and SAEs until the event has resolved, subsided, stabilised, 
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 AE 
of specific interest (clinical symptoms of thrombocytopenia) or SAE, he/ she will 
provide this information to the CRO (Quintiles) using an electronic AE/ AE of specific 
interest (clinical symptoms of thrombocytopenia)/ SAE form in eSource.
The sponsor (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 of specific interest (clinical 
symptoms of thrombocytopenia) or SAE. The Investigator is obliged to assist. If a subject 
dies during participation in the study or during a recognised follow-up period, the CRO 
(Quintiles) will be provided with any available post-mortem findings, including 
histopathology.
(Amended 06 May 2015.)
9.5.2.
Follow-up of pregnancies
Pregnant subjects will be followed to determine the outcome of the pregnancy. At the end 
of the pregnancy, whether full-term or premature, information on the status of the mother 

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and child will be forwarded to the CRO (Quintiles) using the electronic pregnancy form 
and the electronic AE/ SAE form, both in eSource, if applicable. Generally, the follow-up 
period doesn’t need to be longer than 6 to 8 weeks after the estimated date of delivery.
Regardless of the reporting period for SAEs for this study, if the pregnancy outcome is a 
SAE, it should always be reported as SAE.
9.6.
Treatment of adverse events
Treatment of any AE is at the sole discretion of the Investigator and according to local 
standard of care. Any medication administered for the treatment of an SAE should be 
recorded in the subject’s eSource (refer to Section 6.7).
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 vaccine, 
prior to regulatory reporting. The Investigator 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 IWRS/ IVRSthat 
allows the Investigator to have unrestricted, immediate and direct access to the subject’s 
individual study treatment. 
The Investigator has the option of contacting the CRO’s (Quintiles) Medical Expert if 
he/ she needs medical advice or needs the support of the CRO prior to performing the 
unblinding.
Any emergency unblinding must be recorded in IWRS/ IVRS and eSource by the 
Investigator within 24 hours.
9.9.
Subject card
Study subjects and/ or 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/ 
subjects’ 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.

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Subjects/ subjects’ parent(s)/ LAR(s) must be instructed to keep Subject Cards in their 
possession at all times.
9.10.
Safety monitoring by the independent data monitoring 
committee
An IDMC will be appointed to monitor the safety and tolerability of the investigational 
ChAd3-EBO-Z vaccine. The IDMC will consist of clinical experts and a statistician who 
are not involved in the conduct of the study.
The IDMC will review, in an unblinded manner, safety and reactogenicity data from the 
current study, and from the study EBOLA Z CHAD3-005, which will be conducted in 
parallel with the current study. In the study EBOLA Z CHAD-005, the safety, 
reactogenicity and immunogenicity of the investigational ChAd3-EBO-Z vaccine will be 
assessed when administered to adults. Recommendations will be provided to the sponsor 
following each IDMC meeting.
Unblinded IDMC reports including all available safety and reactogenicity data will be 
produced by an independent statistician according to an agreed pre-defined Report and 
Analysis Plan. All data provided to the IDMC that will monitor the data from the above 
described Phase 2 studies, will also be made available to the IDMC that will be set up to 
monitor data from the Phase 3 programme with the investigational ChAd3-EBO-Z 
vaccine.
If, during an IDMC meeting, any safety concern is raised, continuation of vaccination and 
the start of vaccination of subjects in the younger age stratum (if applicable) will be put 
on hold. Vaccination will only resume, and age de-escalation will only proceed if GSK 
Biologicals agrees to it, following discussions with the IDMC. All IECs/ IRBs will be 
notified as applicable.
Refer to the IDMC Charter for more information.
Staggered design and IDMC meetings
No safety concerns have been raised from vaccination with different dosages of the 
investigational ChAd3-EBO-Z vaccine in healthy adults in the ongoing Phase 1 studies.
However, the investigational vaccine has never been administered to children yet. In 
order to ensure maximum safety for the subjects in this study, vaccination in the study 
will only start after a favourable outcome of an IDMC review of the safety and 
reactogenicity data from 100 adults after 1 week follow-up in the study EBOLA Z 
CHAD3-005. In addition, vaccination at Day 0 will be done in a staggered manner, 
starting with vaccination of the children in the oldest age stratum. For each age stratum, 
the IDMC will conduct a review of all available safety data once data is available up to at 
least 7 days after vaccination of at least 50 subjects (25/ group) in that age stratum. In 
order to proceed to vaccination of the subjects in the younger age stratum (6 to 12 years 
of age), possibly with a lower vaccine dose, a favourable outcome of the IDMC review of 
safety data up to at least 7 days after vaccination from at least 50 subjects (25/ group) in 
the oldest age stratum needs to be obtained. The same will be done for moving from the 
6 to 12 years of age stratum to vaccination of the youngest children (1 to 5 years of age).

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Figure 3
Overview of staggered design and independent data monitoring 
committee (IDMC) safety evaluations
Holding rules
During the IDMC meetings depicted in Figure 3, study holding rules will be assessed. If 
any of these holding rules are met (or if any other safety concern is raised), vaccination 
will be put on hold. 
The holding rules will be assessed per age stratum and the frequency of events described 
in the holding rules apply to the Group EBO-Z/ MENACWY-TT only.

Solicited local AEs:

More than 30% of doses are followed by Grade 3 solicited local AE beginning
within 7 days after vaccination (day of vaccination and 6 subsequent days) and 
persisting at Grade 3 for > 2 consecutive days.

Solicited general AEs:

More than 30% of doses are followed by any Grade 3 solicited general AE
considered to be related to vaccination beginning within 7 days after vaccination 
(day of vaccination and 6 subsequent days) and persisting at Grade 3 for 
> 2 consecutive days.

More than 30% of doses are followed by Grade 3 fever considered to be related 
to vaccination beginning within 7 days after vaccination (day of vaccination and 
6 subsequent days) and persisting at Grade 3 for > 2 consecutive days.

Unsolicited AEs:

More than 30% of subjects develop any Grade 3 unsolicited AE considered to be
related to vaccination and persisting at Grade 3 for > 2 consecutive days.

An SAE considered related to vaccination.

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Other IDMC meetings
In addition to the IDMC meeting that will be held before the first vaccination and the 
meetings depicted in Figure 3, the following IDMC evaluations will take place:

IDMC review of all safety and reactogenicity data included in the interim analysis 
that will be conducted when data is available from all subjects up to 30 days after 
vaccination at Day 0 (refer to Section 11.11.2 for more information on this interim 
analysis).

An ad hoc IDMC meeting will be held in case of an SAE considered related to 
vaccination at any time during the study.

Ad hoc IDMC meetings may be held if any safety concern is raised. 
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 to contact those subjects who do not return for 
scheduled visits or follow-up. 
Information relative to the withdrawal will be documented in eSource. The Investigator 
will document whether the decision to withdraw a subject from the study was made by 
the subject himself/herself, 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:

Serious AE.

Protocol violation (specify).

Consent withdrawal, not due to an AE*.

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
Moved from the study area.

Lost to follow-up.

Other (specify).
*In case a subject is withdrawn from the study because he/she/ 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/ subject’s parent(s)/LAR(s) in eSource.
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 9.5.1.2).
10.3.
Extension study
At the end of the study (study conclusion visit), the Investigator will ask each 
subject/ subject’s parent(s)/ LAR(s) if they are interested to participate/ to allow the 
subject to participate in a booster study/long-term follow-up study. If a subject/ subject’s 
parent(s)/ LAR(s) is/ are not interested in participating/ allowing subject participation in 
the booster study/ long-term study, the reason for refusal will be documented in eSource.
10.4.
Screen failures
Screen 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 screen failures:

Informed consent.

Inclusion/ exclusion criteria.

Demographic data.

Any SAEs related to study participation, to concomitant use of GSK products, or any 
fatal SAEs.

Screening conclusion.
11.
STATISTICAL METHODS
11.1.
Primary endpoints

Occurrence of each solicited local and general AE, during a 7-day follow-up period 
after each vaccination in all subjects, in both groups.

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), in all subjects, in 
both groups.

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
Occurrence of haematological (CBC, including differential count and platelet count) 
and biochemical (ALT, creatinine) laboratory abnormalities at Screening, Day 3, 
Day 6, Day 30, Month 6, Month 6 + 6 days, Month 6 + 30 days and Month 12 in all 
subjects in both groups.

Occurrence of clinical symptoms of thrombocytopenia (AE of specific interest), 
during a 7-day follow-up period after vaccination at Day 0 (i.e., Day 0 up to 
Day 6), in all subjects, in both groups. 
(Amended 06 May 2015.)

Occurrence of any SAE, in all subjects, in both groups.
11.2.
Secondary endpoint

Anti-GP EBOV antibody titres, as measured by enzyme-linked immunosorbent assay 
(ELISA):

At Day 0 and Day 30, in all subjects, in both groups.

At Month 6 and Month 6 + 30 days, in all subjects, in the 
Group MENACWY-TT/ EBO-Z.
11.3.
Tertiary endpoints

Anti-GP EBOV antibody titres, as measured by ELISA:

At Month 6 and Month 6 + 30 days, in all subjects, in the 
Group EBO-Z/ MENACWY-TT.

At Month 12, in all subjects, in both groups.

Magnitude, responder rate and cytokine co-expression profile of 
ChAd3-EBO-Z-specific CD4+ or CD8+ T-cell responses, as assessed by intracellular 
cytokine staining (ICS) after stimulation with EBOV GP antigens:

At Day 0, Day 30, Month 6, Month 6 + 30 days and Month 12, in a sub-cohort of 
30 subjects per age stratum, per group.

ChAd3 neutralising antibody titres, as measured by a neutralisation assay:

At Day 0, Day 30, Month 6, and Month 6 + 30 days, in a subset of 30 subjects 
per age stratum, per group.
11.4.
Determination of sample size
The primary objective of this study is to assess the safety of the investigational 
ChAd3-EBO-Z vaccine.
Considering the target sample size of approximately 300 subjects to be enrolled in the 
Group EBO-Z/ MENACWY-TT and approximately 300 subjects to be enrolled in the 
Group MENACWY-TT/ EBO-Z, Table 22 below illustrates the 95% confidence intervals 
(CI) for different possible observed number of AEs within a group before vaccination at 
Month 6 (administration of the investigational ChAd3-EBO-Z vaccine to the children in 
the Group MENACWY-TT/ EBO-Z).

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Table 22
95% exact confidence intervals for the true AE rate at different 
possible observed AE rates within a group (300 subjects)
Observed number of 
adverse events
Observed adverse event 
proportion
95% Exact Confidence Interval
Lower Bound
Upper Bound
0
0.0000
0.0000
0.0122
1
0.0033
0.0001
0.0184
5
0.0167
0.0054
0.0385
15
0.0500
0.0283
0.0811
50
0.1667
0.1263
0.2138
100
0.3333
0.2802
0.3898
150
0.5000
0.4420
0.5580
Another way to present the design is to show the true rates associated with a 90% 
probability to observe a certain number of events (Table 23).
Table 23
True proportions associated with a 90% probability to observe a 
certain number of events 
True proportion
Number of adverse events observed 
with > 90% probability
0.008
> 0
0.013
> 1
0.018
> 2
0.022
> 3
0.027
> 4
0.031
> 5
0.070
> 15
0.126
> 30
11.5.
Cohorts for Analyses
11.5.1.
Total vaccinated cohort
The total vaccinated cohort (TVC) will include all subjects with at least one 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 results are available.
The TVC will be performed per treatment actually administered.
11.5.2.
According-to-protocol cohort for analysis of immunogenicity
The ATP cohort for analysis of immunogenicity will include all evaluable subjects:

Who meet all eligibility criteria.

Who have received at least one dose of study vaccine according to protocol
procedures and to their random assignment.

For whom the randomisation code has not been broken for vaccination at Day 0.

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
Who comply with the procedures and intervals defined in the protocol (refer to 
Table 6).

Who did not receive a concomitant medication/ product/ vaccination leading to 
elimination from an ATP analysis as listed Section 6.7.2.

Who did not present with a medical condition leading to elimination from an 
ATP analysis as listed Section 6.8.

For whom data concerning immunogenicity endpoint measures are available. 
11.6.
Derived and transformed data
Immunogenicity

The cut-off value will be defined by the laboratory before the analysis.

A seronegative subject is a subject whose titre is below the cut-off value.

A seropositive subject is a subject whose titre is greater than or equal to the cut-off 
value.

Seroconversion is defined as the appearance of antibodies (i.e., titre greater than or 
equal to the cut-off value) in the serum of subjects seronegative before vaccination.

The Geometric Mean Titres (GMTs) 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 for the purpose of GMT 
calculation.

Handling of missing data: for a given subject and a given immunogenicity 
measurement, missing or non-evaluable measurements will not be replaced.
Reactogenicity and Safety

Handling of missing data: subjects who missed reporting symptoms (unsolicited or 
concomitant medications) will be treated as subjects without symptoms (unsolicited 
or concomitant medications, respectively). In case of significant non-compliance of 
study procedures for reporting symptoms, the analysis plan will be reassessed to 
ensure more accurate reporting of study data by further analysis.

For the analysis of solicited symptom, missing or non-evaluable measurements will 
not be replaced. Therefore the analysis of the solicited symptoms based on the TVC 
will include only subjects/doses with documented safety data.
11.7.
Analysis of demographics
Demographic characteristics (age at study vaccination in years, gender, and ethnicity) and 
withdrawal status will be summarised by group in the TVC, using descriptive statistics:

Frequency tables will be generated for categorical variable such as centre.

Mean, median, standard deviation will be provided for continuous data such as age.

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Analyses will be performed by age stratum (1 to 5 years, 6 to 12 years, and 13 to 
17 years) and overall.
11.8.
Analysis of safety
The analysis will be performed on the TVC.
All analyses will be descriptive. Analyses will be performed by age stratum (1 to 5 years, 
6 to 12 years, 13 to 17 years) and overall.
In a first step, the safety results will be presented by treatment administered at Day 0 
(ChAd3-EBO-Z vaccine 300 subjects] versus Nimenrix 300 subjects]). In a second step, 
all available data post-vaccination with the investigational ChAd3-EBO-Z vaccine 
(ChAd3-EBO-Z vaccine at Day 0 300 subjects] and ChAd3-EBO-Z vaccine at Month 6 
300 subjects]) will be pooled (600 subjects). The latter aggregated data cannot be 
presented versus control because of the administration of the investigational 
ChAd3-EBO-Z vaccine to the children in the Group MENACWY-TT/ EBO-Z, who 
initially received Nimenrix (population overlap).
(Amended 06 May 2015.)
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 solicited 
follow-up period will be tabulated with exact 95% CI. The same calculations will be 
performed for symptoms rated as Grade 3.
The percentage of subjects reporting each individual solicited local and general AE 
during the solicited follow-up period will be tabulated with exact 95% CI. The same 
tabulation will be performed for Grade 3 AEs and for AEs with relationship to 
vaccination.
Duration and prevalence of fever will be presented.
The verbatim reports of unsolicited symptoms will be reviewed by a physician and the 
signs and symptoms will be coded according to the Medical Dictionary for Regulatory 
Activities (MedDRA). The percentage of subjects with at least one report of unsolicited
AE classified by the MedDRA and reported up to 29 days after vaccination will be 
tabulated with exact 95% CI. The same tabulation will be performed for Grade 3 
unsolicited AEs and for unsolicited AEs with a relationship to vaccination.
At each haematology/ biochemistry sampling time point, by study group, individual 
haematological and biochemical values will be presented as number of subjects out of 
range (above and below normal range) and tabulated by toxicity grading (refer to 
APPENDIX C). In addition, changes from baseline (median/ interquartile range) will be 
presented. 

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SAEs and AEs of specific interest (clinical symptoms of thrombocytopenia) will be 
described in detail.
(Amended 06 May 2015.)
11.9.
Analysis of immunogenicity
The primary analysis will be based on the ATP cohort for analysis of immunogenicity. If, 
in any study group, the percentage of vaccinated subjects with serological results 
excluded from the ATP cohort for analysis of immunogenicity is 5% or more, a second 
analysis based on the TVC will be performed to complement the ATP analysis.
All analyses will be descriptive. Analyses will be performed by age stratum (1 to 5 years, 
6 to 12 years, 13 to 17 years) and overall.
In a first step, the immunogenicity results will be presented by treatment administered at 
Day 0 (ChAd3-EBO-Z vaccine 300 subjects] versus Nimenrix 300 subjects]). In a 
second step, all data post-vaccination with the investigational ChAd3-EBO-Z vaccine 
(ChAd3-EBO-Z vaccine at Day 0 300 subjects] and ChAd3-EBO-Z vaccine at Month 6 
300 subjects]) will be pooled (600 subjects). The latter aggregated data cannot be 
presented versus control because of the administration of the investigational 
ChAd3-EBO-Z vaccine to the children in the Group MENACWY-TT/ EBO-Z, who 
initially received Nimenrix (population overlap).
Humoral immune response
For each study group, each antigen, at each timepoint where a blood sample result is 
available: 

Seropositivity rates (with exact 95% CI) will be calculated by group. 

GMTs with 95% CI will be tabulated. 

Vaccine responses to the antigen (with exact 95% CI) will be calculated. 

Reverse cumulative distribution curves will display antibody titres distributions
The same analyses will be done by baseline anti-GP EBOV serological status.
Cell-mediated immune response
For each study group, at each timepoint where a blood sample result is available, the 
frequency of specific CD4+/ CD8+ T-cells will be summarised (descriptive statistics).
If numbers allow, the same analysis will be done by baseline anti-GP EBOV serological 
status.
11.10.
Interpretation of analyses
Comparative analyses will be descriptive with the aim to characterise the difference in 
reactogenicity/ safety/ immunogenicity between groups.

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11.11.
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.
11.11.1.
Sequence of analyses
All analyses (including the interim analysis) will be conducted on data as clean as 
possible. 
The analyses will be performed stepwise: 

Analyses of safety and reactogenicity data will be performed for the IDMC. Access 
to individual treatment codes will be restricted to the IDMC support statistician in 
charge of the analyses and IDMC members.

An interim analysis will be performed when safety, reactogenicity and 
immunogenicity (including at least anti-GP EBOV data at Day 30) data from all 
subjects are available up to 30 days after vaccination at Day 0. 

A final analysis of all data will be performed when all data up to study conclusion 
are available.
11.11.2.
Statistical considerations for interim analyses
In order to obtain early data on the investigational ChAd3-EBO-Z vaccine, an interim 
analysis will be performed when safety, reactogenicity and immunogenicity (including at 
least anti-GP EBOV data at Day 30) data is available from all subjects up to 30 days after 
vaccination at Day 0. The interim analysis will be conducted on all safety, reactogenicity 
and immunogenicity data available at that time. This analysis will present a descriptive 
summary of safety, reactogenicity and immunogenicity. As the study does not include 
any confirmatory objective, no statistical adjustment will be made.
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 (eSource)
The data collection method used will be electronic source data collection, where the 
Investigator collects all source data electronically using a tablet device. Edit checks are 
run at the time of data capture and the data are stored in the source database. Automatic 
transfer of the study data fields will occur from the source database into the study 
database at the CRO. This method of data capture eliminates the need for site staff to 
transcribe data into a case report form from the source data, and therefore eliminates the 
need for on-site checking of the case report form data against the source data to identify 
transcription errors.
In all cases, subject initials will be collected in eSource, but will not be transmitted to 
GSK. Subject data necessary for analysis and reporting will be entered/ transmitted into a 

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validated database or data system. Clinical data management will be performed in 
accordance with applicable CRO standards and data cleaning procedures.
While completed eSource forms are reviewed by a CRO Site Monitor, omissions or 
inconsistencies detected by subsequent eSource 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. 
(Amended 06 May 2015.)
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.
Refer to the SureSource completion Manual for more information on completion of 
eSource.
12.2.
Study monitoring by the contracted research organisation
The CRO Site Monitor 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 eSource review. 
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 (i.e., 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 

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other than hard copy (i.e., 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.
12.5.
Posting of information on publicly available clinical trial 
registers and publication policy
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrolment of subjects begins.
Summaries of the results of GSK interventional studies (Phase 1 to 4) are posted on 
publicly available results registers within 6 months of the primary completion date for 
studies of authorised vaccines and 18 months for studies of non-authorised vaccines. 
GSK also aims to publish the results of these studies in the searchable, peer reviewed 
scientific literature. Manuscripts are submitted for publication within 24 months of the 
last subject’s last visit. At the time of publication, this protocol will be fully disclosed.
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.

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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
Not applicable. 
14.
REFERENCES
Afolabi, Muhammed, Adetifa, et al. Heterologous prime-boost vaccination with 
candidate malaria vaccines ChAd63 ME-TRAP and MVA.ME-TRAP is safe and highly 
immunogenic for effector T-cell induction in healthy Gambian infants. 61st Annual 
Meeting of the American Society of Tropical Medicine and Hygiene (ASTMH) (Atlanta, 
GA; USA). 2012.
Anderson MS, Glode MP, Smith AL. Meningococcal disease. In: Feigin RD, Cherry JD, 
editor. Textbook of Pediatric Infectious Diseases. Philadelphia:WB Saunders, 1998: 
1143-1156.
Centers for Disease Control and Prevention Metropolitan Atlanta Congenital Defects 
Program (CDC MACDP) guidelines. Birth defects and genetic diseases branch 6-digit 
code for reportable congenital anomalies; 
http://www.cdc.gov/ncbddd/birthdefects/documents/MACDPcode0807.pdf
Colloca S, Barnes E, Folgori A, et al. Vaccine vectors derived from a large collection of 
simian adenoviruses induce potent cellular immunity across multiple species. Sci Transl 
Med. 2012; 4: 115ra2.
Connolly M, Noah N. Is group C meningococcal disease increasing in Europe? A report 
of surveillance of meningococcal infection in Europe 1993-6. Epidemiol Infect. 1999; 
122: 41-49.
EMA Guideline on the exposure to medicinal products during pregnancy: need for post-
authorization data (Doc. Ref. EMEA/CHMP/313666/2005 ) ‘adopted at Community level 
in May 2006);
http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_g 
uideline/2009/11/WC500011303.pdf. Last accessed 08 October 2014.
Feldmann H and Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011; 377: 849-62.
Harrison LH, Trotter CL, Ramsay ME. Global epidemiology of meningococcal disease. 
Vaccine. 2009; 27S: B51-B63.
Kagina BM, Tameris MD2 Geldenhuys H, et al. The novel tuberculosis vaccine, 
AERAS-402, is safe in healthy infants previously vaccinated with BCG, and induces 
dose-dependent CD4 and CD8T cell responses. Vaccine. 2014; 32: 5908-17.

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McElroy AK, Erickson BR, Flietstra TD, et al. Biomarker correlates of survival in 
pediatric patients with ebola virus disease. Emerg Infect Dis. 2014 ; 20.
Ogwang C, Afolabi M, Kimani D, et al. Safety and immunogenicity of heterologous 
prime-boost immunisation with Plasmodium falciparum malaria candidate vaccines, 
ChAd63 ME-TRAP and MVA ME-TRAP, in healthy Gambian and Kenyan adults. PloS 
One. 2013; 8: e57726.
O’Hara GA, Duncan CJ, Ewer KJ, et al. Clinical assessment of a recombinant simian 
adenovirus ChAd63: a potent new vaccine vector. J Infect Dis. 2012; 205: 772-81.
Paris R, Kuschner RA, Binn L, et al, Adenovirus type 4 and 7 vaccination or adenovirus 
type 4 respiratory infection elicits minimal cross-reactive antibody responses to 
nonhuman adenovirus vaccine vectors. Clin Vaccine Immunol. 2014; 21: 783-6.
Peltola H. Meningococcal vaccines. Current status and future possibilities. Drugs. 1998; 
55: 347-366.
Peruzzi D, Dharmapuri S, Cirillo A, et al. A novel chimpanzee serotype-based adenoviral 
vector as delivery tool for cancer vaccines. Vaccine. 2009; 27: 1293-300.
Rüggeberg JU, Gold MS, Bayas JM, et al. Anaphylaxis: case definition and guidelines 
for data collection, analysis, and presentation of immunization safety data. Vaccine. 2007;
25: 5675-84.
Sprangers MC, Lakhai W, Koudstaal W, et al. Quantifying adenovirusneutralizing 
antibodies by luciferase transgene detection: addressing preexisting immunity to vaccine 
and gene therapy vectors. J. Clin. Microbiol. 2003; 41: 5046–5052.
Stanley DA, Honko AN, Asiedu C, et al. Chimpanzee adenovirus vaccine generates acute 
and durable protective immunity against ebolavirus challenge. Nat Med. 2014 Sep 7 
(epub ahead of print).
WHO. Ebola virus disease. Fact sheet N°103. Updated September 2014. 
http://www.who.int/mediacentre/factsheets/fs103/en/. Last accessed 09 October 2014.
WHO. Ebola virus disease, West Africa – update. Disease outbreak news. 27 July 2014. 
http://www.who.int/csr/don/2014_07_27_ebola/en/. Last accessed 09 October 2014.
WHO Ebola Response Team. Ebola Virus Disease in West Africa – The First 9 Months 
of the Epidemic and Forward Projections. N Engl J Med. 2014 (Epub ahead of print).

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APPENDIX A
LABORATORY ASSAYS
Anti-EBOV GP IgG ELISA
Blood samples for antibody determination will be collected at indicated timepoints and 
serum will be separated and frozen at –20°C. 
Antibody level will be determined by evaluating antibody (IgG) responses specific for 
Zaire Ebola Virus Glycoprotein (EBOV GP) using the ELISA developed by Battelle and 
JVAP/USAMRIID and transferred to Quest (Focus) laboratory.
Briefly, microtiter plates are coated with the purified recombinant Zaire GP (rGP) 
specific to the Kikwit-95 strain (the Non-Human Primates (NHP) challenge strain). This 
strain is 98.5% identical to the vaccine Mayinga EBOV strain (11 aa mismatched) and is 
97.5% identical to the isolated Guinea 2014 virus strain (17 aa mismatched). Serial 
diluted test samples, 2 serial-diluted controls (one QC-high and one QC-low) and a 
negative sample control (composed of pooled normal human serum purchased from a 
commercial source) are allowed to incubate in the GP coated wells allowing GP specific 
antibodies to bind. Additionally, a two-fold serial diluted reference standard, obtained 
from a vaccinated donor, is included in duplicate. Each well is then incubated with goat 
anti-human IgG horseradish peroxidase conjugate (HRP). TMB substrate is added to each 
well and the enzymatic reaction is stopped with a sulfuric acid solution. The color change 
is then read in a plate reader and sample titers are based on the standard curve calculated 
using a lol4 parameter logistic curve fit. Results are reported in ELISA units/ml (EU/ml). 
A 2nd generation human standard (microgram/mL) will be evaluated and bridged to the 
current standard.
This assay will be qualified at Quest Diagnostics laboratories before starting the clinical 
testings.
ChAd3-EBO-Z specific CD4+ or CD8+ T-cells
T-cell response will be measured by ICS. In brief, peripheral blood mononuclear cells 
(PBMCs) are prepared by standard Ficoll-Paque Plus centrifugation and stored frozen in 
heat-inactivated foetal calf serum containing 10% dimethylsulfoxide. In vitro
re-stimulation of the PBMCs is performed using a pool of peptides corresponding to the 
open reading frames of the vaccine GP insert. CD4+ and CD8+ T-cells expressing 
immune markers such as IFN-γ and/or TNF-α and/or IL-2 are detected by flow 
cytometry. The method has been qualified at NVITAL laboratories.
ChAd3 neutralising antibodies
In the process of evaluation of the pre-existing or vaccine-induced antibody response 
against ChAd3, it is of interest to quantify the neutralising antibody concentrations. 
Neutralising antibodies are antibodies with a capacity to block functional epitopes on the 
adenovirus, thereby blocking the entry of the virus to the target cells. 
This method utilizes serotype-specific, replication incompetent adenovirus, which has an 
inserted luciferase reporter gene, as described [Paris, 2014; Sprangers, 2003]. Briefly, 
, A549 human lung carcinoma cells are plated in 96-well plates and infected with 
E1-deleted replication-incompetent rAd-luciferase reporter construct. For each sample, a 

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total of seven 2-fold serial dilutions are tested in triplicate. Following a 24-hour 
incubation, the luciferase activity in the cells is measured using the Steady-Glo luciferase 
reagent system (Promega). 90% neutralisation titres are defined as the maximum serum 
dilution that neutralised 90% of luciferase activity. GMTs are calculated at pre- and/or 
post-vaccination and a positive response is defined as any increase in ChAd3 post-
vaccination. The exceptions are those with pre-vaccination titres at the upper limit of 
quantitation (8748). The assay has been qualified for Ad5 and adapted for ChAd3 at 
NVITAL laboratories. 

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APPENDIX B
CLINICAL LABORATORIES (Amended 
06 May 2015)
Table 24
Outsourced laboratories
Laboratory
Address
NIAID Vaccine Immune T-Cell and 
Antibody Laboratory (NVITAL)
Suite 150
9 West Watkins Mill Road
Gaithersburg, MD 20878
United States
Quest Diagnostics
Focus Diagnostics Clinical Trials, Inc. 
(d/b/a Quest Diagnostics)
33608 Ortega Highway 
San Juan Capistrano,
CA 92675-2042,
United States

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APPENDIX C
ACCEPTABLE LIMITS FOR ELIGIBILITY AND 
TOXICITY GRADING SCALES FOR 
HAEMATOLOGY/ BIOCHEMISTRY 
PARAMETERS (Amended 06 May 2015)
ADULTS AND ADOLESCENTS > 12 YEARS OLD
Table 25 outlines the acceptable limits for eligibility when considering laboratory 
Screening values. 
Table 25
Acceptable limits/normal ranges for eligibility determination
(Amended 06 May 2015)
Haemoglobin (g/dL)
≥ 11 (males) or ≥9.5 (females)
Platelet count (x103/L)
≥100
Total white cell count (x103/L)
≥2.75
Creatinine (mg/dL)
< 1.5 
ALT (IU/L)
< 60 (males) or < 40 (females)
ALT = alanine aminotransferase
Blood safety results at each planned timepoint will be presented per study group 
according to the toxicity grading scale presented in Table 26. In addition, for 
haematological values, changes at post vaccination timepoints relative to baseline will be 
presented per study group.
Table 26
Toxicity grading scales for hematology/ biochemistry parameters
Test
Grade 1
Grade 2
Grade 3
Grade 4
Haemoglobin, male (g/dL)
10 to 10.9
9 to 9.9
8 to 8.9
< 8
Haemoglobin, female (g/dL)
8.5 to 9.4
7.5 to 8.4
6.5 to 7.4
< 6.5
Platelets (x103/L) 
75 to 100
50 to 74.999 
25 to 49.999 
< 25
WBC – decrease (x103/L) 
2 to 2.749
1.50 to 1.999
1 to 1.499
<1
Creatinine (mg/dL) 
1.5 to 1.7 
> 1.7 to 2 
> 2.0 to 2.5 
> 2.5
ALT increase by factor 
1.1 to 2.5xULN 
> 2.5 to 5.0xULN 
> 5.0 to 10xULN 
> 10xULN
ALT = alanine aminotransferase; ULN = upper limit of the normal range; WBC = white blood cells
Note: acceptable limits for eligibility and grading scale adapted from Division of AIDS 
table for grading severity of adult and pediatric adverse events December 2004; WHO 
Toxicity Grading Scale for Determining Severity of Adverse Events, February 2003; 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials, Guidance for Industry, 2007.

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CHILDREN ≤12 YEARS OLD
Table 27 outlines the acceptable limits for eligibility when considering laboratory 
Screening values. 
Table 27 
Acceptable limits/normal ranges for eligibility determination
Haemoglobin (g/dL)
≥ 8.5
Platelet count (x 103/L)
≥100 
Total white cell count (x 103/L)
≥4
Creatinine (mg/dL)
< 1.2 
ALT (IU/mL)
< 60 (males) or < 40 (females)
ALT = alanine aminotransferase
Blood safety results at each planned timepoint will be presented per study group 
according to the toxicity grading scale presented in Table 28. In addition, for 
haematological values, changes at post vaccination timepoints relative to baseline will be 
presented per study group.
Table 28
Toxicity grading scales for hematology/ biochemistry parameters
Test
Grade 1
Grade 2
Grade 3
Grade 4
Haemoglobin (g/dL)
7.5 to 8.49
6.5 to 7.49
5 to 6.49
< 5
Platelets (x103/L) 
75 to 99.999
50 to 74.999 
25 to 49.999 
< 25
WBC (x103/L) 
2.5 to 3.999
1.50 to 2.499
1 to 1.499
< 1
Creatinine (mg/dL) 
1.2 to 1.7 
> 1.7 to 2.1
> 2.1 to 2.5 
> 2.5
ALT increase by factor 
1.1 to 2.5xULN 
> 2.5 to 5.0xULN 
> 5.0 to 10xULN 
> 10xULN
ALT = alanine aminotransferase; ULN = upper limit of the normal range; WBC = white blood cells
Note: acceptable limits for eligibility and grading scale adapted from Division of AIDS 
table for grading severity of adult and paediatric adverse events December 2004; WHO 
Toxicity Grading Scale for Determining Severity of Adverse Events, February 2003; 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials, Guidance for Industry, 2007.

C O N FI D E N TI A L
2 0 2 0 9 0 ( E B O L A Z C H A D 3 -0 0 4)
Pr ot o c ol A m e n d m e nt 2 Fi n al
0 6 -M a y -1 5
1 0 9
A P P E N DI X D
A M E N D M E N T S A N D A D M I NI S T R ATI V E 
C H A N G E S T O T H E P R O T O C O L
Gl a x o S mit h Kli n e Bi ol o gi c al s
Vacci ne Val ue & Healt h Scie nce ( V V H S)
Pr ot oc ol A me n d me nt 1
e Tr ac k st u d y n u m ber 
a n d A b bre vi ate d Title
2 0 2 0 9 0 ( E B O L A Z C H A D 3- 0 0 4)
I N D n u m ber
T o be deci de d
E u dr a C T n u m ber
2 0 1 4- 0 0 4 7 1 4- 2 8
A m e n d me nt n u m ber
A me n d me nt 1
A m e n d me nt d ate
2 9 Dece m ber 2 0 1 4
C o -or di n ati n g a ut h or
, Q ui ntiles, Me dical Writi n g
R ati o n ale/ b ac k gr o u n d f or c h a n ges: 

F or r o b ust ness of safet y m o nit ori n g, t he G S K Bi ol o gicals’ i nter nal safet y re vie w 
c o m mittee (i S R C) was re place d b y a n i n de pe n de nt data m o nit ori n g c o m mittee 
(I D M C).

I n dicate t hat safety a n d react o ge nicit y  data will be c ollecte d i n 1 0 0 a d ults after 
1 wee k of f oll o w -u p (st u d y  E B O L A Z C H A D 3-0 0 5) bef ore c o m me nci n g t he 
c urre nt st u d y.

I n dicate t hat safety a n d react o ge nicit y data o btai ne d i n t he c o nte xt of t he a ge 
de- escalati o n pr ocess ma y lea d t o t he selecti o n of a l o wer C h A d 3 -E B O -Z vacci ne 
d ose i n t he y o u n ger a ge gr o u ps.

Clarif y  t hat i nf or me d asse nt will be as ke d fr o m all s u bjects i n t he ol dest a ge 
strat u m ( 1 3 t o 1 7 years of a ge) a n d fr o m y o u n ger s u bjects as per l ocal 
re q uire me nts.

Defi ne gra di n g scales f or l ocal i njecti o n site re d ness/ s welli n g per a ge strat u m.

Clarif y  t hat a nalys is of safet y will be d o ne o n t he t otal vacci nate d c o h ort ( T V C) 
a n d t hat n o acc or di n g -t o-pr ot oc ol ( A T P) c o h ort f or safet y will be defi ne d.

I ncl u de i nf or mati o n o n t he a nti- G P E LI S A testi n g (la b orat or y, test descri pti o n).
I n a d diti o n, s o me mi n or m o dificati o ns/ clarificati o ns were ma de.
P P D

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Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
SYNOPSIS
Rationale for the 
study and study 
design

Rationale for the study
...
Although health care workers will be priority 
vaccination targets, mass vaccination strategies may 
be developed as one of the ways to protect 
populations and contain the epidemics. In this 
context, children will need to be vaccinated too. The 
present Phase 2, randomised, controlled trial will aim 
at collecting safety and immunogenicity data 
following a single intramuscular dose of the 
investigational ChAd3-EBO-Z vaccine. In parallel 
with the current study, the safety and immunogenicity 
of the investigational ChAd3-EBO-Z vaccine will be 
assessed in healthy adults living in countries adjacent 
to the current Ebola outbreak (study EBOLA Z 
CHAD3-005). Study EBOLA Z CHAD3-005 will 
start before the current study as to collect safety and 
reactogenicity data in 100 adults, after 1 week of 
follow-up, living in countries adjacent to the current 
Ebola outbreak before proceeding to vaccination of 
children. (Amended 29 December 2014.)

Rationale for the study design

Investigational ChAd3-EBO-Z vaccine dose
Dose selection for paediatric use will be based on 
information derived from dose-range studies 
conducted with the ChAd3-EBO-Z vaccine 
candidate in adults and on past experience with other 
recombinant adenovirus-based candidate vaccines. 
(Amended 29 December 2014.)
...
Four different investigational vaccine doses are 
currently being evaluated for safety, reactogenicity 
and immunogenicity in adults in Phase 1 studies. As 
for other recombinant adenovirus-based vaccine 
candidates which showed adequate safety upon the 
use of adult doses in children as explained above, it is 
currently proposed that the same vaccine dose as the 
dose selected for adults will be assessed in this study. 

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However, a lower vaccine dose may be selected for 
children of younger age groups based on the safety 
and reactogenicity data accrued during the age 
de-escalation process. 
(Amended 29 December 2014.)
…

Stratification for age and staggered vaccination
...
In order to ensure maximum safety for the subjects in 
this study, vaccination at Day 0 will be done in a 
staggered manner, starting with vaccination of the 
children in the oldest age stratum. For each age 
stratum, an iSRC independent data monitoring 
committee (IDMC) will conduct a review of all 
available safety data once data is available up to at 
least 7 days after vaccination of at least 50 subject 
(25/ group) in that age stratum. Continuation of 
vaccination and the The start of vaccination in the 
younger age stratum will be put on hold if any safety 
concerns are raised by the iSRC, possibly with a 
lower vaccine dose, depends on the outcome of this 
IDMC review. (Amended 29 December 2014.)
Study design

Staggered vaccination: Vaccination at Day 0 will be 
done in a staggered manner, starting with vaccination of 
the children in the oldest age stratum (13 to 17 years of 
age). In order to proceed to vaccination of the subjects in 
the younger age stratum (6 to 12 years of age), possibly 
with a lower vaccine dose, a favourable outcome of the 
iSRC IDMC review of safety data up to at least 7 days 
after vaccination from at least 50 subjects (25/ group) in 
the oldest age stratum needs to be obtained. The same 
will be done for moving from the 6 to 12 years of age 
stratum to vaccination of the youngest children (1 to 5
years of age). (Amended 29 December 2014.)
...

Safety monitoring: An iSRC IDMC will be appointed to 
monitor the safety and tolerability of the investigational 
ChAd3-EBO-Z vaccine. The iSRC will be authorised by 
the GSK Biologicals’ Vaccine Safety Monitoring Board
(VSMB). Core members of the iSRC will include a GSK 
Biologicals’ Safety Physician, a Clinical Research and 
Development Lead (CRDL) and a Biostatistician who are 
not otherwise involved in the conduct of the project. The 
IDMC will consist of clinical experts and a statistician 
who are not involved in the conduct of the study. 

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(Amended 29 December 2014.)
LIST OF ABBREVIATIONS
CRDL:
Clinical Research and Development Lead
iSRC
Internal Safety Review Committee
VSMB:
Vaccine Safety Monitoring Board
1.2.1
Rationale for the study
...
The study will be conducted in healthy children living in countries adjacent to the current 
Ebola outbreak zones. In parallel with the current study, the safety and immunogenicity 
of the investigational ChAd3-EBO-Z vaccine will be assessed in healthy adults living in 
countries adjacent to the current Ebola outbreak (study EBOLA Z CHAD3-005). Study 
EBOLA Z CHAD3-005 will start before the current study as to collect safety and 
reactogenicity data in 100 adults, after 1 week of follow-up, living in countries adjacent 
to the current Ebola outbreak before proceeding to vaccination of children. (Amended 
29 December 2014.)
1.2.2.1
Investigational ChAd3-EBO-Z vaccine dose
Dose selection for paediatric use will be based on information derived from dose-range 
studies conducted with the ChAd3-EBO-Z vaccine candidate in adults and on past 
experience with other recombinant adenovirus-based candidate vaccines. (Amended 
29 December 2014.)
...
Four different investigational vaccine doses are currently being evaluated for safety, 
reactogenicity and immunogenicity in adults in Phase 1 studies. As for other recombinant 
adenovirus-based vaccine candidates which showed adequate safety upon the use of adult 
doses in children as explained above, it is currently proposed that the same vaccine dose 
as the dose selected for adults will be assessed in this study. However, a lower vaccine 
dose may be selected for children of younger age groups based on the safety and 
reactogenicity data accrued during the age de-escalation process. (Amended 
29 December 2014.)
1.2.2.2
Administration of the investigational ChAd3-EBO-Z vaccine
Considering the risk of exposure to Ebola and the potential (based on animal data) for the 
investigational ChAd3-EBO-Z vaccine to afford at least partial protection, all children in 
the study will receive the investigational ChAd3 EBO-Z vaccine. The children in the 

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Group EBO-Z/ MENACWY-TT will receive the investigational ChAd3-EBO-Z vaccine 
at Day 0 of the study, whereas the children in the Group MENACWY-TT/ EBO-Z will 
receive Nimenrix at Day 0 (as a control). At Month 6, the children in the 
Group MENACWY-TT/ EBO-Z will receive the investigational ChAd3-EBO-Z vaccine 
(provided that no safety concerns are raised. Refer to Section 9.10 for more information 
on the internal safety review committee [iSRC] independent data monitoring committee 
[IDMC]) whereas the children in the Group EBO-Z/ MENACWY-TT will receive 
Nimenrix. (Amended 29 December 2014.)
...
1.2.2.4
Stratification for age and staggered vaccination
...
In order to ensure maximum safety for the subjects in this study, vaccination at Day 0 
will be done in a staggered manner, starting with vaccination of the children in the oldest 
age stratum. For each age stratum, an iSRC IDMC will conduct a review of all available 
safety data once data is available up to at least 7 days after vaccination of at least 50 
subject (25/ group) in that age stratum. Continuation of vaccination and the The start of 
vaccination in the younger age stratum will be put on hold if any safety concerns are 
raised by the iSRC, possibly with a lower vaccine dose, depends on the outcome of this 
IDMC review. For more detailed information on the staggered design of the study and on 
the safety monitoring, refer to Section 9.10. (Amended 29 December 2014.)
2.3
Tertiary objectives
...
Refer to Section 11.3 for the definition of the tertiary endpoint(s). (Amended 
29 December 2014)

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3.
Study Design Overview
...
Figure 1
Study design overview (Amended 29 December 2014.)

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
Staggered vaccination: Vaccination at Day 0 will be done in a staggered manner, 
starting with vaccination of the children in the oldest age stratum (13 to 17 years of 
age). In order to proceed to vaccination of the subjects in the younger age stratum 
(6 to 12 years of age), possibly with a lower vaccine dose, a favourable outcome of 
the iSRC IDMC review of safety data up to at least 7 days after vaccination from at 
least 50 subjects (25/ group) in the oldest age stratum needs to be obtained. The same 
will be done for moving from the 6 to 12 years of age stratum to vaccination of the 
youngest children (1 to 5 years of age). Refer to Section 9.10 for more information. 
(Amended 29 December 2014.)
...

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
Safety monitoring: An iSRC IDMC will be appointed to monitor the safety and 
tolerability of the investigational ChAd3-EBO-Z vaccine. The iSRC will be 
authorised by the GSK Biologicals’ Vaccine Safety Monitoring Board (VSMB). 
Core members of the iSRC will include a GSK Biologicals’ Safety Physician, a 
Clinical Research and Development Lead (CRDL) and a Biostatistician who are not 
otherwise involved in the conduct of the project. The IDMC will consist of clinical 
experts and a statistician who are not involved in the conduct of the study. Refer to 
Section 9.10 for detailed description of the safety monitoring. (Amended 
29 December 2014.)
4.3
Inclusion criteria for enrolment
...

Written/ thumb printed informed consent obtained from the subject’ parent(s)/ 
LAR(s) prior to performing any study specific procedure. In addition, written/ thumb 
printed informed assent should be obtained if appropriate (from all subjects aged 
13 to 17 years and from younger subjects as per local requirements). (Amended 
29 December 2014.)
...
5.1
Regulatory and ethical considerations, including the 
informed consent process
...
In accordance with the ICH Harmonised Tripartite Guidelines for Good Clinical Practice, 
subjects who can only be enrolled in the study with the consent of their parent(s)/ LAR(s) 
(e.g., minors), should be informed about the study to the extent compatible with the 
subject’s understanding and, if capable, the subject should sign and personally date a 
written informed assent form (IAF). It should be assessed whether an assent is required 
depending of the age of the study population and the local requirements. In this study, 
written/ thumb printed informed assent should be obtained from the all subjects in the 
oldest age category (13 to 17 year olds) and from younger subjects as per local 
requirements in addition to the informed consent that is to be signed/ thumb printed by 
their parent(s)/ LAR(s). (Amended 29 December 2014.)
...
5.2.2.2.1
Study group and treatment name allocation at Day 0
...
At Day 0, after After obtaining the signed/ thumb printed and dated ICF from the 
subject’s parent(s)/ LAR(s) and signed/ thumb printed and dated IAF from the subject (if 
applicable) and having checked the eligibility of the subject, the site staff in charge of the 
vaccine administration will access IWRS/ IVRS. Upon providing the subject subject’s 
age (1 to 5 years versus 6 to 12 years versus 13 to 17 years of age), gender, centre and the 
subject identification number, the randomisation system will determine the study group 

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and will provide the treatment name to be administered. Access to the IVRS/ IWRS 
system will be limited to unblinded site staff. (Amended 29 December 2014.)
5.5.1
List of study procedures
Table 5
List of study procedures during visits to the vaccination centre
Footnotes:
...
10 Only for subjects in the oldest age stratum (13 to 17 year olds) and younger subjects as per local requirements. 
(Amended 29 December 2014.).
...
5.6.1
Informed consent
The signed/witnessed/thumb printed informed consent of the subject’s parent(s)/ LAR(s) 
must be obtained before study participation. For subjects in the oldest age stratum (13 to 
17 years) and for younger subjects as per local requirements, the signed informed assent 
of the subject should be obtained in addition to the signed informed consent by his/her 
parent(s)/ LAR(s). Refer to Section 5.1 for the requirements on how to obtain informed 
consent as appropriate. (Amended 29 December 2014.)
5.7.3.2
Immune response against Ebola
Table 8
Humoral immunity against Ebola (Amended 29 December 2014)
System
Component
Method
Kit/ Manufacturer
Laboratory *
Serum
anti-GP EBOV
ELISA
TBD
Laboratory designated by 
GSK Biologicals Quest 
Diagnostics
EBOV = Ebola virus Zaire; ELISA = enzyme-linked immunosorbent assay; GP = glycoprotein; GSK = GlaxoSmithKline; 
TBD = to be determined
* Refer to APPENDIX B for the laboratory addresses.

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6.1
Description of study vaccines
...
Table 14
Study vaccines (Amended 29 December 2014)
Treatment 
name
Vaccine/ 
Product name
Formulation
Presentation
Volume to be 
administered
Number 
of doses
ChAd3-EBO-Z
ChAd3-EBO-Z
ChAd3-EBO-Z= 
5*1010vp/mL or
1*1011vp/mL
Liquid in vial
0.5 0.25 mL 
to 1 mL *
1
Nimenrix
MenACWY-TT 
PSA=5µg TT; PSC=5µg 
TT; PSW₁₃₅=5µg TT; 
PsY=5µg TT; TT~=44µg 
Powder in vial
0.5 mL **
1
NaCl 
NaCl=150mM 
Liquid in 
monodose, 
prefilled syringe
ChAd3-EBO-Z = investigational recombinant chimpanzee adenovirus type 3-vectored Ebolavirus Zaire (EBOV) 
vaccine; MenACWY-TT = meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate; NaCl = sodium 
chloride; PSA = Neisseria meningitidis serogroup A polysaccharide; PSC = Neisseria meningitidis serogroup C 
polysaccharide; PSW = Neisseria meningitidis serogroup W-135 polysaccharide; PsY = Neisseria meningitidis
serogroup Y polysaccharide; TT = tetanus toxoid; vp = viral particles
* The volume to be administered will depend on the dosage ChAd3-EBO-Z selected based on Phase 1 data and on the 
concentration of the investigational ChAd3-EBO-Z vaccine and will be described in the Pharmacy Manual.
** Refer to the Pharmacy Manual for the volume after reconstitution.
6.3
Dosage and administration of study vaccines
Table 15
Dosage and administration (Amended 29 December 2014)
Type of contact 
and timepoint
Volume to be 
administered
Treatment name
Study group
Route
Site *
Visit Day 0
0.5 0.25 mL to 1 mL
**
ChAd3-EBO-Z
Group EBO-Z/ MENACWY-TT
IM
Deltoid
0.5 mL
Nimenrix
Group MENACWY-TT/ EBO-Z
IM
Deltoid
Visit Month 6
0.5 mL
Nimenrix
Group EBO-Z/ MENACWY-TT
IM
Deltoid
0.5 0.25 mL to 1 mL
**
ChAd3-EBO-Z
Group MENACWY-TT/ EBO-Z
IM
Deltoid
ChAd3-EBO-Z = investigational recombinant chimpanzee adenovirus type 3-vectored Ebolavirus Zaire (EBOV) 
vaccine; IM = intramuscular
* For small children, the vaccine may be given in the thigh.
** The volume to be administered will depend on the dosage ChAd3-EBO-Z selected based on Phase 1 data on the 
concentration of the investigational ChAd3-EBO-Z vaccine and will be described in the Pharmacy Manual.
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, 
haematology, urinalysis) or other abnormal assessments (e.g., vital signs measurements) 
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 

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are present at baseline and significantly worsen following the start of the study will also 
be reported as AEs or SAEs. (Amended 29 December 2014.)
9.3.3.2.1
Assessment of intensity
...
The maximum intensity of local injection site redness/swelling will be scored as follows:
1. Children 1 to 5 years of age:
0
:
None 
1
:
> 0 mm to ≤ 10 mm
2
:
> 10 mm to ≤ 30 mm
3
:
> 30 mm
2. Children 6 to 12 years of age:
0
:
None
1
:
> 0 mm to ≤ 20 mm
2
:
> 20 mm to ≤ 50 mm
3
:
> 50 mm
3. Children 13 to 17 years of age:
0
:
≤ 20 mm
1
:
> 20 mm to ≤ 50 mm
2
:
> 50 mm to ≤ 100 mm
3
:
> 100 mm
(Amended 29 December 2014.)
...
9.10
Safety monitoring by the internal safety review committee 
independent data monitoring committee
9.10.1
Staggered vaccination and internal safety review committee
An iSRC IDMC will be appointed to monitor the safety and tolerability of the 
investigational ChAd3-EBO-Z vaccine. The iSRC will be authorised by the GSK 
Biologicals’ Vaccine Safety Monitoring Board (VSMB). 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 IDMC will consist of clinical 
experts and a statistician who are not involved in the conduct of the study.
The iSRC IDMC will review, in an unblinded manner, safety and reactogenicity data 
from the current study, and from the study EBOLA Z CHAD3-005, which will be 
conducted in parallel with the current study. In the study EBOLA Z CHAD-005, the 
safety, reactogenicity and immunogenicity of the investigational ChAd3-EBO-Z vaccine 

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will be assessed when administered to adults. Recommendations will be provided to the 
sponsor following each IDMC meeting.
Interim uUnblinded iSRC IDMC reports including all available safety and reactogenicity 
data will be produced by an independent statistician according to an agreed pre-defined 
Report and Analysis Plan. All data provided to the iSRC, which IDMC that will monitor 
the data from the above described Phase 2 studies, will also be made available to the 
independent data monitoring committee (IDMC) that will be set up to monitor data from 
the Phase 3 programme with the investigational ChAd3-EBO-Z vaccine.
If, during an iSRC meeting, any safety concern is raised, continuation of vaccination and 
the start of vaccination of subjects in the younger age stratum (if applicable) will be put 
on hold and the VSMB will decide during an ad hoc meeting whether to suspend, modify 
or continue the conduct of the study(ies) in all age strata or in selected age strata. 
If, during an IDMC meeting, any safety concern is raised, continuation of vaccination 
and the start of vaccination of subjects in the younger age stratum (if applicable) will 
be put on hold. Vaccination will only resume, and age de-escalation will only proceed if 
GSK Biologicals agrees to it, following discussions with the IDMC. All IECs/ IRBs will 
be notified as applicable.
Refer to the iSRC IDMC Charter for more information.
Staggered design and iSRC IDMC meetings
No safety concerns have been raised from vaccination with different dosages of the 
investigational ChAd3-EBO-Z vaccine in healthy adults in the ongoing Phase 1 studies.
However, the investigational vaccine has never been administered to children yet. In 
order to ensure maximum safety for the subjects in this study, vaccination in the study 
will only start after a favourable outcome of an IDMC review of the safety and 
reactogenicity data from 100 adults after 1 week follow-up in the study EBOLA Z 
CHAD3-005. In addition, vaccination at Day 0 will be done in a staggered manner, 
starting with vaccination of the children in the oldest age stratum. For each age stratum, 
the iSRC IDMC will conduct a review of all available safety data once data is available 
up to at least 7 days after vaccination of at least 50 subjects (25/ group) in that age 
stratum. In order to proceed to vaccination of the subjects in the younger age stratum 
(6 to 12 years of age), possibly with a lower vaccine dose, a favourable outcome of the 
iSRC IDMC review of safety data up to at least 7 days after vaccination from at least 50 
subjects (25/ group) in the oldest age stratum needs to be obtained. The same will be done 
for moving from the 6 to 12 years of age stratum to vaccination of the youngest children 
(1 to 5 years of age).

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Figure 2
Overview of staggered design and iSRC IDMC safety evaluations
Holding rules
During the iSRC IDMC meetings depicted in Figure 2, study holding rules will be 
assessed. If any of these holding rules are met (or if any other safety concern is raised), 
vaccination will be put on hold and the VSMB will be consulted. 
The holding rules will be assessed per age stratum and the frequency of events described 
in the holding rules apply to the Group EBO-Z/ MENACWY-TT only.
Holding rules
…
Other iSRC IDMC meetings
In addition to the iSRC IDMC meeting that will be held before the first vaccination and 
the meetings depicted in Figure 2, the following iSRC IDMC evaluations will take place:

iSRC IDMC review of all safety and reactogenicity data included in the interim 
analysis that will be conducted when data is available from all subjects up to 30 days 
after vaccination at Day 0 (refer to Section 11.11.2 for more information on this 
interim analysis).

An ad hoc iSRC IDMC meeting will be held in case of an SAE considered related to 
vaccination at any time during the study.

Ad hoc iSRC IDMC meetings may be held if any safety concern is raised. 
(Amended 29 December 2014.)

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11.4
Determination of sample size
The primary objective of this study is to assess the safety of the investigational 
ChAd3-EBO-Z vaccine. (Amended 29 December 2014.)
...
11.5
Cohorts for Analyses (Amended 29 December 2014)
11.5.2
According-to-protocol cohort for analysis of safety
The ATP cohort for analysis of safety will include all vaccinated subjects: 

Who meet all eligibility criteria.

Who have received at least one dose of study vaccine according to protocol
procedures and to their random assignment. 

Who have not received a concomitant medication/ product/ vaccination that may lead
to elimination from an ATP analysis as listed in Section 6.7.2.

For whom the randomisation code has not been broken for vaccination at Day 0.
11.5.32
According-to-protocol cohort for analysis of 
immunogenicity
The ATP cohort for analysis of immunogenicity will include all evaluable subjects from 
the ATP cohort for analysis of safety:

Who meet all eligibility criteria.

Who have received at least one dose of study vaccine according to protocol 
procedures and to their random assignment.

For whom the randomisation code has not been broken for vaccination at Day 0.

Who comply with the procedures and intervals defined in the protocol (refer to
Table 6).
...
11.8
Analysis of safety
The primary analysis will be performed on the TVC. If in any study group, 5% or more of 
the vaccinated subjects are eliminated from the ATP cohort for analysis of safety, a 
second analysis will be performed on the ATP cohort for analysis of safety. (Amended 
29 December 2014.)
...

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11.11.1
Sequence of analyses
...
The analyses will be performed stepwise: 

Analyses of safety and reactogenicity data will be performed by for the iSRC IDMC.
Access to individual treatment codes will be restricted to the independent iSRC
IDMC support statistician in charge of the analyses and iSRC IDMC members.
(Amended 29 December 2014.)
...
APPENDIX A
LABORATORY ASSAYS (Amended 
29 December 2014)
Anti-GP EBOV Anti-EBOV GP IgG ELISA
Information on these assays was not available yet at the time of protocol finalisation.
Blood samples for antibody determination will be collected at indicated timepoints and 
serum will be separated and frozen at –20°C. 
Antibody level will be determined by evaluating antibody (IgG) responses specific for 
Zaire Ebola Virus Glycoprotein (EBOV GP) using the ELISA developed by Battelle 
and JVAP/USAMRIID and transferred to Quest (Focus) laboratory.
Briefly, microtiter plates are coated with the purified recombinant Zaire GP (rGP) 
specific to the Kikwit-95 strain (the Non-Human Primates (NHP) challenge strain). 
This strain is 98.5% identical to the vaccine Mayinga EBOV strain (11 aa mismatched) 
and is 97.5% identical to the isolated Guinea 2014 virus strain (17 aa mismatched). 
Serial diluted test samples, 2 serial-diluted controls (one QC-high and one QC-low) 
and a negative sample control (composed of pooled normal human serum purchased 
from a commercial source) are allowed to incubate in the GP coated wells allowing GP 
specific antibodies to bind. Additionally, a two-fold serial diluted reference standard, 
obtained from a vaccinated donor, is included in duplicate. Each well is then incubated 
with goat anti-human IgG horseradish peroxidase conjugate (HRP). TMB substrate is 
added to each well and the enzymatic reaction is stopped with a sulfuric acid solution. 
The color change is then read in a plate reader and sample titers are based on the 
standard curve calculated using a 4 parameter logistic curve fit. Results are reported in 
ELISA units/ml (EU/ml). A 2nd generation human standard (microgram/mL) will be 
evaluated and bridged to the current standard.
This assay will be qualified at Quest Diagnostics laboratories before starting the 
clinical testings.

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APPENDIX B
CLINICAL LABORATORIES (Amended 
29 December 2014)
Table 24
Outsourced laboratories
Laboratory
Address
NIAID Vaccine Immune T-Cell and 
Antibody Laboratory (NVITAL)
Suite 150
9 West Watkins Mill Road
Gaithersburg, MD 20878
Quest Diagnostics
Focus Diagnostics Clinical Trials, Inc. 
(d/b/a Quest Diagnostics)
33608 Ortega Highway 
San Juan Capistrano,
CA 92675-2042,
United States of America
APPENDIX C
ACCEPTABLE LIMITS FOR ELLIGIBILITY AND 
TOXICITY GRADING SCALES FOR 
HAEMATOLOGY/ BIOCHEMISTRY 
PARAMETERS (Amended 29 December 2014)

C O N FI D E N TI A L
2 0 2 0 9 0 ( E B O L A Z C H A D 3 -0 0 4 )
Pr ot o c ol A m e n d m e nt 2 Fi n al
0 6 -M a y -1 5
1 2 5
Gl a x o S mit h Kli n e Bi ol o gi c al s
Vacci ne Val ue & Healt h Scie nce ( V V H S)
Pr ot oc ol A me n d me nt 2
e Tr ac k st u d y n u m ber 
a n d A b bre vi ate d Title
2 0 2 0 9 0 ( E B O L A Z C H A D 3- 0 0 4)
I N D n u m ber
1 6 3 0 0
E u dr a C T n u m ber
2 0 1 4- 0 0 4 7 1 4- 2 8
A m e n d me nt n u m ber
A me n d me nt 2
A m e n d me nt d ate
0 6 Ma y 2 0 1 5
C o -or di n ati n g a ut h or
, Q ui ntiles, Me dical Writi n g
R ati o n ale/ b ac k gr o u n d f or c h a n ges: 

I n t he o n-g oi n g P hase 1 st u dies wit h t he i n vesti gati o nal C h A d 3 -E B O -Z vacci ne i n 
t he U nite d States ( U S), U nite d Ki n g d o m ( U K), S witzerla n d a n d Mali, tra nsie nt 
decreases i n t hr o m b oc y te c o u nts were o bser ve d . T hese decreases occ urre d m ostl y 
o n Da y  1 after vaccinati o n a n d ge nerall y  ret ur ne d t o baseli ne b y D a y 7. Alt h o u g h 
m ost of t hese decreases re mai ne d wit hi n t he n or mal ra n ge, t he as per pr ot oc ol 
criteria f or t hr o m bo c y t o pe nia (t hr o m b oc yte c o u nt of < 1 5 0 x 1 0 3/µ L ) were met f or 
2. 6 % ( 7 o ut of 2 7 0 ) of t he vacci nate d s u bjects. N o ne of t he decreases i n 
t hr o m b oc yte c o u nts or t he cases of t hr o m b oc y t o pe nia were cli nically si g nifica nt, 
i.e., n o cli nical si g ns or s y m pt o ms s u g gesti ve of i ncrease d te n de nc y t o blee d were 
re p orte d i n a ny of t he s u bjects. Please refer t o t he In vesti gat or’s Br oc h ure (I B) f or 
m ore i nf or mati o n.
I n t he c urre nt st u d y, a m ore v ul nera ble p o p ulati o n (c hil dre n) will be e nr olle d a n d 
t he acce pta ble li mit f or t he t hr o m b oc yte c o u nt f or st u d y eli gi bilit y (t hr o m b oc yte 
c o u nt of 1 0 0 x 1 0 3/µ L  is acce pta ble) will be l o wer as c o m pare d t o t he P hase 1 
st u dies. In a d diti o n, i n or der t o e ns ure e n ha nce d vi gila nce fr o m t he I n vesti gat ors, 
cli nical blee di n g e ve nts (acc or di n g t o t he Sta n dar dise d Me dical Dicti o nar y f or 
Re g ulat or y  Acti vities [ Med D R A] Q uer y  cli nical hae m orr ha ge) wit hi n 7 da y s after 
vacci nati o n at Da y  0 will be rec or de d a n d re p orte d as a d verse e ve nts (A Es) of 
s pecific i nterest (cli nical s ym pt o ms of t hr o m b oc y t o pe nia).

Base d o n safet y a n d i m m u n o ge nicit y data fr o m t he o n-g oi n g P hase 1 st u dies, t he 
1 x 1 0 1 1 viral particles ( v p) d ose was selecte d f or f urt her assess me nt i n P hase 2 a n d 
P hase 3 cli nical st u dies i n a d ults. T his d ose was deter mi ne d usi n g a hi g h 
perf or ma nce li q ui d c hr o mat o gra p h y ( H P L C) a nal ytical met h o d f or t he vacci ne l ots 
use d i n t he P hase 1 st u dies. T he sa me d ose will als o be use d i n t his pae diatric 
st u d y. H o we ver, de pe n di n g o n t he rec o m me n dati o n of t he i n de pe n de nt data 
m o nit ori n g c o m mittee (I D M C), a l o wer d ose ma y be selecte d base d o n safet y  a n d 
react o ge nicit y data accr ue d duri n g t he a ge de-escalati o n pr ocess f or c hil dre n i n 
y o u n ger a ge strata. I n a d diti o n, beca use a differe nt a nal y tical met h o d was use d t o 
deter mi ne t he v p c o nce ntrati o n f or t he l ots use d i n t his st u d y  (q ua ntitati ve 
P P D

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polymerase chain reaction [qPCR]) as compared to the lots used in the Phase 1 
studies (HPLC), a dose of 2x1011 vp, as determined by qPCR, will be used in this 
study, to administer the equivalent of the 1x1011 vp dose, that was determined by 
HPLC and shown to be optimal in Phase 1 studies. This information was added in 
the protocol. 

Demographic data collection was updated to allow the full date of birth in the 
subject’s eSource, but only month and year of the date of birth will be exported to 
GlaxoSmithKline’s (GSK’s) clinical database to guarantee subject confidentiality. 
The age as calculated in eSource will be used for analysis purposes as the full date 
of birth will not be exported.

The IDMC highlighted that the study is conducted in Malaria endemic countries 
and that the presence of malarial infection may adversely affect the safety and 
immunogenicity evaluations of the investigational ChAd3-EBO-Z vaccine. In 
order to prevent subjects with Malaria from entering the study, all subjects who 
provide informed consent for study participation will be tested for Malaria 
infection at the time of Screening, using a rapid diagnostic test (RDT) procedure. 
Subjects who are diagnosed with Malaria, will receive antimalarial treatment 
according to local/ national standards during the Screening period (e.g., a 3-day 
treatment course of artemisinin-based combination therapy). Hence, only subjects 
for whom the RDT was negative, or for whom the RDT was positive and who 
received a complete course of antimalarial treatment during the Screening period 
can be considered for study participation. Procedures for Malaria Screening and 
treatment, as well as eligibility criteria specific for these procedures were adapted 
in the protocol.

The scope of re-screening subjects has been clarified during the investigator’s 
meeting, i.e., re-screening of subjects must be avoided and redrawing blood from 
the subject is only permitted during the Screening period if, for technical reasons, 
test results are not available or if they are non-interpretable. To comply with this 
recommendation and avoid the risk of inadequate re-screening, footnote 11 under 
Table 5 (List of study procedures) has been removed. 

After consultation with the Principal Investigators and the IDMC, the exclusion 
criterion “Maternal death” was removed. Instead the following exclusion criterion 
was included:
Any condition that in the Investigator’s opinion may potentially compromise 
subject safety or interfere with subject assessment or compliance.
This will allow the investigator also to consider, on a case by case basis, whether 
the family circumstances of the child may allow participation to the study in 
compliance with local regulations, when applicable.

Blood sample volumes for haematology and biochemistry testing were corrected.

Some minor editorial updates were made.

C O N FI D E N TI A L
2 0 2 0 9 0 ( E B O L A Z C H A D 3 -0 0 4)
Pr ot o c ol A m e n d m e nt 2 Fi n al
0 6 -M a y -1 5
1 2 7
A m e n de d te xt h as bee n i ncl u de d i n b ol d it alics a n d delete d te xt i n stri ket hr o u g h i n 
t he f oll o wi n g secti o ns:
TI T L E P A G E
I n vesti g ati o n al Ne w Dr u g 
(I N D) n u m ber
T o be deci de d 1 6 3 0 0
( A me n de d 0 6 M ay 2 0 1 5.)
C o ntri b uti n g a ut h ors
...

 ( C V O-E ur o pe f or G S K 
Bi ol o gicals) a n d 
 ( C R O M S o urce f or 
G S K Bi ol o gic als) , Vacci ne S u p pl y C o or di nat or
( A me n de d 0 6 M ay 2 0 1 5.)
...

 a n d 
( B usi ness & 
Decisi o n Life Scie nces f or G S K Bi ol o gicals), G V C L 
St u d y Ma na ger
( A me n de d 0 6 M ay 2 0 1 5.)
…

 a n d 
( X P E P har ma & 
Scie nce f or G S K Bi ol o gicals), Scie ntific Writer
( A me n de d 0 6 M ay 2 0 1 5.)
C o ntr a ct e d R e s e ar c h Or g a ni s ati o n ( Q ui ntil e s) I nf or m ati o n
4.
Me dic al E x pert f or t he St u d y
, M D
Se ni or Me dical Direct or 
Pe diatric Ce nter of E xcelle nce
Aller g y , Res pirat or y, I D & Vacci nes T D U
P P D
Aller gy, Res pir at ory, I nfecti o us Dise ases & V acci nes
Me dic al Str ate gy & Scie nce
T her a pe utic Scie nce & Str ate gy U nit
( A me n de d 0 6 M ay 2 0 1 5.)
P P D
P P D
P P D
P P D
P P D
P P D

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SYNOPSIS
Rationale for the 
study and study 
design

Rationale for the study design

Investigational ChAd3-EBO-Z vaccine dose
Dose selection for paediatric use will be was based on 
information derived from dose-range studies 
conducted with the ChAd3-EBO-Z vaccine candidate 
in adults and on past experience with other 
recombinant adenovirus-based candidate vaccines. 
(Amended 06 May 2015.)
...
Four different investigational vaccine doses are 
currently being evaluated for safety, reactogenicity 
and immunogenicity in adults in Phase 1 studies. 
Based on data from these studies, the 1x1011 vp dose 
was selected for further assessment in Phase 2 and 
Phase 3 clinical studies in adults. This dose was 
determined using a high performance liquid 
chromatography (HPLC) analytical method for the 
vaccine lots used in the Phase 1 studies. The same 
dose will be used in this paediatric study. However, 
depending on the recommendation of the 
independent data monitoring committee (IDMC), a 
lower dose may be selected based on safety and 
reactogenicity data accrued during the age 
de-escalation process for children in younger age 
strata. It should be noted that the analytical 
method (quantitative polymerase chain reaction 
[qPCR]) that measures the concentration of virus 
particles per mL (vp/mL) present in the 
ChAd3-EBO-Z vials used in the current paediatric 
study is different from the analytical method 
(HPLC) used for the Phase 1 studies. As a result, a 
dose of 2x1011 vp will be used in this study, to 
administer the equivalent of the 1x1011 vp dose that 
was shown to be optimal in Phase 1 studies. As for 
other recombinant adenovirus-based vaccine 
candidates which showed adequate safety upon the 
use of adult doses in children as explained above, it is 
currently proposed that the same vaccine dose as the 
dose selected for adults will be assessed in children 1 
to 17 years of age in this study. However, a lower 
vaccine dose may be selected for children of younger 
age groups based on the safety and reactogenicity data 
accrued during the age de-escalation process.

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(Amended 06 May 2015.)
…

Malaria Screening and treatment
As this study is conducted in Malaria endemic regions 
and the presence of malaria infection may adversely 
affect the safety and immunogenicity evaluations of the 
investigational ChAd3-EBO-Z vaccine, all subjects will 
be tested for Malaria infection using an RDT procedure 
during Screening and all subjects diagnosed with 
Malaria will receive antimalarial treatment according to 
local/ national standards (e.g., a 3-day treatment course
of artemisinin-based combination therapy), during the
Screening period. Hence, only subjects for whom the 
RDT was negative, or for whom the RDT was positive 
and who received a complete course of antimalarial 
treatment during the Screening period can be 
considered for study participation.
(Amended 06 May 2015.)
Study design
...

Blinding: 
...
Single-blind as of the interim analysis at Day 30.
(Amended 06 May 2015.)

Sampling schedule:

A blood sample (fingerprick) will be taken at 
Screening for Malaria RDT.
(Amended 06 May 2015.)

…
Endpoints
Primary
...

Occurrence of haematological (complete blood count 
[CBC], including differential count and platelet count) 
and biochemical (alanine aminotransferase [ALT], 
creatinine) laboratory abnormalities at Screening, Day 3, 
Day 6, Day 30, Month 6, Month 6 + 6 days, Month 6 + 
30 days and Month 12 in all subjects in both groups.

Occurrence of clinical symptoms of thrombocytopenia 
(AE of specific interest), during a 7-day follow-up 
period after vaccination at Day 0 (i.e., Day 0 up to 

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Day 6), in all subjects, in both groups. 
(Amended 06 May 2015.)

Occurrence of any serious adverse event (SAE), in all 
subjects, in both groups.
LIST OF ABBREVIATIONS (Amended 06 May 2015)
HPLC:
High Performance Liquid Chromatography
NA:
Not Applicable
qPCR:
Quantitative Polymerase Chain Reaction
RDT:
Rapid Diagnostic Test
SDV:
Source Document Verification
TBD:
To Be Determined
1.2.2.1
Investigational ChAd3-EBO-Z vaccine dose
Dose selection for paediatric use will be was based on information derived from dose-
range studies conducted with the ChAd3-EBO-Z vaccine candidate in adults and on past
experience with other recombinant adenovirus-based candidate vaccines. (Amended 
06 May 2015.)
...
Four different investigational vaccine doses are currently being evaluated for safety, 
reactogenicity and immunogenicity in adults in Phase 1 studies. Based on data from 
these studies, the 1x1011 vp dose was selected for further assessment in Phase 2 and 
Phase 3 clinical studies in adults. This dose was determined using a high performance 
liquid chromatography (HPLC) analytical method for the vaccine lots used in the 
Phase 1 studies. The same dose will be used in this paediatric study. However, 
depending on the recommendation of the independent data monitoring 
committee (IDMC), a lower dose may be selected based on safety and reactogenicity 
data accrued during the age de-escalation process for children in younger age strata. It 
should be noted that the analytical method (quantitative polymerase chain 
reaction [qPCR]) that measures the concentration of virus particles per mL (vp/mL) 
present in the ChAd3-EBO-Z vials used in the current paediatric study is different 
from the analytical method (HPLC) used for the Phase 1 studies. As a result, a dose of 
2x1011 vp will be used in this study, to administer the equivalent of the 1x1011 vp dose 
that was shown to be optimal in Phase 1 studies. As for other recombinant 
adenovirus-based vaccine candidates which showed adequate safety upon the use of adult 
doses in children as explained above, it is currently proposed that the same vaccine dose 

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as the dose selected for adults will be assessed in children 1 to 17 years of age in this 
study. However, a lower vaccine dose may be selected for children of younger age groups 
based on the safety and reactogenicity data accrued during the age de-escalation process.
(Amended 06 May 2015.)
As this study is conducted in Malaria endemic regions and the presence of Malaria 
infection may adversely affect the safety and immunogenicity evaluations of the 
investigational ChAd3-EBO-Z vaccine, all subjects will be tested for Malaria infection 
using a rapid diagnostic test (RDT) procedure during Screening. Subsequently, all 
subjects diagnosed with Malaria will receive antimalarial treatment according to 
local/ national standards (e.g., a 3-day treatment course of artemisinin-based 
combination therapy), during the Screening period. Hence, only subjects for whom the 
RDT was negative, or for whom the RDT was positive and who received a complete 
course of antimalarial treatment during the Screening period can be considered for 
study participation. (Amended 06 May 2015.)
1.3.2
Benefit assessment
...
Other benefits
All subjects who provide informed consent for study participation will be tested for 
Malaria infection using an RDT procedure at the time of Screening. Subjects who are 
diagnosed with Malaria will receive antimalarial treatment according to local/ national 
standards (e.g., a 3-day treatment course of artemisinin-based combination therapy), 
during the Screening period, to clear the infection prior to vaccination. (Amended 
06 May 2015.)
...
3.
STUDY DESIGN OVERVIEW
...

Blinding: 

…

Single-blind as of the interim analysis at Day 30. (Amended 06 May 2015.)

Sampling schedule:

A blood sample (fingerprick) will be taken at Screening for Malaria RDT.
(Amended 06 May 2015.)

…

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4.3
Inclusion criteria for enrolment
...

A male or female child aged 1 to 17 years inclusive at the time of Screening.
(Amended 06 May 2015.)

Subjects with a negative RDT test for Malaria within 30 days prior to 
randomisation into the study.
OR
Subjects with a positive RDT test for Malaria who completed antimalarial 
treatment at least 5 days prior to randomisation into the study.
(Amended 06 May 2015.)
...
4.4
Exclusion criteria for enrolment
...

Maternal death. (Amended 06 May 2015.)
...

Any condition that in the Investigator’s opinion may potentially compromise
subject safety or interfere with subject assessment or compliance. 
(Amended 06 May 2015.)
5.2.2.1
Diary Card for follow-up adverse events occurring from day 0 to 
day 6 after vaccination
…
Access to the IVRS/ IWRS system unblinded treatment information will be limited to 
unblinded site staff. (Amended 06 May 2015.)
…
5.3
Method of blinding 
The blinding level will change in the course of the study:

Observer-blind from study start until the interim analysis that will be conducted 
when safety, reactogenicity and immunogenicity (including at least anti-GP EBOV 
data at Day 30) data is available from all subjects up to 30 days after vaccination at 
Day 0 (refer to Section 11.11.1 for more information on this interim analysis). By 
observer-blind, it is meant that the vaccine recipient and those responsible for the 
evaluation of any study endpoint will all be unaware of which vaccine was 
administered. To do so, vaccine preparation and administration at Day 0 will be done 

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by authorised medical personnel who will not participate in any of the study clinical 
evaluation assays.
To ensure blinding of the site staff when preparing and administering the study 
vaccine details of vaccine management will be defined in a site vaccine 
management plan before site initiation.
(Amended 06 May 2015.)

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5.5.1
List of study procedures
Table 5
List of study procedures during visits to the vaccination centre (Amended 06 May 2015)
Type of contact
Visit
Visit
Visit
Visit
Visit
Contact *
Visit
Visit 
Visit
Contact *
Visit
Timepoint
Screening 1 Day 0 1 Day 3 Day 6 Day 30
Month 3
Month 6
Month 6 + 
6 days 
Month 6 + 
30 days
Month 9
Month 12
Informed consent
●
Informed assent 10
●
RDT for Malaria
●
Malaria treatment 11
●
Inclusion/exclusion criteria 12
●
●
Demographic data
●
Medical history 12
●
●
Physical examination (including vital signs 2) 
●12
● 3
O
O
O
●
O
O
O
…
Study group and treatment name allocation 6
O
O 
...
Blood sampling:
  Blood for haematology/ biochemistry 
●12
●
●
●
●
●
●
●
  Blood for humoral immunity 
●
●
●
●
●
  Blood for CMI 7
●
●
●
●
●
Safety assessment:
  Record solicited AEs (day 0 to day 6)
●
●
●
● 
●
  Record unsolicited AEs (day 0 to day 29)
●
●
●
●
● 
●
●
Record AEs of specific interest (clinical symptoms of 
thrombocytopenia)
●
●
...
Screening Conclusion 11
…
… RDT = Rapid Diagnostic Test; …
11 Subjects who are Screening failures for a reason that is expected to be temporary may be re-Screened once. A different subject identification number will be assigned to such 
subject at re-Screening.
11 Subjects diagnosed with Malaria at Screening must receive antimalarial treatment according to local/ national standards (e.g., a 3-day treatment course of 
   artemisinin-based combination therapy), during the Screening period.
12 Study procedure must be performed at least 5 days after completion of Malaria treatment for all subjects diagnosed with Malaria at Screening.

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5.6.2
Malaria Screening and treatment (Amended 06 May 2015)
After obtaining the informed consent of the subject’s parent(s)/ LAR(s), all subjects 
should first be tested for Malaria infection using the WHO pre-qualified RDT. 
All subjects diagnosed with Malaria using the RDT must receive antimalarial 
treatment according to local/ national standards (e.g., a 3-day treatment course of 
artemisinin-based combination therapy), during the Screening period. In addition, a 
pregnancy test should be performed for women of childbearing potential in case the 
RDT is positive, so that an antimalarial treatment alternative to artemisinin-based 
combination therapy (e.g., quinine plus clindamycin) is proposed in case the pregnancy 
test is positive.
For subjects whose RDT is positive, the following Screening procedures should be 
postponed until at least 5 days after completion of the Malaria treatment (Figure 2):

Blood sampling for haematology and biochemistry testing.

Physical examination.

Review of eligibility criteria.

Completion of the medical history.

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Figure 2
Screening procedures
ICF = Informed Consent Form; RDT = Rapid Diagnostic Test

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The outcome of the Malaria RDT and completion of Malaria treatment needs to be 
recorded in eSource. 
5.6.2 5.6.3
Check inclusion and exclusion criteria
Check all inclusion and exclusion criteria as described in Sections 4.3 and 4.4 before 
enrolment. 
For subjects diagnosed with Malaria at Screening, a full eligibility check should be 
postponed until at least 5 days after completion of Malaria treatment.
(Amended 06 May 2015.)
5.6.3 5.6.4
Collect demographic data
Record demographic data such as date of birth (month and year only full date of birth 
will be collected in eSource, but only month and year of the date of birth will be 
exported to GSK’s clinical database. The age as calculated in eSource will be used for 
analysis purposes as the full date of birth will not be exported), gender, geographic 
ancestry, and ethnicity, in the subject’s eSource. 
(Amended 06 May 2015.)
5.6.4 5.6.5
Medical history
…
For subjects diagnosed with Malaria at Screening, completion of medical history 
should be postponed until at least 5 days after completion of Malaria treatment.
(Amended 06 May 2015.)
5.6.5 5.6.6
Physical examination
...
For subjects diagnosed with Malaria at Screening, physical examination should be 
postponed until at least 5 days after completion of Malaria treatment.
(Amended 06 May 2015.)
During all other study visits, perform a physical examination only if the subject indicates 
during questioning that there might be some underlying pathology(ies) or if deemed 
necessary by the Investigator or delegate. If a physical examination is performed during 
one of these visits, collected information will not need to be recorded in eSource.
(Amended 06 May 2015.)
...

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5.6.11
Sampling
…

A blood sample (fingerprick) will be taken at Screening for Malaria RDT.
(Amended 06 May 2015.)

…

A volume of approximately 1 0.5 to 2 1.5 mL (depending on the age of the child) of 
whole blood should be drawn from all subjects for each analysis of haematology/
and each analysis of biochemistry parameters at each pre-defined timepoint. 
(Amended 06 May 2015.)
5.6.14
Recording of adverse events, serious adverse events and
pregnancies

Refer to Section 9.3 for procedures for the Investigator to record AEs, serious 
adverse events (SAEs), and pregnancies. Refer to Section 9.4 for guidelines and how 
to report AEs of specific interest (clinical symptoms of thrombocytopenia), SAEs,
and pregnancies to the CRO (Quintiles).
(Amended 06 May 2015.)
...
5.6.14.1
Diary Card for follow-up adverse events occurring from day 0 to 
day 6 after vaccination
Subjects in the sub-cohort for follow-up of AEs and assessment of humoral immunity 
will be followed up for AEs on a daily basis during the 7-day follow-up period after 
vaccination. During this period, AEs with the exception of AEs of specific interest 
(clinical symptoms of thrombocytopenia) will be recorded on a Diary Card.
(Amended 06 May 2015.)
...

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5.7.2
Biological samples
Table 7
Biological samples (Amended 06 May 2015.)
Sample type
Quantity
Unit
Age strata
Timepoint
Sub-cohort *
Number of 
subjects
Blood for 
Malaria 
Screening
Fingerprick NA
1 to 17 years
Screening
All screened subjects
> 600
Blood for 
haematology/ 
biochemistry
1 to 2 0.5 
to 1.5
mL
1 to 17 years
Screening
All screened subjects
> 600
Day 3
All enrolled subjects
600
Day 6
Day 30
Month 6
Month 6 + 6 days
Month 6 + 30 days
Month 12
Blood for 
biochemistry
0.5 to 1.5
mL
1 to 17 years
Screening
All screened subjects
> 600
Day 3
All enrolled subjects
600
Day 6
Day 30
Month 6
Month 6 + 6 days
Month 6 + 30 days
Month 12
…
... NA = not applicable
5.7.3
Laboratory assays
…
In addition to the assays described below, other tests to characterise the safety and/ or the 
immunogenicity of the investigational ChAd3-EBO-Z vaccine may be performed if 
deemed necessary for accurate interpretation of the data and/ or should such test(s) 
become available.
Screening for Malaria infection will be performed using the WHO pre-qualified RDT 
at the site. 
(Amended 06 May 2015.)
5.7.3.2
Immune response against Ebola
Table 8
Humoral immunity against Ebola (Amended 06 May 2015)
System
Component
Method
Kit/ Manufacturer
Laboratory *
Serum
anti-GP EBOV
ELISA
TBD In-house
Quest Diagnostics
... TBD = to be determined ...

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6.
STUDY VACCINES/ PRODUCTS AND ADMINISTRATION 
(AMENDED 06 MAY 2015.)
6.1
Malaria treatment (Amended 06 May 2015.)
All subjects diagnosed with Malaria during Screening will receive antimalarial 
treatment according to local/ national standards (e.g., a 3-day treatment course of 
artemisinin-based combination therapy), during the Screening period.
6.1 6.2
Description of study vaccines
...
Table 14
Study vaccines (Amended 06 May 2015)
Treatment 
name
Vaccine/ 
Product name
Formulation
Presentation
Volume to be 
administered
Number 
of doses
ChAd3-EBO-Z
ChAd3-EBO-Z
ChAd3-EBO-Z= 
12*1011vp/mL*
Liquid in vial
0.25 mL to 
1 mL **
1
Nimenrix
MenACWY-TT 
PSA=5 µg TT; 
PSC=5 µg TT; 
PSW₁₃₅=5 µg TT; 
PsY=5 µg TT; 
TT~=44 µg 
Powder in vial
0.5 mL ***
1
NaCl 
NaCl=150 mM 
Liquid in 
monodose, 
prefilled syringe
...
* The dose used in this study, labelled 2*1011 vp corresponds to the dose, labelled 1*1011 vp, used in the Phase 
I studies that was selected for further clinical development. The difference in vp concentration on the labels of 
the lots used in this study and the Phase I studies is the result of a different analytical method that was used 
to determine the vp concentration. 
** The volume to be administered to children in younger age strata will depend on the dosage ChAd3-EBO-Z 
selected based on Phase 1 data on the concentration of the investigational ChAd3-EBO-Z vaccine and will be 
described in the Pharmacy Manual. the recommendation of the independent data monitoring committee as a 
lower vaccine dose may be selected based on safety and reactogenicity data accrued during the age 
de-escalation process (Refer to Section 1.2.2.1).
*** Refer to the Pharmacy Manual for the volume to be injected after reconstitution.
6.3 6.4
Dosage and administration of study vaccines
Table 15
Dosage and administration (Amended 06 May 2015)
…
... IM = intramuscular; vp = viral particles
...
** The volume to be administered to children in younger age strata will depend on the dosage ChAd3-EBO-Z 
selected based on Phase 1 data on the concentration of the investigational ChAd3-EBO-Z vaccine and will be 
described in the Pharmacy Manual. the recommendation of the independent data monitoring committee as a 
lower vaccine dose may be selected based on safety and reactogenicity data accrued during the age 
de-escalation process (Refer to Section 1.2.2.1).

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7.
OCCURRENCE OF SUSPECTED OR CONFIRMED EBOLA 
VIRUS DISEASE
...

Case details will be captured as part of SAE reporting. In the case of a confirmed 
negative result, the event may be downgraded to non-serious.
(Amended 06 May 2015.)
...
9.1.3.2
Solicited general adverse events
...
Table 17
Solicited general adverse events (Amended 06 May 2015)
…
* Fever is defined as temperature 37.5°C / 99.5°F. Body temperature will may be measured axillary (preferred), 
oral, tympanic, or rectal.
...
9.1.5
Adverse events of specific interest
9.1.5.1
Clinical bleeding within 7 days post vaccination at Day 0
In the Phase 1 studies with the investigational ChAd3-EBO-Z vaccine in healthy 
adults, transient decreases in thrombocyte counts were 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 as per 
protocol criteria for thrombocytopenia (thrombocyte count of < 150x103/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 bleed were reported 
in any of the subjects. Please refer to the IB for more information.
In the current study, a more vulnerable population (children) will be enrolled and the 
acceptable limit for the thrombocyte count for study eligibility (thrombocyte count of 
100x103/µL is acceptable) will be lower as compared to the Phase 1 studies. In 
addition, in order to ensure enhanced vigilance from the Investigators, clinical 
bleeding events (according to the Standardised MedDRA Query clinical haemorrhage) 
within 7 days after vaccination at Day 0 will be recorded and reported as AEs of 
specific interest (clinical symptoms of thrombocytopenia).
(Amended 06 May 2015.)

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9.3.1
Time period for detecting and recording adverse events, 
serious adverse events and pregnancies
...
Adverse events
...
Adverse events of specific interest
All AEs of specific interest (clinical symptoms of thrombocytopenia) starting in the 
7-day follow-up period following vaccination at Day 0 must be recorded in the 
appropriate section of eSource.
(Amended 06 May 2015.)
...
Table 18
Reporting periods for collecting safety information (Amended 
06 May 2015)
Event
Scree-
ning*
Vacc end 7-day 
follow-up
end 30-day 
follow-up
Vacc end 7-day 
follow-up
end 30-day 
follow-up
Study 
Conclusion
Timepoint
D0
D6
D29
M6 M6 + 6 days
M6 + 29
days
M12
...
Unsolicited AEs
AEs of specific 
interest (clinical 
symptoms of 
thrombocyto-
penia)
SAEs
...
9.3.3.2.1
Assessment of intensity
...
Table 19
Intensity scales for solicited symptoms in infants/toddlers and 
children less than 6 years of age (Amended 06 May 2015)
…
...
** Fever is defined as temperature 37.5°C / 99.5°F. Body temperature will may be measured axillary (preferred), 
oral tympanic, or rectal.

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Table 20
Intensity scales for solicited symptoms in children of 6 years of age 
or more (Amended 06 May 2015)
…
...
** Fever is defined as temperature 37.5°C / 99.5°F. Body temperature will may be measured axillary (preferred), 
oral tympanic, or rectal.
...
9.4.1
Prompt reporting of adverse events of specific interest (clinical 
symptoms of thrombocytopenia), serious adverse events and 
pregnancies to the contracted research organisation 
(Quintiles) (Amended 06 May 2015)
Adverse events of specific interest (clinical symptoms of thrombocytopenia) that occur 
in the time period defined in Section 9.3.1 will be reported promptly to the CRO 
(Quintiles) within the timeframes described in Table 18, once the Investigator becomes 
aware of the event.
(Amended 06 May 2015.)
...
Table 21
Timeframes for submitting adverse events of specific interest
(clinical symptoms of thrombocytopenia), serious adverse events, 
and pregnancies to the contracted research organisation (Quintiles)
(Amended 06 May 2015)
Type of Event
Initial Reports
Follow-up of Relevant Information on a 
Previous Report
Timeframe
Documents
Timeframe
Documents
AEs of specific 
interest (clinical 
symptoms of 
thrombocytopenia)
24 hours*
electronic AE/ SAE form 
in eSource
24 hours*
electronic AE/ SAE form 
in eSource
SAEs
24 hours*, ‡
electronic AE/ SAE form 
in eSource
24 hours*
electronic AE/ SAE form 
in eSource
...
...
‡ The Investigator will always provide an assessment of causality be required to confirm review of the SAE causality 
by ticking the ‘reviewed’ box in the electronic AE/ SAE form in eSource within 72 24 hours of submission of the SAE.

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9.4.2
Contact information for reporting adverse events of specific 
interest (clinical symptoms of thrombocytopenia), serious 
adverse events, and pregnancies (Amended 06 May 2015)
Study Contact for Reporting AEs of specific interest, SAEs, and pregnancies 
...
Back-up Study Contact for Reporting AEs of specific interest, SAEs, and 
pregnancies 
…
9.4.3
Reporting of adverse events of specific interest (clinical 
symptoms of thrombocytopenia) to the contract research 
organisation (Quintiles) (Amended 06 May 2015)
Once an Investigator becomes aware that an AE of specific interest (clinical symptoms 
of thrombocytopenia) has occurred in a study subject, the Investigator (or designee) 
must complete the information in the electronic AE/ SAE form in eSource WITHIN 
24 HOURS. The AE and the SAE form in eSource is the same form. When an AE of 
specific interest (clinical symptoms of thrombocytopenia) is indicated on the electronic 
AE/ SAE form, additional follow-up questions will become available, for completion by 
the Investigator (or designee). 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 (clinical symptoms of 
thrombocytopenia), 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. 
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 serious adverse events 
reports to the contracted research organisation (Quintiles)
…
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 AE/ SAE form in eSource within 72 24 hours 
of submission of the SAE.
(Amended 06 May 2015.)

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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 AE of specific interest (clinical symptoms of 
thrombocytopenia)/ SAE form and fax it to the Back-up Study Contact for Reporting 
SAEs 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 AE/ AE of specific 
interest (clinical symptoms of thrombocytopenia)/ SAE form in eSource within 24 hours. 
The final valid information for regulatory reporting will be the information reported 
through the electronic AE of specific interest (clinical symptoms of thrombocytopenia)/
SAE reporting system.
(Amended 06 May 2015.)
9.4.6
Updating of adverse events of specific interest (clinical 
symptoms of thrombocytopenia), serious adverse events, and 
pregnancy information after removal of write access to the 
subject’s eSource (Amended 06 May 2015)
When additional AE of specific interest (clinical symptoms of thrombocytopenia), SAE,
or pregnancy information is received after removal of the write access to the subject’s 
eSource, 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 Back-up Study Contact for Reporting AE of specific interest (clinical symptoms of 
thrombocytopenia), SAEs, and pregnancy information within the designated reporting 
time frames specified in Table 21.
(Amended 06 May 2015.)
9.5.1.1
Follow-up during the study
After the initial AE/ AE of specific interest (clinical symptoms of thrombocytopenia)/ 
SAE report, the Investigator is required to proactively follow each subject and provide 
additional relevant information on the subject’s condition to the CRO (Quintiles) (within 
24 hours for AEs of specific interest (clinical symptoms of thrombocytopenia) and 
SAEs; refer to Table 21).

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All AEs of specific interest (clinical symptoms of thrombocytopenia) 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.
...
(Amended 06 May 2015.)
9.5.1.2
Follow-up after the subject is discharged from the study
The Investigator will follow subjects with AEs of specific interest (clinical symptoms of 
thrombocytopenia) and SAEs until the event has resolved, subsided, stabilised, 
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 AE 
of specific interest (clinical symptoms of thrombocytopenia) or SAE, he/ she will 
provide this information to the CRO (Quintiles) using an electronic AE/ AE of specific 
interest (clinical symptoms of thrombocytopenia) / SAE form in eSource and/ or 
pregnancy report as applicable.
The sponsor (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 of specific interest (clinical 
symptoms of thrombocytopenia) or SAE. The Investigator is obliged to assist. If a subject 
dies during participation in the study or during a recognised follow-up period, the CRO 
(Quintiles) will be provided with any available post-mortem findings, including 
histopathology.
(Amended 06 May 2015.)
11.1
Primary endpoints
...

Occurrence of haematological (CBC, including differential count and platelet count) 
and biochemical (ALT, creatinine) laboratory abnormalities at Screening, Day 3, 
Day 6, Day 30, Month 6, Month 6 + 6 days, Month 6 + 30 days and Month 12 in all 
subjects in both groups.

Occurrence of clinical symptoms of thrombocytopenia (AE of specific interest), 
during a 7-day follow-up period after vaccination at Day 0 (i.e., Day 0 up to 
Day 6), in all subjects, in both groups. 
(Amended 06 May 2015.)
...

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11.8
Analysis of safety
...
All analyses will be descriptive. Depending on the endpoint, data will be presented 
overall or for a sub-cohort of subjects. In a first step, the safety results will be presented 
by treatment administered at Day 0 (ChAd3-EBO-Z vaccine versus Placebo). In a second 
step, all available data post-vaccination with the investigational ChAd3-EBO-Z vaccine 
(ChAd3-EBO-Z vaccine at Day 0 and ChAd3-EBO-Z at Month 6) will be pooled. The 
latter aggregated data cannot be presented versus Placebo subjects because of the 
administration of the investigational ChAd3-EBO-Z vaccine to the subjects in the 
Group Placebo/ChAd3-EBO-Z, who initially received Placebo (population overlap).
(Amended 06 May 2015.)
...
SAEs and AEs of specific interest (clinical symptoms of thrombocytopenia) will be 
described in detail.
(Amended 06 May 2015.)
12.1
Electronic Case Report Form instructions (eSource)
...
In all cases, subject initials will not be collected in eSource, nor but will not be 
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 CRO standards and data cleaning procedures.
While completed eSource forms are reviewed by a CRO Site Monitor at the study site,
omissions or inconsistencies detected by subsequent eSource 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. 
(Amended 06 May 2015.)
...

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APPENDIX B
CLINICAL LABORATORIES (Amended 
06 May 2015)
Table 24
Outsourced laboratories
Laboratory
Address
NIAID Vaccine Immune T-Cell and 
Antibody Laboratory (NVITAL)
Suite 150
9 West Watkins Mill Road
Gaithersburg, MD 20878
United States
Quest Diagnostics
Focus Diagnostics Clinical Trials, Inc. 
(d/b/a Quest Diagnostics)
33608 Ortega Highway 
San Juan Capistrano,
CA 92675-2042,
United States of America
APPENDIX C
ACCEPTABLE LIMITS FOR ELLIGIBILITY AND 
TOXICITY GRADING SCALES FOR 
HAEMATOLOGY/ BIOCHEMISTRY 
PARAMETERS (Amended 06 May 2015)
...
Table 25
Acceptable limits/normal ranges for eligibility determination
(Amended 06 May 2015)
…
…
ALT (IU/mL)
< 60 (males) or < 40 (females)
...

P P D