A Phase 3b, Controlled, Open-Label, Multi-Center Study to Evaluate Safety and Immunogenicity of a Single Dose of GlaxoSmithKline's Meningococcal ACWY Conjugate Vaccine (Menveo), Administered to Healthy Individuals 15 Through 55 Years of Age, Approximately 4-6 Years After Primary ACWY Vaccination
Phase: PHASE3
Conditions: Infections, Meningococcal
Sponsor: GlaxoSmithKline

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CLINICAL STUDY PROTOCOL VS9 77 Version 1 
 
 
 
A Phase 3b, Controlled, Open-Label, Multi-Center Study to Evaluate Safety and 
Inumnogenicity of a Single Dose of GlaxoSmiht Kline's Meningococcal ACWY 
Conjugate Vaccine (Menveo), Administered to Healthy Individuals 15 through 55 years 
of age, approximately 4-6 years after primary ACWY vaccination. 
 
 
Safety and Immunogenicity Study of a Single Dose of Menveo, Administered to Subjects 
15 through 55 years of age, approximately 4-6 years after primary ACWY vaccination 
 
 
 
 
Proper ty of GlaxoSmithKline Biologicals S.A (hereafter refened to as GSK) 
Confidential 
May not be used, divulged, published or otherwise  disclosed without  \VIi tt .en 
co n se nt  of GSK 

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TABLE OF CONTENTS 
TABLE OF CONTENTS ..................................................................................................... 2 
PROTOCOL SYNOPSIS VS9 77 ................................................................................... 7 
LIST OF ABBREVIATIONS ............................................................................................. 20 
1. 
BACKGROUND AND RATIONALE ..................................................................... 21 
1.1 
Background .......................................................................................................... 21 
1.2 
Rationale .............................................................................................................. 22 
2. 
OBJECTIVES ........................................................................................................... 23 
2.1 
Primary Objective(s) ............................................................................................... 23 
2.2 
Secondary Objective(s) ......................................................................................... 23 
2.3 
Exploratory Objective(s) ...................................................................................... 24 
3. 
STUDYDESIGN................................................................................................. 2S 
3.1 OverviewofStudyDesign...............................................................................        2S 
3.2 StudyPeriod ..................................................................................................... 27 
3.3 
Blinding Procedures ............................................................................................. 27 
3.4 
Data Collection ............................................................................................................. 27 
3.4.1 
Data Collected from Subjects .................................................................... 27 
3.4.2 
Tools Used for Data Collection ......................................................................... 28 
3.S Collection of Clinical Specimens .................................................................... 29 
3.6 Stopping/Pausing Guidelines ........................................................................... 30 
3.7 
Data Monitoring Committee ............................................................................ 30 
3.8 
Premature Withdrawal from Study .................................................................. 30 
3.9 EndofStudy ............................................................................................... 33 
4. 
SELECTION OFSTUDY POPULATION .......................................................... 34 
4.1 Inclusion Criteria ............................................................................................. 34 
4.2 Exclusion Criteria ............................................................................................ 3S 
4.3 Criteria for Delay of Vaccination and/or Blood Sampling ............................... 36 
S. 
STUDYPROCEDURES ...................................................................................... 37 
S.1 
Pre-vaccination Clinic Visit(s) ......................................................................... 37 

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5.1.1 
Informed Consent/Assent ............................................................................................ 37 
5.1.2 
Screening ....................................................................................................... 38 
5.1.3 
Enrolment ..................................................................................................... 40 
5.1.4 
Randomization .............................................................................................. 40 
5.1.4.1 Randomization of supplies ....................................................................... 40 
5.1.4.2 Study group and treatment nwnber allocation .................................... 40 
5.2 Vaccination Clinic Visit. ................................................................................. 41 
5.2.1 
Post-vaccination Procedures ...................................................................... 41 
5.2.2 
Post-vaccination Reminders .......................................................................... 42 
5.3 Post-vaccination Visit(s) .................................................................................. 43 
5.3.1 
Follow-up Clinic Visit(s) .......................................................................... 43 
5.3.2 Safety Follow-up Calls .................................................................................. 44 
5.4 Unscheduled Visits .......................................................................................... 44 
5.5 Study Termination Visit. .................................................................................. 44 
5.5.1 
Early Termination Visit. ........................................................................... 45 
6. 
TREA1MENT OFSUBJECTS ..................................................................................... 46 
6.1 StudyVaccine(s) ..................................................................................................... 46 
6.2 Non-Study Vaccines ......................................................................................... 47 
6.3 
Vaccine Preparation and Administration ......................................................... 47 
6.3.1 Replacement of unusable vaccines .................................................................. 48 
6.4 
Vaccine Administration Error or Overdose ofVaccine .................................... 48 
6.5 
Prior and Concomitant Medications and Vaccines .......................................... 49 
6.6 
Vaccine Supply, Labeling, Storage and Tracking .................................................. 50 
7. 
ASSESSMENTS ...................................................................................................... 51 
7.1 SafetyAssessment ............................................................................................ 51 
7.1.1 
Solicited Adverse Events .......................................................................... 51 
7.1.2 
Unsolicited Adverse Events ...................................................................... 53 
7.1.3 
Evaluation of Adverse Events ................................................................... 53 
7.1.4 
Serious Adverse Events ............................................................................. 55 

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7.1.4.1 Adverse Events of Special Interest ..................................................... S6 
7.1.S Methods for Recording Adverse Events and Serious Adverse Events........ S6 
7.1.S.1 Post-Study Events .............................................................................. S8 
7.1.6 Pregnancies............................................................................................... S8 
7.1.7 Safety LaboratoryMeasurements .............................................................. S9 
7.2 Efficacy   Assessment........................................................................................  S9 
7.3 Immunogenicity  Assessment............................................................................  S9 
8. 
STATISTICAL CONSIDERATIONS ..................................................................... 60 
8.1 
Endpoints ......................................................................................................... 60 
8.1.1 
Primary Endpoint(s) ........................................................................................... 60 
8.1.1.1 
Primary SafetyEndpoint(s) ................................................................ 60 
8.1.1.2 
Primary EfficacyEndpoint(s) ............................................................. 60 
8.1.1.3 
Primary Immunogenicity Endpoint(s) ................................................ 60 
8.1.2 
SecondaryEndpoint(s) .............................................................................. 60 
8.1.2.1 
Secondary SafetyEndpoint(s) ........................................................ 60 
8.1.2.2 
Secondary Efficacy Endpoint(s) .......................................................... 61 
8.1.2.3 
Secondary Immunogenicity Endpoint(s) ................................................. 61 
8.1.3 
ExploratoryEndpoint(s) ............................................................................ 61 
8.1.3.1 
Exploratory Safety Endpoint(s) .......................................................... 61 
8.1.3.2 
Exploratory Efficacy Endpoint(s) .......................................................... 61 
8.1.3.3 
Exploratory Immunogenicity Endpoint(s) .......................................... 62 
8.2 
Success Criteria ................................................................................................ 62 
8.2.1 
Success Criteria for Primary Objective(s) .................................................... 62 
8.2.1.1 
Success Criteria for Primary Safety Objective(s) ................................. 62 
8.2.1.2 
Success Criteria for Primary Efficacy Objective(s) ................................ 62 
8.2.1.3 
Success Criteria for Primary Immunogenicity Objective(s) ................. 62 
8.2.2 
Success Criteria for Secondary Objective(s) ....................................... 62 
8.2.2.1 
Success Criteria for Secondary Safety Objective(s) ................................. 62 
8.2.2.2 
Success Criteria for Secondary Efficacy Objective(s) ........................... 62 

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8.2.2.3 
Success Criteria for Secondary Immunogenicity Objective(s) ........... 62 
8.3 
Analysis Sets .................................................................................................... 63 
8.3.1 
All Enrolled Set ......................................................................................... 63 
8.3.2 
All Exposed Set ......................................................................................... 63 
8.3.3 
Safety Set. ................................................................................................. 63 
8.3.4 
Full Analysis Set (FAS) Efficacy/Immunogenicity Set. ............................ 63 
8.3.5 
Per Protocol (PP) Set Efficacy/Immunogenicity Set ................................. 64 
8.3.6 
Other Analysis Sets ................................................................................... 64 
8.3.7 
Subgroups ................................................................................................. 64 
8.3.8 
Protocol Deviations .................................................................................. 64 
8.4 
Statistical Analysis Plan ................................................................................... 65 
8.4.1 
Analysis of Demographic and Baseline Characteristics ............................ 65 
8.4.2 
Analysis of Primary Objective(s) .................................................................. 65 
8.4.2.1 
Analysis of Primary SafetyObjective(s) ........................................ 65 
8.4.2.2 
Analysis of Primary Efficacy Objective(s) ........................................ 65 
8.4.2.3 
Analysis of Primary Immunogenicity Objective(s) ................................ 65 
8.4.2.3.1 
Statistical Hypotheses .................................................................. 65 
8.4.2.3.2 
Analysis Sets ............................................................................... 65 
8.4.2.3.3 
Statistical Methods ....................................................................... 66 
8.4.3 
Analysis of Secondary Objective(s) ............................................................... 66 
8.4.3.1 
Analysis of Secondary Safety Objective(s) ..................................... 66 
8.4.3.1.1 
Analysis of Extent of Exposure ................................................... 66 
8.4.3.1.2 
Analysis of Solicited Local, Systemic and Other Adverse Events 66 
8.4.3.1.3 
Analysis of Unsolicited Adverse Events ..................................... 67 
8.4.3.1.4 
Statistical Hypotheses ...................................................................... 68 
8.4.3.1.5 
5 ................................................................................. Analysis Sets
 68 
8.4.3.1.6 
Statistical Methods ...................................................................... 68 
8.4.3.2 
Analysis of Secondary Efficacy Objective(s) .................................. 68 
8.4.3.3 
Analysis of Secondary ImmunogenicityObjective(s) ........................ 69 

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8.4.3.3.1 
Statisitcal Hypotheses .............................................................. 69 
8.4.3.3.2 
Analysis Sets ............................................................................... 69 
8.4.3.3.3 
Statistical Methods ................................................................................ 69 
8.4.4 
Analysis of ExploratoryObjectives ............................................................... 71 
8.4.4.1 Analysis of ExploratorySafety Objective(s) .............................................. 71 
8.4.4.2 
2  Analysis of Exploratory Efficacy Objective(s) ................................... 71 
8.4.4.3 
Analysis of ExploratoryimmunogenicityObjective(s) .......................... 71 
8.5 
Sample Size and Power Considerations of Primary and Secondary Objectives. 71 
8.6  Interim Analysis ............................................................................................... 74 
9. 
SOURCE DOCUMENTATION, STUDY MONITORING AND AUDITING ...... 75 
9.1 Source Documentation ..................................................................................... 75 
9.2 Study Monitoring, Auditing and Source Data Verification  ................................ 76 
10. 
DATA MANAGEMENT ......................................................................................... 77 
IO. I  Data Entry and Management ................................................................................ 77 
10.2 Data Clarification ............................................................................................. 77 
10.3 Data Protection ................................................................................................ 77 
11. 
RECORD RETENTION .......................................................................................... 78 
12. USE OF INFORMATION AND PUBLICATION ...................................................... 79 
13. 
ETHICAL CONSIDERATIONS ............................................................................. 80 
13.I   Regulatory and Ethical Compliance ..................................................................... 80 
13.2 Infonned Consent Procedures .......................................................................... 80 
13.3 Responsibilitiesof the Investigator and!RB/EC ............................................... 81 
13.4 Protocol Amendments ...................................................................................... 82 
14. 
REFERENCE LIST ............................................................................................................... 84 
APPENDIX I: INVESTIGATOR AGREEMENT ......................................................... 85 

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PROTOCOL SYNOPSIS V59 77 
 
Name of Sponsor: 
GlaxoSmithKline 
Biologicals S.A 
Protoco l number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
Titl e of Study: A Phase 3b, Controlled, Open-Label,Multi-Center Study to Evaluate 
Safety and Immunogenicity of a Single Dose of GlaxoSmiht Kline' s Meningococcal 
ACWY Conjugate Vaccine (Menveo,)Administered to Healthy Individuals 15 througll 
55 years of age, approximately 4-6 years after primary ACWY vaccination. 
Study Pe1i od : Approximately 180 days 
(six months). 
Clinical Phase:3b 
Background and Rationale: 
Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis worldwide, 
capable of causing outbreaks and epidemics of invasive disease. Meningococcal disease 
is associated with higll morbidity and mortality even among patients who receive early 
antibiotictreatment. Most casesof invasive disease worldwide are caused by serogroups 
A, B, C, W and Y. 
The quadrivalent meningococcal oligosaccharide diphtheria CRM-197 conjugate 
vaccine (MenACWY-CRM; Menveo, GSK Vaccines) is approved for active 
inlmunization ofindividuals from 2 months througll 55 years of age in the United 
States, and in over 60 other countries. As of February 2015, more than 30,000of 
subjects have been exposed to MenACWY-CRM vaccine in completed clinical studies 
and more than 24 million doses of the vaccine have been distributed globally. 
The US Advisory Committee on Immunization Practices (ACIP) recommends routine 
vaccination with a quadrivalent conjugated meningococcal vaccine for adolescents at 
11-12 years of age with a booster dose administered 5 years later. While a substantial 
body of data exists showing a robust inlmune response and good antibody persistence 
after a single dose ofMenACWY-CRM in adolescents, the response to a booster dose of 
MenACWY-CRM in this agegroup has only been evaluated in 2 clinical studies with 
limited number of subjects. 
A robust anamnestic inlmune response to a booster dose ofMenveo vaccine 
administered at approximately 5 years after previous vaccination with thesame vaccine 
or a licensed meningococcal oolysaccharide vaccine (Menomune®) was demonstrated in 

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Name of Sponsor: 
GlaxoSmithKline 
Biologicals S.A 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
the phase 2 clinical study V59P6El . High titers of bactericidal antibodies against the 
vaccine serogroups were achieved at 7 and 30 days after booster dose in MenACWY­ 
primed subjects. However, the number of subjects included in this studywas relatively 
small (N=l 0l , including 50 subjects who received a booster dose after the primary 
MenACWY-CRM vaccination). 
In the phase 3b clinical study V59Pl3 El , a booster dose of MenACWY-CRM was 
given 3 years after primary vaccination with either MenACWY-CRM or Menactra®(a 
meningococcal diphtheria toxoid-conjugated MenACWY vaccine, MenACWY-D) in 
adolescents. A booster dose was able to substantially increase antibody titers against all 
4 serogroups irrespective of the priming vaccine. Again, only a small number of 
subjects (N=160) received the MenACWY-CRM booster, (83 who received primary 
MenACWY-CRM and 77 who received MenACWY-D). 
In the light of thecurrent ACIP recommendation for a booster dose of MenACWY­ 
CRM, there exists a need to evaluate the response to a MenACWY-CRM booster given 
at -5  years after primary vaccination in meningococca-lvaccineprimed adolescents. 
Generation of this data would also be of relevance in outbreak management and 
vaccination of travelers to endemic areas. 
The purpose/aim of this study is to assess the safety and antibody response to 
vaccination with a booster dose of Menveo given 4-6 years after primary vaccination 
and the response to a single dose given to vaccine-naivesubjects, and to describe the 
immune response over time after a booster dose of Menveo, administered to subjects 
previously vaccinated with Menveo or Menactra, and after a single dose ofMenveo to 
vaccine-naive subjects. The inclusion of vaccine-naive subjects in a separate study arm 
is to enable comparison of the rapidity and magnitude of an anamnestic response to a 
booster dose (in primed individuals) or the primary response to a first dose (in naive 
individuals) of MenACWY-CRM. 
Study Objectives: 
P1i ma ry Objective(s): Immunogenicity objective: 
1. To demonstrate a sufficient immune response following a booster dose of 
MenACWY-CRM (Menveo) vaccine, !riven to subjects who oreviously 
 
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Name of Sponsor: 
GlaxoSmithKline 
Biologicals S.A 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
received Menveo, as measured bythe percentage of subjects with hSBA 
seroresponsel against N. meningitidis serogroups A, C, Wand Y at Day 29 
after vaccination 
2. To demonstrate a sufficientimmune response following a booster dose of 
MenACWY-CRM (Menveo) vaccine, given to subjects who previously 
received Menactra, as measured by the percentage of subjects with hSBA 
seroresponsel against N . meningitidis serogroups A, C, Wand Y at Day 29 
after vaccination 
Criteria to demonstrate immune response sufficiency The immune response 
sufficiency will be tested sequentially; first in the group of subjects who received 
primary vaccination with Menveo and, if met, also in the group of subjects who 
received primary vaccination with Menactra . The immune response will be 
considered as sufficientif the lowerlimit of the one-sided 97.5% CI for percentage 
of subjects with hSBA seroresponse1 against serogroupsA, C, Wand Y is greater 
than 75%. The studywill beconsidered successful if the immune response 
sufficiency will be demonstrated at least in the group of subjects who received 
primary vaccination with Menveo. 
Secondar y Objective(s): 
Immunogenicity objectives: 
1. To compare the immune responses over time followinga booster dose of 
MenACWY-CRM vaccine, between subjects who previously received Menveo, 
subjects who previously received Menactra, and subjects who previously 
received Menveo or Menactra (pooled vaccine group) and following a single 
dose in vaccine-naive individuals, as measured by the percentages of subjects 
with  hSBA seroresponse1  hSBA titers ,::8 and 2:16, and hSBA GMTs against N. 
, 
menin<ritidis seroornuos A. C Wand Y at Dav1. Dav 4 Dav 6 and Dav 29 
 
 
 
1 Seroresponse is defined forthisstudy asfollows: For subjectswith pre-vaccinationtiters <4, pos­t 
vaccination titers 2: 16; forsubjects with pre-vaccinationtiters 2::4, post vaccination titers at least4 timesthe 
pre-vaccination titers. 
 
 
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Name of Sponsor: 
GlaxoSmithKline 
Biologicals S.A 
Protoco l nu mber: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheriaCRM-197 
conjugatevaccine 
after vaccination 
2. To assess persistence of bactericidal antibodies against serogroups A, C, Wand 
Y at approximately 4-6 years after the primary vaccination with Menveo and 
after the primary vaccination with Menactra in comparison with naturally­ 
acquired levels in vaccine-naiveindividuals, as measured by the percentages of 
subjects with hSBA titers 8 and hSBA GMTs at Day1. 
Safety objectives: 
1. To assess reactogenicity and safety of MenACWY-CRM vaccine when 
administered to subjects who previously received Menveo or Menactra and 
vaccine-naive individuals. 
Study Design: 
This is a phase 3b, controlled, open-label, multi-center studyto evaluate safety and 
inlmunogenicity of MenACWY-CRM after a single vaccination in healthy individuals 
who were vaccinated with Menveo or Menactra 4 to 6 years before and in vaccine-naive 
individuals. 
Study population Approximately 700 healthy subjects 15 througll 55 years of age will 
be enrolled in the study. 
Duration of the study The duration of this study is approximately 6 months per subject. 
Written informed consent and, as applicable according to local guidelines, written 
assent will be obtained before conducting any study-specificprocedures. 
Vaccination schedule: All subjects will receive a single dose of MenACWY-CRM at 
Day1. 
Study groups: 
• Group Menveo-Menveo:approximately 300 subjects, who were vaccinated with a 
single dose ofMenveo 4 to 6 years before, will receive one doseof MenACWY­ 
CRM. 
• Grouo Menactra-Menveo:aooroximatelv 300 subiects, who were vaccinated with a 
 
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Name of Sponsor: 
GlaxoSmithKline 
Biologicals S.A 
Protocol number: 
V59- 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
single dose ofMenactra 4 to 6 years before, will receive one dose ofMenACWY- 
CRM. 
• Group Naive: approximately 100 subjects, of similar age to subjects enrolled in 
other primed groups, with enrolment distributed across all clinical sites, who have 
not received any meningococcal vaccination, will receive one dose ofMenACWY- 
CRM. 
Randomization / Stratification: 
Within eachstudy group, subjects will be randomized into one of two different blood 
draw schedules according to a 1:1 ratio, described as follows: 
• Subjects getting blood draws at Day 1, Day4 andDay29. 
• Subjects getting blood draws at Day 1, Day 6 and Day 29. 
For a schematic overview, see Table 1. 
Table I: 
Schema tic diagra m of the VS9_77 stu dy gro ups 
Vacc.ine History 
Vacc.ination in current 
study 
Blood drawschedule 
Menveo 
N=300 
Menveo 
Blood draw Day I, 4, 29 (N=l50) 
Blood draw Day I, 6, 29 (N=150) 
Menactra 
N=300 
Menveo 
Blood draw Day I, 4, 29 (N=l50) 
Blood draw Day I, 6, 29 (N=l50) 
Vaccine-Naive 
N=l OO 
Menveo 
Blooddraw Day I, 4, 29(N=50) 
Blooddraw Day I, 6, 29(N=50) 
Blinding open-label study. 
Blood samn!P.s: Three (3) blood samples of approximately 10 mL each will be collected 
according to the blood draw schedule in Table 1. 
Data collection: Electronic Case Report Form (eCRF). 
Studv clinic visits: Three (3) clinic visits at Day 1, Day 4 or Day 6 and Day 29 are 
 
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Name ofSponsor: 
GlaxoSmithKline 
Biologicals S.A 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
planned for each subject. 
Reminder Phone calls: Two (2) reminder phone calls will beconducted at Day 3 and 
Day 5 after the study vaccination to remind the subject/ legal guardian to complete the 
diary card. 
Safety phone calls: Three (3) safety phone calls (at Day 15, Day91 and Day181) will 
be conducted to collect any medically-attended AEs, AEs leading to withdrawal, SAEs, 
related medications and any vaccinations. In addition, all unsolicited AEs and related 
medications occurring after the vaccination will be collected during the safety call at 
Day15.The Day 181 Safety Phone call will also serve as the termination visit. 
Solicited Adverse Events (injection site pain, erythema, induration, fatigue, headache, 
myalgia, arthralgia, loss of appetite, nausea, chills and fever) occurring on the day of 
vaccination and the following six days (Day I through Day 7) will be recorded daily 
using a Diary Card for all subjects. 
Unsolicited AEs occurring within 28 days after studyvaccination will be collected. 
Qualified site staff will interview the subject by phone approximately 14 days after 
vaccination and in person at the study site approximately 28 days after study vaccination 
to assess the occurrence of any unsolicited AEs. 
Medically-attended AEs, AEs leading to studywithdrawal and SAEs will be collected 
during the entire study period. These data will be captured by interviewing the subject 
and/or subjects' parents / guardian (as applicable) during the site visits and phone calls 
and by review of available medical records. Subjects and/or parents / guardian will be 
encouraged to call the site in the event of any medically-attendedAEs or any AEs which 
theyperceive as being of concern during the entire studyperiod. 
Table 2: 
Schematic diagram of the VS9_77 study design. 
Day l 
Day 4 
Day 6 
Day15 
Day 29 
Day 91 
Day181 
Blood draw 
(all subjects) 
Blood draw 
(50% of 
Blood draw 
(50% of 
Safety 
Phone call 
Blood draw 
(all subjects) 
Safety 
Phone 
Safety 
Phone call 
Menveo 
subj ects) 
subjects) 
call 
Study 
tennination 
Number of Subjects planned: Aooroximatelv 700 subiects are planned for enrolment 
 
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Name of Sponsor: 
GlaxoSmithKline 
Biologicals S.A 
Protocol number: 
V59- 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
into this study, approximately 300 subjects who previously received Menveo (Menveo- 
Menveo group), 300 subjects who previously received Menactra (Menactra-Menveo 
group) and 100 meningococcal vaccine-naive subjects (Naive group). Assuming a 10% 
drop-out rate that should provide approximately 630 evaluable subjects. 
Study Population and Subject Characte1i stics: The list of inclusion and exclusion 
criteria is included in protocol section 4, Selection of Study Population. 
Stu dy Pro ced ures: The study includes three clinic visits, one vaccination, three blood 
draws, and threesafety phone calls for each subject. All studyprocedures associated 
with the pre-vaccination, vaccination, post-vaccination and study termination visit are 
described in section 5.0. 
Study Vaccines: 
GlaxoSmithKline Meningococcal MenAC\1VY- CRl "\1 vacc in e (M en veo): 
Meningococcal (groups A, C, Wand Y)oligosaccharide diphtheria CRM-197 conjugate 
vaccine is supplied as a vial that contains 10 µg of serogroup A oligosaccharides and 5 
µg of serogroups C, W and Y oligosaccharides, conjugated to Corynebacterium 
diphtheri.ae CRM191protein. Overall injection volume of 0.5 mL. 
The vaccine will be administered intramuscularly, preferably in the deltoid area of the 
non-dominant arm. 
P1i mary Endpoint(s): 
Immunogenicity Endpoints: 
The following measures will be summarized for Menveo-Menveo and Menactra- 
 
 
 
 
 
 
 
 
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Name of Sponsor: 
GlaxoSmithKline 
Biologicals S.A 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
Menveo groups: 
1. Percentage of subjects with hSBA seroresponse1 against N. meningitidis serogroups 
A, C, Wand Yat Day29. 
Secondary Endpoints: 
Immunogenicity endpoints: 
Thefollowing measures will be summarized for Menveo-Menveo, Menactra-Menveo, 
Naive and the pooled (Menveo-Menveo and Menactra-Menveo) groups: 
1. Percentage of subjects with hSBA titer 2:8 and 2:16 againstN. meningitidis 
serogroups A, C, Wand Y at Day 1, Day 4, Day 6 and Day 29 and between-group 
differences; 
2. Percentages of subjects with hSBA seroresponse2 against N. meningitidis serogroups 
A, C, Wand Y at Day4, Day 6 and Day 29 and between-group differences; 
3. hSBA GMTs against N. meningitidis serogroup A, C, Wand Y at Day 1, Day 4, Day 
6 andDay29; 
4. Ratios ofhSBA GMTs at Day 1, Day 4, Day 6 and Day 29 (between study groups). 
5. hSBA Geometric Mean Ratios (G:MRs) at Day 4, Day 6, and Day 29 compared to 
Day 1 (within study groups). 
Safety endpoi nts: 
Safety of the study vaccine will be assessed in the Menveo-Menveo and Menactra­ 
Menveo groups and the pooled vaccine group (Menveo-Menveo and Menactra - 
Menveo) and the vaccine-naive orouo in terms of the fr"'mencies (oercenta2es) of 
 
 
1-2 Seroresponse is defined forthisstudy as follows: Forsubjects with prevaccinationtiters<4, post­ 
vaccination titers 2: 16; forsubjects ,vitbprevaccinationtiters 2:4, post vaccination titers4 timestbe pre­ 
vaccination titers. 
 
 
 
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Name of Sponsor: 
GlaxoSmithKline 
Biologicals S.A 
Protoco l nu mber: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
reported adverse events including 
1. Any unsolicited AEs reported within 30minutes after vaccination; 
2. Solicited local and systemic AEs reported from Day 1 (6 hours) through Day 7 after 
vaccination; 
3. Other indicators of reactogenicity(e.g. use of analgesics/ antipyretics, body 
temperature) within 7 days after vaccination; 
4. All unsolicited AEs reported from Day 1 through Day 29 after vaccination; 
5. Medically-attended AEs, AEs leading to withdrawal and SAEs reported from Day1 
through Day 181 (during the entire study period). 
Statistical Analyses: 
P1i mary Immunogenicity Objective 
The primary population for the analysis of sufficient immune response is the Per 
Protocol Set (PPS), and willconsist of the Menveo-Menveo group (n=270 evaluable 
subjects) and Menactra-Menveogroup (n=270 evaluable subjects).Todemonstrate 
immune response sufficiency after MenACWY-CRM booster vaccine administration, 
the lower limit of the one-sided 97.5% Confidence Interval (CI) for percentage of 
subjects with hSBA seroresponse against eacliof serogroups A, C, Wand Y must be 
greater than 75%. This willbetested sequentially first in the group of subjects who 
received primary vaccination with Menveo and, if met, also in the group of subjects 
who received primary vaccination with Menactra. 
Hypothesis: 
Null hypothesis 
Alternative hypothesis 
pij 
0.75 
pij > 0.75 
Where: Pij is the population booster seroresponse rate; j = 1,2 refer to group Menveo­ 
Menveo (first test) and Menactra-Menveo (secondtest) respectively; i = 1,2,3,4 refer to 
serogroup A, C, Wand Y respectively. 
 
 
 
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Name of Sponsor: 
GlaxoSmithKline 
Biologicals S.A 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
Sample Size: 
Statistical power was estimated based on observed data from study V59P13El. 
Assuming the true booster seroresponse rates in the Menveo-Menveo group range from 
90% to 97% (alternative hypothesis) for each serotype, a sample size of n=270 will have 
at least 96% power to show sufficiency of immune response to a booster dose of 
MenACWY-CRM, compared with a pre-specified reference booster seroresponse of 
75% (null hypothesis) using an exact test with 0.025 one-sided significance level. 
Assuming the true booster seroresponse rates in the Menactra-Menveo group range from 
91% to 100% (alternative hypothesis) for eachserotype, a sample size of n=270 will 
have at least 96% power to show sufficiency of inlmune response to a booster dose of 
MenACWY-CRM, compared with a pre-specified reference booster seroresponse of 
75% (null hypothesis) using an exact test with 0.025 one-sided significance level. 
Overall statistical power to show sufficiency of inlmune response to a booster dose of 
MenACWY-CRM for each serotype in both the Menveo-Menveo and the Menactra­ 
Menveo group will be at least 92%. 
When taking a 10% dropout rate into account, N=300 previously vaccinated subjects 
with Menveo and N=300 previously vaccinated subjects with Menactra have to be 
enrolled in the study. 
Calculations have been done with nQuery Advisor (Version 7.0). 
In terim Analysis: No interim analysis is planned for this study. 
Data Monito1i ng Committ ee: No DMC will be utilized for the study. 
 
 
 
 
 
 
 
 
 
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Table4 
Time and Events Table 
 
Visit Type 
Study period 
Study Day 
Visit Window (Days) 
Visit Number 
Clinic Visit 
Clinic Visit 
Phone Call 
Clinic Visit Phone Call Clinic Visit 
Phone Call Phone Call 
Screening 
Treatment 
Tre.itment 
Treatment 
Treatment T reatment 
Follow- up 
Follow- up 
1 
3, 5 
4/6• 
15 
29 
91 
181 
-5 
to 1 
0 
2 days (- 
1/+l ), 4 
days (0/+2) 
after vacc 
3/5 days 
(-1/+l) 
after vacc 
14 da ys 
(-2/+2) 
after vacc 
28 d ays 
(-7/+14) 
after vacc 
90 da ys 
(-14/+14) 
aftel' vacc 
180 days 
(-14/+14) 
after vacc 
Pre- 
vacc.ination 
1 
N/A 
2 
3 
4 
5 
6 
Stud y Event 
Referen ces 
Study Treatment 
Vaccination (vacc) 
Section 5.2 
X 
Screening and 
Safety 
Informed Consent" 
Section 5.1.1 
X 
Medical HistOJY 
Section 5.1.2 
X 
Physical Exam 
Sections 5.1.2 
and 5.3.l 
X 
x< 
X 
X 
Pregnancy Test 
Sections 3.5 and 
5 .1.2 
X 
x< 
Exclusion/Inclusion 
Criteriad 
Section4 
X 
X 
Randomization 
Section 5.1.4 
x< 
30 Minutes Post 
InjectionAssessment 
Section 5.2.1 
X 
 
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Visit Type 
Study period 
Study Day 
Visit Window (Days) 
Visit Number 
Clinic Visit 
Clinic Visit PhoneCall Clinic Visit Phone Call Clinic Visit Phone Call Phone Call 
Screening 
Treatment Tre.itment Treatment Treatment Treatment Follow-up Follow-up 
1 
3, 5 
4/6• 
15 
29 
91 
181 
-5 
to 1 
0 
2 days (- 
1/+l ), 4 
days(0/+2) 
after vacc 
3/5 da)'S 
(-1/+l ) 
after vacc 
14 da ys 
(-2/+2) 
after vacc 
28days 
(-7/+14) 
after vacc 
90days 
(-14/+14) 
aftel' vacc 
180 da ys 
(-14/+14) 
after vacc 
Pre- 
vacc.ination 
1 
NIA 
2 
3 
4 
5 
6 
Study Event 
References 
SubjectDiary 
Dispensed with 
Training 
Section 5.2.1 
X 
SubjectDiary 
Reminder Call 
Section 5.2.2 
X' 
X' 
SubjectDiary 
Reviewed and 
Collected 
Section 5.3.1 
X 
Assess Unsolicited 
AEs 
Section7.1 
X 
X 
X 
X 
Assess SAEs 
Section 7.1.4 
X 
X 
X 
X 
X 
X 
Assess for medically 
attended AEs and 
AEs leading to 
withdrawal 
Sections 7.I.4.I 
and7.1.3 
X 
X 
X 
X 
X 
X 
Assess relevant 
medications/ 
vaccinations 
Sections5.1.2 
and 6.5 
X 
X 
X 
X 
X 
X 
X 
 
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Visit Type 
Study period 
Study Day 
Visit Window (Days) 
Visit Number 
Clinic Visit 
Clinic Visit PhoneCall Clinic Visit 
Phone Call 
Clinic Visit 
P hone Call Phone Call 
Screening 
Treatment Tre.itment Treatment Treatment Treatment 
Follow- up 
Follow- up 
1 
3, 5 
4/6• 
15 
29 
91 
181 
-5 
to 1 
0 
2 days (- 
1/+l ), 4 
da ys (0/+2) 
after vacc 
3/5 da)'S 
(-1/+l ) 
after vacc 
14 days 
(-2/+2) 
after vacc 
28days 
(-7/+14) 
after vacc 
90days 
(-14/+14) 
aftel' vacc 
180 days 
(-14/+14) 
after vacc 
Pre- 
vacc.ination 
1 
NIA 
2 
3 
4 
5 
6 
Study Event 
I References 
Imm unogenicity 
Serology blooddraw  I 
Section 3.5 
X" 
X 
X 
Study C-0mp lerion 
Pt·ocedure 
Study Tenninatiorn 
I 
Sec tion 5.5 
X 
Notes : 
• Subject will be randomized into a blooddraw schedule in a 1:1 ratio. The second clinic visit will occur at Day 4 OR Day 6. 
b Confirm consent fonn(s) signed prior to any procedures. 
' Procedure to be performed prior to vaccination 
d Reminder for previously vaccinated subjects, appropriate written documentation of the identity of the primary meningococcal vaccination 
(Menveo or Menactra) and vaccination datemust be provided prior to enrollment. 
• If the clinic visit at Day4is overlapping withthe specified window of the Day 3 reminder call, the Day 3 reminder call maybe omitted. 
If the clinic visit at Day 6 is overlapping with the specified window of the Day 5 reminder call,the Day 5 reminder call maybe omitted. 
f    Subjects who  tenninate thestudy early are  recommended to   complete certainstudy-related procedures.   See section  5.5  for    further  details. 
 
 
 
 
 
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LIST OF ABBREVIATIONS 
 
ACIP 
AE 
CI 
CBER 
CRM 
CRO 
EC 
EoS 
eCRF 
EDC 
FAS 
FDA 
GCP 
GMR 
GMT 
GSK 
HIPAA 
hSBA 
IB 
ICF 
ICH 
 
IM 
IRB 
LSLV 
MedDRA 
pp 
Ref. 
SAE 
SDAF 
SBIR 
soc 
SOP 
Advisory Committee on Imm1mization Practices 
Adverse Event 
Confidence Inteival 
Center for Biologics Evaluation and Research 
Cross Reactive material 
Contract Research Organization 
Ethics Committee 
End of Study 
Electronic Case Report Form 
Electronic Data Capture 
Full Analysis Set 
Food and Drug Administration 
Good Clinical Practices 
Geometric Mean Ratio 
Geometric Mean Titer 
GlaxoSmithKline Biologicals 
Health Insurance Portability and AccountabilityAct 
Human Serum Bactericidal Assay 
Investigator' s Brochure 
Informed Consent Form 
International Conference on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use 
Intramuscular 
Institutional Review Board 
Last Subject Last Visit 
Medical Dictionary for Regulatory Activities 
Per Protocol 
Reference 
Serious Adverse Event 
Source Documentation Agreement Form 
Source Data Base for Internet Randomization 
System Organ Class 
Standard Operating Procedure 

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l. 
BACKGROUl''-D M 'D RATIONALE 
 
1.1 
Background 
 
Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis worldwide, 
capable of causing outbreaks and epidemics of invasive disease. Meningococcal disease is 
associated with high morbidity and mortality even among patients who receive early 
antibiotic treatment. Most cases of invasive disease worldwide are caused by serogroups 
A, B, C, W and Y. 
 
The quadrivalent meningococcal oligosaccharide diphtheria CRM-197 conjugate vaccine 
(MenACWY-CRM; Menveo, GSK Biologicals)is approved for active irom1mizati.on of 
individuals from 2 months through 55 years of age in the United States. As of February 
2015, more than 30,000 of subjects have been exposed to MenACWY-CRMvaccine in 
completed clinical studies and more than 24 million doses of the vaccine have been 
distributed globally. 
 
The US Advisory Committee on Immunization Practices (ACIP) recommends routine 
vaccination with a quadrivalent conjugated meningococcal vaccine for adolescents at 11- 
12 years of age with a booster dose administered 5 years later. While a substantial body of 
data exists showing a robust immune response and good antibody persistence after a 
single dose of MenACWY-CRM in adolescents, the response to a booster dose of 
MenACWY-CRM in this age group has only been evaluated in 2 clinical studies with 
limited number of subjects. 
 
A robust anamnestic immune response to a booster dose of Menveo vaccine administered 
at approximately 5 years after previous vaccination with the same vaccine or a licensed 
meningococcal polysaccharide vaccine (Menomune®) was demonstrated in the phase 2 
clinical study V59P6El . Hightiters of bactericidal antibodies against the vaccine 
serogroups were achieved at 7 and 30 days after booster dose in MenACWY-CRM­ 
primed subjects. However, the number of subjects included in this study was relatively 
small (N=101, including 50 subjects who received a booster dose after the primary 
MenACWY-CRM vaccination). 
 
In the phase 3b clinical study V59Pl3 El , a booster dose of MenACWY-CRM was given 
3 years after primary vaccination with either MenACWY-CRM or Menactra®(a 
meningococcal diphtheria toxoid-conjugated MenACWY vaccine, MenACWY-D) in 
adolescents. A booster dose was able to substantially increase antibody titers against all 4 
serogroups irrespective of the priming vaccine. Again, only small number of subjects 
(N=160) received the MenACWY-CRM booster, (83 who received primary MenACWY­ 
CRM and 77 who received MenACWY-D). 

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In the light of the current ACIP recommendation for a booster dose of MenACWY-CRM, 
there exists a need to evaluate the response to a MenACWY-CRM booster given at - 5 
years after primary vaccination in meningococcal-vaccineprimed adolescents. Generation 
of this data would also be of relevance in outbreak management and vaccination of 
travelers to endemic areas. 
 
1.2 
Rationale 
 
The pwpose/aim of this study is to assess the safety and antibody response to vaccination 
with a booster doseofMenveo given 4-6 years after primary vaccination and the response 
to a single dose given to vaccine-naive subjects, and to describe the inunune response 
over time after a booster dose of Menveo, administered to subjects previously vaccinated 
with Menveo or Menactra, and after a single dose of Menveo to vaccine-naive subjects. 
The inclusion of vaccine-naive subjects in a separate study arm is to enable comparison of 
the rapidity and magnitude of an anamnestic response to a booster dose (in primed 
individuals) or the primary response to a first dose (in naive individuals) ofMenACWY­ 
CRM. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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2. 
OBJECTIVES 
 
2.1 
Plimary Objective(s) 
Immunogenicity objective: 
1. To demonstrate a sufficient immune response following a booster doseof 
MenACWY-CRM (Menveo) vaccine, given to subjects who previously received 
Menveo, as measured by the percentage of subjects with hSBA seroresponse1 against 
N. m.eningitidis serogroups A, C, W and Y at Day 29 after vaccination 
2. To demonstrate a sufficient immune response following a booster doseof 
MenACWY-CRM (Menveo) vaccine, given to subjects who previously received 
Menactra, as measured by the percentage of subjects with hSBA seroresponse1 against 
N. m.eningitidis serogroups A, C, W and Y at Day 29 after vaccination 
Criteria to demonstrate immune response sufficiency The immune response 
sufficiency will be tested sequentially; first in the group of subjects who received 
primary vaccination with Menveo and, if met, also in the group of subjects who 
received primary vaccination with Menactra . The immune response will be 
considered as sufficient if the lower limit of the one-sided 97.5% CI for percentage of 
subjects with hSBA seroresponse1 against serogroups A, C, Wand Y isgreater than 
75%. The study will be considered successful if the immune response sufficiency will 
be demonstrated at least in the groupof subjects who received primary vaccination 
with Menveo. 
 
 
2.2 
Secondar y Objective(s) 
 
Secondar y Immunogenicity objectives: 
1. To compare the immune responses over tinie following a booster doseof 
MenACWY-CRM vaccine, between subjects who previously received Menveo, 
subjects who previously received Menactra, and subjects who previously received 
Menveo or Menactra (pooled vaccine group) and following a single dose in vaccine­ 
naive individuals, as measured by the percentages of subjects with hSBA 
 
 
 
1 Seroresponse is defined for thisstudyasfollows: For subjects with pre-vaccinationtiters <4, pos­t 
vaccination titers 2: 16; for subjects with pre-vaccinationtiters2::4, post vaccination titers at least4 timesthe 
pre-vaccination titers. 
 
 
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seroresponse1, hSBA titers  8  and ;,:16 , and hSBA GMfs against N. meningitidis 
serogroups A, C, Wand Y at Day I, Day 4, Day 6, and Day 29 after vaccination. 
2. To assess persistence of bactericidal antibodies against serogroups A, C, Wand Y at 
approximately 4-6 years after the primary vaccination with Menveo and after the 
primary vaccination with Menactra in comparison with naturally-acquired level in 
vaccine-naive individuals, as measured by the percentages of subjects with hSBA 
titers 8 and hSBA GMfs at Day 1. 
Secondar y Safety objectives: 
To assess the reactogenicity and safety of MenACWY-CRM vaccine when administered 
to subjects who previously received Menveo or Menactra and vaccine-naive individuals. 
 
2.3 
Explor atory Objective(s) 
There are no exploratory objectives. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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3. 
STUDY DESIGN 
 
3.1 
Overview of Study Design 
This is a phase 3b, controlled, open-labe multi-center studyto evaluate safety and 
immunogenicityof MenACWY-CRM after a single vaccination in healthy individuals 
who were vaccinated with Menveo or Menactra 4 to 6 years before and in vaccine-naive 
individuals. 
Study population: Approximately 700 healthy subjects 15 through 55 years of age will be 
enrolled in the study. 
Duration of the study The duration of this studyis approximately 6 months per subject. 
 
Written informed consent and, as applicable according to local guidelines, written assent 
willbeobtained before conducting anystudy-specificprocedures. 
 
Vaccination schedule: All subjects will receive a single dose of MenACWY-CRM at Day 
1. 
 
Study groups: 
 
Group Menveo-Menveo: approximately 300 subjects, who were vaccinated with a single 
dose ofMenveo 4 to 6 years before, willreceive one dose of MenACWY-CRM. 
 
Group Menactra-Menveo approximately 300 subjects, who were vaccinated with a single 
dose of Menactra 4 to 6 years before, will receive one dose of MenACWY-CRM. 
 
Group Naive: approximately 100 subjects equally enrolled across all clinical sites, who 
have not received any meningococcal vaccination, willreceive one dose of MenACWY­ 
CRM. 
 
Randomization / Stratification: 
Within each study group, subjects will berandomized into one of two different blood 
draw schedules according to a 1:1 ratio, described as follows: 
• 
Subjects getting blood draws at Day 1, Day 4 and Day 29. 
• 
Subjects getting blood draws at Day 1, Day 6 and Day 29. 
 
For a schematic overview, see Table 1 

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Table 3.1-1: Schematic diagram of the VS9_77 study groups 
 
Vacdne History 
Vaccination in cwTent 
study 
Blood draw schedule 
Menveo 
N=300 
Menveo 
Blood draw Day1, 4, 29 (N=l 50) 
Blood draw Day 1, 6, 29 (N= l 50) 
Menactra 
N=300 
Menveo 
Blood draw Day 1, 4, 29 (N=150) 
Blood draw Day 1, 6, 29 (N= l 50) 
Vaccine-Naive 
N=IOO 
Menveo 
Blood draw Day I, 4, 29 (N=50) 
Blood draw Day I, 6, 29 (N=50) 
 
Blinding· open-label study. 
 
Blood sanmles: Three (3) blood samples of approximately 10 mL each will be collected 
according to the blood draw schedule in Table 3.1.1. 
Data collection: Electronic Case Report Form (eCRF). 
 
Study clinic visits: Three (3) clinic visits at Day I, Day 4 or Day 6 and Day 29 are 
planned for eachsubject. 
Reminder Phone calls: Two (2) reminder phone calls willbe conducted at Day 3 and Day 
S after the study vaccination to remind the subject/legalguardian to complete the diary 
card. 
 
Safety phone calls: Three (3) safety phone calls (at Day IS, Day 91 and Day 181) will be 
conducted to collect any medically-attendedAEs, AEs leading to withdrawal, SAEs, 
related medications and any vaccinations. In addition, all unsolicited AEs and related 
medications occurring after the vaccination will be collected during the safety call at Day 
IS. The Day 181 Safety Phonecall will also serve as the termination visit. 
 
Solicited Adverse Events (injection site pain, erythema, induration, fatigue, headache, 
myalgia, arthralgia, loss of appetite, nausea, chills and fever) occurring on the day of 
vaccination and the following six days (Day 1 through Day 7) willbe recorded daily 
using a Diary Card for all subjects. 
 
Unsolicited AEs occurring within 28 days after studyvaccination will be collected. 
Qualified site staffwillinterview the subject by phone approximately 14 days after 
vaccination and in person at the studysite approximately 28 days after studyvaccination 
to assess the occUITence of any unsolicited AEs. 

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Medically-attended AEs AEs leading to stuqy withdrawal and SAEs will be collected 
during the entire study period. These data will be captured by interviewing the subject 
and/or subjects' parents / guardian (as applicable) during the sitevisits and phone calls 
and by review of available medical records. Subjects and/or parents / guardian will be 
encouraged to call the site in the event of any medically-attendedAEs or any AEs which 
theyperceive as being of concern during the entire study period. 
 
Table 3.1-2: 
Schematic diagram of the V59_77 study design 
 
Day l 
Da y 4 
Da y 6 
Da y 15 
Da y 29 
Da y 91 
Da y 181 
Blood draw 
(allsubjects) 
Blood draw 
(50¾of 
Blood draw 
(50%of 
Safety 
Phone call 
Blood draw 
(all subjects) 
Safety 
Phone 
SafetyPhone 
call 
Menveo 
subjects) 
subjects) 
call 
Study 
termination 
 
3.2 
Study Period 
 
Each subject should expect to participate in the study for 6 months, from the time of 
enrohnent through the last study visit. 
 
3.3 
Blinding Prncedures 
 
The trialis designed as an open-label study. 
 
3.4 
Data Collection 
3.4.l Data Collected from Subjects 
 
The following data will be collected from each subject over the duration of their study 
participation: 
• 
Demographic Information 
• 
Adverse Events 
• 
Medical History 
• 
Concomitant Medications/Vaccinations 
• 
Information on the blood samples 
 
All data collected must only be identified using the Subject ID, as described in section 
S.1.4, Randomization. 

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3.4.2 
Tools Used for Data Collection 
 
Data willbe recorded in the Subject Diary and collected on electronic Case Report Forms 
(eCRFs). 
 
Subject Diar y 
 
Paper Diaries (pDiaries), hereafter referred to as Subject Diaries will be the onlysource 
document allowed for solicited local and systemic adverse events (including body 
temperature measurements), starting after the initial, 30minute post-vaccination period at 
the clinic. The following additional rules apply to documentation of safety information 
collected in the Subject Diary. 
 
The Investigator or delegated staff should monitor the Subject's Diary status throughout 
the study for compliance and anysolicited local and systemic adverse events that were of 
concern to the subject. 
 
• 
No corrections or additions to the information recorded by the subject or 
parent(s)/legal guardian(s) within the Subject Diary willbe allowed after it is 
delivered to the site. 
• 
Any blank or illegible fields on the Subject Diary must be described as missing in the 
eCRF. 
 
Case Rep01t F or ms 
This study utilizes electronic Case Report Fonns (eCRFs) to collect study-related data 
from each subject. A qualified site staff member(s) is required to enter subject data in the 
eCRFs in English based on the medical information available in each subject' s source 
record. 
 
Data should be entered into the eCRF in a timely fashion following each subject' s clinic 
visit,study procedure, or phone call. Each subject's eCRF casebook will be compared 
withthe subject's source records by a GSK-approved study monitor (or designee) over 
the duration of the study in order to ensure data collection accuracy. 
 
The following additional rules apply to documentation of Subject Diary information 
collected in the eCRFs: 
• 
The site must enter all readable entries in the Subject Diary into the eCRF, including 
those values that may be biologically implausible (e.g. bodytemperature: 400°C). 
• 
Any illegible or implausible data should be reviewed with the subject and/or 
parent(s)/legal guardian(s). If an underlying solicited or unsolicited adverse event is 

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described on review with the subject, this should be described in the source document 
and reported as an unsolicited adverse event in the Adverse Event eCRF (e.g., if the 
subject above confinns body temperature of 40°C on the day in which body 
temperature: 400°C was written into his/her Subject Diary, this fever of 40°C should 
be recorded in the Adverse Event eCRF). 
• 
Any newly described safety infonnation (including a solicited adverse event) nrust not 
be written into the Subject Diary and nrust be described in the study file as a verbally 
reported adverse event. Any adverse event reported in this fashion must be described 
as an unsolicited adverse event and therefore entered on the Adverse Event eCRF. 
 
3.5 
Collection of Clinical Specimens 
 
• 
Collected samples will beused for protocol mandated research and purposes related 
to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. This may include the management of the quality of these 
tests, the maintenance or improvement of these tests, the development of new test 
methods, as well as making sure that new tests are comparable to previous methods 
and work reliably. 
• 
It is also possible that future findings may make it desirable to use the samples 
acquired in this study for future research, not described in this protocol. Therefore, all 
subjects in countries where this is allowedwill be asked to give a specific consent to 
allow GSK or a contracted partner to use the samples for future research. Future 
research willbesubject to the laws and regulations in the USAand willonly 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. 
Any sample testing willbedone in line with the consent of the individual 
subject/subject's parent(s). 
 
Refer also to the : Investigator Agreement, where it is noted that the investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s). 
 
If additional testing is performed, the marker priority ranking given in the table below 
may be changed. 
The following clinical specimens are required to be collected from eachsubject in this 
study: 
• 
Blood. 

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• Urine for pregnancy testing (As per routine practice, specimens willbetested at each 
site). 
 
Processing of a specimen should be completed bya qualified site member and in 
accordance with the study-specificLaboratory Manua.l Testing of serum specimens will 
be performed bya GSK or a designated laboratory. Refer to the study-specificClinical 
Specimen Laboratory Manual for additional details. 
Blood Specimens 
 
Approximately 10 mL sample of blood willbedrawn from all subjects at visit Day 1 
before vaccination, and at visit Day 4 or Day 6 and visit Day29. The blood volume will 
not exceed 10 mL at each time point in order to provide the necessary serum volume 
(approximately half of the blood draw volume) for the serology assays. 
The blood will be used for immunological assays. See section 7, Assessments for 
additional details. 
The total amount of blood collected over the study period per subject will be 
approximately 30mL. 
 
U1in e S p eci m e ns 
 
Urine willbe collected for pregnancy testing in females of child bearing potential. Urine 
will be collected at visit Day 1 before vaccination and the results recorded in the source 
document and eCRF. 
3.6 
Stopping/Pausing Guidelines 
There are no predetermined stopping rules in this study. Subjects may be withdrawn from 
the study according to investigator discretion as described in section 3.8, Premature 
Withdrawal from Study. 
 
3.7 
Data Monitoting Committee 
No DMC willbeutilized for the study. 
3.8 
Prema tur e \Vithdrawal from Study 
Subjects may withdraw at any time, or be dropped from the study at the discretion of the 
investigator should any untoward effects occur and/or forsafety reasons. In addition, a 
subject may be withdrawn by theinvestigator or the Sponsor if he/sheviolates the study 

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plan or for dministrative reasons. The investigator or study coordinator nrust notify the 
Sponsor immediately when a subject has been withdrawn due to an adverse event. 
The circumstances above are referred to as premature withdrawal from the study, and the 
reason for premature withdrawal should be clearly documented and detailed in the source 
documentation. The investigator should make every attempt to evaluate the subject's 
safety, including resolution of ongoing AEs, at the time of premature withdrawal. If a 
subject wants to withdraw from the study before or prior to the last planned study visit, 
the subject will be asked to be followed for safety for the duration of the study. When a 
subject withdraws, or is withdrawn, from the study, the procedures described in section 
S.5.1, Early Termination Visit should be completed if possible. 
The reasons for premature withdrawal from the study include: Adverse event, death, 
withdrawal of consent, lost to follow-up, administrative reason, and protocol deviation. 
These reasons are described in greater detail below. 
AdverseEvent 
 
For any subject withdrawn from study participation prior to the planned Study 
Termination Visit, it is important to determine if an AE was associated with the reason for 
discontinuing the study. This AE must be identified on the AE eCRF page by indicating 
"Withdrawn from study due to AE". Any ongoing AEs at the time of studywithdrawal 
must be followed until resolution or stabilization 
 
Death 
 
For anysubject withdrawn from study participation due to death, this should be noted on 
the StudyTermination eCRF page and the associated SAE that led to the death must be 
reported. 
, v ithdrawal of consent 
 
The subject and/or parent(s)/legal guardian(s) can withdraw consent for participation in 
the study at any time without penalty or loss of benefit to which the subject is otherwise 
entitled. Reason for early termination should be deemed as " withdrawal of consent'' if the 
subject withdraws from participation due to a non-medical reason (i.e., reason other than 
AE). If the subject and/or parent(s)/legal guardian(s) intends to withdraw consent from 
the study, the investigator should clarify if the subject will withdraw completely from the 
study or if the subject willcontinue study participation for safety, or a subset of other 
study procedures. If the subject requests complete withdrawal from the study, no further 
study interventions will be performed with the subject. 

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If a subject and/or parent(s)/legal guardian(s) withdraws consent but does not revoke the 
HIPAA authorization, the Sponsor will have fullaccess to the subject's medical records, 
including termination visit information. If a subject and/or parent(s)/legal guardian(s) 
revokes only the HIPAA authorization, the Sponsor will have fullaccess to all of the 
subject's medical records prior to the date and time of written revocation. 
 
Lost to Follow-Up 
 
For subjects who fail to show up for finalvisits (clinic or telephone contacts), or for three 
consecutive visits, study staff are encouraged to make at least three documented attempts 
to contact the subject by telephone and at least one documented written attempt to contact 
the subject and/or parent(s)/legal guardian(s) to encourage the completion of study 
teimination procedures. These efforts to contact the subject should be recorded in the 
source document. The termination date for the subject to be captured on the Study 
Termination eCRF page is the date of the last successful contact (clinic visit or telephone) 
withthe subject. 
AdministrativeReason 
 
Examples forsubjects withdrawn from the study due to administrativereason can include: 
Sponsor decision to terminate the study, subject discontinuation for insurance issues, 
moving, no time, etc. This reason should be noted in the StudyTermination eCRF page 
and any ongoing AEs at the time of studywithdrawal should be followed until 
resolution/stabilization, if possible. 
If the clinical studyis prematurely terminated bythe Sponsor, the investigator is to 
promptly inform the study subjects and local EC/IRB and should assure appropriate 
therapy and follow up for the subjects. All procedures and requirements pertaining to the 
archiving of study documents should be followed. All other study materials (study 
medication/vaccine,setc.) must be returned to the Sponsor. 
For subjects who are withdrawn from the study due to receipt of an excluded 
medication/vaccination or due to significant protocol non-compliance, this reason should 
be noted in the StudyTermination eCRF page. 
 
Protoco l Devia tion 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. In general, subjects associated with protocol deviations 
may remain in the study unless continuation in the study jeopardizes thesubject's health, 
safety, or rights. 

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Investigators will apply due diligence to avoid protocol deviation.sUnder no 
circumstances should the investigator contact GSK or its agents, if any, monitoring the 
study to request approval of a protocol deviation, as no authorized deviations are 
pennitted. If the investigator feels a change to the protocol would improve theconduct of 
the studythis must be considered a protocol amendmen,tand unless such an amendment 
is agreed upon by GSK and approved by the IRB/EC and health authorities it cannot be 
implemented. 
Anysubject who becomes pregnant during thestudy, despite the protocol requirement for 
adequate contraception should be encouraged to continue participating in the study for 
safety follow-up only. The site must complete a Pregnancy Report CRF (initial report) as 
soon as possible after learning of pregnancy occurrence (see section 7.1.6, Pregnancies 
for further details). If the subject withdraws fromthe study for any of the above 
categories except death, the site will obtain permission from the subject to continue to 
remain in contact with heruntil the outcome of the pregnancy is known, evenif the 
outcome is not known until after thesubject reaches theend of follow-up period. 
 
3.9 
End of St udy 
Most clinical trials intended to support theefficacy/immunogenicityand safety of an 
InvestigationalProduct proceed to full completionof planned sample size accrual. For the 
pwpose of this protocol, End of Study (EoS) is defined as the date of the last 
testing/reading released of human biologicals samples, related to primary and secondary 
end points, to be achieved no later than 8 months after Last Subject Last Visit (LSLY.) 
 
If the completion of testing occurs prior the completion of the Last Subject Last Visit 
(LSLV) the latter date defines the end of study visit. 

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4. 
SELECTION OF STUDYPOPULATION 
 
4.1 
Inclusion C1i teria 
 
In order to participate in this study, all subjects must meet ALL of the inclusion criteria 
described. 
 
I. Individuals of IS through SS years of age on the day of informed consent or assent. 
2. Individuals who received Menveo 4 to 6 years prior to enrolment at an age of 11 years 
or older (Menveo-Menveo group) 
OR 
Individuals who received Menactra 4 to 6 years prior to enrolment at an age of 11 
years or older (Menactra-Menveo group) 
OR 
Individuals who have not received any previous meningococcal vaccine (Naive 
group). 
3. Individuals who have voluntarilygiven written informed consent (and/or assent, if 
applicable) after the nature of the studyhas been explained according to local 
regulatory requirements, prior to study entry. If the subject is under age 18 at the time 
of enrolment, the parent(sJ/legal guardian(s) of the subject should have voluntarily 
given written informed consent. 
4. Individuals who can comply with study procedures including follow-up1 
S. Males 
Or 
Females of non-childbearing potential2 
Or 
 
 
 
1 A subjectand/or parent(s)/Jegal guardian(s) is/are consideredto be compliant if the Investigator judges 
thatthesubject will completetheSubject Diary and return for all thefollow-up visitsscheduled in the 
study. 
2 A female is considered to be of non-childbearingpotential prior to menarche and after natural or induced 
menopause. Natural menopause is recognized to have occurred after 12 consecutive months of amenorrhea 
for which thereis nootherobvious pathological or physiological cause. Induced menopause is recognized 
to have occurred after hysterectomy, after bilateral oophorecotmy, or iatrogenic ablation of ovarian 
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Females of childbearing potential who are using aneffective birth control method1 
which they intend to use for at least 30 days after the study vaccination 
4.2 
Exclusion Crite1i a 
 
Each subject must not have: 
1. History of any meningococcal vaccine administrationother than the single 
vaccination given 4 to 6 years before (Menveo-Menveoand Menactra-Menveo 
groups) 
OR 
History of any meningococcal vaccine administration (Naive group). 
2. Current or previous, confirmed or suspected disease caused by N. meningitidis. 
3. Household contact with and/or intimate exposure to an individual with any laboratory 
confirmed N. meningitidis infection within 60 days prior to study vaccination 
4. Progressive, unstable or \lllcontrolled clinical conditions. 
S. Hypersensitivity, including allergy, to any component of vaccines, medicinal products 
or medical equipment whose use is foreseen in this study. 
6. Clinical conditions representing a contraindication to intramiscular vaccination (IM) 
and blood draws. 
7. Abnormal function of the immlllle system resulting from: 
a. Clinical conditions. 
b. Systemic administration of corticosteroids (PO/IV/IM) for more than 14 
consecutive days within 90 days prior to study vaccination 
c. Administration of antineoplastic and immllllomodulating agents or radiotherapy 
within 90 days prior to study vaccination 
 
 
 
1 The following birth control methods areconsidered effective: 
Abstinence 
Hormonal contraceptive(such asoral,injection, transdennal patch, implant) if used for at least 30 
days prior to informed consent 
Diaphragm preferably with spermicide, tubal occlusion device 
Intrauterine device (IUD) 
Tubal ligation 
Male par1ner using condom preferably with spermicide 
Male par1ner having been vasectomized at least six months priorto informed consent 
 
 
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8. Received immunoglobulins or any blood products within 180 days prior to informed 
consent. 
9. Received systemic antibiotic treatment (PO/IV/IM) within 3 days prior to study 
vaccination or blood draw. 
10. Received an investigational or non-registered medicinal product within 30 days prior 
to study vaccination. 
11. Study personnel as an immediate family or household member. 
12. Individuals who have received any other vaccines within 7 days (for inactivated 
vaccines) or 14 days (for live vaccines) prior to vaccination in this study or who are 
planning to receive any vaccine within 28 days from the study vaccination. 
13. Individuals who have experienced a moderate or severe acute infection and/or fever 
defined as a temperature 38°C (100.4°F) within 3 days prior to study vaccination. 
14. Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the subject due to participation in the study. 
4.3 
C1ite1ia for De.lay of Vaccination and/or Blood Sampling 
 
There may be instances when individuals meet all eligibility criteria for vaccination yet 
have a transient clinical circumstance which may warrant delay of vaccination: body 
temperature elevation [ 38.0° C 
100 .4° F) within 3 days prior to intended study 
vaccination], systemic antibiotic treatment within 3 days prior to study vaccination or 
blood draw. Under such circumstances, a subject may be considered eligible for study 
enrolment after the appropriate window for delay has passed and inclusion/exclusion 
criteria have been rechecked, and if the subject is confirmed to be eligible. 
 
There is a clinical circumstance that warrants delay of blood collection for 
immunogenicityassessments in this study subject has received a dose of systemic 
antibiotics less than 3 days before the intended blood collection. In the event that a 
subject meets this criterion for delay of blood collection, blood collection may proceed 
once the window for delay has passed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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5. 
STUDY PROCEDURES 
 
The sections that follow provide an overview of the procedures that are to be followed in 
enrolling, evaluating, and following subjects who participate in this clinical study. Visits 
can be either clinic visits or safety follow-up telephone calls, as specified in the Table 
below and in the T ime and Events Table4. 
 
Table 5-1 
Study Procedur es 
 
Visit Category 
Procedures 
Pre-vaccinationClinic Visit(s) 
Section 5.1 describes procedures to be followed 
priorto study vaccination: informed consent/assent, 
screening, enrolment, andrandomization 
VaccinatiooClinic Visit(s) 
Section 5.2 describes procedures to be followed 
during each clinic visit involving vaccination: 
vaccination, post-vaccination procedures, and post- 
vaccination reminders 
Post-vaccination Visit(s) 
Section 5.3 describes follow-up clinic visits and 
safety follow-up calls 
Unscheduled Visit(s) 
Section 5.4 
Unscheduled visits are not expected withinthis 
protocol. 
Study Termination Visit 
Section 5.5 describes procedures to be followed at 
the last study visit for a subject (may include early 
termination visit) 
 
 
5.1 
Pre-vacc inati on Clinic Visit.(s) 
 
This section describes the procedures that must be performed for each potential subject 
prior to vaccination, including obtaining informed consent/assent, screening, enrolment 
and randomization. 
5.1. l 
Informed Consent/Assent 
 
"Informed consent" is the voluntary agreement of an individual or his/her legal 
guardian(s) to participate in research. Consent must be given with free willof choice, and 
without undue inducement. The individual must have sufficient knowledge and 
understanding of the nature of the proposed research, the anticipated risks and potential 
benefits, and the requirements of the research to be able to make an informed decision. 
 
"Assent" is a term used to express willingness to participate in research by persons who 
are by definition too young to give informed consent but who are old enough to 
 
 
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understand the proposed research in general, its expected risks and possible benefits, and 
the activities expected of them as subjects. Assent by itself is not sufficient, however. If 
assent is given, informed consent must still be obtained from the subject's parent(s) or 
legal guardian(s). Local laws define who constitutes a "child," and such definitions dictate 
whether or not a person can legally consent to participate in a protocol (Levine 1988). 
 
Info11lled consent of the parent(s)/legal guardian(s) and assent of subject following local 
IRB/EC guidance must be obtained before conducting any study-specific procedures (i.e., 
all of the procedures described in the protocol). The process of obtaining informed 
consent and assent should be documented in the subject source document in addition to 
maintaining a copy of the signed and dated informed consent. Additional specifics 
regarding the informed consent and assent processes are located in section 13.2, Info11lled 
Consent Procedures. 
If a subject and/or parent(s)/legalguardian(s) is unable to read, an impartial witness 
should be present during the entire informed consent and assent discussion. An impartial 
witness is defined as a person who is independent from study conduct, who cannot be 
unfairly influenced by those involved with the study, who attends the informed consent 
process if the subject or the subject's legally acceptable representative cannot read, and 
who reads the informed consent form and any other written information supplied to the 
subject. After the written informed consent form and any other written information to be 
provided to subjects, is read and explained to the subject and/or parent(s)/legal 
guardian(s) and after the subject and/or parent(s)/legal guardian(s) has verbally consented 
to the subject's participation in the study and, if capable of doing so, has signed and 
personally dated the informed consent fo11ll, the witness should sign and personally date 
the consent form. By signing the consent fo11ll, the witness attests that the information in 
the consent form and any other written information was accurately explained to, and 
apparently understood by, the subject and/or parent(s)/legal guardian(s) and that informed 
consent was freely given by the subject and/or parent(s)/legal guardian(s). 
5.1.2 
Screening 
Subject identification numbers will be assigned sequentially to the subjects who have 
consented to participate in the study, according to the range of subject identification 
numbers allocated to each study center. The eligibility of the subject will be determined 
based on the inclusion and exclusion criteria listed in section 4, Selection of Study 
Population and evaluated during this screening procedure. 
 
Prior to study enrolment, demographic data will be collected from the subject, including: 
date of birth, gender, race, ethnicity, prior vaccination against meningitis. Note: 
Appropriate written documentation of the brand of primary vaccination (Menveo or 
Menactra) and vaccination date must be provided prior to enrollment. 

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Medical history willalso be collected, including but not limited to any medical history 
that may be relevant to subject eligibility for study participation such as prior 
vaccinations, concomitant medications, and previous and ongoing illnesses or injuries. 
Relevant medical history can also include any medical history that contributes to the 
understanding of an adverse event that occurs during study participation, if it represents 
an exacerbation of an underlying disease/pre-existing problem. 
 
Review of systems is a structured interview that queries the subject and/or parent(s)/legal 
guardian(s) as to any complaints the subject has experienced across each organ system 
This will beperformed before enrolment and used to guide physical examination. 
 
If applicable, prior and concomitant medications or vaccinations taken prior to start of 
study should be collected (refer to section 6.5, Prior and Concomitant Medications and 
Vaccines for further details). 
 
Collect vital signs (heart rate, blood pressure, and temperature (preferably taken orally). 
Measure height and weight. 
Perform pregnancy testing in women of childbearing potential (refer to section 3.5, 
Collection of Clinical Specimens for additional information) 
A general physical examination is to be performed by a qualified health care practitioner. 
"Qualified health care practitioner" refers to any licensed health care professional who is 
permitted by institutional policy to perform physical examinations and who is identified 
within the Study Staff Signature Log. 
 
The data collected through study assessments listed above willbewritten in the source 
document (see section 9.1, Source Documentation). Should the physical assessment 
reveal any abnormal values or events, these must be documented in the CRF Adverse 
Events Form 
 
Prior to vaccination, approximately 10 mL of blood will bedrawn from all subjects for 
the immunological testing see section 3.5, Collection of Clinical Specimens. 
In the event that the individual is determined ineligible for studyparticipation, he/she is 
considered a screen failure. The reason for screen failure must be documented in the 
Screening and Enrolment log. If the individual is determined to be eligible for the study, 
he/she willbeenrolled into the study. 

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5.1.3 
Em·olment 
 
After signing the informed consent, if an individual is determined to be eligible for study 
participation, the investigator will enroll the subject and enter the subject information into 
randomization system, Source Data Base for Internet Randomization (SBIR). 
5.1.4 
Randomization 
 
5.1.4.1 Randomization of supplies 
The randomization of supplies within blocks will be performed at GSK, using MATerial 
EXcellence (MATEX), a program developed for use in Statistical Analysis System 
(SAS®) (Cary, NC, USA) by GSK. Entire blocks will be shipped to the study centre. 
 
5.1.4.2 Study group and tJ·ea tm e n t numb e r all oc a tio n 
Enrolled subjects willbe randomized in the SBIR system to one of two different blood 
draw schedules according to a 1:1 ratio, described as follows: 
• 
Subjects getting blood draws at Day 1, Day 4 and Day 29. 
• 
Subjects getting blood draws at Day 1, Day 6 and Day 29. 
Allocation of the subject to a blood draw schedules at the investigator site will be 
performed using a central randomization system on internet (SBIR). 
The randomization algorithm will use 3 minimizationprocedure accounting for the 
previous vaccination status (Menveo, Menactra or Vaccine-Nai've study group). 
 
For each dose, the study staffin charge of vaccine administration will access SBIR, 
provide the subject ID, and the system will provide a treatment number consistent with 
the allocated treatment arms. 
 
SBIR will also be used to ensure adequate and appropriate distribution of enrolment of 
naivesubjects across all sites. 
 
For any question regarding SBIR, please refer to the SBIR user guide and SBIR Manual 
for specific instructions. If for any reason, after signing the informed consent form (ICF), 
the subject who is eligible and enrolled fails to be randomized, this is called a 
randomization failure and the early termination study procedures must be applied. The 
reason for all randomization failures should be recorded in the Screening and Enrolment 
Log and in the source document as specified in the Source Documentation Agreement 
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kept distinct from subjects who are screen failures, as described in section S.1.2, 
Screening. 
If for any reason, after enrolment the subject fails to undergo treatment/study procedures 
this is an Early Termination and the reason should be recorded in source document as 
specified in the Source Documentation Agreement (SD.AF). The information on these 
Early Termination subjectsshould be kept distinct in the source documentation from 
subjects who are screen failures, as described in section 5.1.2, Screening. 
5.2 
Vaccination Clinic Visit 
 
The first vaccination will be performed on Day 1. 
 
For studies which have visits for concomitant vaccinations or treatments, see section 6.5, 
Prior and Concomitant Medications and Vaccines for those visit procedures. 
 
Ensure all blood samples are taken p1i or to the vaccination . 
 
After completing the pre-vaccination procedures on day 1, administer the vaccine to the 
subject according to the procedures described in section 6.3, Vaccine Preparation and 
Administration. Observe the blinding procedures described in section 3.3, Blinding 
Procedures. 
Prior to administrationof study vaccination, confirm that the subject does not meet any 
criteria for delaying additional study vaccinations as described in section 4, Selection of 
Study Population. 
5.2.1 
Post-vaccination Procedures 
 
The following post-vaccination procedures will be performed on day 1. 
 
• 
After vaccination, the subject willbe observed for at least 30 minutes including 
observation for unsolicited adverse events, solicited adverse events, and body 
temperature measurement. Record all safetydata collected during this time in the 
subject's source document. 
• 
A Subject Diary will be used in this studyto document solicited adverse events. The 
Subject Diary is the only source for collection of these data; therefore, it is critical that 
the subject completes the Subject Diary correctly. The subject should be trained on how 
and when to complete eac!J field of the Subject Diary. 
• 
The subject and/or parent(s)/legal guardian(s) should be trained on how to self­ 
measure localsolicited adverse events. The measurement of solicited local adverse 
events is to be performed using the ruler provided by the site. 
 
 
 
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• 
The subject and/or parent(s)/legal guardian(s) should be instructed how to perform 
bodytemperature measurement using the thermometer provided by the site.If the 
subject feels unusually hot or cold during the day, the subject and/or parent(s)/legal 
guardian(s) should check body temperature. If the subject has fever, the highest body 
temperature observed that dayshould be recorded in the Subject Diary. 
 
Subject Diary training should be directed at the individual(s) who will perform the 
measurements of adverse events and who will enter the information into the Subject 
Diary. This individual may not be the subject and/or parent(s)/legal guardian(s), but if a 
person other than the subject and/or parent(s)/legal guardian(s) enters information into the 
Subject Diary, this person's identity must be documented in the Subject Diary or subject' s 
source record. Any individual that makes entries into the Subject Diary must receive 
training on completion of the Subject Diary at the time of the visit. This training must be 
documented in the subject's source record. 
 
The same individual should complete the Subject Diary throughout the course of the 
study. 
 
• 
The site should schedule the next study activity clinic visit on Day 4 or Day 6 
depending to which blood draw schedule subject was randomized to with the subject 
and/or parent(s)/legalguardian(s). 
 
The subject and/or parent(s)/legal guardian(s) will be reminded to complete the Subject 
Diary and to contact the site if there are any questions, and to contact the siteimmediately 
(or as soon as the subject is medically stable) if the subject has a medical condition that 
leads to a hospitalization or an emergency roomvisit or to a visit to/by a doctor or is of 
concern. 
5.2.2 
Post-vaccination Reminders 
 
Reminder calls or alerts are not intended to be an interview for collection of safety data. If 
the subject and/or parent(s)/legal guardian(s) wishes to describe safety information, this 
information should only be collected by a healthcare professional at the site, and the 
safety data described must be written down in the subject's medical chart. 
 
Subject Diary Reminder Calls 
 
Subject Diary reminder calls will be performed on day 3 and day S. The purpose of this 
callis to remind the subject and/or parent(s)/legal guardian(s) about completion of the 
Subject Diary. The call follows the Subject Diary Reminder Telephone Call Script 
provided to the site. The subject and/or parent(s)/legalguardian(s) should be reminded to 
contact the site via the telephone number provided in the informed consent to discuss 

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medical questions. If the clinic visit at Day 4 or Day 6 overlaps with the specified window 
of the Day 3 or Day 5 reminder call, the Day 3/Day 5 reminder call maybe omitted. 
 
5.3 
Post-vaccination Visit(s) 
 
Post-vaccinationvisits will be performed on Day 4 or Day 6 according to the blood draw 
schedule to which subject was randomized and Day 29. 
 
5.3.l 
Follow-up Clinic Visit(s) 
 
Follow-up clinic visits willbe performed on Day 4 or Day 6 according to the blood draw 
schedule to which subject was randomized and on Day 29. During the follow-up clinic 
visit: 
 
• 
Subject Diary willbe reviewed at Day 29. No changes to the information recorded 
within the Subject Diary are permissible. For details on the Subject Diary see sections 
3.4.2, Tools Used for Data Collection and 5.2.1, Post-vaccinationProcedures. The 
subject and/or parent(s)/legal guardian(s) will be interviewed to determine if any 
unsolicited adverse events occurred and if any concomitant medications or vaccines 
were taken/received in the time since the last clinic visit. This interview will follow a 
script which will facilitate the collection of relevant safety information. The 
healthcare professional reviewing these data will discuss the symptoms (if any) 
reported by the subject and will determine if any additional diagnoses and/or adverse 
events are present. Adverse events reported by the subject and/or parent(s)/legal 
guardian(s) at this follow-up clinic visit must be recorded in the subject's source 
document and on an Adverse Events CRF, as specified in section 7.1, Safety 
Assessment, and not written on the script used for the interview. 
• 
Perform a brief symptom-directed physical examination if necessary according to 
symptoms the subject has reported. This is a physical examination that will include an 
examination of organ systems that are relevant to the investigator based on review of 
the subject's reported adverse events and concomitant medication use. This 
assessment may include: measurement of vital signs, bodytemperature and a check of 
general appearance. The physical assessment must be performed by the investigator or 
designee of the investigator, who is qualified to perform a physical assessment in 
accordance with their institutional policy. Corresponding information is documented 
in the subject's source document and CRF(s). 
• 
Collect a blood sample (see section 3.5, Collection of Clinical Specimens for 
additional information). 
 
The site should schedule the next study activity safety call withthe subject and/or 
parent(s)/legal guardian(s). 

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Thesubject and/or parent(s)/legal guardian(s) will receive a written reminder of the next 
planned study activity. The subject and/or parent(s)/legal guardian(s) will be reminded to 
contact the site if there are any questions and to contact the site immediately (or as soon 
as the subject is medically stable) if the subject has a medical condition that leads to a 
hospitalizationor an emergency roomvisit. 
5.3.2 Safety Follow-upCalls 
 
Safety follow-up call will be performed on Day 15, Day 91 and Day 181. 
 
Safety follow-up calls are calls made to the subject by a healthcare professional 
designated on the site log. These calls will follow a script which will facilitate the 
collection of relevant safety information. The subject and/or parent(s)/legalguardian(s) 
will be interviewed according to the script, and information related to unsolicited adverse 
events (only at Day 15), serious adverse events (SAEs), medically attended adverse 
events, AEs leading to withdrawal and concomitant medications or vaccinations 
associated with those events will be reviewed. All safety information described by the 
subject must be written down in a designated location within the source document and not 
written on the script used for the telephone call. 
 
Thesite should schedule the next study activity with the subject and/or parent(s)/legal 
guardian(s). 
 
The subject and/or parent(s)/legal guardian(s) will be reminded to contact the site if there 
are any questions and to contact the site immediately (or as soon as the subject is 
medically stable) if the subject has a medical condition that leads to a hospitalizationor 
an emergency room visit. 
5.4 
Unscheduled Visits 
 
Unscheduled visits are not expected within this protocol. 
 
5.5 
Study Termination Visit 
 
The study termination visit willoccur on Day 181. The termination visit will be a 
telephone call. The date of termination is the date of the last contact (clinic visit or 
telephonecall) in which the subject's health status was assessed or, in cases where the 
subject does not agree to any further safety follow-up, it is the date consent is withdrawn. 
This date should be recorded on the termination CRF page. For visit procedures to be 
performed for a subject whose planned study participation ends prematurely, please see 
section 5.5.1, Early Termination Visit. 

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During the telephone call, the following procedures will be performed: interview of 
subject and/or parent(s)/legal guardian(s) to collect medically attended adverse events, 
AEs leading to withdrawal, SAEs, as well as interview of subject and/or parent(s)/legal 
guardian(s) to collect concomitant medications/ vaccinations associated with those events. 
All safety infollillltiondescribed by the subject must be written down in a designated 
location within the source document and not written on the script used for the telephone 
call. 
 
The site will review with the subject and/or parent(s)/legal guardian(s) the plan of when 
infonnation relating to the subject's participation in the study may be available  (e.g., 
study results, treatment assignments). It will also be discussed how information relating to 
the subject' s participation in the study will be shared with the subject's healthcare 
provider, if the subject and/or parent(s)/legalguardian(s)  chooses to  share this 
infonnation. 
 
The site willcomplete the termination CRF page, and this will mark the completion of the 
subject's participation in the study. 
5.5.1 Early Termination Visit 
 
When a subject is withdrawn from treatment or withdraws from the study, the investigator 
will notifythe Sponsor and, when possible, will perform the procedures listed below. The 
reason(s) for the early termination will be included in the subject's source documentation. 
If the EarlyTermination Visit is a telephone call, collect as muclt information as possible. 
Early Termination Visits include subjects who were randomized but not treated. 
 
At the clinic visit or during the telephone call, the following procedures will be 
performed: interview of subject and/or parent(s)/legal guardian(s) to collect adverse 
events, medically attended adverse events, AEs leading to withdrawal, SAEs, interview of 
subject and/or parent(s)/legalguardian(s) to collect concomitant  medications/ 
vaccinations. 
 
The site will review with the subject and/or parent(s)/legal guardian(s) the plan of when 
infonnation relating to the subject's participation in the study may be available  (e.g., 
study results, treatment assignments). It will also be discussed how information relating to 
the subject's participation in the study will be shared with the subject's healthcare 
provider, if the subject and/or parent(s)/legalguardian(s)  chooses to  share this 
infonnation. 
 
The sitewillcomplete the termination CRF page and this will mark the completion of the 
subject's participation in the study. 

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6. 
TREATME1''TOF SUBJECTS 
 
All vaccines associated with this study are to be stored separately from other vaccines and 
medications in a secure location under appropriate storage conditions with temperature 
monitoring. All vaccines associa ted with this study must be checked for  expir ation 
date p1i or to use. Expired vaccines must not be administered to subjects. 
6.1 
Study Vaccine(s) 
 
The term 'study vaccine ' refers to those vaccines provided by the Sponsor, which will be 
evaluated as part of the study objectives. The study vaccines specific to this study are 
described below. The study vaccines specific to this study is the MenACWY-CRM 
vaccine (Menveo® , GSK Biologicals). 
 
The Meningococcal ACWY conjugate vaccine is obtained by extemporaneous mixing 
just before injection of the lyophilized MenA-CRM component with the MenCWY-CRM 
fullliquid vaccine. The pharmaceutical form is Powder and solution for solution for 
injection. Menveo® is provided as vial/vial presentation. MenA lyophilised conjugate 
component (glass vial) and MenCWY liquid conjugate component (glass vial). After 
reconstitution, MenACWY-CRM will have the following composition per O.S mL of 
injectable solution (SeeTable 6.1-1): 
Table 6.1-1: MenAC\VY-CR"l\1 Com position 
 
Name of Ingredient 
Unit and/ol' Percentage Fol'mula 
(Dose 0.5 mL) 
D1111gSubstances 
CRM191-MenA conjug;ite 
10 µg MenA,16.7- 33.3µgCRM191 
CRM191-MenCconjug;ite 
5 µgMenC, 7.1 - 12.5 µg CRM197 
CRM191-MenWconjugate 
5 µg MenW, 3.3-  8.3µgCRM191 
CRM191-MenYconjug;ite 
5 µg MenY, 5.6- 10µgCRM197 
Sodium chloride 
4.5mg 
Excipients 
Sucrose 
12.5 mg 
Sodium phosphate buffer 
Sodium dihydrogen phosphate 
Disodium hydrogen phosphate dehydrate 
l0mM 
2.5mM 
7.5mM 
Potassium dihydrogen phosphate 
5mM 
Water for Injection 
q.s 0.5 mL 
VolumeofFormulation 
0.6mL 
 
 
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Name of Ingredient 
Unit and/ol' Percentage Fol'mula 
(Dose 0.5 mL) 
Appearance 
Colorlesstolight yellow 
Vaccine Presentation 
Asingle dose of two vials 
One 0.5 mL dose ofMenACWY will be administered by intranruscular (IM) injection in 
the deltoid area of non-dominant arm (preferably.) 
 
For more detailed information, refer to the latest version of Investigator Brochure and 
SPC for Menveo® , which are included in the investigator site file. 
6.2 
Non-Study Vaccines 
Not applicable. 
6.3 
Vaccine Preparation and Administra tion 
The investigator or designee will beresponsible for oversight of the administration of 
vaccine to subjects enrolled in the study according to the procedures stipulated in this 
study protocol All vaccines will be administered onlyby personnel who are qualified to 
perform that function under applicable local laws and regulations for the specific study 
site. 
All studyvaccines to be administered to the subjects must be stored in a safe and locked 
place with no access by unauthorized personnel. 
The study vaccines will be stored at the defined temperature range (i.e. +2 to +8 C). The 
storage temperature of the vaccines will be monitored daily withtemperature monitoring 
devices and willberecorded. 
Any temperature deviation, i.e. temperature outside the range (+2 to +8°C), must be 
reported to thesponsor as soon as detected. Following the exposure to such a temperature 
deviation, vaccines will not be used until written approval has been given by the sponsor. 
The study vaccine should be allowed to reach room temperature before administration, 
according to local vaccination practice. 
MenACWY-CRM (Menveo) vaccine is prepared by aseptically withdrawing all fluid 
fromthe vial containing the MenCWY-CRM liquid conjugate component and injecting 
the liquid into the vial containing the MenA-CRM lyophilized portion. Invert and shake 
the vial well until the vaccine is dissolved. The finalmixed vaccine is then ready for 
administrationof the MenACWY formulation (0.5 mLJdose of injectable solution). 
 
 
 
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Detailed vaccine preparation and administration instructions willbe provided to 
investigators in the Clinical Trials Supply Manual prior to study start. 
 
PRECAUTIONS TO BE OBSERVED IN ADMINISTERINGSTUDY VACCINE: 
 
Prior to vaccination, subjects must be determined to be eligible for studyvaccination and 
it must be clinically appropriate in the judgment of the investigator to vaccinate. 
Eligibilityfor vaccination prior to first study vaccine dministration is detennined by 
evaluating the entry criteria outlined in protocol sections 4.1, Inclusion Criteria and 4.2, 
Exclusion Criteria. 
 
Eligibility for non-study vaccines should be determined by the investigator, pending the 
review of the package insert of the relevant vaccine. 
 
Study vaccines should not be administered to individuals with known hypersensitivity to 
any component of the vaccines. 
 
Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or 
stress-related reactions may occur in association with vaccination as a psychogenic 
response to the needle injection. It is important that procedures are in place to avoid 
injury from fainting. 
Standard immunization practices are to be observed and care should be taken to 
administer the injection intramuscularly. Before dminist"'1'ing vaccine, the vaccination 
site is to be disinfected with a skin disinfectant (e.g., 70% alcohol). Allow the skin to dry. 
DO NOT inject intravascularly. 
 
As with all injectable vaccines, trained medical personnel and appropriate medical 
treatment should be readily available in case of anaphylactic reactions following vaccine 
administration. For example, epinephrine 1:1000, diphenhydramine, and/or other 
medications for treating anaphylaxis should be available. 
6.3.1 Replacement of unusable vaccines 
 
In addition to the vaccine doses provided for the planned number of subjects (including 
extra doses to allow flexibility in enrolment at the different sites), at least 15% additional 
vaccine doses willbe supplied to replace those that are unusable. 
6.4 
Vaccine Adminish·ation Error or Overdose of Vaccine 
 
Vaccine administration error is defined as receiving a dose of studyvaccine that was not 
reconstituted as instructed or administered by a different route from the intended route of 
administration. An overdose of studyvaccine (whether accidental or intentional) is 
 
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defined when a dosage higher than the recommended dosage is administered in one dose 
of study vaccine. 
6.5 
Plior and Concomitant Medications and Vaccines 
All medications, vaccines and blood products taken or received by the subject within 30 
days prior to the start of the study are to berecorded on the Prior and Concomitant 
Medications CRF. 
In addition, the following are considered prior medications for this protocol: all 
medication/vaccinesdescribed in theinclusion and exclusion criteria of this protocol 
including: 
 
• Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive 
days within 90 days prior to study vaccination; 
• 
Administration of antineoplastic and imm1momodulating agents or radiotherapy 
within 90 days prior to study vaccination; 
• Tmmnnnglobulins or anyblood products within 180 days prior to informed consent; 
• Systemic antibiotic treatment within 3 days prior to study vaccination or blooddraw; 
• Any investigationalor non-registered medicinal product within 30 days prior to study 
vaccination; 
• Administration of vaccines within 7 days (for inactivated vaccines) or 14 days (for 
live vaccines) prior to vaccination in this study or who are planning to receive any 
vaccine within 28 days fromthe studyvaccination. 
Use of analgesics/antipyreticsto prevent or treat solicitedAEs will be captured in the 
Subject Diary from day 1-7 following each vaccination. Medications taken for 
prophylaxis are those intended to prevent the onset of symptoms. Medications taken for 
treatment are intended to reduce or eliminate the presence of symptoms that are present. 
Concomitant medications include all prescription and non-prescription medications 
(including vaccines) taken by/administeredto the subject during the 30 days after study 
vaccination andmust be documented on the Concomitant Medications CRF. Mineral 
supplements and vitamins are not considered concomitant medications. 
When recording concomitant medications/vaccine,sthey should be clJecked against the 
study entry and continuation criteria in section 4, Selection of Study Population to ensure 
that the subject should be enrolled/continue in the study. 
 
 
 
 
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Concomitant medication dministered for treatment of AEs with medically-attended 
visits, AEs leadingto study withdrawal andSAEs must be documented during the entire 
study period. 
Any vaccine not foreseen in the studyprotocol in the period starting at Day1 and ending 
at Day 181 must be recorded in the eCRF. 
6.6 
Vaccine Supply, Labeling, Storage and Tracking 
Detailed vaccine supply, labeling, storage and tracking instructions will be provided to 
investigators in the Clinical Trials Supply Manual prior to study start. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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7. 
ASSESSMENTS 
 
7.1 
Safety Assessment 
The measures of safety used in this study areroutine clinical procedures. They include a 
close vigilance for, and stringent reporting of, selected local and systemic adverse events 
routinely monitored in vaccine clinical studies as indicators of reactogenicity. 
An adverse event (AE) is defined as anyuntoward medical occurrence in a subject or 
clinical investigation subject administered a pharmaceutical product at any dose that does 
not necessarily have to have a causal relationship withthis treatment. Therefore, an AE 
can be any unfavorable and unintended sign (including an abnonnal laboratory finding, 
for example), symptom, or disease temporally associated with the use of an 
investigational product, whether or not considered related to the investigational product. 
This defintiion includes intercurrent illnesses or injuries and exacerbation of pre-existing 
conditions. 
The period of observation for AEs extends fromthe time the subject signs informed 
consent until he or she completes the specified safety follow-up period of 180 days or 
terminates the study early (whichever comes first). AEs occurring after the informed 
consent form is signed but prior to receiving studyvaccinep/roduct will be documented as 
an adverse event and recorded within source document. However, any AEs occurring 
prior to receipt of anystudyvaccine will be analyzed separately from" treatment 
emergent'' AEs (AEs occurring after administration of the first study vaccine). 
Adverse events are collected as either solicited or unsolicited adverse events. Solicited 
events arederived from organized data collection systems, such as Subject Diaries. 
7.1.1 Solicited Adverse Events 
 
The term"reactogenicity" refers to solicited signs and symptoms ("solicited adverse 
events") occurring in the hours and days following a vaccination, to be collected by the 
subject and/or parent(s)/legalguardian(s) for 7 consecutive days, using a pre-defmed 
Subject Diary. 
The following solicited adverse events are included in the Subject Diary. Each adverse 
event is to be assessed using the scoring system reported in parentheses below: 
 
 
 
 
 
 
 
 
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Solicited  Local   AdverseEvents 
Injection site pain, erythema, induration 
Solicited Systemic Adverse Events 
Fatigue, headache, myalgia, arthralgia, loss of appetite, nausea, chills, and fever. 
Table 7.1.1-1 
Severity grading for solicited local and systemic AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fever is defined and measured by a body temperature 38.0°C(100.4°F). Route of 
temperature measurement is preferably oral. 
 
Other Indicators of Reactogenicity: 
• 
Use of analgesics / antipyretics for prophylaxis (Days 1-7) 
• Use of analgesics / antipyretics for treatment (Days 1-7) 
• Body temperature, described in degrees Celsius and summarized by route of 
measurement and in 05°C increments from 36.·o c . 
 
 
 
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]',fil d 
Moderate 
Se.vel'e 
Pain 
No inteiference with 
dailyactivity 
Inteifereswith daily 
activity 
Prevents daily activity 
Erythema 
25-50mm 
51- lOOmm 
> l OOmm 
lnduration 
25-50 mm 
51- lOOmm 
> l OOmm 
Fatigue 
No inteiference with 
dailyactivity 
Inteiferes with daily 
activity 
Prevents daily activity 
Headache 
No inteiference with 
activity 
Inteiferes with daily 
activity 
Prevents daily a activity 
Myalgia 
No inteiference with 
activity 
Inteiferes with daily 
activity 
Prevents daily activities 
Arthralgja 
No inteiference with 
activity 
Inteiferes with daily 
activity 
Prevents daily activity 
Loss ofappetite 
Eating less than usual 
with no effect on normal 
activity 
Eating less thanusual / 
inteifered with normal 
activity 
Not eating at all 
Nausea 
No inteiference with 
dailyactivity 
Inteiferes with daily 
activity 
Prevents daily activity 
Chills 
No inteiference with 
activity 
Inteiferes with daily 
activity 
prevents daily activity 

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The study staff must review the data entered into the Subject Diary as described in section 
3.4.2, Tools Used for Data Collection and section S.3.1, Follow-up Clinic Visit(s). 
Note: Anysolicited adverse event that meets any of the following criteria must be entered 
into subjects' source document (see section 9.1, Source Documentation) and also as an 
adverse event on the Adverse Event CRF: 
 
• Solicited local or systemic adverse event that continues beyond day7 after 
vaccination. 
• Solicited local or systemic adverse event that leads to a visit to a healthcare provider 
(medically attended adverse event, see section 7.1.3, Evaluation of Adverse Events). 
• Solicited local or systemic adverse event leading to thesubject withdrawing fromthe 
study or the subject being withdrawn from the studyby the investigator(adverse event 
leading to withdrawal, see section 7.1.3, Evaluation of Adverse Events). 
• Solicited local or systemic adverse event that otherwise meets the definition of a 
serious adverse event (see section 7.1.4, Serious Adverse Events). 
7.1.2 Unsolicited Adverse Events 
An unsolicited adverse event is an adverse event that was not solicited using a Subject 
Diary and that was spontaneously commtmicated bya subject and/or parent(s)/legal 
guardian(s) who has signed the informed consent. 
 
Potential unsolicited AEs may be medically attended (defined as symptoms or illnesses 
requiring hospitalization, or emergency room visit, or visit to/by a health care provider,) 
or were of concern to the subject and/or parent(s)/legal guardian(s). In case of such 
events, subjects and/or parent(s)/legal guardian(s) will be instructed to contact the site as 
soon as possible to report the event(s). The detailed information about the reported 
unsolicited AEs willbe collected by the qualified site personnel during the interview and 
will be documented in the subject's records. 
 
Unsolicited AEs that arenot medically attended nor perceived as a concern by subjects 
and/or parent(s)/legalguardian(s) will be collected during interview with the subject 
[and/or parent(s)/legalguardian(s) and by review of available medical records at the next 
visit (see section 5.3, Post-vaccination Visit(s). 
7.1.3 Evaluation of Adverse Events 
Adverse events, reported at a clinic visit or at a scheduled safety call, should be recorded 
in the eCRF verbatim, as reported by the subject. 
 
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Theseverity of events reported on the Adverse Events CRF willbe determined by the 
investigator as: 
 
Mild: 
Moderate: 
Severe: 
transient with no limitation in normal daily activity. 
somelimitation in normal daily activity. 
unable to perform normal daily activity. 
 
The relationship of the studytreatment to an AE will be determined by the investigator 
based on the following definitions: 
 
1. Not Related 
The AE is not related to an investigational vaccine if there is evidence that clearly 
indicates an alternative explanation. If the subject has not received the vaccine, the timing 
of the exposure to the vaccine and the onset of the AE are not reasonably related in time, 
or other facts, evidence or arguments exist that reasonably suggest an alternative 
explanation, then the AE is not related. 
2. Possibly Related 
 
The administrationof the investigational vaccine and AE are considered reasonably 
related in time and the AE could be explained by exposure to the investigational vaccine 
or by other causes. 
3. Probably Related 
 
Exposure to the investigational vaccine and AE are reasonably related in time and no 
alternative explanation has been identified. 
 
The relationship of the studytreatment to an unsolicited AE will be determined by the 
investigator. 
 
Note: solicited AEs will not be evaluated for relationship to studytreatment. Grading for 
severity of solicited local and systemic AEs is described in section 7.1.1, Solicited 
Adverse Events. 
 
Adverse events will also be evaluated by the investigator for the co-existence of any of 
the other following conditions: 
 
• "Medically attended adverse event": an adverse event that leads to a visit to a 
healthcare provider. 
• 
AEs leading to withdrawal: adverse events leading to study or vaccine withdrawal. 
 
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If solicited or unsolicited adverse events have been reported and the subject and/or 
parent(s)/legal guardian(s)] indicated that the symptoms required medical attendance or 
were of concern, the subject and/or parent(s)/legalguardian(s) must be contacted for 
further information. 
When the subject and/or parent(s)/legal guardian(s) is contacted for any of these reasons, 
the contact must be documented in thesubject's source documentation. 
All AEs, regardless of severity, will be monitored until resolution or until the investigator 
assesses them as chronic or stable. All subjects experiencing AEs - whether considered 
associated with the use of the study vaccine or not - must bemonitored until symptoms 
subside and any abnormal laboratory values have returned to baseline, or until there is a 
satisfactory explanation for the changes observed, or until death, in which case a full 
pathologist's report should be supplied, if possible. The investigator'sassessment of 
ongoing Adverse Events at the time of each subject' s last visit should be documented in 
the subject' s medical chart. 
7.1.4 Serious Adverse Events 
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any 
dose results in one or more of the following: 
• 
Death. 
• 
Is life-threatening (i.e., the subject was, in theopinion of the investigator, at 
immediate risk of death from the event as it occurred); it does not refer to anevent 
which hypothetically might have caused death if it were more severe. 
• 
Required or prolonged hospitalization. 
• 
Persistentor significant disability/incapacity(i.e., the event causes a substantial 
disruption of a person's ability to conduct normal life functions.) 
• 
Congenital anomaly/or birth defect. 
• 
An important and significant medical event that may not be immediately life 
threatening or resulting in death or hospitalization but, based upon appropriate 
medical judgment, may jeopardize the subject or may require intervention to prevent 
one of the other outcomes listed above. 
Adverse events which do not fall into these categories are defined as non-serious. 
It should be noted that a severe adverse event need not be serious in nature and that a 
serious adverse event need not, bydefinition, be severe. 
 
 
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Serious adverse events will be captured both on the Vaccines Serious Adverse Event 
(VSAE) form as well as on the AE CRF. All SAEs will be evaluated by the investigator 
for relationship of the event to studyvaccine. SAEs that are judged to be possibly or 
probably related to the studyvaccine should be reported to the Sponsor as related events. 
 
The relationship of the studytreatment to an SAE will be determined by the investigator 
based on the following definitions: 
 
1. Related 
 
The SAE is judged by the investigator to be possibly or probably related to the study 
vaccine on the AE CRF page (see section 7.1.3, Evaluation of Adverse Events). 
 
2. Not Related 
The SAE is not related if exposure to the study vaccine has not occurred, or the 
occurrence of the SAE is not reasonably related in time, or the SAE is considered 
unlikely to be related to use of the study vaccine, i.e., there are no facts (evidence) or 
arguments to suggest a causal relationship. 
 
The relationship of the studyvaccine to an SAE will be determined by the investigator. 
 
In addition, SAEs willbe evaluated by the Sponsor or designee for "expectedness." An 
unexpected AE is one that is not listed in the ct11Tent Summary of Product Characteristics 
or the Investigator's Brochure or an event that is by nature more specific or more severe 
than a listed event 
 
In addition, a pre-existing event or condition that results in hospitalization should be 
recorded on the Medical History CRF. If the onset of an event occt11Ted before the subject 
entered the study (e.g., any pre-planned hospitalization for conditions like cosmetic 
treatments or for non-emergency routine visits for a pre-existing condition), the 
hospitalizationwould not lead to an AE being classified as serious unless, in the view of 
the investigator, hospitalization was prolonged as a result of participation in the clinical 
study or was necessary due to a worsening of the pre-existing condition. 
 
7.1.4.1 
Adverse Events of Special Interest 
Adverse Events of Special Interest (AESis) will not be assessed during the study. 
 
7.1.S Methods for Recording Adverse Events and Se1ious Adverse Events 
 
Findings regarding Adverse Events must be reported on an Adverse Events CRF, as 
specified in section 7.1.1, Solicited Adverse Events, and on the VSAE form, if applicable, 
 
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which is part of the Investigator Site File. All findings in subjects experiencing AEs must 
be reported also in the subject's source document. 
All SAEs which occur during the course of the study, whether considered to be associated 
withthe study vaccination or not, must be reported wi thin 24 hours of the site becoming 
aware of the event to GSK or its designee. Specific instructions and contact details for 
collecting and reporting SAEs to GSK will be provided to the investigator. Specifically, 
once an investigator becomes aware that a SAE has occurred in a study subject, the 
investigator (or designate) must complete a paper expedited Adverse Events report and 
forward it to GSK WITHIN 24 HOURS. The report will always be completed as 
thoroughly as possible with all available details of the event and then dated and signed by 
the investigator (or designate). Even if the investigator does not have all information 
regarding a SAE, the report should still be completed and forwarded to GSK within 24 
hours. Once additional relevant information is received, the report should be updated and 
forwarded to GSK WITHIN 24 HOURS. The investigator will always provide an 
assessment of causality at the time of the initial report. All SAEs are also to be 
documented on the Adverse Events CRF. Any medication or other therapeutic measures 
used to treat the AE will be recorded on the appropriate CRF(s) in addition to the 
outcome of the AE. 
After receipt of the initial report, representatives of GSK or its designee will contact the 
investigator if it is necessary to obtain further information for assessment of the event. Of 
note, after the initial AE/SAE report, the investigator is required to proactively follow 
each subject and provide additional relevant information on the subject's condition to 
GSK Biologicals (within 24 hours for SAEs, and within 2 weeks for pregnancies). 
 
All SAEs must be reported by the investigator to his/her corresponding EC/ IRB 
applicable regulatory authorities in accordance with institutional policy/regulatory 
requirements and adequate documentation of this notification must be provided to the 
Sponsor. 
 
GSK or its designee must also comply with the applicable regulatory requirement(s) 
related to the reporting of suspected unexpected serious adverse vaccine reactions (also 
known as SUSARs) to the regulatory authority(ies) and the IRB/EC. If a SUSAR or other 
safety signal relating to use of one of the study vaccines is reported to GSK or its 
designee, the Sponsor will communicate the information to the investigator and the 
investigator will be responsible for submitting this information to the EC/IRB and other 
relevant authorities. 

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7.1.5.1 
Post-Study Events 
 
AnySAEthat occurs outside of the protocol-specifiedfollow-up period and considered to 
be caused by the study vaccine nrust be reported to GSK or its designee. These SAEs will 
be processed by GSK or its designee as during the course of the study, until I month after 
Last Subject Last Visit (LSLV). Instructions and contact details for collecting and 
reporting these suspected SAEs will be provided to the investigato.r 
 
7.1.6 
Pregnancies 
 
To ensuresubjects' safety, each pregnancy in a subject after study vaccination must be 
reported to GSK or delegate in due time of the site learning of its occurrence. If the 
subject agrees to submit this information, the pregnancy must be followed to determine 
outcome, including spontaneous or voluntary termination, details of the birth, and the 
presence or absence of any birth defects, congenital abnormalities, or maternal and/or 
newborn complications. This follow-up should occur even if intended duration of safety 
follow-up for the study has ended. 
 
Pregnancy data must be recorded on a Pregnancy Report CRF (initial report) and 
Pregnancy Follow-Up CRF (outcome report) and reported to GSK or delegate. 
Instructions and contact details for submitting the Pregnancy CRFs will be provided to the 
investigator. 
 
Any pregnancy outcome meeting the definition of a SAE (see section 7.1.4, Serious 
Adverse Events) must also be reported on the VSAE Report Form 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 
still birth (intrauterine death of foetus after 22 weeks of gestation). 
Note: the 22 weeks cut-off in gestational age is based on WHO-ICD 10 noted in the 
EMA Guideline on pregnancy exposure. It is recognized 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 the Metropolitan Atlanta Congenital 
Defects Program (E rro r! Refer ence sour ce not foun d.) guidelines) identified in the 
offspring of a study subject (either during pregnancy, at birth or later) regardless of 

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, 
 
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. 
 
7.1.7 
Safety La bora tor y l\ lll eas ur em e n ts 
 
No safety laboratory measurements will be done in this study. 
 
7.2 
Efficacy Assessment 
This section is not applicable. This studyhas no efficacy measurements. 
 
7.3 
Immunogenicity A55essm en t 
 
The functional measure of inununogenicity used in this study, Serum Bactericidal Assay 
(SBA), is a measure of the ability of antibodies, in concert with human complement, to 
kill meningococci, and is widely used and generally recognized as the serological 
correlate of protection. The key measures of inununogenicitywillbe the percentages of 
subjects with seroresponse 1 percentages of subjects who achieve hSBA titers 8 and, and 
the hSBA GMTs against serogroups A, C, W and Y reference strains 
 
These measurements willbe assessed in serology samples collected at Visit Day 1, 4 or 6 
and Day 29. The measures of inununogenicityused in this study are standard, i.e., widely 
used and generally recognized as reliable, accurate, and relevant (able to describe the 
quality and extent of the inunune response). 
 
All subjects will have a blood draw at Day1, before vaccination. Subsequent blood draws 
willbe at either Day 4 or Day6 post vaccination, and at Day 29 post vaccination. 
 
Testing willbe conducted by qualified and certified laboratories. All assays will be 
performed in GSK Clinical Laboratory Sciences or delegate laboratory, as provided in the 
protocol ancillary document. 
 
 
 
 
 
 
 
 
1 Seroresponse is defined forthisstudy asfollows: Seroresponse to N. meningitidis serogroups A, C, Wand 
Y is defined as: For subjects with pre-vaccination titers <4, post-vaccinatioo titers 2: 16; for subjects with 
pre-vaccination titers2:4, post vaccination titersat least 4 times the pre-vaccinationtiters. 
 
 
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8. 
STATISTICAL CONSIDERATIO NS 
 
8.1 
E ndpoints 
8.1.1 
Plim a i-y En d p oin t(s) 
 
8.1.1.1 
P1im a r y Saf ety En d p oin t (s) 
 
There are no primary safety endpoints in this study. 
 
8.1.1.2 
P1imar y Efficacy En dpoint (s) 
 
There are no primary efficacy endpoints in this study. 
 
8.1.1.3 
P1imar y I mmunogenicity E ndpoin t(s) 
The following measure willbe summarized for the Menveo-Menveo and Menactra­ 
Menveo groups: 
1. Percentage of subjects with hSBA seroresponse1 against N. meningitidis 
serogroups A, C, W and Y at Day 29. 
8.1.2 
Secondary Endpoin t(s) 
 
8.1.2.1 
Secondar y Safety Endpoint(s) 
 
Safety of the study vaccine willbe assessed in the Menveo-Menveo, Menactra-Menveo, 
Naive and the pooled (Menveo-Menveo and Menactra-Menveo) groups in temlSof the 
frequencies (percentages) of reported adverse events including: 
 
1. Any unsolicited AEs reported within 30 minutes after vaccination; 
2. Solicited local and systemic AEs reported from Day 1 (6 hours) through Day 7 
after vaccination; 
3. Other indicators of reactogenicity (e.g. use of analgesics / antipyretics, body 
temperature) within 7 days after vaccination; 
4. All unsolicited AEs reported from Day 1 through Day 29 after vaccination; 
 
 
1 Seroresponse is defined forthisstudy asfollows: For subjectswith pre-vaccinationtiters <4, pos­t 
vaccination titers 2: 16; for subjects with pre-vaccinationtiters2::4, post vaccination titers at least4 timesthe 
pre-vaccinationtiters.titers. 
 
 
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5. Medically-attendedAEs, AEs leading to withdrawal and SAEs reported from Day 
1 through Day 181 (entire study period). 
Adverse events will be coded using MedDRA preferred terms as applicable. 
 
8.1.2.2 
Secondary Efficacy Endpoint(s) 
There are no secondary efficacy endpoints in this study. 
 
8.1.2.3 
Secondary Immunogenicity Endpoint(s) 
The following measures will be summarized for Menveo-Menve,oMenactra-Menveo, 
Naive and the pooled (Menveo-Menveoand Menactra-Menveo)groups: 
 
1. Percentage of subjects with hSBA titer 8 and 16 againstN. meningitidis 
serogroups A, C, Wand Y at Day 1, Day 4, Day 6 and Day 29 and between-group 
differences; 
2. Percentagesof subjects with hSBA seroresponse1 against N. meningitidis 
serogroups A, C, Wand Y at Day 4, Day 6 and Day 29 and between-group 
differences; 
3. hSBA GMfs againstN. meningitidis serogroup A, C, Wand Y at Day 1, Day 4, 
Day 6 and Day 29; 
4. Ratios ofhSBA GMfs atDay 1, Day 4, Day 6 and Day 29 (between study 
groups). 
5. hSBA Geometric Mean Ratios (GMRs) at Day 4, Day6, and Day 29 compared to 
Day 1 (within study groups). 
8.1.3 
Explora tory Endpoint(s) 
 
8.1.3.1 
Exploratory Safety Endpoint(s) 
There are no exploratory safety endpoints in this study. 
 
8.1.3.2 
Explor atory Efficacy Endpoint(s) 
There are no exploratory efficacy endpoints in this study. 
 
 
1 Seroresponse is defined forthisstudy asfollows: For subjectswith pre-vaccinationtiters <4, pos­t 
vaccination titers 2: 16; forsubjects with pre-vaccinationtiters2::4, post vaccinationtiters at least4 timesthe 
pre-vaccination titers. 
 
 
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8.1.3.3 
Exploratory Immunogenicity Endpoin t(s) 
 
There are no exploratory immunogenicity endpoints in this study. 
 
8.2 
Success C1iteria 
 
8.2.1 
Success C1iteria for P1imary Objective(s) 
 
8.2.1.1 
Success C1ite1ia for P1imary Safety Objective(s) 
There are no primary safety objectives in this study. 
8.2.1.2 
Success C1iteria for Primar y Efficacy Objective(s) 
There are no primary efficacy objectives in this study. 
8.2.1.3 
Success C1ite1ia for P1imary Immunogenicity Objective(s) 
 
To demonstrate immune response sufficiency after MenACWY-CRM booster vaccine 
administration, the lower limit of the one-sided 97.5% Confidence Interval(CI) for 
percentage of subjects with hSBA booster seroresponse against each of serogroups A, C, 
Wand Ymust be greater than 75%. This will be tested sequentially first in the group of 
subjects who received primary vaccination with Menveo and, if met, also in the group of 
subjects who received primary vaccination with Menactra. 
 
8.2.2 
Success C1iteria for Secondar y Objective(s) 
 
8.2.2.l 
Success C1ite1ia for Secondar y Safety Objective(s) 
 
There are no success criteria associated with the secondary safety objectives. 
 
8.2.2.2 
Success C1ite1ia for Secondary Efficacy Objective(s) 
There are no secondary efficacy objectives in this study. 
8.2.2.3 
Success C1ite1ia for Secondary Immunogenicity Objective(s) 
There areno success criteria associated with the secondary immunogenicity objectives in 
this study. 
 
 
 
 
 
 
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8.3 
Analysis Sets 
 
8.3.l 
All Enrolled Set 
 
All screened subjects who provide informed consent and provide demographic and/or 
baseline screening assessments, regardless of the subject's randomization and treatment 
status in the study, and received a Subject ID. 
 
8.3.2 All Exposed Set 
 
All subjects in the enrolled set who receive a study vaccination. 
 
8.3.3 Safety Set 
 
Solicited Safety Set (solicited local and systemic adverse events and other solicited 
adverse events) 
 
All subjects in the Exposed Set with any solicited adverse event data. 
 
Unsolicited Safety Set (unsolicited adverse events) 
 
All subjects in the Exposed Set with unsolicited adverse event data. 
 
Overall Safety Set 
 
All subjects who are in the Solicited Safety Set and/or Unsolicited SafetySet. 
 
8.3.4 Full Analysis Set (FAS) Efficacy/Immunogenicity Set 
Full Analysis Set Immunogenicity 
FAS <Day 1) 
All subjects in the All Enrolled Set who: 
• are randomized; 
• 
provide evaluable serum samples at Day 1 whose result is available for at least one 
serogroup. 
FAS <Day29) 
All subjects in the All Enrolled Set who: 
• are randomized; 
• 
receive the study vaccination; 
 
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• provide evaluableserum samples at Day1 whose result is available for at least one 
serogroup (except for hSBA titer 8 and 16, GMTs and GMRs calculated at specific 
timepoints); 
• provide evaluableserum samples at Day 29 whose result is available for at least one 
serogroup. 
8.3.S Per Protocol (PP) Set Efficacy/l mmunogenicity Set 
A PPSwill be defined for each FAS described in the previous Section with additional 
criteria specified below. 
All subjects in the FAS Immunogenicitywho 
• Have no protocol deviationsleadingto exclusion (see section 8.3.8, Protocol 
Deviation)s as defined prior to unblinding / analysis. 
• 
Are not excluded due to other reasons defmed prior to unblinding or analysis (see 
section 8.3.8, Protocol Deviations) 
Examples for subjects excluded due to other reasons than protocol deviations are: 
Subjects who withdrew informed consent. 
8.3.6 
Other Analysis Sets 
 
There are no other analysis sets used in this study. 
8.3.7 
Subgroups 
 
Using the PPS (Day 29), the analyses of the primaryobjectives will be replicated bysex 
and race. 
8.3.8 
Protocol Deviations 
 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. A protocol deviation may be a reason to remove data from 
an analysis set at the time of analysis. CSR-reportableprotocol deviations will be defined 
as exclusionary fromthe analysis according to protocol objectives and endpoint,swhich 
will be specified in the statistical analysis plan. In some cases exclusion of data may be 
due to a reason other than a protocol deviation, e.g. earlytermination. 

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8.4 
Statistical Analysis Plan 
 
8.4.1 
Analysis of Demographic and Baseline Characteristics 
 
Descriptive statistics (mean, standard deviation, median, minimwn and maximwn) for 
age, height and weight at enrolment will be calculated overall and by study group. 
Distributions of subjects by sex, race and ethnic origin will be summarized overall and by 
study group. 
 
8.4.2 
Analysis of Primary Objective(s) 
 
8.4.2.l 
Analysis of Primary Safety Objective(s) 
There are no primary safety objectivesin this study. 
8.4.2.2 
Analysis of Primar y Efficacy Objective(s) 
There are no primary efficacy objectives in this study. 
 
8.4.2.3 
Analysis of Primary Immunogenicity Objective(s) 
 
8.4.2.3.1 
Statistical Hypotheses 
Null hypothesis: 
P,j 
0.75 
Alternative hypothesis: 
Pij > 0.7 5 
Where: P,j is the population booster seroresponse rate; j = 1,2 refer to group Menveo­ 
Menveo (first test) and Menactra-Menveo(second test) respectively; i = 1,2,3,4 refer to 
serogroup A, C, Wand Y respectivel.yThelevel of significance is fixed at one-sided 
0.025. 
8.4.2.3.2 
Analysis Sets 
 
The analysis population to be used for the primary objectives is the PPS (Day 29). 
Analyses of primary objectives willbe repeated on the FAS (Day 29) to assess robustness 
of results. 

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8.4.2.3.3 
Statistical Methods 
General 
Missing immunogenicityvalues are assumed MCAR (Missing Completely At Random) 
and therefore may not contain information that impact the result of the analysis (i.e., not 
informative). Imputation methods will therefore not be used. 
 
Overall significance level for all hypothesis tests is one-sided a = 2.5%. 
Seroresponse (Day 29) 
Seroresponse for this booster study is defined as: a) post-vaccination hSBA titer ,::16 for 
subjects with a pre-vaccination hSBA titer <4; b) forsubjects with a pre-vaccination 
hSBA titer ,::4, an increase of at least four times the pre-vaccinationhSBA titer. 
For each individual vaccine group (Menveo-Menveo and Menactra-Menveo) and each 
ACWY serogroup, the percentage of subjects with seroresponse will be computed, along 
with associated two-sided 95% Clopper-Pearson Cis. 
 
Further details of the statistical methods will be provided in the SAP. 
 
8.4.3 
Analysis of Seconda ry O bjective(s) 
 
8.4.3.1 
Analysis of Seconda ry Safety O bjective(s) 
 
8.4.3.1.1 
Analysis of Ext ent of Exposur e 
 
Subjects will be analyzed to the extent that they were exposed to study vaccines and 
according to the available safety data for the subject during any study period. Subjects 
who withdraw early or who are lost to follow-up will be removed from the summary table 
denominator for the time period in which they have no available safety data collected. 
 
8.4.3.1.2 
Analysis of Solicited Local,Systemic and Other Adverse Events 
 
All solicited adverse events will be summarized according to defined severity grading 
scales. 
 
Frequencies and percentages of subjects experiencing each adverse event willbe 
presented for eachsymptom severity. Summary tables showing the occurrence of any 
localor systemic adverse event overall and at each time point will also be presented. 

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Post-vaccinationsolicited adverse events reported from Day 1 to Day 7 will be 
summarized for the intervals Day 1 (6 hours) - Day 3, Days 4-7, Day 1 (6 hours) - Day 7 
by maximal severity and by study group. Separate analyses will be performed for 
solicited AEs reported 30 minutes after vaccination.Theseverity of solicited local 
adverse events, including injection-site erythema and induration, will be categorized 
based on linear measurement: None (0-24 mm), Mild (2S-SOmm), Moderate (S1-100 
mm), Severe (> 100mm). 
 
Injection site pain and systemic reactions, including fatigue, headache, myalgia, 
arthralgia, chills, nausea, loss of appetite, occurring up to 7 days after each vaccination 
will be nmmari7ed according to"mild", "moderate" or"severe". 
Each solicited local and systemic adverse event will also be further summarized as"none" 
versus ''anY'. 
Use of antipyretics and analgesics will be summarized by frequency, by type of use 
(prophylactic versus treatment) and percentage of subjects reporting use. 
Body tefl1lElraturewill be summarized separately according to the 3 schemes described 
below and will be broken down according to route of measurement: 
• by O.S °C increments from 36.0°C upto ,::40°C; 
• by 1°C increments: <36.0, 36 .0-36 .9, 37.0-37 .9, 38.0-38 .9, 39.0-39 .9, ,::40°C; 
• According to different cut-offs (< versus ,::): 38 .0, 38 .S, 39 .0, 39 .S, 40 .0 °C . 
8. 4.3 .1. 3 Anal y sis of U n so licited Advene Events 
 
This analysis applies to all adverse events occurring during the study, judged either as 
probably related, possibly related, or not related to vaccination bythe investigato,r 
recorded in AE CRF, with a start date on or after the dateof first vaccination. AE starting 
prior to the first vaccination willonly be listed. The original verbatim terms used by 
investigators to identify adverse events in the CRFs will be mapped to preferred terms 
using the MedDRA dictionary. The adverse events will then be grouped by MedDRA 
preferred terms into frequency tables according to systemorgan class (SOC). 
 
All reported adverse events, as well as adverse events judged by theinvestigator as at 
least possibly related to study vaccine, will be summarized according toSOC and 
preferred term within SOC. These summaries will be presented bystudy group and by 
interval of study observation. When an adverse event occurs more than once for a 
subject, the maximal severity and strongest relationship to the vaccine will be counted. 
Separate summaries will be produced for the following categories: 

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• 
Adverse events that are possibly or probably related to vaccine 
• 
Unsolicited AEs reported within 30 minutes after vaccination 
• 
Unsolicited AEs reported within 29 days after vaccination 
• 
Adverse events leading to withdrawal 
• 
Adverse events leading to a medically attended visit 
• 
Serious adverse events 
• 
Data listings of all adverse events will be provided by subject. In addition, adverse events 
in the categories above will be provided as listed data. 
 
8.4.3.1.4 Statistical Hypotheses 
 
There are no statistical hypotheses associated withthe secondary safety objectives. 
 
8.4.3.LS Analysis Sets 
 
Analyses of solicited adverse events - and other solicited reactions - and unsolicited 
adverse events will be performed on the relevant safety sets. 
 
8.4.3.1.6 StatisticalMethods 
 
For unsolicited adverse events, the entirestudy period will be divided into the following 
intervals: onset within30 minutes after vaccination, onset within 28 days after 
vaccination; and from Day 1 through Day 181. For solicited adverse events, the solicited 
study period will be divided into intervals: from 6 hours through day 3; from day 4 
through day 7; and from 6 hours through day 7. 
No imputation methods willbe used to address missing safety data. 
 
SnmmariP.s of safety will be presented using frequencies and percentages within each 
study group. No statistical comparisons among the studygroups with respect to any of the 
safety parameters will be performed. 
8.4.3.2 
Analysis of Seconda ry Efficacy Objective(s) 
There are no secondary efficacy objectives associated with this study. 

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8.4.3.3 
Analysis of Secondary Immunogenicity Objective(s) 
 
8.4.3.3.1 
Statistical Hypotheses 
Analyses related to the secondary immunogenicityobjectives willbedescriptiv;eno 
formal statistical tests will be performed. 
 
8.4.3.3.2 
Analysis Sets 
 
Analyses of secondary imm1mogenicity will be based on the PPS and repeated on the 
FAS. 
8.4.3.3.3 
Statistical Methods 
General 
The hSBA titers at each visit will belogarithmicallytransformed (basel 0) to obtain 
approximately normally distributed data. 
 
For comparison of percentages and GMT ratios, unadjusted estimates will beobtained 
along with adjusted estimates from regression models to account for potential baseline 
imbalance between study groups. 
For eachN. m.eningitidis serogroup A, C, Wand Y, unadjustedGMTs will becalculate,d 
withtheir associated two-sided 95% Cls, by exponentiating the corresponding log­ 
transformed means and their 95% Cls. Adjusted GMTs willbeobtained from Analysis of 
Covariance (ANCOVA) models. 
 
See section 8.4.2.3.3 for other relevant details. 
 
Seroresponse (Day 4, Day 6, and Day 29) 
 
The percentage of subjects withseroresponse and associated two-sided 95% Clopper­ 
Pearson Cls willbecomputed by group (Menveo-Menveo, Menactra-Menveo, the Nai've 
and the pooled [Menveo-Menveo and Menactra-Menveo]groups) andN. m.eningitidis 
serogroups A, C, W and Y test strains. Differences in percentages and associated 95% Cls 
between study groups willbecalculated using the Miettinen & Nurminen score method. 
 
In a descriptive fashion - using the difference in percentages and 95% Cls - each of the 
previously vaccinated groups (individually and pooled [Menveo-Menveoand Menactra­ 
Menveo]) will becompared to the nai've group. Also the two previously vaccinated study 
groups willbecompared to each other. 

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As sensitivity analyses, the difference in percentages willalso be obtained from a log­ 
linear model adjusting for pre-vaccinationtiter. Please see SAP for technical details. 
 
Percenta ge of Subjects \Vith  hSBA titer<'.'.8  (Da   y  I ,  Da   y  4 ,  Da   y  6,   and 
Da   y  29) 
F or each study group and in the pooled group (Menveo-Menveo and Menactra-Menveo), 
the percentage of subjects with hSBA titer 8 and 16 and associated two-sided 95% 
Clopper-Pearson Cls willbecomputed by the N. meningitidis serogroups A, C, W and Y 
teststrains on Day 1, Day 4, Day 6 and Day 29 (as applicable, depending on blood draw 
schedule). 
 
Differences in percentages and associated 95% Cis between study groups will be 
calculated using the Miettinen & Nurminen score method. 
 
In a descriptive fushion - using the difference in percentages and 95% Cis - the previously 
vaccinated groups (individually and pooled [Menveo-Menveo and Menactra-Menveo]) 
will becompared to the nai've group . Also the two previously vaccinated groups will be 
compared to each other. 
 
As sensitivity analyses, the difference in percentages willalso be obtained from a log­ 
linear model adjusting for pre-vaccinationtiter. Please see SAP for technical details. 
 
Between-gr oup Ratios of Gl\ lll T s (A d jus te d a nd Un ad ju sted) 
 
The between -group ratio ofhSBA GMTs and corresponding 95% CI, at each of Visit Day 
1 (Persistence), Day 4, Day 6 and Day 29 against each N. meningitidis serogroups A, C, 
W and Y test strains willbeobtained by exponentiatingthe mean between-group 
differences in log-transformed titers and the corresponding 95% Cls at each of the 
timepoints specified. 
Additionally, adjusted ratio of GMTs willbeobtained fromANCOVA models including 
pre-vaccination titer as fuctors in the model. 
 
The previously vaccinated groups (individually and pooled [Menveo-Menveoand 
Menactra-Menveo])willbecompared to the nai've group at each timepoint - descriptively 
- using the ratios of GMTs. 
The two previously vaccinated groups willbecompared at each timepoint using GMT 
ratios. 
\Vit hin-gro up GMRs (Adjusted and Unadjusted) 
 
Within each study group and for each serogroup, GMRs will be calculated, as applicable, 
at: 

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• 
Visit Day4 versus at Visit Day 1; 
• 
Visit Day 6 versus at Visit Day 1; and 
• 
Visit Day 29 versus at Visit Day 1. 
 
The unadjusted GMR.s and 95% Cis willbeconstructed by exponentiating the mean 
within-groupdifferences in log-transformed titers and the corresponding 95% Cis. 
Further details of the statistical methods willbeprovided in the Statistical Analysis Plan 
(SAP). 
 
8.4.4 
Analysis of E xplora tory O bjectives 
 
8.4.4.1 Analysis of E xplora tory Safety O bjective(s) 
There are no exploratory safety objectives in this study. 
8.4.4.2 
Analysis of Explora tory Efficacy Objective(s) 
There are no exploratory efficacy objectives in this study. 
8.4.4.3 
Analysis of Explora tory Immunogeoicity Objective(s) 
There are no exploratory immunogenicityobjectives in this study. 
8.5 
Sample Size and Power Considera tions of Primary and Secondary Objectives 
 
Statistical power was estimated based on observed data from a previous study 
(V59Pl3 El) assessing the immunogenicityof a booster dose ofMenveo among subjects 
who had previously been vaccinated with either Menveo or Menactra 3 years prior in 
another study (V59P13) whilesubjects were 11-18 years old. Data from study V59Pl3 El , 
were used to compute booster seroresponse rates at one-monthpost booster dose of 
MenACWY-CRM using the following definition of booster seroresponse: a) post­ 
vaccination hSBA titer,:: 16 for subjects with a pre-vaccinationhSBA titer <4; b) for 
subjects with a pre-vaccination hSBA titer ,::4, an increase of at least four times the pre­ 
vaccination hSBA titer (cf. table 8.5-1). 

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Table 8.5-1: 
hSBASeroresponse at One Month Following the Booster at 3 
Years After Vaccination, bySerogroup - Booster- PP Population 
 
 
 
Vaccination 
ACWY/A 
Group IV
Y 
l\fenactr a/ACWY 
Gt·onp V 
<I'. 
.
Q.. 
:, e .e. 
"' 
Overall 
Seroresponse 
68(97%) 
(90-100) 
N=70 
70 (100%) 
(95-100) 
N=70 
u 
.
Q.
. 
:, e .e. 
"' 
Overall 
Seroresponse 
66(93%) 
(84-98) 
N=71 
65 (93%) 
(84-98) 
N=70 
.
Q.
. 
:, e 
e 
Overall 
Seroresponse 
63 (91%) 
(82-97) 
N=69 
64 (93%) 
(84-98) 
N=69 
> 
.
Q.
. 
:, e .e. 
"' 
Overall 
Seroresponse 
63 (90%) 
(80-96) 
N=70 
64 (91%) 
(82-97) 
N=70 
 
 
Assuming the true booster seroresponse rates in the Menveo-Menveogroup range from 
90% to 97% (alternative hypothesis) for each serotype, a sample sizeof n=270will have 
at least 96% power to show sufficiency of immune response to a booster dose of 
MenACWY-CRM, compared with a pre-specifiedreference booster seroresponse of7S% 
(null hypothesis) using an exact test with 0.02Sone-sidedsignificance level (cf table 8.S- 
2a). 
 
Assuming the true booster seroresponse rates in the Menactra-Menveogroup range from 
91% to 100% (alternative hypothesis) for each serotype, a sample sizeof n=270will have 
at least 96% power to show sufficiency of immune response to a booster dose of 
 
 
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MenACWY-CRM, compared with a pre-specified reference booster seroresponse of 75% 
(null hypothesis) using an exact test with 0.02Sone-sided significance level (cf table 8.S- 
2b). 
 
Table 8.S-2a: 
Statistical Power to Test for Sufficiency of Immune Response 
Given a Range of True Booster Seror esponse Ra tes for 
Evaluable Sample Size of 270 subjects in the Menveo-Menveo 
group 
Serot}11e 
T111e Seroresponse Rate 
Power 
A 
0.97 
0.99 
C 
0.93 
0.99 
w 
0.91 
0.99 
y 
0.90 
0.99 
Total Power 
0.96 
 
Calculations havebeendone with nQuety Advisor (Version 7.0). 
 
Table 8.S-2b: 
Statistical Power to Test for Sufficiency of Immune Response 
Given a Range of True BoosterSeroresponse Rates for 
Evaluable Sample Size of 270 subjectsin the Menactra-1\lle n veo 
gro u p 
 
Se.-0!}11e 
T111e Seroresponse Rate 
Power 
A 
>0.99 
0.99 
C 
0.93 
0.99 
w 
0.93 
0.99 
y 
0.91 
0.99 
Total Power 
0.96 
Calculations havebeendone with nQuety Advisor (Version 7.0). 
 
Overall statistical power to show sufficiency of immune response to a booster dose of 
MenACWY-CRM for each serotype in both the Menveo-Menveo and the Menactra­ 
Menveo group will be at least 92%. 
 
When taking a 10% dropout rate into account, N=300 previously vaccinated subjects with 
Menveo and N=300 previously vaccinated subjects with Menactra have to be enrolled in 
the study. 
 
A total of 100 meningococcal vaccine-naive subjects are planned to be enrolled in the 
study for comparisonof immune responses after a single dose in unprimed subjects with 
the booster response in primed subjects. The sample size of 100 naive subjects is based on 
 
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previous MenACWY studies Pxamining the response to a booster and to ensure a 
rniuirnnm sample sizeof sosubjects in each blood draw schedule for adequate 
compansons. 
 
8.6 
Interim Analysis 
No interim analysis of data from this studyis planned. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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9. 
SOURCE DOCUMENTATION, STUDY MONITORING AND AUDITING 
In order to ensure consistency across sites, study monitoring and auditing willbe 
standardized and performed in accordance with the Sponsor's or delegated contract 
research organization' s (CRO) standard operating procedures and applicable regulatory 
requirements (e.g., FDA, EMA, and ICH guidelines). 
Prior to enrolment of the first study subject, GSK or delegate willtrain investigators 
and/or their study staff on the study protoco allapplicable studyprocedures, 
documentation practices and all electronic systems. CRFs supplied by the Sponsor must 
be completed for each randomized subject (see section 8.3.1, All Enrolled Set for 
definition of enrolled subject). Documentation of screened but not enrolled subjects must 
be maintained at the site and made available for review by the site monitor. Data and 
documents willbechecked by the Sponsor and/or monitor. 
9.1 
Source Documentatoi n 
 
Prior to the start of the study, the site staff participating in the study conduct will be 
instructed on what documents willberequired for review as source documents. The kinds 
of documents that willserve as source documents willbe agreed between Sponsor or 
delegate and investigator and designees and specified in the SDAF prior to subject 
enrolment. 
 
In addition, source documentation must include all of the following: subject identification 
(on each page), eligibility and participation, proper informed consent procedures, dates of 
visits, adherence to protocol procedures, adequate reporting and follow-up of adverse 
events,: documentation of prior/concomitant medication/vaccines, study vaccine 
receipt/dispensing/return records, study vaccine administration information, any data 
collected by a telephone conversation with the subject and/or parent(s)/legal guardian(s) 
and date of completion and reason. 
 
The subject and/or parent(s)/legal guardian(s) must also allow access to the subject's 
medical records. Each subject and/or the parent(s)/legal guardian(s) must be informed of 
this prior to the start of the study and consent for access to medical records may be 
required in accordance with local regulations. 
All safetydata reported by subjects must be written down in source documents prior to 
entry of the data into CRFs. If there are multiple sources of information (e.g., Subject 
Diary, verbal report of the subject, telephone contact details, medical chart) supporting 
the diagnosis of an adverse event, thesesources must be identified in the source 
documents, discrepancies between sources clarified, the ultimate diagnosis must be 
justified and written in the source documents, and this diagnosis must be captured in the 

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Adverse Event CRF (AE CRF). The AE CRF must also capture which source(s) of 
infonnation were used to detennine the adverse event (e.g., subject recall, medical chart, 
Subject Diary). 
9.2 
Study Monitoring, Auditing and Sow·ce Data Verification 
Prior to enrolment of the first study subject, GSK or its designee (e.g., a CRO) will 
develop a Clinical Monitoring Plan to specify how centralized and/or on-site monitoring, 
including clinical specimens reconciliation, will be performed for the study. Study 
progress will be monitored byGSK or its designee as frequently as necessary to ensure: 
• that the rights and well-beingof human subjects are protected, 
• the reported study data are accurate, complete, and verifiable from the source 
documents and 
• the conduct of the studyis in compliance with the cUITent approved 
protocol/amednment(s), GCP and applicable regulatory requirements. 
Contact details for the GSK teamor its designee involved in study monitoring will be 
provided to the investigator. Study data recorded on CRFs will be verified by checking 
the CRFentries against source documents in order to ensure data completeness and 
accuracy as required by study protocol. . 
Data verification may also be performed through a centralized review of data (e.g., 
checking for outliers or other anomalies). Additional documents such as the investigator 
site file, pharmacy records, and infonned consent documentation must also be available 
for review if requested. Arrangements for monitoring visits will be made in advance in 
accordance with the monitoring plan, except in case of emergency. 
The investigator and/or site staff must make source documents of subjects enrolled in this 
study available for inspection by GSK or its representative at the time of each monitoring 
visit and Sponsor audits, when applicable. These documents must also be available for 
inspection, verification and copying, as required by regulation,sbyofficials of the 
regulatory health authorities (e.g., FDA, EMA and others) and/or ECs/IRBs. The 
investigator and study site staff must comply with applicable privacy, data protection and 
medical confidentialitylaws for use and disclosure of infonnation related to the study and 
enrolled subjects. 

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DATA MANAGEME1''T 
10.1 
Data Enh·y and Management 
Page n of86 
 
In this study, all clinical data (including, but not limited to, AEISAEs, concomitant 
medications, medical history, and physical assessments), safety data, and immllllogenicity 
data will be entered onto case report fonns (CRFs) in a timely fashion by the investigator 
and/or the investigator 's dedicated site staff. Data entered onto CRFs are stored on a 
secure website. The data collected on this secure website are assimilated into an 
electronic data capture (EDC) system, which is compliant with Title 21 Part 11 policies of 
the Code of Federal Regulations (FDA 1997). The data system includes password 
protection and internal quality checks. The EDC system will be designed and validated by 
the Sponsor prior to activation for data entry by sites. The investigator or designated 
delegate nrust review data entered and electronicallysign the CRFs to verify their 
accuracy. 
 
Access to the EDC system for data entryor review will require training and distinct 
individual access code assignments to those site staff members who willbe entering study 
data and those involved in study oversight who may review study data. Data are collected 
within the EDC system, to which the Sponsor and site monitors have exclusively "read 
only" access. 
 
10.2 
Data Cla1ifi cati on 
 
As part of the conduct of the trial, the Sponsor may have questions about the data entered 
by the site, referred to as queries. The monitors and the Sponsor are the only parties that 
can generate a query. All corrections and clarifications will be entered into the EDC 
system and will be identified by the person entering the information, tlJe reason for the 
change, as well as the time of tlJe changes made. If changes are made to a previously and 
electronically signed CRF, the investigator must confirm and endorse the changes. 
 
10.3 
Data Protection 
 
GSK respects the subjects' rights to privacy and willensure the confidentiality of their 
medical information in accordance with all applicablelaws and regulations. 

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11. 
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 nrust be easily accessible, when needed (e.g. audit or 
inspection,)and must be available for review in conjunction with assessment of the 
facility, supporting systems, and staff. Where permitted by applicable laws/regulations or 
institutional policy, some or all of these records can be maintained in a validated format 
other than hard copy (e.g. microfiche, scanned, electronic); howeve,rcaution needs to be 
exercised before such action is taken. The investigator nrust ensure that all reproductions 
are legible and are a true and accurate copy of the original and meet accessibility and 
retrieval standards, including re-generatinga 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 reproduction.s 
GSK will inform theinvestigato/rinstitutionof the time period fur retaining these records 
to comply with all applicable regulatory requirements. Thi,, minimmn 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, 
otherwise, the minimum retention period will default to 25 years after completion of the 
study report. 
The investigator/institutionnrust 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 leavesthe site. 
 
The principles for the storage of laboratory samples are provided below: 
Collected samples will be stored for a maximum of20 years (countingfrom 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. 

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12. 
USE OF Jll,'FO RMATION AND PUBLICATION 
 
GSK assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov, and in compliance with cUITent re gulations. 
 
GSK also assures that key results of this clinical study will be posted in a publicly 
accessible database within the required time-frame from theend of study as defined in 
section 3.9, End of Study. 
In accordance withstandard editorial, ethical practices and cUITent guidelines of Good 
Publication Practice (Graf 2009), GSK will generally support publication ofmulticenter 
studies only in their entirety and not as individual center data. In this case, a coordinating 
investigator will be designated by mutual agreement prior to the start of the study. The 
coordinating investigator will also sign the clinical study report on behalf of the principal 
investigators (CPMP/EWP/2747/00). Authorship will be determined by mutual agreement 
and in line with International Committee of Medical Journal Editors authorship 
requirements. Any fonnal publication of the studyin which contribution ofGSK 
personnel exceeded that of conventional monitoring will be considered as a joint 
publication by the investigator and the appropriate GSK personnel. 
 
GSK must be notified of any intent to publish data collected from the study and prior 
approval from GSK must be obtained prior to submission for publication. 

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13. 
ETIDCAL CONSIDERATIONS 
 
13.1 
Regulatory and Ethical Compliance 
The study will beconducted in compliance with the protocol, GCP and applicable 
regulatory requirement(s). 
This clinical study was designed and shall be implemented and reported in accordance 
withthe ICH Harmonized Tripartite Guidelines for GoodClinical Practice, with 
applicable local regulations including European Directive 2001/20/EC, US Code of 
Federal Regulations Title 21, and Japanese Ministry ofHealth, Labor, and Welfare, GSK 
codes on protection of human rights, and with the ethical principles laid down in the 
Declaration of Helsinki (European Council 2001, US Code of Federal Regulations, ICH 
1997). 
 
13.2 
Informed Conse nt Proced ures 
 
Eligible subjects may be included in the study only after providing writteninformed 
consent or assent, as described in section 5.1.1, Informed Consent/Assent. Before the start 
of the study, the investigatorwill have the informed consent and any other materials that 
will be provided to the subjects reviewed and approved bythe IRB/EC. This review and 
approval will be documented and stored with other studydocuments. The investigator or 
designee must fully inform thesubject or legal guardian of all pertinent aspects of the 
study. A copy of the written informed consent will be given to the subject or the designee. 
The subject/designee must be allowed ample time to ask about thedetails of the study and 
to make a decision as to whether or not to participate in the study. The subject and/or 
legal guardian(s) must sign the consent form indicating their agreement to participate in 
the studybefore anystudy-related procedures are conducted. The informed consent 
process may be conducted up to 5 days prior to vaccination on Day 1. If the subject 
and/or legal guardian(s) is unable to read and write, a witness must be present during the 
informed consent discussion and at the time of informed consent signature. 
Prior to the start of the study, GSK will provide to investigators a proposed informed 
consent form that complies with the ICH GCP guideline and regulatory requirements and 
is considered appropriate for this study. Any changes to the proposed consent form 
suggested by the investigator nrust be agreed to byGSK before submission to the IRB/EC 
and a copy of the approved version must be provided to the GSK monitor after IRB/EC 
approval 
Women of childbearing potential should be informed that taking the study medication 
may involve unknown risks to the fetus if pregnancy were to occur during the study and 
agree that in order to participate in the study they must adhere to the contraception 

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requirements indicated in the protocol for the duration of the study. In case of doubts on 
the ability of a subject to adhere to these requirements, that subject should not be allowed 
in the study 
 
Before the start of the study, the investigator will have the informed assent, the informed 
consent, and any other materials that will be provided to the subject and/or parent(s)/legal 
guardian(s) reviewed and approved by the IRB/EC. This review and approval will be 
documented and stored with other study documents. The investigator or designee must 
fully inform the subject and/or parent(s)/legalguardian(s) of all pertinent aspects of the 
study. A copy of the written informed consent and informed assent will be given to the 
subject and/or parent(s)/legal guardian(s). 
In addition, the investigator or designee should explain pertinent aspects of the study in an 
age appropriate manner to pediatric subjects who are eligible for informed assent in 
accordance with local policies. The subject and parent(s)/legal guardian(s) must be 
allowed ample time to ask about the details of the study and to make a decision as to 
whether or not to participate in the study. The subject and parent(s)/legal guardian(s) must 
sign the consent/assent forms indicating their agreement to participate in the study before 
any study-related procedures are conducted. If the subject and/or parent(s)/legal 
guardian(s) are unable to read and write, a witness must be present during the informed 
consent/assentdiscussion and at the time of informed consent/assentsignature. 
13.3 
Responsibilities of the Investigator a nd IRB/EC 
 
The protocol and the proposed informed consent form must be reviewed and approved by 
a properly constituted IRB/EC before study start. Properly constituted IRB/EC is defined 
in ICH Guideline for Good Clinical Practice E6 (RI), Section 3 (ICH 1997). A signed and 
dated statement that the protocol and informed consent have been approved by the 
IRB/EC must be given to GSK before study initiation. Prior to studystart and at any time 
the protocol is amended during studyconduct, the investigator is required to sign a 
protocol signature page confirming his/her agreement to conduct the study in accordance 
withthese documents and all of the instructions and procedures found in this protocol and 
to give access to all relevant data and records to GSK monitors, auditors, GSK Clinical 
Quality Assurance representatives, designated agents of GSK, IRBs/ECs, and regulatory 
authorities as required. If an inspection of the clinical site is requested by a regulatory 
authority, the investigator must inform GSK immediately that this request has been made. 
The investigator also responsible for the following: 
• 
Maintaining a list of appropriately qualified persons to whom the investigator has 
delegated significant study-related duties. 

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• Demonstrating the capability of recruiting the required number of suitable subjects 
within the recruitment period. 
• Demonstrating sufficient time and staffing to properly conduct and complete the study 
within the agreed study period. 
• Ensuring that all persons assisting with the study are adequately informed about the 
protoco the investigationalproduct()s, and their study-related duties and functions. 
• Ensuring that appropriately trained health care professionals are responsible for all 
study-related medical decisions and for ensuring appropriate medical care of subjects 
experiencing any adverse event related to the study. 
• If permission to do so is given by the subject and/or parent(s)/legalguardian(s), 
ensuring that the subject's primary healthcare provider is informed of the subject's 
participation in the study. 
The investigator should not implement any deviation from, or changes of the protocol 
without agreement by the Sponsor and prior review and documented approval/favourable 
opinion from theIRB/IEC of an amendment, except where necessary to eliminate an 
immediate hazard(s) to study subjects, or when thechange(s) involves only logistical or 
administrative aspects of the study (e.g., change in monitor(s,)change of telephone 
nwnber(s)). In addition, the investigato,ror person designated by the investigato,rshould 
document and explain any deviation from the approved protocol. 
 
The investigator may implement a deviation from, or a change of, the protocol to 
eliminate an immediate hazard(s) to study subjects without prior IRB/IEC 
approval/favourable opinion. As soon as possible, the implemented deviation or change, 
the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be 
submitted: 
(a) to theIRB/IEC for review and approval/favourable opinion, 
(b) to the Sponsor for agreement and, if required, 
(c) to the regulatory authority(ies). 
13.4 
Protocol Amendments 
An amendment is a written description of change(s) to or formal clarification of a study 
protocolwhich may impact on the conduct of the clinical study, potential benefit of the 
clinical study, or may affect subject safety, including changes of study objectives, study 
design, subject population, sample sizes, studyprocedures, or significant administrative 
aspects. An administrative change of a studyprotocol is a minor correction or 
clarification that has no significant impact on the waythe clinical study is to be conducted 

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and no effect on subject safety (e.g., change of telephone number(s), logistical changes). 
Protocol amendments nrust be approved by GSK, health authorities where required, and 
the IRB/EC. In cases when the amendment is required in order to protect the subject 
safety, the amendment can be implemented prior to IRB/EC approval. Notwithstanding, 
the need for formal approval of a protocol amendmen,tthe investigator is expected to take 
any inunediate action required for the safety of anysubject included in this study, evenif 
this action represents a deviation from the protocol. In such cases, GSK should be notified 
of this action, the IRB/EC at the study site, and, if required bylocal regulations, the 
relevant health authority) should be informed within 10 working days. 

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14. 
REFERENCE LIST 
Code of Federal Regulations (1997): Food and Drug Administration, U.S. Depar1ment of 
Health and Human Services: Title 21, Part 11: Electronic Records Electronic Signatures. 
Federal Register 62: 13464 
European Medicines Agency (2005): EMEA/CHMP/313666/2005 Guideline on the 
exposure to medicinal products during pregnancy: need for post-authorisationdata, 
London, 14 November 2005 
European Parliament (1995): Directive 95/46/EC of the European Parliament and of the 
Council of 4 April 2001. Official Journal of the European Communities. L 281/31-39 
European Parliament (2001): Directive 2001/20/EC of the European Parliament and of 
the Council of 4 April 2001. Official Journal of the European Communities. L 121/34-44 
Graf C, Battisti WP, Bridges D (2009). Good publication practice for communicating 
company Sponsored medical research: the GPP2 guidelines. BMJ; 339: b4330 
ICH (1997) ICH Harmonised Tripartite ICH Guideline for Good Clinical Practices E6 
(RI). Federal Register, 62 (90): 25691-25709 
 
ICH (1998) ICH Harmonised Tripartite ICH Guideline for Statistical Principles for 
Clinical Trials E9. Federal Register, 63 (179): 49583 
Levine RJ. (1988) Ethics and Regulations of Clinical Research. New Haven: Yale 
University Press. 
Metropolitan Atlanta Congenital Defects Program (MACDP) 
http://www.cdc.gov/ncbddd/birthdefects/documents/macdpcode0807.pdf 
 
U.S. Depar1ment of Health and Human Services, Food and Drug Administration, CBER 
(2009): Guidance for Industry Patient-Reported Outcome Measures: Use in Medical 
Product Development to Support Labeling Claims 
59th World Medical Association General Assembly (October 2008) Declaration of 
Helsinki - Ethical Principles for Medical Research Involving Human Subjects. Seoul, 
Korea 

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Appendix 1: In vestiga tor Agreement 
I agree: 
 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrativechanges, 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 responsibilityfor the proper conduct of the study at this site. 
• 
That I am aware of, and willcomply 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' study vaccine(s)/product(s) and other study-related duties and 
functions as described in the protocol. 
• 
To acquire the reference ranges for laboratory tests perfonned locally and, if required 
by local regulations, obtain the laboratory's cUITent certification or Quality Assurance 
procedure manual. 
• 
To ensure that no clinical samples (including serumsamples) are retained onsite or 
elsewhere without the approval of GSK Biologicals and the express written informed 
consent of the subject and/or the subject's legally acceptable representative. 
• 
To perform no other biological assays on the clinical samples except those described 
in the protocol or its amendment(s). 
• 
To co-operate with a representative of GSK Biologicals in the monitoring process of 
the study and in resolution of queries about the data. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator' s ownership interest in 
the sponsor or the investigationalvaccine(s)/product(s), and more generally about 
his/her financial tieswith 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. 

Protocol V59_77 
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24 JUN16 Final Protocol Version 1 
Confidential 
PR0-01 TEMP 06 / Atlas No. 293620 
VersionNo.4 / VersionDate: January29, 2015 
 
 
 
• 
Agree that GSK Biologicals may disclose any infonnation it has about such 
ownership interests and financial ties to regulatory authoritie.s 
• 
Agree to provide GSK Biologicals with an updated Curriculum Vitae and other 
documents required by regulatory agencies for this study. 
 
eTrack study number and 
Abbreviated Title 
IND number: 
Date of protoco:l 
Detailed Title: 
 
 
 
 
 
Investigator name: 
 
 
Signature: 
 
 
Date: 
205352 (MENACWY CONJ-038 (V59_77)) 
 
 
IND11278 
 
 
A Phase 3b, Controlled, Open-Label, Multi-Center 
Study to Evaluate Safety and Immunogenicity of a 
Single Dose of GlaxoSmithKline's Meningococcal 
ACWY Conjugate Vaccine (Menveo), Administered to 
Healthy Individuals 15 through 55 years of age, 
approximately 4-6 years after primary ACWY 
vaccination. 
 
 
 
 
 
 
 
 
 

 
---- 
I
Novartis 
 
 
 
PPo• -    - 
-' 
Document A !J!roval Ce rtificate / 
PPD 
/   
 
1.,;.. 
_ 
 
 
 
Theindivi:luals listed have appl'()ved this document for ii!Jplementation using an electronic signaturein the 
Atlas EDMS. tFPO 
I 
S 
U serName:pp-o• -   -   - 
.. PP D 
Ti tl e: C l u ster  Phys ician -Meningi 
t is an d Sepsis Franchise 
Date: Friday, 12 August 20 16 , 12 :44 GMT 
Meaning: As an approver, I agree with the content and format of this document 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ai 
 
::, z 
u 
8 

Protocol V59_77 
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Regulatory Review Protocol Version 2 
PR0--01 TEMP 06 / Atlas No. 293620 
VersionNo.4  /  VersionDate: January29,2015 
 
 
 
 
 
CLINICAL STUDY PROTOCOL VS9 77 Version 2 
 
 
 
A Phase 3b, Controlled, Open-Label, Multi-Center Study to Evaluate Safety and 
Inumnogenicity of a Single Dose of GlaxoSmiht Kline's Meningococcal ACWY 
Conjugate Vaccine (Menveo), Administered to Healthy Individuals 15 through 55 years 
of age, approximately 4-6 years after primary ACWY vaccination. 
 
 
Safety and Immunogenicity Study of a Single Dose of Menveo, Administered to Subjects 
15 through 55 years of age, approximately 4-6 years after primary ACWY vaccination 
 
 
 
 
Property of GlaxoSmithKline Vaccines (hereafter referred to as GSK) 
Confidential 
May not be used, divulged, published or otherwise disclosed without  \VIi tt .en 
co n se nt  of GSK 

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TABLE OF CONTENTS 
TABLE OF CONTENTS ..................................................................................................... 2 
PROTOCOL SYNOPSIS VS9 77 ................................................................................... 7 
LIST OF ABBREVIATIONS ............................................................................................. 20 
1. 
BACKGROUND AND RATIONALE ..................................................................... 21 
1.1 Background .......................................................................................................... 21 
1.2 Rationale .............................................................................................................. 22 
2. 
OBJECTIVES ........................................................................................................... 23 
2.1 Primary Objective(s) ........................................................................................... 23 
2.2 Secondary Objective(s) ........................................................................................ 23 
2.3 
Exploratory Objective(s) ...................................................................................... 24 
3. 
STUDYDESIGN................................................................................................. 2S 
3.1 OverviewofStudyDesign...............................................................................        2S 
3.2 StudyPeriod ..................................................................................................... 27 
3.3 
Blinding Procedures ............................................................................................. 27 
3.4 
Data Collection ................................................................................................ 28 
3.4.1 
Data Collected from Subjects .................................................................... 28 
3.4.2 
Tools Used for Data Collection ................................................................. 28 
3.S 
Collection of Clinical Specimens ......................................................................... 29 
3.6 Stopping/Pausing Guidelines ........................................................................... 30 
3.7 
Data Monitoring Committee ............................................................................ 30 
3.8 
Premature Withdrawal from Study .................................................................. 30 
3.9 EndofStudy ............................................................................................... 33 
4. 
SELECTION OFSTUDY POPULATION .......................................................... 34 
4.1 Inclusion Criteria ............................................................................................. 34 
4.2 Exclusion Criteria ............................................................................................ 3S 
4.3 Criteria for Delay of Vaccination and/or Blood Sampling ............................... 36 
S. 
STUDYPROCEDURES ...................................................................................... 37 
S.1 
Pre-vaccination Clinic Visit(s) ......................................................................... 37 

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5.1.1 
Informed Consent/Assent ......................................................................... 37 
5.1.2 
Screening ....................................................................................................... 38 
5.1.3 
Enrolment ................................................................................................. 39 
5.1.4 
Randomization .............................................................................................. 40 
5.2 Vaccination Clinic Visit. ................................................................................. 41 
5.2.1 
Post-vaccinationProcedures ........................................................................... 41 
5.2.2 
Post-vaccination Reminders ......................................................................... 42 
5.3 Post-vaccinationVisit(s) ........................................................................................ 43 
5.3.1 
Follow-up Clinic Visit(s) ........................................................................... 43 
5.3.2 
Safety Follow-up Calls .................................................................................. 44 
5.4 
Unscheduled Visits .............................................................................................. 44 
5.5 Study Termination Visit. ........................................................................................ 44 
5.5.1 
Early Termination Visit. ........................................................................... 45 
6. 
TREATMENT OF SUBJECTS ................................................................................ 47 
6.1 StudyVaccine(s) ..................................................................................................... 47 
6.2 Non-Study Vaccines ......................................................................................... 48 
6.3 Vaccine Preparationand Administration .......................................................... 48 
6.4 Vaccine Administration Error or Overdose ofVaccine .................................... 50 
6.5 Prior and Concomitant Medications and Vaccines .......................................... 50 
6.6 Vaccine Supply, Labeling, Storage and Tracking ................................................. 51 
7. 
ASSESSMENTS .................................................................................................. 53 
7.1 SafetyAssessment ............................................................................................ 53 
7.1.1 
Solicited Adverse Events .......................................................................... 53 
7.1.2 
Unsolicited Adverse Events ....................................................................... 55 
7.1.3 
Evaluation of Adverse Events ................................................................... 55 
7.1.4 
Serious Adverse Events ............................................................................. 57 
7.1.4.1 AdverseEvents of Special Interest ...................................................... 58 
7.1.5 
Methods for Recording Adverse Events and Serious Adverse Events ....... 59 
7.1.5.1 Post-Study Events ............................................................................... 59 

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7.1.6 
Pregnancies ................................................................................................... 60 
7.1.7 
Safety Laboratory Measurements .............................................................. 60 
7.2 Efficacy Assessment ............................................................................................. 60 
7.3 ImmunogenicityAssessment ................................................................................ 60 
8. 
STATISTICAL CONSIDERATIONS ..................................................................... 62 
8.1 
Endpoints .............................................................................................................. 62 
8.1.1 
Primary Endpoint(s) ....................................................................................... 62 
8.1.1.1 
Primary SafetyEndpoint(s) ................................................................ 62 
8.1.1.2 
Primary Efficacy Endpoint(s) ................................................................. 62 
8.1.1.3 
Primary ImmunogenicityEndpoint(s) ..................................................... 62 
8.1.2 
SecondaryEndpoint(s) .............................................................................. 62 
8.1.2.1 
Secondary SafetyEndpoint(s) ............................................................ 62 
Adverse events will be coded using MedDRA preferred teims as applicable .... 63 
8.1.2.2 
Secondary Efficacy Endpoint(s) ............................................................. 63 
8.1.2.3 
Secondary ImmunogenicityEndpoint(s) ............................................ 63 
8.1.3 
ExploratoryEndpoint(s) ............................................................................ 63 
8.1.3.1 
Exploratory Safety Endpoint(s) ............................................................... 63 
8.1.3.2 
Exploratory Efficacy Endpoint(s) ........................................................... 63 
8.1.3.3 
Exploratory ImmunogenicityEndpoint(s) ............................................... 63 
8.2 Success Criteria ..................................................................................................... 64 
8.2.1 
Success Criteria for Primary Objective(s) ......................................................64 
8.2.1.1 
Success Criteria for Primary Safety Objective(s) ....................................64 
8.2.1.2 
Success Criteria for Primary Efficacy Objective(s) ................................ 64 
8.2.1.3 
Success Criteria for Primary ImmunogenicityObjective(s) ............... 64 
8.2.1.3.l Rationale for Combining the Menveo-Menveo and Menactra-Menveo 
groups ............................................................................................. 64 
8.2.2 
Success Criteria for Secondary Objective(s) ............................................. 65 
8.2.2.1 
Success Criteria for Secondary Safety Objective(s) ........................... 65 
8.2.2.2 
Success Criteria for Secondary Efficacy Objective(s) ........................ 65 

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8.2.2.3 Success Criteria for Secondary ImmunogenicityObjective(s) ............... 66 
8.3 Analysis Sets .................................................................................................... 66 
8.3.1 
All Enrolled Set .................................................................................... 66 
8.3.2 
All Exposed Set ......................................................................................... 66 
8.3.3 
Safety Set. ........................................................................................... 66 
8.3.4 
Full Analysis Set (FAS) Efficacy/Immunogenicity Set. .............................. 66 
8.3.5 
Per Protocol (PP) Set Efficacy/Immunogenicity Set ................................... 68 
8.3.6 
Other Analysis Sets ................................................................................... 68 
8.3.7 
Subgroups ...................................................................................................... 68 
8.3.8 
Protocol Deviations ....................................................................................... 68 
8.4 Statistical Analysis Plan ................................................................................... 68 
8.4.1 
Analysis of Demographic and BaselineCharacteristics ............................ 68 
8.4.2 
Analysis of Primary Objective(s) .............................................................. 69 
8.4.2.1 Analysis of Primary SafetyObjective(s) ............................................. 69 
8.4.2.2 Analysis of Primary Efficacy Objective(s) ............................................... 69 
8.4.2.3 Analysis of Primary Immunogenicity Objective(s) ............................. 69 
8.4.2.3.1 
Statistical Hypotheses ............................................................. 69 
8.4.2.3.2 
Analysis Sets ............................................................................... 69 
8.4.2.3.3 
Statistical Methods .................................................................. 69 
8.4.3 
Analysis of Secondary Objective(s) ......................................................... 70 
8.4.3.1 Analysis of Secondary Safety Objective(s) ................................................ 70 
8.4.3.1.1 
Analysis of Extent ofExposure .................................................... 70 
8.4.3.1.2 
Analysis of Solicited Local, Systemic and Other Adverse Events 70 
8.4.3.1.3 
Analysis of Unsolicited Adverse Events ...................................... 71 
8.4.3.1.4 
Statistical Hypotheses ................................................................. 72 
8.4.3.1.5 
Analysis Sets ............................................................................... 72 
8.4.3.1.6 
Statistical Methods ....................................................................... 72 
8.4.3.2 Analysis of Secondary Efficacy Objective(s) ..................................... 72 
8.4.3.3 Analysis of Secondary Immunogenicity Objective(s) ........................ 72 

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8.4.3.3.1 
Statisitcal Hypotheses .............................................................. 72 
8.4.3.3.2 
Analysis Sets ............................................................................... 72 
8.4.3.3.3 
Statistical Methods ....................................................................... 73 
8.4.4 
Analysis of Exploratory Objectives .............................................................. 75 
8.4.4.1 Analysis of Exploratory Safety Objective(s) ............................................. 75 
8.4.4.2 Analysis of Exploratory Efficacy Objective(s)........................................ 75 
8.4.4.3 Analysis of Exploratory Immunogenicity Objective(s) .......................... 75 
8.5 Sample Size and Power Considerations of Primary Objectives ....................... 75 
8.6 Interim Analysis ............................................................................................... 76 
9. 
SOURCE DOCUMENTATION, STUDY MONITORING AND AUDITING ........ 77 
9.1 Source Documentation .................................................................................... 77 
9.2 Study Monitoring, Auditing and Source Data Verification  ..................................78 
10. 
DATA MANAGEMENT .......................................................................................... 79 
IO. I Data Entry and Management ................................................................................. 79 
10.2 Data Clarification ............................................................................................ 79 
10.3 Data Protection ................................................................................................ 79 
11. 
RECORD RETENTION........................................................................................... 80 
12. USE OF INFORMATION AND PUBLICATION ................................................... 81 
13. 
ETHICAL CONSIDERATIONS ............................................................................. 82 
13.I  Regulatory and Ethical Compliance ...................................................................... 82 
13.2 Infonned Consent Procedures .......................................................................... 82 
13.3 Responsibilitiesof the Investigator and!RB/EC ............................................... 83 
13.4 Protocol Amendments .......................................................................................... 84 
14. 
REFERENCE LIST ............................................................................................................... 86 

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PR OTO COL SYNOPSIS V59 77 
 
Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1ic name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
Titl e of Study: A Phase3b, Controlled, Open-Label,Multi-Center Study to Evaluate 
Safety and Immunogenicity of a Single Dose of GlaxoSmiht Kline' s Meningococcal 
ACWY Conjugate Vaccine (Menveo,)Administered to HealthyIndividuals 15 througll 
55 years of age, approximately 4-6 years after primary ACWY vaccination. 
Study Pe1i od : Approximately 180 days 
(six months). 
Clinical Phase: 3b 
Background and Rationale: 
Neisseria meningitidis is a leadingcause of bacterial meningitis and sepsis worldwide, 
capable of causing outbreaks and epidemics of invasive disease. Meningococcal disease 
is associated with higll morbidity and mortality even among patients who receive early 
antibiotictreatment. Most cases of invasive disease worldwide are caused byserogroups 
A, B, C, W and Y. 
The quadrivalent meningococcal oligosaccharidediphtheria CRM-197 conjugate 
vaccine (MenACWY-CRM; Menveo, GSK Vaccines) is approved for active 
immunization of individuals from 2 months througll 55 years of age in the United 
States. As of February 2015, more than 30,000of subjects have been exposed to 
MenACWY-CRM vaccine in completed clinical studies and more than 24million doses 
of the vaccine have been distributed globally. 
The US Advisory Committee on Immunization Practices (ACIP) recommends routine 
vaccination with a quadrivalentconjugated meningococcal vaccine for adolescents at 
11-12 years of age with a booster dose administered 5 years later. While a substantial 
body of data exists showing a robust immune response and good antibody persistence 
after a single dose of MenACWY-CRM in adolescents, the response to a booster dose of 
MenACWY-CRM in this agegroup has only been evaluated in 2 clinical studies with 
limited number of subjects. 
A robust anamoestic immune response to a booster doseofMenveo vaccine 
administered at approximately 5 years after previous vaccination with the same vaccine 
or a licensed meningococcal oolysaccharide vaccine (Menomune®) was demonstrated in 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
the phase 2 clinical study V59P6El . High titers of bactericidal antibodies against the 
vaccine serogroups were achieved at 7 and 30 days after booster dose in MenACWY­ 
primed subjects. However, the number of subjects included in this studywas relatively 
small (N=l 0l , including 50 subjects who received a booster dose after the primary 
MenACWY-CRM vaccination). 
In the phase 3b clinical study V59Pl3 El , a booster dose of MenACWY-CRM was 
given 3 years after primary vaccination with either MenACWY-CRM or Menactra®(a 
meningococcal diphtheria toxoid-conjugated MenACWY vaccine, MenACWY-D) in 
adolescents. A booster dose was able to substantially increase antibody titers against all 
4 serogroups irrespective of the priming vaccine. Again, only a small number of 
subjects (N=160) received the MenACWY-CRM booster, (83 who received primary 
MenACWY-CRM and 77 who received MenACWY-D). 
In the light of the current ACIP recommendation for a booster dose of MenACWY­ 
CRM, there exists a need to evaluate the response to a MenACWY-CRM booster given 
at -5  years after primary vaccination in meningococca-lvaccineprimed adolescents. 
Generation of this data would also be of relevance in outbreak management and 
vaccination of travelers to endemic areas. 
The purpose/aim of this study is to assess the safety and antibodyresponse to 
vaccination with a booster dose of Menveo given 4-6 years after primary vaccination 
and the response to a single dose given to vaccine-naive subjects, and to describe the 
inlmune response over time after a single dose of Menveo, administered to subjects 
previously vaccinated with Menveo or Menactra or to vaccine-naive subjects. The 
inclusion of vaccine-naive subjects in a separate study arm is to enable comparison of 
the rapidity and magnitude of an aoarooestic response to a booster dose (in primed 
individuals) or the primary response to a first dose (in naive individuals) of 
MenACWY-CRM. 
Study O bjectives: 
P1i ma ry Objective(s): Immunogenicity objective: 
L To demonstrate a sufficient inlmune response following a single dose of 
MenACWY-CRM (Menveo) vaccine, !riven to sub jects who previously received 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
Menveo or Menactra, as measured by the percentage of subjects with hSBA 
seroresponse againstN. meningitidis serogroups A, C, W and Y at Day 29 after 
vaccination 
Criteria to demonstrate immune response sufficiency: The immune response will be 
considered as sufficient if the lower limit of the one-sided 97.5% CI for percentage 
of subjects with hSBA seroresponse against serogroups A, C, Wand Y is greater 
than 80% (in pooled group of subjects who received primary vaccination with 
Menveo or Menactra). 
Seco ndary O bjec tive(s) : 
Immunogenicity objectives: 
1. To compare the immunogenicityofa single dose ofMenACWY-CRM vaccine, 
between subjects who previously received Menveo, subjects who previously 
received Menactra and vaccine-naive individuals, as measured by the percentage of 
subjects with hSBA titer 8, withhSBA seroresponse, and hSBA GMTs againstN. 
meningitidis serogroups A, C, W and Y at Day 29 after vaccination 
2. To compare the immune responses following a single dose ofMenACWY-CRM 
vaccine, between subjects who previously received Menveo, subjects who 
previously received Menactra and vaccine-naive individuals, as measured by the 
percentage of subjects with hSBA titer ,::8 and hSBA GMTs againstN. meningitidis 
serogroups A, C, Wand Y at Day I, Day 4, Day 6, and Day 29 after vaccination 
3. To assess persistence of bactericidal antibodies against serogroups A, C, Wand Y at 
approximately 4-6 years after the primary vaccination with Menveo and after the 
primary vaccination with Menactra in comparison with naturally-acquiredlevel in 
vaccine-naive individuals, as measured by the percentage of subjects with hSBA 
titer ,::8 and hSBA GMTs at Day 1. 
4. To compare the immune response to a single dose ofMenACWY-CRM vaccine, 
between subjects who previously received Menveo, subjects who previously 
received Menactra and vaccine-naive individuals, by age group (15-25 and 26 
years of age), as measured by percentages of subjects with hSBA titer ,::8, hSBA 
seroresponse and hSBA GMTs at Day 29. 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protoco l nu mber: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
Safety objec tives: 
1. To assess reactogenicity and safety of MenACWY-CRM vaccine when administered 
to subjects who previously received Menveo or Menactra and vaccine-naive 
individuals 
Stud y Design: 
This is a phase 3b, controlled, open-label, multi-center studyto evaluate safety and 
inlmunogenicity of MenACWY-CRM after a single vaccination in healthy individuals 
who were vaccinated with Menveo or Menactra 4 to 6 years ago and in vaccine-naive 
individuals. 
Study population: AJ>proximately 700 healthy subjects 15 throug!I 55 years of age will 
be enrolled in the study. 
Duration of the study The duration of this study is approximately 6 months per subject. 
Written informed consent and, as applicable according to local guidelines, written 
assent will be obtained before conducting any study-specificprocedures. 
Vaccination schedule: All subjects will receive a single dose ofMenACWY-CRM at 
Day I. 
Study groups: 
• Group Menveo-Menveo: approximately 300 subjects, who were vaccinated with a 
single dose of Menveo 4 to 6 years ago, will receive one dose of MenACWY-CRM. 
• Group Menactra-Menveo:approximately 300 subjects, who were vaccinated with a 
single dose ofMenactra 4 to 6 years ago, will receive onedose of MenACWY­ 
CRM. 
• Group Naive: approximately 100 subjects, ofsimilar age to subjects enrolled in 
other primed groups, equally enrolled across allclinical sites, who have not received 
any meningococcal vaccination, will receive one dose of MenACWY-CRM. 
Randomization/ Stratification: 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
Within eachstudy group, subjects will be enrolled across age range of 15 to 55 years of 
age as follows: 
• Menveo-Menveo and Menactra-Menveo groups: approximately 80% of subjects will 
be enrolled in age group of 15 to 25 years and 20% of subjects willbe enrolled in 
26-55 years age group; 
• Naive group approximately 50% of subjects will be enrolled in age group of 15 to 
25 years and 50% of subjects willbe enrolled in age group of26-55 years. 
Within each age category in each studygroup, subjects willbe randomized into one of 
two different blood draw schedules according to a 1:1 ratio, described as follows: 
• Subjects getting blood draws at Day 1, Day 4 and Day 29. 
• Subjects getting blood draws at Day 1, Day 6 and Day 29. 
For a schematic overview, see Table 1. 
Ta ble I: 
Schema tic diagra m of the VS9_77 stu dy gro ups 
Vacdne 
History 
Vacdnation in 
c.un  ent study 
Age Category 
Blood drawschednle 
Menveo 
N=300 
Menveo 
15-25 years 
(N=240) 
Blood draw Day I, 4, 29 (N=l 20) 
Blood draw Day I, 6, 29 (N= l20) 
26-55 years 
(N=60) 
Blood draw Day 1, 4, 29 (N=30) 
Blood draw Day I, 6, 29 (N=30) 
Menactra 
N=300 
Menveo 
15-25 years 
(N=240) 
Blood draw Day I, 4, 29 (N=l 20) 
Blood draw Day I, 6, 29 (N= l20) 
26-55 years 
(N=60) 
Blood draw Day 1, 4, 29 (N=30) 
Blood draw Day I, 6, 29 (N=30) 
Vaccine- 
Naive 
N= l OO 
Menveo 
15-25 years 
(N=50) 
Blood draw Day 1, 4, 29 (N=25) 
Blood draw Day I, 6, 29 (N=25) 
26-55 years 
(N=50) 
Blood draw Day 1, 4, 29 (N=25) 
Blood draw Day I, 6, 29 (N=25) 
Blinding: open-label study. 

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Regulatory Review Protocol Version 2 
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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
Blood samn!P.s: Three (3) blood samples of approximately 10 mL each will be collected 
according to the blood draw schedule in Table I. 
Data collection: Electronic Case Reporting Form (eCRF). 
Study clinic visits: Three (3) clinic visits at Day 1, Day 4 or Day 6 and Day 29 are 
planned for each subject. 
Reminder Phone calls: Two (2) reminder phone calls will beconducted at Day 3 and 
Day 5 after the study vaccination to remind the subject/ legal guardian to complete the 
diary card. 
Safety phone calls: Three (3) safety phone calls (at Day 15, Day91 and Day181) will 
be conducted to collect any medically-attended AEs, AEs leading to withdrawal, SAEs, 
related medications and any vaccinations. In addition, all unsolicited AEs and related 
medications occurring after the vaccination will be collected during the safety call at 
Day15. The Day 181 Safety Phone call will also serve as the termination visit. 
Solicited Adverse Events (injection site pain, erythema, induration, fatigue, headache, 
myalgia, arthralgia, loss of appetite, nausea, chills and fever) occurring on the day of 
vaccination and the following six days (Day I through Day 7) will be recorded daily 
using a Diary Card for all subjects. 
Unsolicited AEs occurring within 28 days after studyvaccination will be collected. 
Qualified site staff will interview the subject by phone approximately 14 days after 
vaccination and in person at the studysite approximately 28 days after study vaccination 
to assess the occurrence of any unsolicited AEs. 
Medically-attended AEs AEs leading to studywithdrawal and SAEs will be collected 
during the entire study period. These data will be captured by interviewing the subject 
and/or subjects' parents / guardian (as applicable) during the site visits and phone calls 
and by review of available medical records. Subjects and/or parents / guardian will be 
encouraged to call the site in theevent of any medically-attendedAEs or any AEs which 
theyperceive as being of concern during the entire studyperiod. 

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Name ofSponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59- 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
Table 2: 
Schematic diagram of the VS9_77 study design. 
Day l 
Day 4 
Day 6 
Day 15 
Day 29 
Day 91 
Day181 
Blood draw 
(all subjects) 
Menveo 
Blood draw 
(50%) 
Blood draw 
(50%) 
Safety 
Phone call 
Blood draw 
(all subjects) 
Safety 
Phone 
call 
Safety 
Phone call 
Study 
tennination 
Number of Subjects planned: Approximately 700 subjects are planned for enrollment 
into this study, approximately 300 subjects who previously received Menveo (Menveo- 
Menveo group), 300 subjects who previously received Menactra (Menactra-Menveo 
group) and 100 meningococcal vaccine-naive subjects (Naive group). Assuming a 10% 
drop-out rate that should provide approximately 630 evaluable subjects. 
Study Population and Subject Characte1i stics: The list of inclusion and exclusion 
criteria is included in protocol section 4, Selection of Study Population. 
Stu dy Pro ced ures: The study includes three clinic visits, one vaccination, three blood 
draws, and threesafety phone calls for each subject. All studyprocedures associated 
with the pre-vaccination, vaccination, post-vaccination, unscheduled and study 
temiination visit are described in section 5.0. 
Study Vaccines: 
GlaxoSmithKline Meningococcal MenAC\VY-CR.1!"1 vacc in e (M e n veo) : 
Meningococcal (groups A, C, Wand Y)oligosaccharide diphtheria CRM-197 conjugate 
vaccine is supplied as a vialcontain 10 µg of serogroup A oligosaccharides and 5 µg of 
serogroups C, W and Y oligosaccharides, conjugated to Corynebacterium diphtheriae 
CRM191 protein. Overall injection volume of 0.5 mL. 
The vaccine will be administered intramuscularly, preferably in the deltoid area of the 
non-dominant arm 
P1i mary Endpoint(s): 
 
 
 
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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
Immunogenicity Endpoints: 
The following measures will be summarized for the pooled (Menveo-Menveo and 
Menactra-Menveo) group. 
2. Percentage of subjects with hSBA seroresponse1 against N. meningitidis serogroups 
A, C, Wand Y at Day29. 
SecondaryEndpoints: 
Immunogenicity  endpoints: 
The following measures will be summarized for Menveo-Menveo, Menactra-Menveo, 
Naive and the pooled (Menveo-Menveo and Menactra-Menveo) groups unless 
otherwise noted: 
1. Percentage of subjects with hSBA titer 8 against N. meningitidis serogroups A, C, 
Wand Y at Day 1, Day 4, Day 6 and Day 29; 
2. Percentages of subjects with hSBA seroresponse against N. meningitidis serogroups 
A, C, Wand Y at Day4, Day 6 and Day 29 (Day 29: Except the pooled group); 
3. hSBA GMfs against N. meningitidis serogroup A, C, Wand Y at Day 1, Day 4, Day 
6 andDay29; 
4. Ratios ofhSBA GMTs at Day 1, Day 4, Day 6 and Day29 (between study groups). 
5. Ratios ofhSBA GMfs at Day 4, Day 6, and Day 29 compared to Day 1 (within 
study groups). 
Safety endpoints: 
Safety of the study vaccine will be assessed in the pooled vaccine group (Menveo­ 
Menveo and Menactra-Menveo) and the vaccine-naive group in terms of the frem1encv 
 
 
1 Seroresponse is defined as: a) post-vaccination hSBA 8 for subjectswith a pre-vaccination hSBA <4; b) 
for subjects with a pre-vaccinationhSBA - an increase of at least four timesthe pre-vaccinationhSBA. 
 
 
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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
(percentage) of reported adverse events including: 
1. Any unsolicited AEs reported within30 minutes after vaccination; 
2. Solicited local and systemic AEs reported from Day 1 (6 hours) through Day 7 after 
vaccination; 
3. Other indicators of reactogenicity(e.g. use of analgesics / antipyretics, body 
temperature) within 7 days after vaccination; 
4. All unsolicited AEs reported from Day 1 through Day 29 after vaccination; 
5. Medically-attended AEs, AEs leading to withdrawal and SAEs reported from Day 1 
through Day 181 (during the entire studyperiod). 
Statistical Analyses: 
P1i mary Immunogenicity Objective 
The primary population for the analysis of sufficient immune response is the Full 
Analysis Set (FAS), and will consist of pooled data from the Menveo-Menveoand 
Menactra-Menveo group (n=540 evaluable). 
To demonstrate immune response sufficiency after MenACWY-CRM booster vaccine 
administration, the lower limit of the one-sided 97.5% Confidence Interval (CI) for 
percentage of subjects with hSBA seroresponse against each of serogroups A, C, W and 
Y must be greater than 80% (in the pooled group of subjects who received primary 
vaccination with Menveo or Menactra) 
Hypothesis: 
Null hypothesis 
Alternative hypothesis 
P, s 0.80 
P, > 0.80 
Where: P., is the population seroresponse rate for the pooled Menveo-Menveo and 
Menactra-Menveo group; i = 1,2,3,4 refer to serotypes A, C, Wand Y respectively. 
Sample Size: 
Statistical nower was estimated based on observed data from studv V59Pl3El, where 
 
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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59- 77 
Gene1ic name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
seroresponse rates at one-month post booster dose of MenACWY-CRM ranged from: 
97% (90%-100%)to 100% (95%-100%) for serogroupA; 93% (85%-98%)for 
serogroup C; 91% (82%-97%)to 93% (84%-98%) forserogroup W; and 90% (80%- 
96%) to 93% (84%-98%) forserogroup Y among subjects primed with MenACWY- 
CRM or Menactra in the three years preceding the study. 
Assuming the true seroresponse rates in the pooled group range from 90% to 97% 
(alternative hypothesis) for each serotype, a sample size of n=540 will have at least 96% 
power to show sufficiency of immune response to a booster dose of MenACWY-CRM 
in the pooled group, compared with a pre-specifiedreference seroresponse of 80% (null 
hypothesis) using anexact test with 0.025 one-sidedsignificance level When taking a 
10% dropout rate into account, N=600 previously vaccinated subjects have to be 
enrolled in the study. Calculations have been done with nQuery Advisor (Version 7.0). 
Tabl e 3: 
 Stati stic al Po wer to Tes t for Suffi ciency of Immun e Res ponse 
Given a Range of  True  Seroreponse  Rates  for Evaluable 
Sample Size of 540 subjects 
Se.-oty pe 
T111e Serores po nse Rate 
Powel' 
A 
0.97 
0.99 
C 
0.93 
0.99 
w 
0.91 
0.99 
y 
0.90 
0.99 
Total Power 
0.96 
In terim Analysis: No interinIanalysis is planned for this study. 
Data Monito1ing Committee: No DMC will be utilized for the study. 
 
 
 
 
 
 
 
 
 
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Table 4 
Time and Events Table 
 
Visit Type 
Study period 
Study Day 
Visit Window (Days) 
Visit Number 
Clinic Visit 
Clinic Visit 
Phone Call Clinic Visit Phone Call Clinic Visit 
Phone Call Phone Call 
Screening 
Treatment 
Tre.itment 
Treatment 
Treatment 
Treatment 
Follow-up 
Follow-up 
1 
3, 5 
4/6• 
15 
29 
91 
181 
-5 
to 1 
0 
2 days (- 
1/+l ), 4 
da ys (0/+2) 
after vacc 
3/5 days 
(-1/+l) 
after vacc 
14 days 
(-2/+2) 
after vacc 
28days 
(-7/+14) 
after Yacc 
90days 
(-14/+14) 
aftel' vacc 
180 days 
(-14/+14) 
after vacc 
Pre- 
vacc.ination 
1 
N/A 
2 
3 
4 
5 
6 
Study Event 
References 
Study Treatment 
Vaccination (vacc) 
Section 5.2 
X 
Screening and 
Safety 
Informed Consent" 
Section 5.1.1 
X 
Medical History 
Section 5.1.2 
X 
Physical Exam 
Sections 5.1.2 
and 5 .3.1 
X 
x< 
X 
X 
Pregnancy Test 
Sections 3.5 and 
5 .1.2 
X 
x< 
Exclusion/Inclusion 
Criteria 
Section4 
X 
Randomization 
Section 5.1.4 
x< 
30 Minutes Post 
InjectionAssessment 
Section 5.2.1 
X 
 
 
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Visit Type 
Study period 
Study Day 
Visit Window (Days) 
Visit Number 
Clinic Visit 
Clinic Visit PhoneCall Clinic Visit Phone Call Clinic Visit Phone Call 
PhoneCall 
Screening 
Treatment Tre.itment 
Treatment Treatment Treatment 
Follow-up 
Follow-up 
1 
3, 5 
4/6• 
15 
29 
91 
181 
-5 
to 1 
0 
2 days (- 
1/+l ), 4 
days(0/+2) 
after vacc 
3/5 da)'S 
(-1/+l ) 
after vacc 
14 days 
(-2/+2) 
after vacc 
28days 
(-7/+14) 
after Yacc 
90days 
(-14/+14) 
aftel' vacc 
180 days 
(-14/+14) 
after vacc 
Pre- 
vacc.ination 
1 
NIA 
2 
3 
4 
5 
6 
Study Event 
References 
Subject Diary 
Dispensed with 
Training 
Section 5.2.1 
X 
Subject Diary 
Reminder Call 
Section 5.2.2 
xi 
xi 
Subject Diary 
Reviewed and 
Collected 
Section 5.3.1 
X 
Assess Unsolicited 
AEs 
Section 7.1 
X 
X 
X 
X 
Assess SAEs 
Section 7.1.4 
X 
X 
X 
X 
X 
X 
Assess for medically 
attended AEs and 
AEs leading to 
withdrawal 
Sections 7.I.4.I 
and7.1.3 
X 
X 
X 
X 
X 
X 
Assess relevant 
medications/ 
vaccinations 
Sections5.1.2 
and 6.5 
X 
X 
X 
X 
X 
X 
X 
 
 
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Visit Type 
Study period 
Stud y Da y 
Visit Window (Days) 
Visit Number 
ClinicVisit 
Clinic Visit Phone Call Clinic Visit 
Phone Call Clinic Visit 
Phone Call Phone Call 
Screening 
Treatment Tre.itment Treatment Treatment Treatment 
Follow- up 
Follow- up 
1 
3, 5 
4/6• 
15 
29 
91 
181 
-5 
to 1 
0 
2 da ys (- 
1/+l ), 4 
days (0/+2) 
after vacc 
3/5 da)'S 
(-1/+l ) 
after vacc 
14 days 
(-2/+2) 
after vacc 
28days 
(-7/+14) 
after Yacc 
90 days 
(-14/+14) 
aftel' vacc 
180 days 
(-14/+14) 
after vacc 
Pre- 
vacc.ination 
1 
NIA 
2 
3 
4 
5 
6 
Study Event 
I References 
Imm unogenicity 
Serology blooddraw  I 
Section 3.5 
X" 
X 
X 
S tu dy C-0mp le rio n 
Pt·ocedure 
StudyTennination' I 
Section 5.5 
X 
Notes : 
• Subject will berandomized into a blooddraw schedule in a I: I ratio. Toe second clinic visit will occur at Day 4 OR Day 6. 
b Confirm consent fonn(s) signed prior to any procedures. 
' Procedure to be performed prior to vaccination 
d If the clinicvisit at Day 4 is overlapping with the specified window of theDay 3 reminder c.ill, the Day 3 reminder call may be omitted. 
If the clinic visit at Day 6 is overlapping with the specified window of the Day 5 reminder call, the Day 5 reminder call may beomitted. 
• Subjects who tenninate the study early are recommended to complete certainstudy-related procedures. See section 5.5 for further details. 
 
 
 
 
 
 
 
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LIST OF ABBREVIATIONS 
 
ACIP 
AE 
CI 
CBER 
CRM 
CRO 
EC 
eCRF 
EDC 
FAS 
FDA 
GCP 
GMR 
GMT 
GSK 
hSBA 
1B 
ICF 
ICH 
 
IM 
IRB 
LSLV 
MedDRA 
pp 
Ref. 
SAE 
soc 
SOP 
Advisory Committee on Tmm1mization Practices 
Adverse Event 
Confidence Inteival 
Center for Biologics Evaluation and Research 
Cross Reactive material 
Contract Research Organization 
Ethics Committee 
Electronic Case Report Form 
Electronic Data Capture 
Full Analysis Set 
Food and Drug Administration 
Good Clinical Practices 
Geometric Mean Ratio 
Geometric Mean Titer 
GlaxoSmithKline Vaccines 
Human Serum Bactericidal Assay 
Investigator' s Brochure 
Informed Consent Form 
International Conference on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use 
Intramuscular 
Institutional Review Board 
Last Subject Last Visit 
Medical Dictionary for Regulatory Activities 
Per Protocol 
Reference 
Serious Adverse Event 
System OrganClass 
Standard Operating Procedure 

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l. 
BACKGROlU
''-D  M'D   RATIONALE 
 
1.1 
Background 
 
Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis worldwide, 
capable of causing outbreaks and epidemics of invasive disease. Meningococcal disease is 
associated with high morbidity and mortality even among patients who receive early 
antibiotic treatment. Most cases of invasive disease worldwide are caused by serogroups 
A, B, C, W and Y. 
 
The quadrivalent meningococcal oligosaccharide diphtheria CRM-197 conjugate vaccine 
(MenACWY-CRM; Menveo, GSK Vaccines) is approved for active immunization of 
individuals from 2 months through 55 years of age in the United States. As of February 
2015, more than 30,000 of subjects have been exposed to MenACWY-CRMvaccine in 
completed clinical studies and more than 24 million doses of the vaccine have been 
distributed globally. 
 
The US Advisory Committee on Immunization Practices (ACIP) recommends routine 
vaccination with a quadrivalent conjugated meningococcal vaccine for adolescents at 11- 
12 yearsof age with a booster dose administered 5 years later. While a substantial body of 
data exists showing a robust immune response and good antibody persistence after a 
single dose of MenACWY-CRM in adolescents, the response to a booster dose of 
MenACWY-CRM in this age group has only been evaluated in 2 clinical studies with 
limited number of subjects. 
 
A robust anamnestic immune response to a booster dose of Menveo vaccine administered 
at approximately 5 years after previous vaccination withthe same vaccine or a licensed 
meningococcal polysaccharide vaccine (Menomune®) was demonstrated in the phase 2 
clinical study V59P6El . Hightiters of bactericidal antibodies against the vaccine 
serogroups were achieved at 7 and 30 days after booster dosein MenACWY-CRM­ 
primed subjects. However, the number of subjects included in this study was relatively 
small (N=101, including 50 subjects who received a booster dose after the primary 
MenACWY-CRM vaccination). 
 
In the phase 3b clinical studyV59Pl3El , a booster dose of MenACWY-CRM was given 
3 years after primary vaccination with either MenACWY-CRMor Menactra®(a 
meningococcal diphtheria toxoid-conjugated MenACWYvaccine, MenACWY-D) in 
adolescents. A booster dose was able to substantially increase antibody titers against all 4 
serogroups irrespective of the priming vaccine. Again, only small number of subjects 
(N=160) received the MenACWY-CRM booster, (83 who received primary MenACWY­ 
CRM and 77 who received MenACWY-D). 

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In the light of the current ACIP recommendation for a booster dose ofMenACWY-CRM, 
there exists a need to evaluate the response to a MenACWY-CRM booster given at - 5 
years after primary vaccination in meningococcal-vaccineprimed adolescents. Generation 
of this data would also be of relevance in outbreak management and vaccination of 
travelers to endemic areas. 
 
1.2 
Rationale 
 
The pwpose/aim of this study is to assess the safety and antibody response to vaccination 
with a booster doseofMenveo given 4-6 years after primary vaccination and the response 
to a single dosegiven to vaccine-naive subjects, and to describe the immune response 
over time after a singledose of Menveo, dministi>red to subjects previously vaccinated 
with Menveo or Menactra or to vaccine-naive subjects. The inclusion of vaccine-naive 
subjects in a separate study arm is to enable comparison of the rapidity and magnitude of 
an anamnestic response to a booster dose (in primed individuals) or the primary response 
to a first dose (in naive individuals) of MenACWY-CRM. 

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2. 
OBJECTIVES 
 
2.1 
Plimary Objective(s) 
 
Plimary Immunogeoicity Objective(s) 
 
1. To demonstrate a sufficient immune response following a single dose of MenACWY­ 
CRM (Menveo) vaccine, given to subjects who previously received Menveo or 
Menactra, as measured by the percentage of subjects with hSBA seroresponse against 
N. m.eningitidis serogroups A, C, W and Y at Day 29 after vaccination 
Criteria to demonstrate immune response sufficiency: The immune response will be 
considered as sufficient if the lower limit of the one-sided 97.5%CI for percentage of 
subjects with hSBA seroresponse against serogroups A, C, Wand Y is greater than 
80% (in pooled group of subjects who received primary vaccination with Menveo or 
Menactra). 
 
2.2 
Second ar y O bjecti ve(s) 
 
Second ar y I mm un og eni city O b je cti ve(s) 
 
1. To compare the immunogenicityof a single dose of MenACWY-CRM vaccine, 
between subjects who previously received Menveo, subjects who previously received 
Menactra and vaccine-naive individuals, as measured by the percentage of subjects 
withhSBA titer ;,:8, with hSBA seroresponse, and hSBA GMTs against N. 
meningitidis serogroups A, C, W and Y at Day 29 after vaccination 
2. To compare the immune responses following a single dose of MenACWY-CRM 
vaccine, between subjects who previously received Menveo, subjects who previously 
received Menactra and vaccine-naive individuals, as measured by the percentage of 
subjects with hSBA titer 8 and hSBA GMTs againstN. m.eningitidis serogroups A, 
C, Wand Y at Day1, Day 4, Day 6, and Day 29 after vaccination 
3. To assess persistence of bactericidal antibodies against serogroups A, C, Wand Y at 
approximately 4-6 years after the primary vaccination with Menveo and after the 
primary vaccination with Menactra in comparison with naturally-acquired level in 
vaccine-naive individuals, as measured by the percentage of subjects with hSBAtiter 
8 and hSBA GMTs at Day 1. 
4. To compare the immune response to a single dose of MenACWY-CRM vaccine, 
between subjects who previously received Menveo, subjects who previously received 
Menactra and vaccine-naive individuals, by age group (15-25 and ;,:26 years of age), 
as measured by percentages of subjects with hSBA titer 8, hSBA seroresponse and 
hSBA GMTs at Day 29. 

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Secondary Safety Objective(s) 
1. To assess reactogenicityandsafety of MenACWY-CRMvaccine when administered 
to subjects who previously received Menveo or Menactra and vaccine-naive 
individuals. 
2.3 
Explor atory Objective(s) 
There are no exploratoryobjectives. 

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3. 
STUDY DESIGN 
 
3.1 
Overview of Study Design 
 
This is a phase 3b, controlled, open-labe multi-center studyto evaluate safety and 
immunogenicityof MenACWY-CRM after a single vaccination in healthy individuals 
who were vaccinated with Menveo or Menactra 4 to 6 years ago and in vaccine-naive 
individuals 
Study population: Approximately 700 healthy subjects 15 through 55 years of age willbe 
enrolled in the study. 
Duration of the study: The duration of this studyis approximately 6 months per subject. 
 
Written informed consent and, as applicable according to local guidelines, written assent 
willbe obtained before conducting anystudy-specificprocedures. 
 
Vaccination schedule: All subjects will receive a single dose of MenACWY-CRM at Day 
1. 
 
Study groups: 
 
Group Menveo-Menveo: approximately 300 subjects, who were vaccinated with a single 
dose ofMenveo 4 to 6 years ago, will receive one dose of MenACWY-CRM. 
 
Group Menactra-Menveo approximately 300 subjects, who were vaccinated with a single 
dose of Menactra 4 to 6 years ago, will receive one doseof MenACWY-CRM. 
 
Group Naive: approximately 100 subjects equally enrolled across all clinical sites, who 
have not received any meningococcal vaccination, will receive one dose of MenACWY­ 
CRM. 
Randomization / Stratification: 
Within each study group, subjects will be enrolled across age range of 15 to 55 years of 
age as follows: 
• 
Menveo-Menveo and Menactra-Menveo groups: approximately 80% of subjects will 
be enrolled in age groupof 15 to 25 years and 20% of subjects will be enrolled in 26- 
55 years age group. 
• 
Naive group: approximately 50% of subjects willbe enrolled in age groupof 15 to 25 
years and 50% of subjects will be enrolled in age group of26-55 years. 

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Within each age category in each study group, subjects willberandomized into one of 
two different blood draw schedules according to a 1:1 ratio, described as follows: 
• 
Subjects getting blood draws at Day 1, Day 4 and Day 29. 
• 
Subjects getting blood draws at Day 1, Day 6 and Day 29. 
 
For a schematic overview, see Table 1 
 
Table 3.1-1: Schematic diagr am of the VS9_77 study groups 
 
Vacc.ine 
History 
V ac c.inatio n in 
cun ent study 
Age Category 
Blood dra w schedule 
Menveo 
N=300 
Menveo 
15-25 years 
(N=240) 
Blood draw Day 1, 4, 29 (N=l20) 
Blood draw Day I, 6, 29 (N=l20) 
26-55 years 
(N=60) 
Blood draw Day I, 4, 29 (N=30) 
Blood draw Day I, 6, 29 (N=30) 
Menactra 
N=300 
Menveo 
15-25 years 
(N=240) 
Blood draw Day 1, 4, 29 (N=120) 
Blood draw Day I, 6, 29 (N=l20) 
26-55 years 
(N=60) 
Blood draw Day I, 4, 29 (N=30) 
Blood draw Day I, 6, 29 (N=30) 
Vaccine-Naive 
N=IOO 
Menveo 
15-25 years 
(N=50) 
Blood draw Day I, 4, 29 (N=25) 
Blood draw Day I, 6, 29 (N=25) 
26-55 years 
(N=50) 
Blood draw Day I, 4, 29 (N=25) 
Blood draw Day I, 6, 29 (N=25) 
 
Blinding- open-label study. 
 
Blood sanmles: Three (3) blood samples of approximately 10 mL each will becollected 
according to the blood draw schedule in Table 3.1.1. 
 
Data collection: Electronic Case Reporting Form (eCRF). 
 
Study clinic visits: Three (3) clinic visits at Day 1, Day 4 or Day 6 and Day 29 are 
planned for eachsubject. 
 
Reminder Phone calls: Two (2) reminder phone calls willbeconducted at Day 3 and Day 
S after the study vaccination to remind the subject/ legal guardian to complete the diary 
car d. 
 
Safety phone calls: Three (3) safety phone calls (at Day 1S, Day 91 and Day 181) willbe 
conducted to collect any medically-attendedAEs, AEs leading to withdrawal, SAEs, 

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related medications and any vaccinations. In addition, all unsolicited AEs and related 
medications occurring after the vaccination will be collected during the safety call at Day 
15. The Day 181 Safety Phone call will also serve as the termination visit 
 
SolicitedAdverse Events (injection site pain, erythema, induration, fatigue, headache, 
myalgia, arthralgia, loss of appetite, nausea, chills and fever) occurring on the day of 
vaccination and the following six days (Day 1 through Day 7) will be recorded daily 
using a Diary Card for all subjects. 
 
Unsolicited AEs occurring within 28 days after studyvaccination will be collected. 
Qualified site staffwill interview the subject by phone approximately 14 days after 
vaccination and in person at the studysite approximately 28 days after studyvaccination 
to assess the occurrence of any unsolicited AEs. 
 
Medically-attended AEs AEs leading to study withdrawal and SAEs will be collected 
during the entire study period. These data will be captured by interviewing the subject 
and/or subjects' parents / guardian (as applicable) during the sitevisits and phone calls 
and by review of available medical records. Subjects and/or parents / guardian will be 
encouraged to call the site in the event of any medically-attended AEs or any AEs which 
theyperceive as being of concern during the entire study period. 
 
Table 3.1-2: 
Schematic diagram of the V59_77 study design 
 
Day l 
Day 4 
Day 6 
Day 15 
Day 29 
Day 91 
Day 181 
Blooddraw 
(allsubjects) 
Menveo 
Blood draw 
(50%) 
Blood draw 
(50°/c,) 
Safety 
Phone call 
Blood draw 
(all subjects) 
Safety 
Phone 
call 
Safety Phone 
call 
Study 
termination 
 
 
3.2 
St u dy Pe riod 
 
Each subject should expect to participate in the study for 6 months, from the time of 
enrolment through the last study visit. 
 
3.3 
Blinding Procedur es 
The trialis designed as an open-label study. 

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3.4 
Data Collection 
 
3.4.1 
Data Collected from Subjects 
Thefollowing data will becollected from each subject over the duration of their study 
participation: 
• 
Demographic Information. 
• 
Adverse Events. 
• 
Medical History. 
• 
Concomitant Medications/Vaccination.s 
• 
Information on the blood samples. 
 
All data collected must only be identified using the Subject ID, as described in section 
S.1.4, Randomization. 
3.4.2 
Tools Used for Data Collection 
 
Data willberecorded in the Subject Diary and collected on electronic Case Report Fo11l1S 
(eCRFs) . 
 
S ubj ect Diar y 
Paper Diaries (pDiaries), hereafter referred to as Subject Diaries will betheonlysource 
document allowed for solicited local and systemic adverse events (including body 
temperature measurements), starting after the initial, 30minute post-vaccination period at 
the clinic. The following additional rules apply to documentation of safety information 
collected in the Subject Diary. 
 
The Investigator or delegated staffshould monitor the Subject's Diary status throughout 
the study for compliance and anysolicited local and systemic adverse events that were of 
concern to the subject 
 
• 
No corrections or additions to the information recorded by the subject or 
parent(s)/legal guardian(s) within the Subject Diary willbeallowed after it is 
delivered to the site. 
• 
Any blank or illegible fields on the Subject Diary must be described as missing in the 
eCRF. 

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Case Rep01t Forms 
This study utilizes electronic Case Report Forms (eCRFs) to collect study-related data 
from each subject. A qualified site staffmember(s) is required to enter subject data in the 
eCRFs in English based on the medical information available in each subject' s source 
record. 
Data should be entered into the eCRF in a timely fashion following each subject's clinic 
visit,study procedure, or phone call. Each subject's eCRF casebook will be compared 
withthe subject's source records by a GSK-approved study monitor (or designee) over 
the duration of the study in order to ensure data collectionaccuracy. 
The following additional rules apply to documentation of Subject Diary information 
collected in the eCRFs: 
• The site must enter all readable entries in the Subject Diary into the eCRF, including 
those values that may be biologically implausible (e.g. bodytemperature: 400°C). 
• Any illegible or implausible data should be reviewed with thesubject and/or 
parent(s)/legal guardian(s). If an underlying solicited or unsolicited adverse event is 
described on review with the subject, this should be described in the source document 
and reported as an unsolicited adverse event in the Adverse Event eCRF (e.g., if the 
subject above confinns body temperature of 40°C on the day in which body 
temperature: 400°C was written into his/her Subject Diary, this fever of 40°C should 
be recorded in the Adverse Event eCRF). 
• 
Any newly described safety information (including a solicited adverse event) nrust not 
be written into the Subject Diary andnrust be described in the study file as a verbally 
reported adverse event. Any adverse event reported in this fashion must be described 
as an unsolicited adverse event and therefore entered on the Adverse EventeCRF. 
 
3.5 
Collection of Clinical Specimens 
The following clinical specimens are required to be collected from each subject in this 
study: 
• 
Blood. 
• Urine for pregnancy testing (As per routine practice, specimens will betested at each 
site). 
 
Processing of a specimen should be completed bya qualified site member and in 
accordance with the study-specificClinical Specimen Laboratory Manual. Testing of 
serum specimens will be performed by a GSK or a designated laboratory. Refer to the 
study-specific Clinical Specimen Laboratory Manual for additional details. 
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Blood Specimens 
Approximately 10 mL sample of blood willbedrawn from all subjects at visit Day 1 
before vaccination, and at visit Day 4 or Day 6 and Day 29. The blood volume willnot 
exceed 10mL at each time point in order to provide the necessary serum volume 
(approximately half of the blood draw volume) for the serology assays. 
The blood will be used for inummological assays. See section 7, Assessments for 
additional details. 
The total ammmt of blood collected over the study period per subject will be 
approximately 30mL. 
U1in e S p eci m e ns 
Urine willbe collected for pregnancy testing in females of child bearing potential. Urine 
will becollected at visit Day 1 before vaccination and the results recorded in the source 
document and eCRF. 
3.6 
Stopping/Pausing Guidelines 
 
There are no predetermined stopping rules in this study. Subjects may be withdrawn from 
the study according to investigator discretion as described in section 3.8, Premature 
Withdrawal from Study. 
3.7 
Data Monitming Committee 
No DMC willbeutilized for the study. 
3.8 
Premature \Vithdrawal from Study 
 
Subjects may withdraw at any time, or be dropped from the study at the discretion of the 
investigator should any untoward effects occur and/or forsafety reasons. In addition, a 
subject may be withdrawn by theinvestigator or the Sponsor if he/she violates the study 
plan or for administrative reasons. The investigator or study coordinator nrust notify the 
Sponsor immediately when a subject has been withdrawn due to an adverse event. 
The circumstances above are referred to as premature withdrawal from the study, and the 
reason for premature withdrawal should be clearly documented and detailed in the source 
documentation. The investigator should make every attempt to evaluate thesubject's 
safety, including resolution of ongoing AEs, at the time of premature withdrawal. If a 
subject wants to withdraw from the study before or prior to the last planned study visit, 
the subject will be asked to be followed for safety for the duration of the study. When a 

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subject withdraws, or is withdrawn, from the study, the procedures described in section 
S.5.1, Early Termination Visit should be completed if possible. 
 
The reasons for premature withdrawal from the study include: Adverse event, death, 
withdrawal of consent, lost to follow-up, administrative reason, and protocol deviation. 
These reasons are described in greater detail below. 
Adverse Event 
 
For any subject withdrawn from study participation prior to the planned Study 
Termination Visit, it is important to determine if an AE was associated with the reason for 
discontinuing the study. This AE nrust be identified on the AE eCRF page by indicating 
"Withdrawn from study due to AE". Any ongoing AEs at the time of studywithdrawal 
must be followed until resolution or stabilization 
 
Death 
 
For anysubject withdrawn from study participation due to death, this should be noted on 
the StudyTermination eCRF page and the associated SAE that led to the death must be 
reported. 
, v ithdrawal of consent 
 
The subject and/or parent(s)/legal guardian(s) can withdraw consent for participation in 
the study at any time without penalty or loss of benefit to which the subject is otherwise 
entitled. Reason for early termination should be deemed as " withdrawal of consent'' if the 
subject withdraws from participation due to a non-medical reason (i.e., reason other than 
AE). If the subject and/or parent(s)/legal guardian(s) intends to withdraw consent from 
the study, the investigator should clarify if the subject will withdraw completely from the 
study or if the subject willcontinue study participation for safety, or a subset of other 
study procedures. If the subject requests complete withdrawal from the study, no further 
study interventions will be performed with the subject. 
If a subject and/or parent(s)/legalguardian(s) withdraws consent but does not revoke the 
HIPAA authorization, the Sponsor will have fullaccess to the subject' s medical records, 
including termination visit information. If a subject and/or parent(s)/legal guardian(s) 
revokes only the HIPAA authorization, the Sponsor will have fullaccess to all of the 
subject's medical records prior to the date and time of written revocation. 
 
Lost to Follow-Up 
For subjects who fail to show up for finalvisits (clinic or telephone contacts), or for three 
consecutive visits, study staff are encouraged to make at least three documented attempts 

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to contact the subject by telephone and at least one documented written attempt to contact 
the subject and/or parent(s)/legal guardian(s) to encourage the completion of study 
termination procedures. These efforts to contact the subject should be recorded in the 
source document. The termination date for the subject to be captured on the Study 
Termination eCRF page is the date of the last successful contact (clinic visit or telephone) 
withthe subject. 
 
Administrative Reason 
 
Examples for subjects withdrawn from the study due to administrative reason can include: 
Sponsor decision to terminate the study, subject discontinuation for insurance issues, 
moving, no time, etc. This reason should be noted in the StudyTermination  eCRF page 
and any ongoing AEs at the time of studywithdrawal should be followed until 
resolution/stabilization, if possible. 
If the clinical study is prematurely terminated by the Sponsor, the investigator is to 
promptly inform the study subjects and local EC/IRB and should assure appropriate 
therapy and follow up for the subjects. All procedures and requirements pertaining to the 
archiving of study documents should be followed. All other study materials (study 
medication/vaccines, etc.) must be returned to the Sponsor. 
For subjects who are withdrawn from the study due to receipt of an excluded 
medication/vaccination or due to significant protocol non-compliance, this reason should 
be noted in the StudyTermination eCRF page. 
Protocol Deviation 
 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. In general, subjects associated with protocol deviations 
may remain in the study unless continuation in the study jeopardizes the subject's health, 
safety, or rights. 
 
Investigators will apply due diligence to avoid protocol deviations. Under no 
circumstances should the investigator contact GSK or its agents, if any, monitoring the 
study to request approval of a protocol deviation, as no authorized deviations are 
permitted. If the investigator feels a change to the protocol would improve the conduct of 
the studythis must be considered a protocol amendment, and unless such an amendment 
is agreed upon by GSK and approved by the IRB/EC and health authorities it cannot be 
implemented. 
 
Any subject who becomes pregnant during the study, despite the protocol requirement for 
adequate contraception should be encouraged to continue participating in the study for 

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safety follow-up only. The site nrust complete a Pregnancy Report CRF (initial report) as 
soon as possible after learning of pregnancy occurrence (see section 7.1.6, Pregnancies 
for further details). If the subject withdraws fromthe study for any of the above 
categories except death, the sitewill obtain permission from the subject to continue to 
remain in contact with her until the outcome of the pregnancy is known, even if the 
outcome is not known until after the subject reaches the end of follow-up period. 
 
3.9 
End of Study 
 
Most clinical trials intended to support the efficacy/immunogenicityand safety of an 
Investigational Product proceed to fullcompletion of planned sample size accrual. 
 
Evaluation of the primary and/or secondary immunogenicity/efficacyobjectives requires 
the testing of biological samples from the study subjects, which can only be completed 
after all samples are collected. The last samples for the analysis of the primary and/or 
secondary objectives will be taken at the last clinic visit, Day 29. For the purpose of this 
protocol, end of study is defined as the completion of the testing of such biological 
samples, to be achieved no later than 8 months after collection of the last biological 
sample at Day 29 visit 
 
If thecompletionof testing occurs prior the completion of the Last Subject Last Visit 
(LSLV) the latter date defines the end of study visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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.... 
 
4. 
SELECTION OF STUDY POPULATION 
 
4.1 
Inclusion C1iteria 
 
In order to participate in this study, all subjectsmust meet ALL of the inclusion criteria 
described. 
 
1. Individuals of IS through SS years of age on the day of informed consent or assent. 
2. Individuals who received Menveo 4 to 6 years prior to enrollment at an age of 11 
years or older (Menveo-Menveo group) 
OR 
Individuals who received Menactra 4 to 6 years prior to enrollment at an age of 11 
years or older (Menactra-Menveo group) 
OR 
Individuals who have not received any previous meningococcal vaccine (Naive 
group). 
3. Individuals who have voluntarily given written informed consent or assent after the 
nature of the study has been explained according to local regulatory requirements, 
prior to study entry. If the subject is under age 18 at the tinie of enrollment, the 
parent(s)l1egal guardian(s) of the subject should have voluntarily given written 
informed consent. 
 
4. Individuals who can comply with study procedures including follow-up2 
S. Males 
Or 
Females of non-childbearingpotential3 
Or 
 
 
2 A subject and/or parent(s)/Jegal guardian(s) is/are considered to be compliant if the Investigator judges 
thatthesubjectwill completetheSubject Diary and return for all thefollow-up visitsscheduled in the 
study. 
3 A female is considered to be of non-childbearingpotential prior to menarcheand after natural or induced 
menopause. Natural menopause is recognized to have occuned after 12 consecutive months of amenorrhea 
for which thereis nootherobvious pathological or physiologicalcause. Induced menopause is recognized 
to have occurred after hysterectomy, after bilateral oophorectomy, or iatrogenic ablation of ovarian 
ftmction. 
 
 
 
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Females of childbearing potential who are using aneffective birth control method4 
which they intend to use for at least 30 days after the last study vaccination. 
4.2 
Exclusion Crite1i a 
 
Each subject must not have: 
1. History of any meningococcal vaccine administrationother than the single 
vaccination given at 4 to 6 years ago (Menveo-Menveo and Menactra-Menveo 
groups) 
OR 
History of any meningococcal vaccine administration (Naive group) 
2. Current or previous, confirmed or suspected disease caused by N. meningitidis. 
3. Household contact with and/or intimate exposure to an individual with any laboratory 
confirmed N. meningitidis infection within 60 days prior to study vaccination. 
4. Progressive, unstable or uncontrolled clinical conditions. 
S. Hypersensitivity, including allergy, to any component of vaccines, medicinal products 
or medical equipment whose use is foreseen in this study. 
6. Clinical conditions representing a contraindication to intramiscular vaccination (IM) 
and blood draws. 
7. Abnormal function of the iimnune system resulting from: 
a. Clinical conditions. 
b. Systemic administration of corticosteroids (PO/IV/IM) for more than 14 
consecutive days within 90 days prior to study vaccination. 
c. Administration of antineoplastic and iimnunomodulating agents or radiotherapy 
within 90 days prior to study vaccination. 
 
 
 
4 The following birth control methods areconsidered effective: 
Abstinence 
Hormonal contraceptive (such asoral,injection, transdennal patch, implant) if used for at least 30 
days prior to informed consent 
Diaphragm preferably with spermicide, tubal occlusiondevice 
Intrauterine device (IUD) 
Tubal ligation 
Male par1ner using condom preferably with spermicide 
Male par1ner having been vasectomized at least six months prior toinformed consent 
 
 
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8. Received immunoglobulins or any blood products within 180 days prior to informed 
consent. 
9. Received systemic antibiotic treatment within 3 days prior to study vaccination or 
blood draw. 
10. Received an investigational or non-registered medicinal product within 30 days prior 
to study vaccination . 
11. Study personnel as an immediate family or household member. 
12. Individuals who have received any other vaccines within 7 days (for inactivated 
vaccines) or 14 days (for live vaccines) prior to vaccination in this study or who are 
planning to receive any vaccine within 28 days from the study vaccination. 
13. Individuals who have experienced a moderate or severe acute infection and/or fever 
defined as a temperature 38°C (100.4°F) within 3 days prior to study vaccination. 
14. Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the subject due to participation in the study. 
 
 
4.3 
C1ite1i a for Delay of Vaccination and/or BloodSampling 
 
There may be instances when individuals meet all eligibility criteria for vaccination yet 
have a transient clinical circumstance which may warrant delay of vaccination: body 
temperature elevation [ 38.0° C 
100 .4° F) within 3 days prior to intended study 
vaccination], systemic antibiotic treatment within 3 days prior to study vaccination or 
blood draw. Under such circumstances, a subject may be considered eligible for study 
enrolment after the appropriate window for delay has passed and inclusion/exclusion 
criteria have been rechecked, and if the subject is confirmed to be eligible. 
 
There is a clinical circumstance that warrants delay of blood collection for 
immunogenicityassessments in this study. This situation is listed below. In the event that 
a subject meets this criterion for delay of blood collection, blood collection may proceed 
once the window for delay has passed. 
 
Subject has received a dose of systemic antibiotics lessthan 3 days before the intended 
blood collection. 
 
 
 
 
 
 
 
 
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5. 
STUDY PROCEDURES 
 
The sections that follow provide an overview of the procedures that are to be followed in 
enrolling, evaluating, and following subjects who participate in this clinical study. Visits 
can be either clinic visits or safety follow-up telephone calls, as specified in the Table 
below and in the Time and Events Table4. 
 
Table 5-1 
Study Procedur es 
 
Visit Category 
Procedures 
Pre-vaccinationClinic Visit(s) 
Section 5.1 describes procedures to befollowed 
prior to study vaccination: informed coosent/assent, 
screening, enrolment, andrandomization 
VaccinatiooClinic Visit(s) 
Section 5.2 describes procedures to befollowed 
during each clinicvisit involving vaccination: 
vaccination, post-vaccination procedure,sand post- 
vaccination reminders 
Post-vaccination Visit(s) 
Section 5.3 describes follow-up clinic visits and 
safety follow-up calls 
Unscheduled Visit(s) 
Section 5.4 describes possible procedures to be 
followed at unscheduled clinic visit 
Study Termination Visit 
Section 5.5 describes procedures to befollowed at 
the last study visit for a subject (mayinclude early 
termination visit) 
 
5.1 
Pre-vaccination Clinic Visit(s) 
 
This section describes the procedures that must be performed for each potential subject 
prior to vaccination, including obtaining informed consent/assent, screening, enrolment 
and randomization. 
5.1.l 
Informed Consent/Assent 
 
"Informed consent" is the voluntary agreement of an individual or his/her legal 
guardian(s) to participate in research. Consent must be given with free willof choice, and 
without undue inducement. The individual must have sufficient knowledge and 
understanding of the nature of the proposed research, the anticipated risks and potential 
benefits, and the requirements of the research to be able to make an informed decision. 
 
"Assent" is a term used to express willingness to participate in research by persons who 
are by definition too young to give informed consent but who are old enough to 
understand the proposed research in general, its expected risks and possible benefits, and 
 
 
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the activities expected of them as subjects. Assent by itself is not sufficient, however. If 
assent is given, informed consent must still be obtained from the subject's parent(s) or 
legal guardian(s). Local laws define who constitutes a "child,"and such definitions dictate 
whether or not a person can legally consent to participate in a protocol (Levine 1988). 
 
Infonned consent of the parent(s)/legal guardian(s) and assent of subject following local 
!RB/EC guidance must be obtained before conducting any study-specific procedures (i.e., 
all of the procedures described in the protocol). The process of obtaining informed 
consent and assent should be documented in the subject source document in addition to 
maintaining a copy of the signed and dated informed consent. Additional specifics 
regarding the informed consent and assent processes are located in section 13.2, Infonned 
Consent Procedures. 
If a subject and/or parent(s)/legalguardian(s) is unable to read, an impartial witness 
should be present during the entire informed consent and assent discussion. An impartial 
witness is defined as a person who is independent from study conduct, who cannot be 
unfairly influenced by those involved with the study, who attends the informed consent 
process if the subject or the subject's legally acceptable representative cannot read, and 
who reads the informed consent form and any other written information supplied to the 
subject. After the written informed consent form and any other written information to be 
provided to subjects, is read and explained to the subject and/or parent(s)/legal 
guardian(s) and after the subject and/or parent(s)/legal guardian(s) has verbally consented 
to the subject's participation in the study and, if capable of doing so, has signed and 
personally dated the infonned consent fonn, the witness should sign and personally date 
the consent form. By signing the consent fonn, the witness attests that the information in 
the consent form and any other written information was accurately explained to, and 
apparently understood by, the subject and/or parent(s)/legal guardian(s) and that informed 
consent was freely given by the subject and/or parent(s)/legal guardian(s). 
 
5.1.2 
Screening 
 
After an individual has consented to participate in the study and infonned consent/assent 
is signed, that individual will begiven a unique Screening Number manually created by 
the investigator. The subject' s unique Screening Number will bedocumented in the 
Screening and Enrolment log. The eligibility of the subject will bedetermined based on 
the inclusion and exclusion criteria listed in section 4, Selection of Study Population and 
evaluated during this screening procedure. 
Prior to study enrolment, demographic data willbecollected from the subject, including: 
date of birth, gender, race, ethnicity, prior vaccination against meningitis. 
 
 
 
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Medical history will also be collected, including but not limited to any medical history 
that may be relevant to subject eligibility for study participation such as prior 
vaccinations, concomitant medications, and previous and ongoing illnesses or injuries. 
Relevant medical history can also include any medical history that contributes to the 
understanding of an adverse event that occurs during study participation, if it represents 
an exacerbation of an underlying disease/pre-existing problem. 
Review of systems is a structured interview that queries the subject and/or parent(s)/legal 
guardian(s) as to any complaints the subject has experienced across each organ system 
This will be performed before enrolment and used to guide physical examination. 
 
If applicable, prior and concomitant medications or vaccinations taken prior to start of 
study should be collected (refer to section 6.5, Prior and Concomitant Medications and 
Vaccines for further details). 
 
Collect vital signs (heart rate, blood pressure, and temperature (preferably taken orally). 
Measure height and weight. 
Perform pregnancy testing in women of childbearing potential (refer to section 3.5, 
Collection of Clinical Specimens for additional information) 
A general physical examination is to be performed by a qualified health care practitioner. 
"Qualified health care practitioner" refers to any licensed health care professional who is 
permitted by institutional policy to perform physical examinations and who is identified 
within the Study Staff Signature Log. 
 
The data collected through study assessments listed above will be written in the source 
document (see section 9.1, Source Documentation). Should the physical assessment 
reveal any abnormal values or events, these must be documented in the CRF Adverse 
Events Form 
 
Prior to vaccination, approximately 10 mL of blood will be drawn from all subjects for 
the immunological testing see section 3.5, Collection of Clinical Specimens. 
In the event that the individual is determined ineligible for studyparticipation, he/she is 
considered a screen failure. The reason for screen failure must be documented in the 
Screening and Enrolment log. If the individual is determined to be eligible for the study, 
he/she will be enrolled into the study. 
5.1.3 
Em·olment 
 
 
 
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After signing the informed consent/assent fonn, if an individual is determined to be 
eligible for study participation, the investigator will emoll the subject. 
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5.1.4 
Randomization 
 
Upon entering subject demographic data in IRT, the systemwillassign a 7 digit subject 
ID number consisting of the 3 digit site number and 4 digit order of randomization at the 
site. Access to IRT can be obtained by the site staffeither via web or telephone (as back 
up). The Subject ID willbethesubjec'ts unique identification number for all CRFs and 
associated study documentation that will beused for duration of the study. After 
randomization, the Screening Number ceases to be used and remains in the Screening and 
Enrolment Log only.: During the randomization transaction in IRT Subjects will be 
assigned a kit number for Menveo vaccination and will berandomized to a blood draw 
schedule (1:1 according to age group and previous vaccination status).The list of 
randomization assignments is produced by the IRT service provider and approved by 
GSK Randomization Office according to applicable GSK Standard Operating Procedure 
(SOP). 
 
IRT will also be used to ensure adequate and appropriate distribution of enrolment of 
naivesubjects across all sites. Further details may be found in study-specific plans, for eg, 
the IRT User Manual and the Randomization Configuration Document. 
 
If for any reason, after signing the info11lled consent form (ICF), the subject who is 
eligible and enrolled fails to be randomized, this is called a randomization failure and the 
early termination studyprocedures must be applied. The reason for all randomization 
failures should be recorded in the Screening and Enrolment Log and in the source 
document as specified in the Source Data Agreement (SDA). The information on subjects 
who are randomization failures should be kept distinct from subjects who are screen 
failures, as described in section 5.1.2, Screening. 
If for any reason, after randomization the subject fails to undergo treatment, this is an 
Early Termination and the reason should be recorded in source document as specified in 
the SDA. The information on these Early Termination subjects should be kept distinct in 
the source documentation from randomization failures. 
 
Within each study group, subjects willbeenrolled across age rangeof 15 to 55 years of 
age as follows: 
• 
Menveo-Menveo and Menactra-Menveo groups: approximately 80% of subjects will 
beenrolled in age groupof 15 to 25 years and 20% of subjects willbeenrolled in 26- 
55 years age group; 
• 
Naive group: approximately 50% of subjects willbeenrolled in age groupof 15 to 25 
years and 50% of subjects will beenrolled in age group of26-55 years. 
 
 
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Within each age category in each study group, subjects will be randomized into one of 
two different blood draw schedules according to a 1:1 ratio, described as follows: 
• 
Subjects getting blood draws at Day 1, Day 4 and Day 29. 
• 
Subjects getting blood draws at Day 1, Day 6 and Day 29. 
 
If for any reason, after enrolment the subject fails to undergo treatment/study procedures 
this is an Early Tennination and the reason should be recorded in source document as 
specified in the Source Data Agreement (SDA). The information on these Early 
Termination subjects should be kept distinct in the source documentation from subjects 
who are screen failures, as described in section S.1.2, Screening. 
5.2 
Vaccination Clinic Visit 
 
The first vaccination will be performed on Day 1. 
 
For studies which have visits for concomitant vaccinations or treatments, see section 6.5, 
Prior and Concomitant Medications and Vaccines for those visit procedures. 
 
Ensure all blood samples are taken p1i or to the vaccination. 
 
After completing the pre-vaccination procedures on day 1, administer the vaccine to the 
subject according to the procedures described in section 6.3, Vaccine Preparation and 
Administration. Observe the blinding procedures described in section 3.3, Blinding 
Procedures. 
Prior to administrationof study vaccination, confirm that the subject does not meet any 
criteria for delaying additional study vaccinations as described in section 4, Selection of 
Study Population. 
5.2.1 
Post-vaccination Procedures 
 
The following post-vaccination procedures will be performed on day 1. 
 
• 
After vaccination, the subject will be observed for at least 30 minutes including 
observation for unsolicited adverse events, solicited adverse events, and body 
temperature measurement. Record all safetydata collected during this time in the 
subject's source document. 
• 
A Subject Diary will be used in this studyto document solicited adverse events. The 
Subject Diary is the only source for collection of these data; therefore, it is critical that 
the subject completes the Subject Diary correctly. The subject should be trained on 
how and when to complete each field of the Subject Diary. 
 
 
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• 
The subject and/or parent(s)/legal guardian(s) should be trained on how to self­ 
measure localsolicited adverse events. The measurement of solicited local adverse 
events is to be performed using the ruler provided by the site. 
• 
The subject and/or parent(s)/legal guardian(s) should be instructed how to perform 
bodytemperature measurement using the thermometer provided by the site. If the 
subject feels unusually hot or cold during the day, the subject and/or parent(s)/legal 
guardian(s) should check body temperature. If the subject has fever, the highest body 
temperature observed that dayshould be recorded in the Subject Diary. 
 
Subject Diary training should be directed at the individual(s) who will perform the 
measurements of adverse events and who will enter the information into the Subject 
Diary. This individual may not be the subject and/or parent(s)/legalguardian(s), but if a 
person other than the subject and/or parent(s)/legal guardian(s) enters information into the 
Subject Diary, this person's identity must be documented in the Subject Diary or subject' s 
source record. Any individual that makes entries into the Subject Diary must receive 
training on completion of the Subject Diary at the time of the visit. This training must be 
documentedin the subject's source record. 
 
The same individual should complete the Subject Diary throughout the course of the 
study. 
 
• 
The site should schedule the next study activity clinic visit on Day 4 or Day 6 
depending to which blood draw schedule subject was randomized to with the subject 
and/or parent(s)/legalguardian(s). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
"6'; 
The subject and/or parent(s)/legal guardian(s) will be reminded to complete the Subject 
Diary and to contact the site if there are any questions, and to contact the siteinunediately 
(or as soon as the subject is medically stable) if the subject has a medical condition that 
leads to a hospitalization or an emergency roomvisit or to a visit to/by a doctor or is of 
concern. 
5.2.2 
Post-vaccination Reminders 
 
Reminder calls or alerts are not intended to be an interview for collection of safety data. If 
the subject and/or parent(s)/legal guardian(s) wishes to describe safety information, this 
information should only be collected by a healthcare professional at the site, and the 
safety data described must be written down in the subject's medical chart. 
 
Subject Diary ReminderCalls 
Subject Diary reminder calls will be performed on day 3 and day S. The purpose of this 
callis to remind the subject and/or parent(s)/legal guardian(s) about completion of the 
 
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Subject Diary. The call follows the Subject Diary Reminder Telephone Call Script 
provided to the site. The subject and/or parent(s)/legalguardian(s) should be reminded to 
contact the site via the telephone number provided in the informed consent to discuss 
medical questions. If the clinic visit at Day 4 or Day 6 overlaps with the specified window 
of the Day 3 or Day 5 reminder call, the Day 3/Day 5 reminder call maybe omitted. 
5.3 
Post-vaccination Visit(s) 
 
Post-vaccinationvisits will be performed on Day 4 or Day 6according to the blood draw 
schedule to which subject was randomized and Day 29. 
 
5.3.l Follow-up Clinic Visit(s) 
 
Follow-upclinic visits will be performed on Day 4 or Day 6 according to the blood draw 
schedule to which subject was randomized and on Day 29.During the follow-up clinic 
visit: 
 
• 
Subject Diary will be reviewed at Day 29. No changes to the information recorded 
within the Subject Diary are permissible. For details on the Subject Diary see sections 
3.4.2, Tools Used for Data Collection and 5.2.1, Post-vaccinationProcedures. The 
subject and/or parent(s)/legal guardian(s) will be interviewed to determine if any 
unsolicited adverse events occurred and if any concomitant medications or vaccines 
were taken/received in the time since the last clinic visit. This interview will follow a 
script which will facilitate the collection of relevant safety information. The 
healthcare professional reviewing these data will discuss the symptoms (if any) 
reported by the subject and will determine if any additional diagnoses and/or adverse 
events are present. Adverse events reported by the subject and/or parent(s)/legal 
guardian(s) at this follow-up clinic visit must be recorded in the subject's source 
document and on an Adverse Events CRF, as specified in section 7.1, Safety 
Assessment, and not written on the script used for the interview. 
• 
Performa brief symptom-directed physical examination if necessary according to 
symptoms the subject has reported. This is a physical examination that will include an 
examination of organ systems that are relevantto the investigator based on review of 
the subject's reported adverse events, concomitant medication use. This assessment 
may include: measurement of vital signs, body temperature and a check of general 
appearance. The physical assessment must be performed by the investigator or 
designee of the investigator, who is qualified to perform a physical assessment in 
accordance with their institutional policy. Corresponding information is documented 
in the subject' s source document and CRF(s). 
• 
Collect a blood sample (see section 3.5, Collection of Clinical Specimens for 
additional information). 
 
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Thesite should schedule the next study activity safety call withthe subject and/or 
parent(s)/legal guardian(s). 
 
The subject and/or parent(s)/legal guardian(s)] will receive a written reminder of the next 
planned study activity. The subject and/or parent(s)/legal guardian(s) will be reminded to 
contact the site if there are any questions and to contact the site immediately (or as soon 
as the subject is medically stable) if the subject has a medical condition that leads to a 
hospitalizationor an emergency roomvisit. 
 
5.3.2 Safety Follow-up Calls 
 
Safety follow-up call will be performed on Day 1S, Day 91 and Day 181. 
 
Safety follow-up calls are calls made to the subject by a healthcare professional 
designated on the site log. These calls will follow a script which will facilitate the 
collection of relevant safety information. The subject and/or parent(s)/legalguardian(s) 
will be interviewed according to the script, and information related to unsolicited adverse 
events (only at Day 1S), serious adverse events (SAEs),  medically attended adverse 
events, AEs leading to withdrawal and concomitant medications or vaccinations 
associated with those events will be reviewed. All safety information described by the 
subject must bewritten down in a designated location within the source document and not 
written on the script used for the telephone call. 
 
The site should schedule the next study activity with the subject and/or parent(s)/legal 
guardian(s). 
 
The subject and/or parent(s)/legal guardian(s) will be reminded to contact the site if there 
are any questions and to contact the site immediately (or as soon as the subject is 
medically stable) if the subject has a medical condition that leads to a hospitalizationor 
an emergency room visit. 
5.4 
Unscheduled Visits 
 
Unscheduled visits are not expected within this protocol. 
 
5.5 
Study Termination Visit 
 
The study termination visit willoccur on Day 181. The termination visit will be a 
telephone call. The date of termination is the date of the last contact (clinic visit or 
telephonecall) in which the subject's health status was assessed or, in cases where the 
subject does not agree to any further safety follow-up, it is the date consent is withdrawn. 
This date should be recorded on the termination CRF page. For visit procedures to be 

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performed for a subject whose planned study participation ends prematurely, please see 
section 5.5.1, Early Termination Visit. 
During the telephone call, the following procedures will be performed: interview of 
subject and/or parent(s)/legal guardian(s) to collect medically attended adverse events, 
AEs leading to withdrawal, SAEs, as well as interview of subject and/or parent(s)/legal 
guardian(s) to collect concomitant medications/ vaccinations associated with those events. 
All safety information described by the subject nrust be written down in a designated 
location within the source document and not written on the script used for the telephone 
call. 
The site will review with the subject and/or parent(s)/legal guardian(s) the plan of when 
infonnation relating to the subject's participation in the study may be available  (e.g., 
study results, treatment assignments). It will also be discussed how information relating to 
the subject' s participation in the study will be shared with the subject's healthcare 
provider, if the subject and/or parent(s)/legalguardian(s)  chooses to  share this 
infonnation. 
 
The sitewillcomplete the termination CRF page and this will mark the completion of the 
subject's participation in the study. 
5.5.1 Early Termination Visit 
When a subject is withdrawn from treatment or withdraws from the study, the investigator 
will notifythe Sponsor and, when possible, will perform the procedures listed below. The 
reason(s) for the early termination will be included in the subject' s source documentation. 
If the EarlyTermination Visit is a telephone call, collect as much infonnation as possible. 
Early Termination Visits include subjects who were randomized but not treated. 
 
At the clinic visit or during the telephone call, the following procedures will be 
performed: interview of subject and/or parent(s)/legal guardian(s) to collect adverse 
events, medically attended adverse events, AEs leading to withdrawal, SAEs, interview of 
subject and/or parent(s)/legalguardian(s) to collect concomitant medications/ 
vaccinations. 
 
The site will review with the subject and/or parent(s)/legal guardian(s) the plan of when 
infonnation relating to the subject's participation in the study may be available  (e.g., 
study results, treatment assignments). It will also be discussed how information relating to 
the subject' s participation in the study will be shared with the subject's healthcare 
provider, if the subject and/or parent(s)/legalguardian(s)  chooses to  share this 
infonnation. 

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Thesitewillcomplete the termination CRF page and this willmark the completion of the 
subject's participation in the study. 

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6. 
TREATMENT OF SUBJECTS 
 
All vaccines associated with this study are to be stored separately from other vaccines and 
medications in a secure location under appropriate storage conditions with temperature 
monitoring. All vaccines associated with  this study  must  be  checked  for  expiration 
date p1i or to use . Expired vaccines must not be administered to subjects. 
6.1 
Study Vaccine(s) 
 
The term 'study vaccine ' refers to those vaccines provided by the Sponsor, which will be 
evaluated as part of the study objectives. The study vaccines specific to this study are 
described below. The study vaccines specific to this study is the MenACWY-CRM 
vaccine (Menveo® , GSK)  . 
 
The Meningococcal ACWY conjugate vaccine is obtained by extemporaneous mixing 
just before injection of the lyophilized MenA-CRM component with the MenCWY-CRM 
fullliquid vaccine. The pharmaceutical form is Powder and solution for solution for 
injection. Menveo® is provided as vial/vial presentation. MenA lyophilised conjugate 
component (glass vial) and MenCWY liquid conjugate component (glass vial). After 
reconstitution, MenACWY-CRM will have the following composition per O.S mL of 
injectable solution (SeeTable 6.1-1): 

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Table 6.1-1: MenAC\VY-CR"l\1 Com position 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
One 0.5 mL dose ofMenACWY willbe 
. . 
. . 
administered by mtranruscular (IM) tnJection m 
the deltoid area of non-dominant ann (preferably). 
 
For more detailed infonnation, refer to the latest version of Investigator Brochure and 
SPC for Menveo® , which are included in the investigator site file. 
 
6.2 
Non-Study Vaccines 
Not applicable. 
6.3 
Vaccine Pr epa ration a nd Administra tion 
 
The investigator or designee will be responsible for oversight of the administration of 
vaccine to subjects enrolled in the study according to the procedures stipulated in this 
study protocol All vaccines will be administered onlyby personnel who are qualified to 
perform that function under applicable local laws and regulations for the specific study 
site. 
All studyvaccines to be administered to the subjects must be stored in a safe and locked 
place with no access by unauthorized personnel. 
Name of Ingredient 
Unit and/orPercentage Formula 
(Dose 0.5 mL) 
D111g S ubstances 
CRM191-MenA conjug;ite 
10 µgMenA, 16.7-33.3µgCRM191 
CRM191-MenC conjug;ite 
5 µgMenC, 7.1-12.5 µgCRM197 
CRM191-MenWconjugate 
5 µg MenW, 3.3-  8.3µgCRM191 
CRM191-MenYconjug;ite 
5 µgMenY, 5.6- 10µgCRM197 
Sodium chloride 
4.5mg 
Excipients 
Sucrose 
12.5 mg 
Sodium phosphate buffer 
Sodium dihydrogen phosphate 
Disodium hydrogen phosphate dehydrate 
!0mM 
2.SmM 
7.SmM 
Potassium dihydrogen phosphate 
5mM 
Water for Injection 
q.s 0.5 mL 
VolumeofFormulation 
0.6mL 
Appearance 
Colorlesstolight yellow 
Vaccine Presentation 
Asingle dose of two vials 

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The study vaccines will be stored at the defined temperature range (i.e. +2 to +8C). The 
storage temperature of the vaccines will bemonitored daily with temperature monitoring 
devices and willberecorded. 
Any temperature deviation, i.e. temperature outside the range (+2 to +8°C), must be 
reported to thesponsor as soon as detected. Following the exposure to such a temperature 
deviation, vaccines will not be used until written approval has been given by the sponsor. 
The study vaccine should be allowed to reach room temperature before administration, 
according to local vaccination practice. 
MenACWY-CRM (Menveo) vaccine is prepared by aseptically withdrawing all fluid 
fromthe vial containing the MenCWY-CRM liquid conjugate component and injecting 
the liquid into the vial containing the MenA-CRM lyophilizedportion. Invert and shake 
the vial well until the vaccine is dissolved. The finalmixed vaccine is then ready for 
administrationof the MenACWY fornrulation (0.5 mLJdose of injectable solution). 
 
Detailed vaccine preparation and administrationinstructions willbe provided to 
investigators in the Protocol Ancillary Document prior to study start. 
 
PRECAUTIONS TO BE OB SERVE D IN ADMINISTERINGSTUDY VACCINE: 
 
Prior to vaccination, subjects must be determined to be eligible forstudyvaccination and 
it must be clinically appropriate in the judgment of the investigator to vaccinate. 
Eligibilityfor vaccination prior to first study vaccine arlroinislTation is determined by 
evaluating the entry criteria outlined in protocol sections 4.1, Inclusion Criteria and 4.2, 
Exclusion Criteria. 
Eligibilityfor non-studyvaccines should be determined by the investigator, pending the 
review of the package insert of the relevant vaccine. 
 
Study vaccines should not be administered to individuals with known hypersensitivity to 
any component of the vaccines. 
Standard immunization practices are to be observed and care should be taken to 
administer the injection: intramuscularly. Before administering vaccine, the vaccination 
site is to be disinfected with a skin disinfectant (e.g., 70% alcohol.)Allow the skin to dry. 
DO NOT inject intravascularly. 
 
As with all injectable vaccines, trained medical personnel and appropriate medical 
treatment should be readily available in case of anaphylactic reactions following vaccine 
administration. For example, epinephrine 1:1000, diphenhydramine, and/or other 
medications for treating anaphylaxis should be available. 
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.... 
 
6.4 
Vaccine Adminish·ation En or or Overdose of Vaccine 
Vaccine administration error is defined as receiving a dose of studyvaccine that was not 
reconstituted as instructed or administered bya different route from theintended route of 
administration. An overdose of studyvaccine (whether accidental or intentional) is 
defined when a dosage higher than the recommended dosage is administered in one dose 
of study vaccine. 
Any vaccine administrationerror or overdose of study vaccine detailed in this protocol 
must be reported as an adverse event, and if the vaccine administrationerror or overdose 
is associated with a serious adverse event, it must be reported as such within 24hours to 
the Sponsor. 
6.5 
Plior and Concomitant Medications and Vaccines 
 
All medicatoi ns, vaccines and blood products taken or received by the subject within 30 
days prior to the start of the study are to be recorded on the Prior and Concomitant 
Medications CRF. 
In addition, the following are considered prior medications for this protocol: all 
medication/vaccines described in theinclusion and exclusion criteria of this protocol 
including: 
 
• Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive 
days within 90 days prior to study vaccination; 
• 
Administration of antineoplastic anrl imm1momodulating agents or radiotherapy 
within 90 days prior to study vaccination; 
• Tmmnonglobulins or anyblood products within 180 days prior to informed consent; 
• Systemic antibiotic treatment within 3 days prior to study vaccination or blood draw; 
• Any investigationalor non-registered medicinal product within 30 days prior to study 
vaccination; 
• Administration of vaccines within 7 days (for inactivated vaccines) or 14 days (for 
live vaccines) prior to vaccination in this study or who are planning to receive any 
vaccine within 28 days fromthe studyvaccination. 
Use of analgesics/antipyreticsto prevent or treat solicitedAEs will be captured in the 
Subject Diary from day 1-7 following each vaccination. Medications taken for 
prophylaxis arethose intended to prevent the onset of symptoms. Medicationstaken for 
treatment are intended to reduce or eliminate the presence of symptoms that are present. 
 
 
 
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Concomitant medications include all prescription and non-prescriptionmedications 
(including vaccines) taken by/administeredto the subject during the 30 days after study 
vaccination and nrust be documented on the Concomitant Medications CRF. Mineral 
supplements and vitamins are not considered concomitant medications. 
 
When recording concomitant medications/vaccines, they should be checked against the 
study entry and continuation criteria in section 4, Selection of Study Population to ensure 
that the subject should be enrolled/continue in the study. 
Concomitant medication dministered for treatment of AEs with medically-attended 
visits, AEs leading to study withdrawal and SAEs must be documented during the entire 
study period. 
 
Any vaccine not foreseen in the studyprotocol in the period starting at Day 1 and ending 
at Day 181 must be recorded in the eCRF. 
 
6.6 
Vaccine Supply, Labeling, Storage and Tracking 
 
The Sponsor will ensure the following 
 
• 
Supply the study vaccine(s). 
• 
Appropriate labeling of all studyvaccines provided that corq>lies with the legal 
requirements of each country where the study is to be performed. 
The investigator must ensure the following: 
 
• 
Acknowledge receipt of the study vaccines by a designated staff member at the site, 
including 
Confirmation that the vaccines were received in good condition 
Confirmation to the Sponsor of the temperature range during shipment from the 
Sponsor to the investigator' s designated storage location 
Confirmation by the Sponsor that the vaccines are authorized for use. 
• Proper storage of the studyvaccines, including: 
Storage in a secure, locked, temperature-controlled location. 
Proper storage according to the instructions specified on the labels. 
Appropriate record keeping and inventory of the study vaccines, including regular 
documentation of adequate storage temperature. 
• 
Appropriate use of the study vaccines, including: 

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Not use of vaccines prior to receipt of authorization for use fromthe Sponsor. 
Use only in accordance with the approved protocol 
Proper han dling, including confirmation that the vaccine has not expired prior to 
administration. 
• 
Appropriate documentation of administrationof vaccines to study subjects including: 
- Date, dosage, batch/lot numbers, expiration dates, unique identifying numbers 
assigned to subjects and study vaccines, and time of vaccine administration.1bis 
information will bemaintained in an accountability log that will bereviewed by 
the site monitor. 
- Reconciliation of all vaccines received from the Sponsor. Reconciliationis 
defined as maintaining records of which and how many vaccines were received, 
which vaccines were administered to subjects, which vaccines were destroyed at 
the site, and which vaccines were returned to the Sponsor, as applicable. 
- Proper adherence to the local institutional policy with respect to destruction of 
study vaccines. 
• 
Complete record keeping of vaccine use, wastage, return or destruction, including 
documentation of 
Copy of the site's procedure for destruction of hazardous material. 
Number of doses destroyed, date of destruction, destruction code (if available), 
method of destruction, and name of individual performing destruction. 
Vaccines that have been stored differently from the manufacturer's indications must not 
be used unless the Sponsor provides written authorization for use. In the event that the use 
cannot be authorized, the Sponsor willmake every effort to replace the vaccine supply. 
All vaccines used in conjunction with this protocol must be stored separately from normal 
hospital/practicestocks to prevent unintentional use of study vaccines outside of the 
clinical study setting. 
 
Monitoring of vaccine accountability will be performed by the study monitor during site 
visits and at the completion of the study. 
 
At the conclusion of the study, and as appropriate during the course of the study, the 
investigator must ensure that all unused studyvaccines, packaging and supplementary 
labels are destroyed locally (upon approval fromSponsor) or returned to the Sponsor or to 
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7. 
ASSESSMENTS 
 
7.1 
Safety Assessment 
The measures of safety used in this study areroutine clinical procedures. They include a 
close vigilance for, and stringent reporting of, selected local and systemic adverse events 
routinely monitored in vaccine clinical studies as indicators of reactogenicity. 
An adverse event (AE) is defined as anyuntoward medical occurrence in a subject or 
clinical investigationsubject administered a pharmaceutical product at any dose that does 
not necessarily have to have a causal relationshipwiththis treatment. Therefore, an AE 
can be any unfavorable and unintended sign (including an abnormal laboratoryfinding, 
for example), symptom, or disease temporally associated with the use of an 
investigational product, whether or not considered related to the investigaitonalproduct. 
This definition includes intercurrent illnesses or injuries and exacerbation of pre-existing 
conditions. 
The period of observation for AEs extends fromthe time the subject signs informed 
consent until he or she completes the specified safety follow-up period of 180 days or 
terminates the study early (whichever comes first). AEs occurring after the informed 
consent form is signed but prior to receiving studyvaccine/productwill be documented as 
an adverse event and recorded within source document. However, any AEs occurring 
prior to receipt of anystudyvaccine will be analyzed separately from" treatment 
emergent'' AEs (AEs occurring after administration of the first study vaccine). 
Adverse events are collected as either solicited or unsolicited adverse events. Solicited 
events arederived from organized data collection systems, such as Subject Diaries or 
interview. 
7.1.1 
Solicited Adverse Events 
 
The term"reactogenicity'' refers to solicited signs and symptoms ("solicited adverse 
events") occurring in the hours and days following a vaccination, to be collected by the 
subject and/or parent(s)/legalguardian(s) for 7 consecutive days, using a pre-defmed 
Subject Diary. 
The following solicited adverse events are included in the Subject Diary. Each adverse 
event is to be assessed using the scoring system reported in parentheses below: 
 
 
 
 
 
 
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Solicited LocalAdverseEvents 
Injectionsite pain, erythema, induration, Solicited Systemic Adverse Events 
Fatigue, headache, myalgia, arthralgia, loss of appetite, nausea, chills and fever. 
Table 7.1.1-1 
Severity grading for solicited local and systemic AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fever is defined and measured by a body temperature 38.0°C(100.4F). Route of 
temperature measurement is preferably oral. 
 
Other Indicators of Reactogenicity: 
• Use of analgesics / antipyretics for prophylaxis (Days 1-7) 
• Use of analgesics / antipyretics for treatment (Days 1-7) 
• Body temperature, described in degrees Celsius and summarized by route of 
measurement and in 05°C increments from 36.·o c . 
The study staff must review the data entered into the Subject Diary as described in section 
3.4.2, Tools Used for Data Collection and section S.3.1, Follow-up Clinic Visit(s). 
 
 
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]',fil d 
Moderate 
Se.vel'e 
Pain 
No interference with 
dailyactivity 
Interfereswith daily 
activity 
Prevents daily activity 
Erythema 
25-50mm 
51- IOOmm 
> l OOmm 
lnduration 
25-50 mm 
51- IOOmm 
> l OOmm 
Fa ti gue 
No interference with 
dailyactivity 
Interfereswith daily 
activity 
Prevents daily activity 
Headache 
No interference with 
activity 
Interfereswith daily 
activity 
Prevents daily activities 
Myalgia 
No interference with 
activity 
Interfereswith daily 
activity 
Prevents daily activities 
Arthralgja 
No interference with 
activity 
Interferes with daily 
activity 
Prevents daily activities 
Loss ofa ppetite 
Eating less than usual 
with no effect on normal 
activity 
Eating less thanusual / 
interfered with normal 
activity 
Not eating at all 
Nausea 
No interference with 
dailyactivity 
Interferes with daily 
activity 
Prevents daily activity 
Chills 
No interference with 
activity 
Interfereswith daily 
activity 
prevents daily activities 

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Note: Anysolicited adverse event that meets any of the following criteria must be entered 
into subjects' source document(see section 9.1, Source Documentation) and also as an 
adverse event on the Adverse Event CRF: 
 
• 
Solicited local or systemic adverse event that continues beyond day 7 after 
vaccination. 
• 
Solicited local or systemic adverse event that leads to a visit to a healthcare provider 
(medically attended adverse event, see section 7.1.3, Evaluation of Adverse Events). 
• Solicited local or systemic adverse event leading to thesubject withdrawing fromthe 
study or the subject being withdrawn from the study by the investigator (adverse event 
leadingto withdrawal, see section 7.1.3, Evaluation of Adverse Events). 
• Solicited local or systemic adverse event that otherwise meets the definition of a 
serious adverse event (see section 7.1.4, Serious Adverse Events). 
7.1.2 Unsolicited Adverse Events 
An unsolicited adverse event is an adverse event that was not solicited using a Subject 
Diary and that was spontaneously communicated bya subject and/or parent(s)/legal 
guardian(s) who has signed the informed consent. 
Potential unsolicited AEs may be medically attended (defined as symptoms or illnesses 
requiring hospitalization, or emergency room visit, or visit to/by a health care provider,) 
or were of concern to the subject and/or parent(s)/legal guardian(s). In case of such 
events, subjects and/or parent(s)/legal guardian(s) will be instructed to contact the site as 
soon as possible to report the event(s). The detailed information about the reported 
unsolicited AEs willbe collected by the qualified site personnel during the interview and 
will be documented in the subject's records. 
 
Unsolicited AEs that arenot medically attended nor perceived as a concern by subjects 
and/or parent(s)/legal guardian(s) will be collected during interview with the subject 
[and/or parent(s)/legalguardian(s) and by review of available medical records at the next 
visit (see section 5.3, Post-vaccination Visit(s). 
7.1.3 Evaluation of Adverse Events 
Everyeffort should be made by the investigator to evaluate safety information reported by 
a subject for an underlying diagnosis and to capture this diagnosis as the event in the AE 
page. In other words, the practice of reporting only symptoms (e.g., "cough" or "ear 
pain") are better reported according to the underlying cause (e.g., "asthma exacerbation" 
or "otitismedia"). 
 
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Theseverity of events reported on the Adverse Events CRF willbe determined by the 
investigator as: 
 
Mild: 
Moderate: 
Severe: 
transient with no limitation in normal daily activity. 
somelimitation in normal daily activity. 
unable to perform normal daily activity. 
 
The relationship of the studytreatment to an AE will be determined by the investigator 
based on the following definitions: 
 
1. Not Related 
The AE is not related to an investigational vaccine if there is evidence that clearly 
indicates an alternative explanation. If the subject has not received the vaccine, the timing 
of the exposure to the vaccine and the onset of the AE are not reasonably related in time, 
or other facts, evidence or arguments exist that reasonably suggest an alternative 
explanation, then the AE is not related. 
2. Possibly Related 
 
The administrationof the investigational vaccine and AE are considered reasonably 
related in time and the AE could be explained by exposure to the investigational vaccine 
or by other causes. 
 
3. Probably Related 
 
Exposure to the investigational vaccine and AE are reasonably related in time and no 
alternative explanation has been identified. 
 
The relationship of the studytreatment to an unsolicited AE will be determined by the 
investigator. 
 
Note: solicited AEs will not be evaluated for relationship to studytreatment. Grading for 
severity of solicited local and systemic AEs is described in section 7.1.1, Solicited 
Adverse Events. 
 
Adverse events will also be evaluated by the investigator for the co-existence of any of 
the other following conditions : 
 
• 
"Medically attended adverse event": an adverse event that leads to a visit to a 
healthcare provider. 
• 
AEs leading to withdrawal: adverse events leading to study or vaccine withdrawal. 

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If solicited or unsolicited adverse events have been reported and the subject and/or 
parent(s)/legalguardian(s)] indicated that the symptoms required medical attendance or 
were of concern, the subject and/or parent(s)/legalguardian(s) must be contacted for 
further information. 
When the subject and/or parent(s)/legal guardian(s) is contacted for any of these reasons, 
the contact must be documented in thesubject's source documentation. 
All AEs, regardless of severity, willbe monitored until resolution or until the investigator 
assesses them as chronic or stable. All subjects experiencing AEs - whether considered 
associated with the use of the study vaccine or not - must bemonitored until symptoms 
subside and any abnormal laboratory values have returned to baseline, or until there is a 
satisfactory explanation for the changes observed, or until death, in which case a full 
pathologist's report should be supplied, if possible. The investigator'sassessment of 
ongoing Adverse Events at the time of each subject's last visit should be documented in 
the subject' s medical chart. 
7.1.4 Serious Adverse Events 
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any 
dose results in one or more of the following: 
• 
Death. 
• 
Is life-threatening (i.e., the subject was, in theopinion of the investigator, at 
immediate risk of death from the event as it occUITed); it does not refer to anevent 
which hypothetically tnight have caused death if it were more severe. 
• Required or prolonged hospitalization. 
• Persistentor significant disability/incapacity(i.e., the event causes a substantial 
disruption of a person's ability to conduct normal life functions). 
• 
Congenital anomaly/or birth defect. 
• 
An important and significant medical event that may not be immediately life 
threatening or resulting in death or hospitalization but, based upon appropriate 
medical judgment, may jeopardize the subject or may require intervention to prevent 
one of the other outcomes listed above. 
Adverse events which do not fall into these categories are defined as non-serious. 
It should be noted that a severe adverse event need not be serious in nature and that a 
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Serious adverse events will be captured both on the Vaccines Serious Adverse Event 
(VSAE) form as well as on the AE CRF. All SAEs will be evaluated by the investigator 
for relationship of the event to studyvaccine. SAEs that are judgedto be possibly or 
probably related to the studyvaccine should be reported to the Sponsor as 
related/suspected events. 
 
The relationship of the studytreatment to an SAE will be determined by the investigator 
based on the following definitions: 
 
1. Related/suspected 
 
The SAE is judged by the investigator to be possibly or probably related to the study 
vaccine on the AE CRF page (see section7.1.3, Evaluation of Adverse Events). 
 
2. Not Related 
 
The SAE is not related if exposure to the study vaccine has not occurred, or the 
occurrence of the SAE is not reasonably related in time, or the SAE is considered 
unlikely to be related to use of the study vaccine, i.e., there are no facts (evidence) or 
arguments to suggest a causal relationship. 
 
The relationship of the studyvaccine to an SAE will be determined by the investigator. 
 
In addition, SAEs will be evaluated by the Sponsor or designee for "expectedness." An 
unexpected AE is one that is not listed in the cUITent Summary of Product Characteristics 
or the Investigator's Brochure or an event that is by nature more specific or more severe 
than a listed event 
 
In addition, a pre-existing event or condition that results in hospitalization should be 
recorded on the Medical History CRF. If the onset of an event occUITed before the subject 
entered the study (e.g., any pre-planned hospitalization for conditions like cosmetic 
treatments or for non-emergency routine visits for a pre-existing condition), the 
hospitalizationwould not lead to an AE being classified as serious unless, in the view of 
the investigator, hospitalization was prolonged as a result of participation in the clinical 
study or was necessary due to a worsening of the pre-existing condition. 
7.1.4.1 
Adverse Events of Special Interest 
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7.1.S Methods for Recording Adverse Events and Se1ious Adverse Events 
 
Findings regarding Adverse Events must be reported on an Adverse Events CRF, as 
specified in section 7.1.1, Solicited Adverse Events, and on the VSAE form, if applicable, 
which is part of the Investigator Site File. All findings in subjects experiencing AEs nrust 
be reported also in the subject's source document. 
 
All SAEs which occur during the course of the study, whether considered to be associated 
withthe study vaccination or not, must be reported wi thin 24 hours of the site becoming 
awar e of the event to GSK or its designee. Specific instructions and contact details for 
collecting and reporting SAEs to GSK willbeprovided to the investigator. 
 
All SAEs are also to be documented on the Adverse Events CRF. Any medication or 
other therapeutic measures used to treat the AE will berecorded on the appropriate 
CRF(s) in addition to the outcome of the AE. 
 
After receipt of the initial report, representatives of GSK or its designee willcontact the 
investigator if it is necessary to obtain further information for assessment of the event. 
 
All SAEs must be reported by the investigator to his/her corresponding EC/ IRB 
applicable regulatory authorities in accordance with institutional policy/regulatory 
requirements and adequate documentation of this notification must be provided to the 
Sponsor. 
 
GSK or its designee must also comply with the applicable regulatory requirement(s) 
related to the reporting of suspected unexpected serious adverse vaccine reactions (also 
known as SUSARs) to the regulatory authority(ies) and the IRB/EC. If a SUSAR or other 
safety signal relating to use of one of the study vaccines is reported to GSK or its 
designee, the Sponsor willcommunicate the information to the investigator and the 
investigator will beresponsilbe forsubmitting this infonnation to the EC/IRB and other 
relevant authorities. 
 
7.1.S. l 
Post-S tudy Even ts 
 
Any SAE that occurs outside of the protocol-specifiedfollow-up period and considered to 
be caused by the study vaccine nrust be reported to GSK or its designee. These SAEs will 
be processed by GSK or its designee as during the course of the study, until 1 month after 
Last Subject Last Visit (LSLV). Instructions and contact details for collecting and 
reporting these suspected SAEs will beprovided to the investigato.r 
 
 
 
 
 
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7.1.6 
Pregnancies 
 
To ensuresubjects' safety, each pregnancy in a subject after study vaccination must be 
reported to GSK or delegate within 72 hours of the site learning of its occurrence. If the 
subject agrees to submit this information, the pregnancy must be followed to determine 
outcome, including spontaneous or voluntary termination, details of the birth, and the 
presence or absence of any birth defects, congenital abnormalities, or maternal and/or 
newborn complications. This follow-up should occur even if intended duration of safety 
follow-up for the study has ended. 
 
Pregnancy data must be recorded on a Pregnancy Report CRF (initial report) and 
Pregnancy Follow-Up CRF (outcome report) and reported to GSK or delegate. 
Instructions and contact details for submitting the Pregnancy CRFs will be provided to the 
investigator. 
Any pregnancy outcome meeting the definition of a SAE (see section 7.1.4, Serious 
Adverse Events) must also be reported on the VSAE Report Form. 
 
7.1.7 
Safety La bora tory l\ lll eas ur em e n ts 
No safety laboratorymeasurements will be done in this study. 
 
7.2 
Efficacy Assessment 
This section is not applicable. This studyhas no efficacy measurements. 
 
7.3 
Immunogenicity Assessment 
 
The functional measure of immunogenicity used in this study, Serum Bactericidal Assay 
(SBA), is a measure of the ability of antibodies, in concert with human complement, to 
kill meningococci, and is widely used and generally recognized as the serological 
correlate of protection The key measures of irom1mogenicitywillbe the percentages of 
subjects with seroresponse
[I J  , percentages of subjects who achieve hSBA titers  8  and, 
and the hSBA GMfs against serogroups A, C, W and Y reference strains 
 
These measurements willbe assessed in serology samples collected at Visit Day 1, 4 or 8 
and Day 29. The measures of immunogenicity used in this study are standard, i.e., widely 
 
 
[I J Seroresponse to N. meningitidis serogroups A, C, W and Y is defined as: for subjects with a pre­ 
vaccination hSBA titer < 4, a post-vaccinationhSBA titer 2:8; for subjectswith a pre-vaccination hSBAtiter 
2:4, an increase in hSBA titer of at least four times the pre-vaccinationtiter. 
 
 
 
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used and generally recognized as reliable, accurate, and relevant (able to describe the 
quality and extent of the immune response). 
All subjects will have a blood draw at Day I, before vaccination. Subsequent blood draws 
willbe at either Day 4 or Day 6 post vaccination, and at Day 29 post vaccination. 
Primary: 
Collected samples may be used in other assays, for test improvement or development of 
analytical methods related to the study vaccines or the disease under evaluation to allow a 
more reliable measurement of the vaccine response. Under these circumstances, 
additional testing on the samples may be performed by GSK outside the scope of the 
protocol Any sample testing willbe done in line with the consent of the individual 
subject's parent/ guardian. 
 
Testing willbe conducted by qualified and certified laboratories. All assays will be 
performed in GSK, Clinical Laboratory Sciences, or a delegate laboratory. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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8. 
STATISTICALCONSIDERATIONS 
 
8.1 
Endpoints 
8.1.1 
Plimai-y En dpoint(s) 
 
8.1.1.1 
P1im ary Safety Endpoint(s) 
 
There are no primary safety endpoints in this study. 
8.1.1.2 
P1imar y Efficacy Endpoint(s) 
 
There are no primary efficacy endpoints in this study. 
 
8.1.1.3 
P1imary Immunogenicity Endpoint(s) 
 
Thefollowing measure willbe summarized for the pooled (Menveo-Menveo and 
Menactra-Menveo) group 
 
1. Percentage of subjects with hSBA seroresponse5 against N. meningitidis 
serogroups A, C, W and Y at Day 29. 
8.1.2 
Secondary Endpoin t(s) 
 
8.1.2.1 
Secondary Safety Endpoint(s) 
 
Safety of the study vaccine willbe assessed in the pooled vaccine group (Menveo­ 
Menveo and Menactra-Menveo) and the vaccine-naive group in terms of the frequency 
(percentage) of reported adverse events including 
 
1. Any unsolicited AEs reported within 30 minutes after vaccination; 
2. Solicited local and systemic AEs reported from Day 1 (6 hours) through Day 7 
after vaccination; 
3. Other indicators of reactogenicity (e.g. use of analgesics/ antipyretics, body 
temperature) within 7 days after vaccination; 
4. All unsolicited AEs reported from Day 1 through Day 29 after vaccination; 
 
 
 
 
5 Seroresponse is defined as: a) post-vaccination hSBA?:8 for subjectswith a pre-vaccination hSBA <4; b) 
for subjects with a pre-vaccinationhSBA ?:4, an increase of at least four timesthe pre-vaccinationhSBA. 
 
 
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5. Medically-attendedAEs, AEs leading to withdrawal and SAEs reported from Day 
1 through Day 181 (entire study period). 
Adverse events will be coded using MedDRA preferred terms as applicable. 
 
8.1.2.2 
Secondar y Efficacy Endpoint(s) 
There are no secondary efficacy endpoints in this study. 
 
8.1.2.3 
Secondar y Immunogenicity Endpoint(s) 
The following measures will be nmmari:i:ed for Menveo-Menveo, Menactra-Menveo, 
Naive and the pooled (Menveo-Menveoand Menactra-Menveo)groups unless otherwise 
noted: 
 
1. Percentage of subjects with hSBA titer 8 against N. meningitidis serogroups A, C, 
Wand Y at Day 1, Day 4, Day6 and Day 29; 
2. Percentagesof subjectswith hSBA seroresponse against N. meningitidis 
serogroups A, C, Wand Y at Day 4, Day6 and Day 29 (Day 29: Except the 
pooled group); 
3. hSBA GMfs againstN. meningitidis serogroup A, C, Wand Y at Day 1, Day 4, 
Day 6 and Day 29; 
4. Ratios of hSBA GMfs atDay 1, Day 4, Day 6 and Day 29 (between study 
groups). 
5. Ratios of hSBA GMfs atDay 4, Day6, and Day 29 compared to Day 1 (within 
study groups). 
8.1.3 
Explora tory Endpoint(s) 
 
8.1.3.1 
Exploratory Safety Endpoint(s) 
There are no exploratory safety endpoints in this study. 
 
8.1.3.2 
Exploratory Efficacy Endpoint(s) 
There are no exploratory efficacy endpoints in this study. 
 
8.1.3.3 
Exploratory Immunogenicity Endpoint(s) 
 
There are no exploratory immunogenicity endpoints in this study. 
 
 
 
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8.2 
Success C1iteria 
 
8.2.1 
Success C1iteria for P1imary Objective(s) 
 
8.2.1.1 
Success C1ite1ia for P1imary Safety Objective(s) 
There are no primary safety objectives in this study. 
8.2.1.2 
S uccess C1ite1ia for P1ima ry Efficacy O bjective(s) 
There are no primary efficacy objectives in this study. 
8.2.1.3 
Success C1ite1ia for P1imary Immunogenicity Objective(s) 
To demonstrate immune response sufficiency after MenACWY-CRM booster vaccine 
administration, the lower limit of the one-sided 97.S% Confidence Interval(CI) for 
percentage of subjects with hSBA seroresponse against each of serogroups A, C, Wand 
Y must be greater than 80% (in the pooled group of subjects who received primary 
vaccination with Menveo or Menactra). The threshold of80% was previously agreed for 
demonstration of immune response adequacy in other age groups (e.g. in infants, study 
VS9_36). 
 
8.2.1.3.1  Rationale for Combining the Menveo-Menveo and Menach·a-Menveo 
groups 
Table 8.2.1.3.1-1 shows excerpt of data from a previous study (VS9Pl3El) assessing the 
immunogenicityof a booster dose of Menveo among subjects who had previously been 
vaccinated with either Menveo or Menactra 3 years prior in another study (VS9P13) while 
subjects were 11-18 years old. The table shows almost identical seroreponse rates and 
95% Cls at one-month post-booster dose of Menveo for subjects previous vaccinated with 
Menveo and Menactra. This suggests that data from the two groups can be pooled or 
combined for analysis of seroresponse following a booster doseof Menveo as planned in 
the current studyVS9_77. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table8.2.l.3.l -1: 
 hSBASeroresponse at One Month Following the Booster at 3 
Years After Vaccination, by Serogroup - Booster- PP Population 
 
Vaccination 
ACWY/ACWY 
Gt·oup IV 
MenactJ"a/A 
GroupV 
Y 
Difference' 
G1·onp IV - G1·onp V 
<I'. 
Q. 
:, eco   Overall Seroresponse 
e 
68 (97%) 
(90-100) 
70(100°/o) 
(95 -100) 
(-3%) 
(-10-2) 
N=70 
N=70 
u 
Q. 
:, eco   Overall Seroresponse 
e 
66 (93%) 
65 (93%) 
(0%) 
(84-98) 
(84-98) 
(-9-10) 
N=71 
N=70 
Q. 
:, 
ee  Overall Seroresponse 
63 (91%) 
(82-97) 
64 (93%) 
(84-98) 
(-! %) 
(-11-8) 
N=69 
N=69 
> 
Q. 
:, 
.
ec.
o   Overall Seroresponse 
e "' 
63 (90%) 
(80-96) 
65 (93%) 
(84-98) 
(-3%) 
(-13-7) 
N=70 
N=70 
Source: Table 14.2.1.7 of Clinical Study Report for V59Pl 3El; 'Data represented as (difference in %)(95% 
CI of difference). 
 
 
8.2.2 Success C1iteria for Secondary Objective(s) 
 
8.2.2.1 
Success C1ite1ia for Secondar y Safety Objective(s) 
 
There are no success criteria associated with the secondary safety objectives. 
 
8.2.2.2 
S uccess C1ite1ia for Secondar y Efficacy Objective(s) 
There are no secondary efficacy objectives in this study. 
 
 
 
 
 
 
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8.2.2.3 
Success C1ite1ia for Secondary Immunogenicity Objective(s) 
 
There are no success criteria associated withthe secondary immunogenicity objectives in 
this study. 
 
8.3 
Analysis Sets 
8.3.l 
AllEnrolled Set 
 
All screened subjects who provide informed consent and provide demographic and/or 
baseline screening assessments, regardless of the subject's randomization and treatment 
status in the study, and received a Subject ID . 
8.3.2 
All Exposed Set 
 
All subjects in the enrolied set who receive a study vaccination. 
 
8.3.3 
Safety Set 
 
Solicited Safety Set (solicited local and systemic adverse events and other solicited 
adverse events) 
 
All subjects in the Exposed Set with any solicited adverse event data. 
Unsolicited Safety Set (unsolicited adverse events) 
All subjects in the Exposed Set with unsolicited adverse event data. 
Overall Safety Set 
All subjects who are in the Solicited Safety Set and/or Unsolicited SafetySet. 
 
Subjects will be analyzed as "treated" (i.e., according to the vaccine a subject received, 
rather than the vaccine to which the subject may have been randomized). 
 
8.3.4 
Full AnalysisSet (FAS)Efficacy/l mmunogenicity Set 
Full Analysis Set Immunogenicity 
FAS <Day 1) 
All subjects in the All Enrolled Set who: 
• 
are randomized; 
 
 
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• 
provide evaluable serum samples at Day 1 whose result is available for at least one 
serogroup. 
FAS (Day4) 
All subjects in the All Enrolled Set who: 
• 
are randomized; 
• 
receive the study vaccination; 
• 
provide evaluable serum samples at Day 1 whose result is available for at least one 
serogroup (except for hSBA titer 8, GMTs and between-group GMRs calculated at 
specific timepoints); and 
• 
provide evaluable serum samples at Day 4 whose result is available for at least one 
serogroup. 
FAS(Day6) 
 
All subjects in the All Enrolled Set who: 
• 
are randomized; 
• 
receive the study vaccination; 
• 
provide evaluable serum samples at Day 1 whose result is available for at least one 
serogroup (except for hSBA titer 8, GMTs and between-group GMRs calculated at 
specific timepoints); 
• 
provide evaluable serum samples at Day 6 whose result is available for at least one 
serogroup. 
FAS (Day29) 
All subjects in the All Enrolled Set who: 
• 
are randomized; 
• 
receive the study vaccination; 
• 
provide evaluable serum samples at Day 1 whose result is available for at least one 
serogroup (except for hSBA titer 8, GMTs and between-group GMRs calculated at 
specific timepoints); 
• 
provide evaluable serum samples at Day 29 whose result is available for at least one 
serogroup. 
In case of vaccination error, subjects in the FAS sets will be analyzed " as randomized" 
(i.e., according to the vaccine a subject was designated to receive, which may be different 
fromthe vaccine the subject actually received). 
 
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8.3.S 
Per Protocol (PP) Set Efficacy/l mmunogenicity Set 
 
A PPS will be defined for each FAS described in the previous Section with additional 
criteria specified below:_All subjects in the FAS Immunogenicitywho: 
• 
Correctly receive the study vaccine (i.e., receive the vaccine to which the subjects is 
randomized and at the scheduled time points). 
• 
Have no protocol deviations leadingto exclusion (see section 8.3.8, Protocol 
Deviations) as defined prior to unblinding / analysis. 
• 
Are not excluded due to other reasons defmed prior to unblinding or analysis (see 
section 8.3.8, Protocol Deviations) 
 
Examples for subjects excluded due to other reasons than protocol deviations are: 
Subjects who withdrew informed consent. 
8.3.6 
Other Analysis Sets 
 
There are no other analysis sets used in this study. 
 
8.3.7 
Subgroups 
 
Using the FAS (Day 29), the analyses of the primary objectives will be replicatedby: age 
group; center; gender; and race. 
8.3.8 
Protocol Deviations 
 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. A protocol deviation may be a reason to remove data from 
an analysis set at the time of analysis. CSR-reportable protocol deviations will be defined 
as exclusionary fromthe analysis according to protocol objectives and endpoints, which 
will be specified in the statistical analysis plan. In some cases exclusion of data may be 
due to a reason other than a protocol deviation, e.g. earlytermination. 
 
8.4 
Statistical Analysis Plan 
 
8.4.l 
An alysis of Demogr aphic an d Baseline C hara cteristics 
 
Descriptive statistics (mean, standard deviation, median, minimum and maximum) for 
age, height and weight at enrolment will be calculated overall and by study group. 
 
Distributions of subjects by sex and ethnic origin will be summarized overall and by 
study group. 
 
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8.4.2 
Analysis of Primary Objective(s) 
 
8.4.2.1 
Analysis of Primary Safety Objective(s) 
There are no primary safety objectivesin this study. 
8.4.2.2 
Analysis of Primar y Efficacy Objective(s) 
There are no primary efficacy objectives in this study. 
8.4.2.3 
Analysis of Pr imar y Immun ogenicity Objective(s) 
 
8.4.2.3.1 
Sta tistical Hypotheses 
Null  hypothesis: 
P, :::; 0 ,8 0 
Al ternative hypothesis: 
P, > 0 .80 
 
Where: P, is the population seroresponse rate for the pooled Menveo-Menveo and 
Menactra-Menveo group; i =,1 2, 3 4 refer to serogroup A, C, Wand Y respectively. The 
level of significance is fixed at one-sided 0.025. 
 
8.4.2.3.2 
Analysis Sets 
 
The analysis population to be used for the primary objectives is the FAS (Month l) Set. 
Analyses of primary objectives willberepeated on the PPS (Month 1) to assess 
robustness of results. 
 
8.4.2.3.3 
Statistical Methods 
 
General 
 
Missing immunogenicityvalues are assumed MCAR (Missing Completely At Random) 
and therefore may not contain information that impact the result of the analysis (i.e., not 
informative). Imputation methods willtherefore not be used. 
 
Overall significance level for all hypothesis tests is one-sided a = 2.5%. 
 
 
 
 
 
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Seroresponse (Day 29) 
Seroresponse is defined as: a) post-vaccination hSBA titer 8 forsubjects with a pre­ 
vaccination hSBA titer <4; b) forsubjects with a pre-vaccinationhSBA titer 4, an 
increase of at least four times the pre-vaccination hSBA. 
For each ACWY serogroup, the percentage of subjects withseroresponse willbe 
computed, along with associated two-sided 95%Clopper-Pearson Cls. 
Further details of the statistical methods will be provided in the SAP. 
8.4.3 
Analysis of Seconda ry Objective(s) 
8.4.3.1 
Analysis of Seconda ry Safety Ob jective(s) 
8.4.3.1.1 
Analysis of Extent of Exposure 
Subjects will be analyzed to the extent that they were exposed to study vaccines and 
according to the available safety data for the subject during any study period. Subjects 
who withdraw early or who are lost to follow-upwill be removed from the summary table 
denominator for the time period in which they have no available safety data collected. 
8.4.3.1.2 
Analysis of Solicited Local, Systemic an d Oth er Adverse Events 
 
All solicited adverse events will be summarized according to defined severity grading 
scales. 
Frequencies and percentages of subjects experiencing each adverse event willbe 
presented for each symptom severity. Summary tables showing the occUITence of any 
localor systemic adverse event overall and at each time point will also be presented. 
Post-vaccinationsolicited adverse events reported from Day 1 to Day 7 willbe 
summarized for the intervals Day 1 (6 hours) - Day 3, Days 4-7, Day 1 (6 hours) - Day 7 
by maximal severity and by study group. Separate analyses will be performed for 
solicited AEs reported 30 minutes after vaccination. Theseverity of solicited local 
adverse events, including injection-site erythema and induration, will be categorized 
based on linear measurement: None (0-24 mm), Mild (25-50 mm), Moderate (51-100 
mm), Severe (> 100mm). 
Injection site pain and systemic reactions, including fatigue, headache, myalgia, 
arthralgia, chills, nausea, lossof appetite, occurring up to 7 days after each vaccination 
will be summarized according to "mild", "moderate" or "severe". 

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Each solicited local and systemic adverse event will also be further summarized as "none" 
versus ''anY'. 
Use of antipyretics and analgesics will be summarized by frequency, by type of use 
(prophylactic versus treatment) and percentage of subjects reporting use. 
Body teJl1)erature will be summarized separately according to the 3 schemes described 
below and will be broken down according to route of measurement: 
• 
by O.S °C increments from 36.0°Cup to ,::40°C; 
• 
by 1°C increments: <36.0, 36.0-36.9, 37.0-37.9, 38.0-38.9, 39.0-39.9, ,::40°C; 
• 
According to different cut-offs (< versus ::::): 38 . 0 , 38 .S , 39 . 0 , 39 . S , 40 .0 ° C . 
 
8 .4 .3 .1. 3 
An al ys i s o f U n so li cited Advene Events 
 
1bis analysis applies to all adverse events occurring during the study, judged either as 
probably related, possibly related, or not related to vaccination by the investigator, 
recorded in AE CRF, with a start date on or after the dateof first vaccination. AE starting 
prior to the first vaccination willonly be listed. The original verbatim terms used by 
investigators to identify adverse events in the CRFs will be mapped to preferred terms 
using the MedDRA dictionary. The adverse events will then be grouped by MedDRA 
preferred terms into frequency tables according to system organ class (SOC). 
 
All reported adverse events, as well as adverse events judged by the investigator as at 
least possibly related to study vaccine, will be summarized according to SOC and 
preferred term within SOC. These summaries will be presented by study group and by 
interval of study observation. When an adverse event occurs more than once for a subject, 
the maximal severity and strongest relationship to the vaccine will be counted. 
 
Separate summaries will be produced for the following categories: 
• 
Adverse events that are possibly or probably related to vaccine 
• 
Unsolicited AEs reported within 30 minutes after vaccination 
• 
Unsolicited AEs reported within 30 days after vaccination 
• 
Adverse events leading to withdrawal 
• 
Adverse events leading to a medically attended visit 
• 
Serious adverse events 
Data listings of all adverse events will be provided by subject. In addition, adverse events 
in the categories above will be provided as listed data. 

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8.4.3.1.4 StatisticalHypotheses 
 
There are no statistical hypotheses associated with the secondary safety objectives. 
 
8.4.3.1.S Analysis Sets 
 
Analyses of solicited adverse events - and other solicited reactions - and unsolicited 
adverse events will be performed on the relevant safety sets. 
 
8.4.3.1.6 StatisticalMethods 
 
For unsolicited adverse events, the entirestudy period will be divided into the following 
intervals: onset within30 minutes after vaccination , onset within 28 days after 
vaccination; and from Day 1 through Day 181. For solicited adverse events, the solicited 
study period will be divided into intervals: from 6 hours through day 3; from day 4 
through day 7; and from 6 hours through day 7. 
 
No imputation methods will be used to address missing safety data. 
 
Snmmarif>s of safety will be presented using frequencies and percentages within each 
study group. No statistical comparisons among the studygroups with respect to any of the 
safety parameters will be performed. 
 
8.4.3.2 
Analysis of Secondary Efficacy Objective(s) 
 
There are no secondary efficacy objectives associated with this study. 
 
8.4.3.3 
Analysis of Seconda ry Immunogenicity Objective(s) 
 
8.4.3.3.1 
Sta tistical Hypotheses 
 
Analyses related to the secondary immunogenicityobjectives will be descriptive; no 
formal statistical tests will be performed. 
8.4.3.3.2 
Analysis Sets 
 
Analyses of secondary imm1mogenicity will be based on the FAS and repeated on the 
PPS. 
 
 
 
 
 
 
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8.4.3.3.3 
Statistical Methods 
 
General 
The hSBA titers at each visit will be logarithmicallytransformed (baselO) to obtain 
approximately nonnally distributed data. 
 
For comparison of percentages and GMT ratios, unadjusted estimates will be obtained 
along with adjusted estimates from regression models to account for potential baseline 
imbalance between study groups. 
For eachN. meningitidis serogroup A, C, Wand Y, unadjusted GMTs will be calculated, 
withtheir associated two-sided 95% Cls, by exponentiating the corresponding log­ 
transformed means and their 95% Cls. Adjusted GMR.s will be obtained from Analysis of 
Covariance (ANCOVA) models. 
 
See section 8.4.2.3.3 for other relevant details. 
 
Seroresponse (Day 29) 
 
The percentage of subjects with seroresponse and associated two-sided 95% Clopper­ 
Pearson Cls will be computed by group (Menveo-Menveo, Menactra-Menveo, and Naive) 
and N. meningitidis serogroups A, C, W and Y test strains. Differences in percentages and 
associated 95% Cls between study groups will be calculated using the Miettinen & 
Nurminen score method. 
 
In a descriptive fushion - using the difference in percentages and 95% Cls - each of the 
previously vaccinated groups will be compared to the nai:ve group . Also the two 
previously vaccinated study groups will be compared to each other. 
 
As sensitivity analyses, the difference in percentages will also be obtained from a log­ 
linear model adjusting for center, pre-vaccinationtiter and age-group. Please see SAP for 
technical details. 
 
 
 
 
 
 
 
 
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Percentage of Subjects \Vith hSBA titere::8 (Da y I, Da y 4, Da y 6, and Da y 29 ) 
For each study group and in the pooled group, the percentage of subjects with hSBA titer 
8 andassociatedtwo-sided 95% Clopper-Pearson Cls will be computed by the N. 
meningitidis serogroups A, C, W and Y teststrains on Day 1, Day 4, Day 6 and Day 29 
(as applicable, depending on blood draw schedule). 
Differences in percentages and associated 95% Cls between study groups will be 
calculated using the Miettinen & Nurminen score method. 
 
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In a descriptive fashion - using the difference in percentages and 95% Cls - the previously 
vaccinated groups (individually and pooled) will be compared to the naive group. Also 
the two previously vaccinated groups will be compared to each other. 
 
As sensitivity analyses, the difference in percentages will also be obtained from a log­ 
linear model adjusting for center, pre-vaccinationtiter and age-group. Please see SAP for 
technical details. 
 
Between-group Ratios of Gl\ lll T s (A d jus ted and U nad ju sted) 
 
The between -group ratio ofhSBA GMTs and corresponding 95% CI, at each of Visit Day 
1 (Persistence), Day 4, Day 6 and Day 29 against each N. meningiti.dis serogroups A, C, 
W and Y test strains will be obtained by exponentiatingthe mean between-group 
differences in log-transformed titers and the corresponding 95% Cls at each of the 
timepoints specified. 
Additionally, adjusted ratio of GMTs will be obtained fromANCOVA models including 
center, pre-vaccination titer and age-group as factors in the model. 
 
The previously vaccinated groups (individually and pooled) will be compared to the naive 
group at each timepoint - descriptively - using the ratios of GMTs. 
The two previously vaccinated groups will be compared at each timepoint using GMT 
ratios. 
\Vithin-gro up Ratios of Gl\ lll T s (Ad jus ted an d U na d ju sted) 
 
Within each study group and for each antigen/serotype, ratios of GMT will be calculated, 
as applicable, at: 
• 
Visit Day 4 versus at Visit Day 1; 
• 
Visit Day 6 versus at Visit Day 1; and 
• 
Visit Day 29 versus at Visit Day 1. 
 
The unadjusted GMRs and 95% Cis will be constructed by exponentiating the mean 
within-groupdifferences in log-transformed titers and the corresponding 95% Cls. 
Adjusted GMRs will be obtained from Analysis of Covariance (ANCOVA) models 
including center and age-group as factors in the model. 
 
 
Further details of the statistical methods will be provided in the Statistical Analysis Plan 
(SAP). 
 
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8.4.4 
Analysis of Explora tor y Objectives 
 
8.4.4.1 Analysis of Explora tor y Safety Objective(s) 
There are no exploratory safety objectivesin this study. 
8.4.4.2 
Analysis of Explora tor y Efficacy Objective(s) 
There are no exploratory efficacy objectives in this study. 
8.4.4.3 
Analysis of Explora tor y Immunogeoicity Objective(s) 
There are no exploratory immunogenicityobjectives in this study. 
8.5 
Sam ple Size an d Power Considera tions of Pti mar y Objectives 
Statistical power was estimated based on observed data from study V59Pl3El , where 
seroresponse rates at one-monthpost booster dose of MenACWY-CRM ranged from 
97% (90%-100%) to 100% (95%-100%)for serogroup A, 93% (85%-98%) for serotype 
C; 91% (82%-97%) to 93% (84%-98%) for serogroup W; and 90% (80%-96%) to 93% 
(84%-98%) for serogroup Y among subjects printed with MenACWY-CRM or Menactra 
in the three years preceding the study. 
Assuming the true seroresponse rates in the pooled group range from 90% to 97% 
(alternative hypothesis) for each serotype, a sample size of n=540will have at least 96% 
power to show sufficiency of immune response to a booster dose of MenACWY-CRM in 
the pooled group, compared with a pre-specified reference seroresponse of 80% (null 
hypothesis) using an exact test with 0.025 one-sided significance level. When taking a 
10% dropout rate into account, N=600 previously vaccinated subjects have to be enrolled 
in the study. Calculations have been done with nQuery Advisor (Version 7.0). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 8.5-1: 
Statistical Power to Test for Sufficiency of Immune Response 
Given a Range of True Sero response Rates for Evaluable Sample 
Size of 540 subjects 
 
Ser ot}11e 
T111e Seroresponse Rate 
Power 
A 
0.97 
0.99 
C 
0.93 
0.99 
w 
0.91 
0.99 
y 
0.90 
0.99 
Total Power 
0.96 
 
8.6 
Interim Analysis 
No interim analysis of data from this studyis planned. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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9. 
SOURCE DOCUMENTATION, STUDY MONITORING AND AUDITING 
In order to ensure consistency across sites, study monitoring and auditing will be 
standardized and performed in accordance with the Sponsor's or delegated contract 
research organization' s (CRO) standard operating procedures and applicable regulatory 
requirements (e.g., FDA, EMA, and ICH guidelines). 
Prior to enrolment of the first study subject, GSK or delegate willtrain investigators 
and/or their study staff on the study protoco allapplicable studyprocedures, 
documentation practices and all electronic systems. CRFs supplied by the Sponsor must 
be completed for each randomized subject (see section 8.3.1, All Enrolled Set for 
definition of enrolled subject). Documentation of screened but not enrolled subjects must 
be maintained at the site and made available for review by the site monitor. Data and 
documents willbechecked by the Sponsor and/or monitor. 
9.1 
Source Documentation 
 
Prior to the start of the study, the site staff participating in the study conduct will be 
instructed on what documents willberequired for review as source documents. The kinds 
of documents that willserve as source documents willbe agreed between Sponsor or 
delegate and investigator and designees and specified in the SDA prior to subject 
enrolment. 
 
In addition, source documentation must include all of the following: subject identification 
(on each page), eligibility and participation, proper informed consent procedures, dates of 
visits, adherence to protocol procedures, adequate reporting and follow-up of adverse 
events,: documentation of prior/concomitant medication/vaccines, study vaccine 
receipt/dispensing/return records, study vaccine administration information, any data 
collected by a telephone conversation with the subject and/or parent(s)/legal guardian(s) 
and date of completion and reason. 
 
 
 
 
 
 
 
 
 
 
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The subject and/or parent(s)/legal guardian(s) must also allow access to the subject's 
medical records. Each subject and/or the parent(s)/legal guardian(s) must be informed of 
this prior to the start of the study and consent for access to medical records may be 
required in accordance with local regulations. 
All safetydata reported by subjects must be written down in source documents prior to 
entry of the data into CRFs. If there are multiple sources of information (e.g., Subject 
Diary, verbal report of the subject, telephone contact details, medical chart) supporting 
the diagnosis of an adverse event, thesesources must be identified in the source 
documents, discrepancies between sources clarified, the ultimate diagnosis must be 
justified and written in the source documents, and this diagnosis must be captured in the 
 
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Adverse Event CRF (AE CRF). The AE CRF must also capture which source(s) of 
infonnation were used to detennine the adverse event (e.g., subject recall, medical chart, 
Subject Diary). 
9.2 
Study Monit01ing, Auditin g a nd So urce Data Verification 
Prior to enrolment of the first study subject, GSK or its designee (e.g., a CRO) will 
develop a Clinical Monitoring Plan to specify how centralized and/or on-site monitoring, 
including clinical specimens reconciliation, will be perfonned for the study. Study 
progress will be monitored byGSK or its designee as frequently as necessary to ensure: 
• 
that the rights and well-beingof human subjects are protected, 
• the reported study data are accurate, complete, and verifiable from the source 
documents and 
• 
the conduct of the studyis in compliance with the cUITent approved 
protocol/amednment(s), GCP and applicable regulatory requirements. 
Contact details for the GSK teamor its designee involved in study monitoring will be 
provided to the investigator. Study data recorded on CRFs will be verified by checking 
the CRFentries against source documents in order to ensure data completeness and 
accuracy as required by study protocol. . 
Data verification may also be performed through a centralized review of data (e.g., 
checking for outliers or other anomalies). Additional documents such as the investigator 
site file, phannacy records, and infonned consent documentation must also be available 
for review if requested. Arrangements for monitoring visits will bemade in advance in 
accordance with the monitoring plan, except in case of emergency. 
The investigator and/or site staff must make source documents of subjects enrolled in this 
study available for inspection by GSK or its representative at the time of each monitoring 
visit and Sponsor audits, when applicable. These documents must also be available for 
inspection, verification and copying, as required by regulation,sbyofficials of the 
regulatory health authorities (e.g., FDA, EMA and others) and/or ECs/IRBs. The 
investigator and study site staffmust comply with applicable privacy, data protection and 
medical confidentialitylaws for use and disclosure of infonnation related to the study and 
enrolled subjects. 
 
 
 
 
 
 
 
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10. 
DATA MANAGEME1''T 
 
10.1 
Data Entry and Management 
 
In this study, all clinical data (including, but not limited to, AF/SAEs, concomitant 
medications, medical history, and physical assessments), safety data, and immllllogenicity 
data will be entered onto case report forms (CRFs) in a timely fashion by the investigator 
and/or the investigator 's dedicated site staff. Data entered onto CRFs are stored on a 
secure website. The data collected on this secure website are assimilated into an 
electronic data capture (EDC) system, which is compliant with Title 21 Part 11 policies of 
the Code of Federal Regulations (FDA 1997). The data system includes password 
protection and internal quality checks. The EDC system will be designed and validated by 
the Sponsor prior to activation for data entry by sites. The investigator or designated 
delegate nrust review data entered and electronicallysign the CRFs to verifytheir 
accuracy. 
 
Access to the EDC system for data entryor review will require training and distinct 
individual access code assignments to those site staff members who willbe entering study 
data and those involved in study oversight who may review study data. Data are collected 
within the EDC system, to which the Sponsor and site monitors have exclusively "read 
only" access. 
 
10.2 
Data Cla1ifi cation 
 
As part of the conduct of the trial, the Sponsor may havequestions about the data entered 
by the site, referred to as queries. The monitors and the Sponsor are the only parties that 
can generate a query. All corrections and clarifications will be entered into the EDC 
system and will be identified by the person entering the information, the reason for the 
change, as well as the time of the changes made. If changes are made to a previously and 
electronically signed CRF, the investigator must confirm and endorse the changes. 
 
10.3 
Data Protection 
 
GSK respects the subjects' rights to privacy and willensure the confidentiality of their 
medical information in accordance with all applicablelaws and regulations. 
 
 
 
 
 
 
 
 
 
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11. 
RECORD RETENTION 
 
Investigators must retain all study records required by GSK and by the applicable 
regulations in a secure and safe facility. The investigator must consult a GSK 
representativebefore disposal of any studyrecords, andmust notify the Sponsor of any 
change in the location, disposition, or custody of the study files. Essential documents 
must be retained for 1S years. "Essential documents" are defined as documents that 
individually and collectively pennit evaluation of the conduct of a study and the quality 
of the data produced. These documents should be retained for a longer period, however, if 
required by the applicable national regulatory or institutional requirements. 
 
These principles of record retention will also be applied to the storage of immtmogenicity 
samples, provided that the integrity of the stored sample pennits testing. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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12. 
USE OF Jll,'FORMATION AND PUBLICATION 
 
GSK assures that the key design elements of this protocol willbe posted in a publicly 
accessible database such as clinicaltrials.gov, and in compliance with ct11Tent regulations. 
 
GSK also assures that key results of this clinical study will be posted in a publicly 
accessible database within the required time-frame from theend of study as defined in 
section 3.9, End of Study. 
In accordance withstandard editorial, ethical practices and ct11Tent guidelines of Good 
Publication Practice (Graf 2009), GSK will generally support publication ofmulticenter 
studies only in their entirety and not as individual center data. In this case, a coordinating 
investigator will be designated by mutual agreement prior to the start of the study. The 
coordinating investigator will also sign the clinical study report on behalf of the principal 
investigators (CPMP/EWP/2747/00). Authorship willbe determined by mutual agreement 
and in line with International Committee of Medical Journal Editors authorship 
requirements. Any fonnal publication of the studyin which contribution of GSK 
personnel exceeded that of conventional monitoring will be considered as a joint 
publication by the investigator and the appropriate GSK personnel. 
 
Novartis must be notified of any intent to publish data collected from the study and prior 
approval from GSK must be obtained prior to submission for publication. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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13. 
ETIDCAL CONSIDERATIONS 
 
13.1 
Regulatory and Ethical Compliance 
The study will beconducted in compliance with the protocol, GCP and applicable 
regulatory requirement(s). 
This clinical study was designed and shall be implemented and reported in accordance 
withthe ICH HarmonizedTripartite Guidelines for GoodClinical Practice, with 
applicable local regulations including European Directive 2001/20/EC, US Code of 
Federal Regulations Title 21, and Japanese Ministry ofHealth, Labor, and Welfare, GSK 
codes on protection of human rights, and with the ethical principles laid down in the 
Declaration of Helsinki(EuropeanCouncil 2001, US Code of Federal Regulations, ICH 
1997). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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13.2 
Informed Consent Procedures 
 
Eligiblesubjects may only be included in the study after providing written informed 
consent or assent, as described in section 5.1.1, Informed Consent/Assent. Before the start 
of the study, the investigatorwill have the informed consent and any other materials that 
will be provided to the subjects reviewed and approved bythe IRB/EC. This review and 
approval will be documented and stored with other studydocuments. The investigator or 
designee must fully inform thesubject or legalguardian of all pertinent aspects of the 
study. A copy of the written informed consent will be given to the subject or the designee. 
The subject/designee must be allowed ample time to ask about thedetails of the study and 
to make a decision as to whether or not to participate in the study. The subjectand/or 
legal guardian(s) mu st sign the consent form indicating their agreement to participate in 
the studybefore anystudy-related procedures are conducted. The informed consent 
process may be conducted up to 5 days prior to vaccination on Day I. If the subject 
and/or legal guardian(s) is unable to read and write, a witness must be present during the 
informed consent discussion and at the time of informed consent signature. 
Prior to the start of the study, GSK will provide to investigators a proposed informed 
consent form that complies with the ICH GCP guideline and regulatory requirements and 
is considered appropriate for this study. Any changes to the proposed consent form 
suggested by the investigator must be agreed to byGSK before submission to the IRB/EC 
and a copy of the approved version must be provided to the GSK monitor after IRB/EC 
approval 
Women of childbearing potential should be informed that taking the study medication 
may involve unknown risks to the fetus if pregnancy were to occur during the study and 
agree that in order to participate in the study they must adhere to the contraception 
 
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requirements indicated in the protocol for the duration of the study. If case of doubts on 
the ability of a subject to adhere to these requirements, that subject should not be allowed 
in the study 
 
Before the start of the study, the investigator will have the informed assent, the informed 
consent, and any other materials that will be provided to the subject and/or parent(s)/legal 
guardian(s) reviewed and approved by the IRB/EC. This review and approval will be 
documented and stored with other study documents. The investigator or designee must 
fully inform the subject and/or parent(s)/legal guardian(s) of all pertinent aspects of the 
study. A copy of the written informed consent and informed assent will be given to the 
subject and/or parent(s)/legal guardian(s). 
In addition, the investigator or designee should explain pertinent aspects of the study in an 
age appropriate manner to pediatric subjects who are eligible for informed assent in 
accordance with local policies. The subject and parent(s)/legal guardian(s) must be 
allowed ample time to ask about the details of the study and to make a decision as to 
whether or not to participate in the study. The subject and parent(s)/legal guardian(s) must 
sign the consent/assentforms indicating their agreement to participate in the study before 
any study-related procedures are conducted. If the subject and/or parent(s)/legal 
guardian(s) are unable to read and write, a witness must be present during the informed 
consent/assentdiscussion and at the time of informed consent/assentsignature. 
13.3 
Responsibilities of the Investiga tor a nd IRB/EC 
 
The protocol and the proposed informed consent form must be reviewed and approved by 
a properly constituted IRB/EC before study start. Properly constituted IRB/EC is defined 
in ICH Guideline for Good Clinical Practice E6 (RI), Section 3 (ICH 1997). A signed and 
dated statement that the protocol and informed consent have been approved by the 
IRB/EC must be given to GSK before study initiation. Prior to study start and at any time 
the protocol is amended during studyconduct, the investigator is required to sign a 
protocol signature page confirming his/her agreement to conduct the study in accordance 
with these documents and all of the instructions and procedures found in this protocol and 
to give access to all relevant data and records to GSK monitors, auditors, GSK Clinical 
Quality Assurance representatives, designated agents of Novartis, IRBs/ECs, and 
regulatory authorities as required. If an inspection of the clinical site is requested by a 
regulatory authority, the investigator must inform GSK immediately that this request has 
been made. 
 
The investigator also responsible for the following: 
• 
Maintaining a list of appropriately qualified persons to whom the investigator has 
delegated significant study-related duties. 

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• Demonstrating the capability of recruiting the required number of suitable subjects 
within the recruitment period. 
• Demonstrating sufficient time and staffing to properly conduct and complete the study 
within the agreed study period. 
• Ensuring that all persons assisting with the study are adequately informed about the 
protoco the investigationalproduct(s,)and their study-related duties and functions 
• Ensuring that appropriately trained health care professionals are responsible for all 
study-related medical decisions and for ensuring appropriate medical care of subjects 
experiencing any adverse event related to the study. 
• 
If permission to do so is given by the subject and/or parent(s)/legal guardian(s), 
ensuring that the subject's primary healthcare provider is informed of the subject's 
participation in the study. 
The investigator should not implement any deviation from, or changes of the protocol 
without agreement by the Sponsor and prior review and documented approval/favourable 
opinion from theIRB/IEC of an amendment, except where necessary to eliminate an 
immediate hazard(s) to study subjects, or when thechange(s) involves only logistical or 
administrative aspects of the study (e.g., change in monitor(s), change of telephone 
nwnber(s)). In addition, the investigato,ror person designated by the investigato,rshould 
document and explain any deviation from the approved protocol. 
 
The investigator may implement a deviation from, or a change of, the protocol to 
eliminate an immediate hazard(s) to study subjects without prior IRB/IEC 
approval/favourable opinion. As soon as possible, the implemented deviation or change, 
the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be 
submitted: 
(a) to theIRB/IEC for review and approval/favourable opinion, 
(b) to the Sponsor for agreement and, if required, 
(c) to the regulatory authority(ies). 
13.4 
Protocol Amendments 
An amendment is a written description of change(s) to or formal clarification of a study 
protocolwhich may impact on the conduct of the clinical study, potential benefit of the 
clinical study, or may affect subject safety, including changes of study objectives, study 
design, subject population, samplesizes, studyprocedures, or significant administrative 
aspects. An administrative change of a study protocol is a minor correction or 
clarification that has no significant impact on the waythe clinical study is to be conducted 

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and no effect on subject safety (e.g., change of telephone number(s), logistical changes.) 
Protocol amendments nrust be approved by GSK, health authorities where required, and 
the IRB/EC. In cases when the amendment is required in order to protect the subject 
safety, the amendment can be implemented prior to IRB/EC approval. Notwithstanding, 
the need for formal approval of a protocol amendmen,tthe investigator is expected to take 
any inunediate action required for the safety of anysubject included in this study, evenif 
this action represents a deviation from the protocol. In such cases, GSK should be notified 
of this action, the IRB/EC at the study site, and, if required bylocal regulations, the 
relevant health authority) should be informed within 10 working days. 

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14. 
REFERENCE LIST 
 
Code of Federal Regulations (1997): Food and Drug Administration, U.S. Depar1ment of 
Health and Human Services: Title 21, Part 11: Electronic Records Electronic Signatures. 
Federal Register 62: 13464 
European Parliament (1995): Directive 95/46/EC of the European Parliament and of the 
Council of 4 April 2001. Official Journal of the European Communities. L 281/31-39 
European Parliament (2001): Directive 2001/20/EC of the European Parliament and of 
the Council of 4 April 2001. Official Journal of the European Communities. L 121/34-44 
Graf C, Battisti WP, Bridges D (2009). Good publication practice for communicating 
company Sponsored medical research: the GPP2 guidelines. BMJ; 339: b4330 
ICH (1997) ICH Harmonised Tripartite ICH Guideline for Good Clinical Practices E6 
(RI). Federal Register, 62 (90): 25691-25709 
ICH (1998) ICH Harmonised Tripartite ICH Guideline for Statistical Principles for 
Clinical Trials E9. Federal Register, 63 (179): 49583 
Levine RJ. (1988) Ethics and Regulations of Clinical Research. New Haven: Yale 
University Press. 
U.S. Depar1ment of Health and Human Services, Food and Drug Administration, CBER 
(2009): Guidance for Industry Patient-Reported Outcome Measures: Use in Medical 
Product Development to Support Labeling Claims 
 
59th World Medical Association General Assembly (October 2008) Declaration of 
Helsinki - Ethical Principles for Medical Research Involving Human Subjects. Seoul, 
Korea 

 
---- 
.... 
Novartis 
 
 
 
PPo• -    - 
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Document A !J!roval Ce rtificate / 
PPD 
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Theindivi:luals listed have appl'()ved this document for ii!Jplementation using an electronic si 
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Atlas EDMS. JPPD 
 
 
 
U serName:pp-o• -   -   - 
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Ti tl e : C l u ster  Phys ician -Meningi 
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Date: Friday, 12 February 20 16 , 09:32 GMT 
Meaning: As an approver, I agree with the content and format of this document 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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8 

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CLINICALSTUDY PROTOCOL VS9 77 Version 3 
 
 
 
A Phase 3b, Controlled, Open-Label, Multi-Center Studyto Evaluate Safety and 
Inumnogenicity of a Single Dose of GlaxoSmiht Kline's Meningococcal ACWY 
Conjugate Vaccine (Menveo), Administered to Healthy Individuals 15 through 55 years 
of age, approximately 4-6 years after primary ACWY vaccination. 
 
 
Safety and Immunogenicity Study of a Single Dose of Menveo, Administered to Subjects 
15 through 55 years of age, approximately 4-6 years after primary ACWY vaccination 
 
 
 
 
Property of GlaxoSmithKline Vaccines (hereafter referred to as GSK) 
Confidential 
May not be used, divulged, published  or otherwise  disclosed  without  \VIi tt .e n 
co n se n t o f GS K 

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TABLE OF CONTENTS 
TABLE OF CONTENTS ..................................................................................................... 2 
PROTOCOL SYNOPSIS VS9 77 ................................................................................... 7 
LIST OF ABBREVIATIONS ............................................................................................. 20 
1. 
BACKGROUND AND RATIONALE ..................................................................... 21 
1.1 
Background .......................................................................................................... 21 
1.2 
Rationale .............................................................................................................. 22 
2. 
OBJECTIVES ........................................................................................................... 23 
2.1 
Primary Objective(s) ........................................................................................... 23 
2.2 
Secondary Objective(s) ........................................................................................ 23 
2.3 
Exploratory Objective(s) ...................................................................................... 24 
3. 
STUDYDESIGN................................................................................................. 2S 
3.1 OverviewofStudyDesign...............................................................................        2S 
3.2 StudyPeriod ..................................................................................................... 27 
3.3 
Blinding Procedures ............................................................................................. 27 
3.4 
Data Collection ............................................................................................................. 27 
3.4.1 Data Collected from Subjects .................................................................... 27 
3.4.2 Tools Used for Data Collection ........................................................................... 28 
3.S Collectionof Clinical Specimens ..................................................................... 29 
3.6 Stopping/Pausing Guidelines ........................................................................... 30 
3.7 
Data Monitoring Committee ............................................................................ 30 
3.8 
Premature Withdrawal from Study .................................................................. 30 
3.9 EndofStudy ............................................................................................... 32 
4. 
SELECTION OFSTUDY POPULATION ................................................................ 34 
4.1 
Inclusion Criteria .................................................................................................. 34 
4.2 
Exclusion Criteria ............................................................................................ 3S 
4.3 Criteria for Delay of Vaccination and/or Blood Sampling ................................ 36 
S. 
STUDYPROCEDURES ...................................................................................... 37 
S.1 
Pre-vaccination Clinic Visit(s) .................................................................................. 37 

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5.1.1 
Informed Consent/Assent ......................................................................... 37 
5.1.2 
Screening ....................................................................................................... 38 
5.1.3 
Enrolment ................................................................................................. 39 
5.1.4 
Randomization .............................................................................................. 40 
5.2 Vaccination Clinic Visit. ................................................................................. 41 
5.2.1 
Post-vaccinationProcedures ........................................................................... 41 
5.2.2 
Post-vaccination Reminders ......................................................................... 42 
5.3 Post-vaccination Visit(s) ........................................................................................ 42 
5.3.1 
Follow-up Clinic Visit(s) ........................................................................... 43 
5.3.2 
Safety Follow-up Calls ..................................................................................44 
5.4 
Unscheduled Visits .............................................................................................. 44 
5.5 Study Termination Visit. ........................................................................................ 44 
5.5.1 
Early Termination Visit. ........................................................................... 45 
6. 
TREATMENT OF SUBJECTS ................................................................................ 46 
6.1 
StudyVaccine(s) ..................................................................................................... 46 
6.2 
Non-Study Vaccines ......................................................................................... 47 
6.3 
Vaccine Preparationand Administration .......................................................... 47 
6.4 
Vaccine Administration Error or Overdose ofVaccine .................................... 48 
6.5 
Prior and Concomitant Medications and Vaccines .......................................... 49 
6.6 
Vaccine Supply, Labeling, Storage and Tracking ................................................. 50 
7. 
ASSESSMENTS .................................................................................................. 52 
7.1 
SafetyAssessment ............................................................................................ 52 
7.1.1 
Solicited Adverse Events .......................................................................... 52 
7.1.2 
Unsolicited Adverse Events ........................................................................ 54 
7.1.3 
Evaluation of Adverse Events ........................................................................ 54 
7.1.4 
Serious Adverse Events ............................................................................. 56 
7.1.4.1 
Adverse Events of Special Interest ..................................................... 57 
7.1.5 
Methods for Recording Adverse Events and Serious Adverse Events ....... 58 
7.1.5.1 
Post-Study Events .............................................................................. 58 

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7.1.6 Pregnancies...............................................................................................    S9 
7.1.7 Safety  LaboratoryMeasurements  .............................................................. S9 
7.2 Efficacy Assessment........................................................................................ S9 
7.3 Immunogenicity  Assessment............................................................................  S9 
8. 
STATISTICAL CONSIDERATIONS .................................................................. 61 
8.1 
Endpoints ......................................................................................................... 61 
8.1.1 
Primary Endpoint(s) ........................................................................................... 61 
8.1.1.1 
Primary SafetyEndpoint(s) ................................................................ 61 
8.1.1.2 
Primary EfficacyEndpoint(s) ............................................................. 61 
8.1.1.3 
Primary Immunogenicity Endpoint(s) ................................................... 61 
8.1.2 
Secondary Endpoint(s) .................................................................................. 61 
8.1.2.1 
Secondary Safety Endpoint(s) .................................................................. 61 
8.1.2.2 
Secondary Efficacy Endpoint(s) .............................................................. 62 
8.1.2.3 
Secondary Immunogenicity Endpoint(s) .................................................. 62 
8.1.3 
ExploratoryEndpoint(s) ............................................................................ 62 
8.1.3.1 
Exploratory Safety Endpoint(s) .......................................................... 62 
8.1.3.2 
Exploratory Efficacy Endpoint(s) .................................................................. 62 
8.1.3.3 
Exploratory Immunogenicity Endpoint(s) .......................................... 62 
8.2 
Success Criteria ................................................................................................ 63 
8.2.1 
Success Criteria for Primary Objective(s) .................................................. 63 
8.2.1.1 
Success Criteria for Primary Safety Objective(s) .................................... 63 
8.2.1.2 
Success Criteria for Primary Efficacy Objective(s) ................................ 63 
8.2.1.3 
Success Criteria for Primary Immunogenicity Objective(s) ................. 63 
8.2.1.3.l Rationalefor Combining the Menveo-Menveoand Menactra-Menveo 
groups ....................................................................................... 63 
8.2.2 
Success Criteria for Secondary Objective(s) ................................................... 64 
8.2.2.1 
Success Criteria for Secondary Safety Objective(s) ............................... 64 
8.2.2.2 
Success Criteria for Secondary Efficacy Objective(s) ......................... 64 
8.2.2.3 
Success Criteria for Secondary Immunogenicity Objective(s)............. 6S 

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8.3 
Analysis Sets .................................................................................................... 65 
8.3.1 
All Enrolled Set ......................................................................................... 65 
8.3.2 
All Exposed Set ......................................................................................... 65 
8.3.3 
Safety Set. ................................................................................................. 65 
8.3.4 
Full Analysis Set (FAS) Efficacy/Immunogenicity Set. .............................. 65 
8.3.5 
Per Protocol (PP) Set Efficacy/Immunogenicity Set ................................... 67 
8.3.6 
Other Analysis Sets ................................................................................... 67 
8.3.7 
Subgroups ................................................................................................. 67 
8.3.8 
Protocol Deviations .................................................................................. 67 
8.4 
Statistical Analysis Plan ................................................................................... 67 
8.4.1 
Analysis of Demographic and Baseline Characteristics ............................ 67 
8.4.2 
Analysis of Primary Objective(s) ................................................................. 68 
8.4.2.1 
1   Analysis of Primary SafetyObjective(s) ................................... 68 
8.4.2.2 
Analysis of Primary Efficacy Objective(s) .......................................... 68 
8.4.2.3 
Analysis of Primary Immunogenicity Objective(s) ................................ 68 
8.4.2.3.1 
Statistical Hypotheses ..................................................................... 68 
8.4.2.3.2 
2 ................................................................................. Analysis Sets
 68 
8.4.2.3.3 
Statistical Methods ...................................................................... 68 
8.4.3 
Analysis of Secondary Objective(s) ......................................................... 69 
8.4.3.1 
Analysis of Secondary Safety Objective(s) ...................................... 69 
8.4.3.1.1 
Analysis of Extent of Exposure ................................................... 69 
8.4.3.1.2 
Analysis of Solicited Local, Systemic and Other Adverse Events 69 
8.4.3.1.3 
Analysis of Unsolicited Adverse Events ..................................... 70 
8.4.3.1.4 
Statistical Hypotheses ...................................................................... 71 
8.4.3.1.5 
5 ................................................................................. Analysis Sets
 71 
8.4.3.1.6 
Statistical Methods ...................................................................... 71 
8.4.3.2 
Analysis of Secondary Efficacy Objective(s) .................................. 71 
8.4.3.3 
Analysis of Secondary ImmunogenicityObjective(s) ......................... 71 

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8.4.3.3.1 
Statistical Hypotheses ...................................................................... 71 

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8.4.3.3.2 
Analysis Sets ................................................................................ 71 
8.4.3.3.3 
Statistical Methods ...................................................................... 72 
8.4.4 
Analysis of Exploratory Objectives ............................................................... 74 
8.4.4.1 Analysis of ExploratorySafety Objective(s) .................................................. 74 
8.4.4.2 
Analysis of ExploratoryEfficacy Objective(s) ...........................................74 
8.4.4.3 
Analysis of Exploratorylmmunogenicity Objective(s)  ........................74 
8.5 
Sample Size and Power Considerations of Primary Objectives .............................. 74 
8.6 
Interim Analysis............................................................................................................ 75 
9. 
SOURCE DOCUMENTATION, STUDY MONITORING AND AUDITING ... 76 
9.1 
Source Documentation ..................................................................................................76 
9.2 
Study Monitoring, Auditing and Source Data Verification  ..................................77 
10. 
DATA MANAGEMENT .......................................................................................... 78 
10.1 Data Entry and Management ....................................................................................... 78 
10.2 Data Clarification ...................................................................................................... 78 
10.3 Data Protection .............................................................................................................. 78 
11. 
RECORD RETENTION ...................................................................................... 79 
12. USE OF INFORMATION AND PUBLICATION ..................................................... 80 
13. 
ETHICAL CONSIDERATIONS ............................................................................. 81 
13.1 Regulatory and Ethical Compliance ..................................................................... 81 
13.2 Informed Consent Procedures .............................................................................. 81 
13.3 Responsibilities of the Investigatorand IRB/EC ................................................. 82 
13.4 Protocol Amendments ............................................................................................... 83 
14. 
REFERENCE LIST ................................................................................................... 85 

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PR OTO COL SYNOPSIS V59 77 
 
Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1ic name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
Title of Stud y: A Phase 3b, Controlled, Open-Label,Multi-Center Study to Evaluate 
Safety and Immunogenicity of a Single Dose of GlaxoSmiht Kline' s Meningococcal 
ACWY Conjugate Vaccine (Menveo), Administered to Healthy Individuals 15 througll 
55 years of age, approximately 4-6 years after primary ACWY vaccination. 
Study Pe1i od : Approximately 180 days 
(six months). 
Clinical Phase: 3b 
Background and Rationale: 
Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis worldwide, 
capable of causing outbreaks and epidemics of invasive disease. Meningococcal disease 
is associated with higll morbidity and mortality even among patients who receive early 
antibiotic treatment. Most cases of invasive disease worldwide are caused byserogroups 
A, B, C, W and Y. 
The quadrivalent meningococcal oligosaccharide diphtheria CRM-197 conjugate 
vaccine (MenACWY-CRM; Menveo, GSK Vaccines) is approved for active 
immunization of individuals from 2 months througll 55 years of age in the United 
States. As of February 2015, more than 30,000of subjectshave been exposed to 
MenACWY-CRM vaccine in completed clinical studies and more than 24million doses 
of the vaccine have been distributed globally. 
The US Advisory Committee on Immunization Practices (ACIP) recommends routine 
vaccination with a quadrivalent conjugated meningococcal vaccine for adolescents at 
11-12 years of age with a booster dose administered 5 years later. While a substantial 
body of data exists showing a robust immune response and good antibody persistence 
after a single dose ofMenACWY-CRM in adolescents, the response to a booster dose of 
MenACWY-CRM in this agegroup has only been evaluated in 2 clinical studies with 
limited number of subjects. 
A robust anamoestic immune response to a booster doseofMenveo vaccine 
administered at approximately 5 years after previous vaccination with thesame vaccine 
or a licensed meningococcal oolysaccharide vaccine (Menomune®) was demonstrated in 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
the phase 2 clinical study V59P6El . High titers of bactericidal antibodies against the 
vaccine serogroups were achieved at 7 and 30 days after booster dose in MenACWY­ 
primed subjects. However, the number of subjects included in this studywas relatively 
small (N=101, including 50 subjects who received a booster dose after the primary 
MenACWY-CRM vaccination). 
In the phase 3b clinical study V59Pl3 El , a booster dose of MenACWY-CRM was 
given 3 years after primary vaccination with either MenACWY-CRM or Menactra®(a 
meningococcal diphtheria toxoid-conjugated MenACWY vaccine, MenACWY-D) in 
adolescents.A booster dose was able to substantially increase antibody titers against all 
4 serogroups irrespective of the priming vaccine. Again, only a small number of 
subjects (N=160) received the MenACWY-CRM booster, (83 who received primary 
MenACWY-CRM and 77 who received MenACWY-D). 
In the light of thecurrent ACIP recommendation for a booster dose of MenACWY­ 
CRM, there exists a need to evaluate the response to a MenACWY-CRM booster given 
at -5  years after primary vaccination in meningococca-lvaccineprimed adolescents. 
Generation of this data would also be of relevance in outbreak management and 
vaccination of travelers to endemic areas. 
The purpose/aim of this study is to assess the safety and antibodyresponse to 
vaccination with a booster dose of Menveo given 4-6 years after primary vaccination 
and the response to a single dose given to vaccine-naive subjects, and to describe the 
immune response over time after a single dose of Menveo, administered to subjects 
previously vaccinated with Menveo or Menactra or to vaccine-naive subjects. The 
inclusion of vaccine-naive subjects in a separate study arm is to enable comparison of 
the rapidity and magnitude of an aoarooestic response to a booster dose (in primed 
individuals) or the primary response to a first dose (in naive individuals) of 
MenACWY-CRM. 
Study Objectives: 
P1i mary Objective(s): Immunogenicity objective: 
L To demonstrate a sufficient immune response following a single dose of 
MenACWY-CRM (Menveo) vaccine, !riven to sub jects who previously received 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
Menveo or Menactra, as measured by the percentage of subjects with hSBA 
seroresponse againstN. meningitidis serogroups A, C, W and Y at Day 29 after 
vaccination 
Criteria to demonstrate immune response sufficiency: The immune response will be 
considered as sufficient if thelowerlimit of theone-sided 97.5% CI for percentage 
of subjects with hSBA seroresponse against serogroups A, C, Wand Y is greater 
than 80% (zn pooled group of subjects who received primary vaccination with 
Menveo or Menactra). 
Seco ndary O bjec tive(s) : 
Immunogenicity objectives: 
1. To compare the immunogenicityofa single dose ofMenACWY-CRM vaccine, 
between subjects who previously received Menveo, subjects who previously 
received Menactra and vaccine-naive individuals, as measured by the percentage of 
subjects with hSBA titer 8, withhSBA seroresponse, and hSBA GMTs againstN. 
meningitidis serogroups A, C, W and Y at Day 29 after vaccination 
2. To compare the immune responses over time following a single dose of 
MenACWY-CRM vaccine, between subjects who previously received Menveo, 
subjects who previously received Menactra and vaccine-naive individuals, as 
measured by the percentage of subjects with hSBA titer ,::8 and hSBA GMTs against 
N. meningitidis serogroups A, C, Wand Y at Day I, Day 4, Day 6, and Day 29 after 
vaccination 
3. To assess persistence of bactericidal antibodies against serogroups A, C, Wand Y at 
approximately 4-6 years after the primary vaccination with Menveo and after the 
primary vaccination with Menactra in comparison with naturally-acquired level in 
vaccine-naive individuals, as measured by the percentage of subjects with hSBA 
titer ,::8 and hSBA GMTs at Day 1. 
Safety objectives: 
1. To assess reactogenicity and safety of MenACWY-CRM vaccine when administered 
to subjects who previously received Menveo or Menactra and vaccine-naive 
individuals 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protoco l number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheriaCRM-197 
conjugate vaccine 
Study Design: 
This is a phase 3b, controlled, open-label, multi-center studyto evaluate safety and 
immunogenicity of MenACWY-CRM after a single vaccination in healthy individuals 
who were vaccinated with Menveo or Menactra 4 to 6 years ago and in vaccine-naive 
individuals. 
Study population: Approximately 700 healthy subjects 15 througll 55 years of age will 
be enrolled in the study. 
Duration of the study: The duration of this study is approximately 6 months per subject. 
Written informed consent and, as applicable according to local guidelines, written 
assent will be obtained before conducting any study-specificprocedures. 
Vaccination schedule: All subjects will receive a single dose ofMenACWY-CRM at 
Day I. 
Study groups: 
• Group Menveo-Menveo: approximately 300 subjects, who were vaccinated with a 
single dose of Menveo 4 to 6 years ago, will receive one dose of MenACWY-CRM. 
• Group Menactra-Menveo:approximately 300 subjects, who were vaccinated with a 
single dose ofMenactra 4 to 6 years ago, will receive onedose of MenACWY­ 
CRM. 
• Group Naive:approximately 100 subjects, ofsimilar age to subjects enrolled in 
other primed groups, equally enrolled across allclinical sites, who have not received 
any meningococcal vaccination, will receive one dose of MenACWY-CRM. 
Randomization/ Stratification: 
Within each study group, subjects will be randomized into one of two different blood 
draw schedules according to a 1:1 ratio, describedas follows: 
• Subjects getting blood draws at Day1, Day4 and Day 29. 
• Subjects getting blood draws at Day1, Day 6 and Day 29. 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
For a schematic overview, see Table 1. 
Ta ble I: 
Schema tic diagra m of the VS9_77 stu dy gro ups 
Vacc.ine History 
Vacc.ination in current 
study 
Blood drawschedule 
M enveo 
N=300 
Menveo 
Blood draw Day 1, 4, 29 (N=l50) 
Blood draw Day 1, 6, 29 (N=l50) 
Menactra 
N=300 
Menveo 
Blood draw Day 1, 4, 29 (N=l50) 
Blood draw Day 1, 6, 29 (N=l50) 
Vaccine-Naive 
N=IOO 
Menveo 
Blooddraw Day I, 4, 29(N=50) 
Blooddraw Day I, 6, 29(N=50) 
Blinding: open-label study. 
Blood samn!P.s: Three (3) blood samples of approximately 10 mL each willbe collected 
according to the blood draw schedule in Table I. 
Data collection: Electronic Case Reporting Form (eCRF). 
Study clinic visits: Three (3) clinic visits at Day 1, Day 4 or Day 6 and Day 29 are 
piaruied for each subject. 
Reminder Phone calls: Two (2) reminder phone calls will beconducted at Day 3 and 
Day 5 after the study vaccination to remind the subject/ legal guardian to complete the 
diary card. 
Safety phone calls: Three (3) safety phone calls (at Day 15, Day91 and Day181) will 
be conducted to collect any medically-attended AEs, AEs leading to withdrawal, SAEs, 
related medications and any vaccinations. In addition, all unsolicited AEs and related 
medications occurring after the vaccination willbe collected during the safety call at 
Day15.The Day 181 Safety Phone call will also serve as the termination visit. 
Solicited Adverse Events (injection site pain, erythema, induration, fatigue, headache, 
myalgia, arthralgia, loss of appetite, nausea, chills and fever) occurring on the day of 
vaccination and the following six davs ffiav I throu h Dav7) will be recorded daily 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59- 77 
Gene1ic name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
using a Diary Card for all subjects. 
Unsolicited AEs occurring within 28 days after studyvaccination willbecollecte.d 
Qualified site staff willinterview the subject by phone approximately 14 days after 
vaccination and in person at the study site approximately 28 days after study vaccination 
to assess the occurrence of any unsolicited AEs. 
Medicall}'.-attended AEs AEs leading to stud}'.withdrawal and SAEs will be collected 
during the entire study period. These data will becaptured by interviewing the subject 
and/or subjects' parents / guardian (as applicable) during the site visits and phone calls 
and by review of available medical records. Subjects and/or parents / guardian willbe 
encouraged to call the site in the event of any medically-attended AEs or any AEs which 
theyperceive as being of concern during the entire studyperiod. 
Table 2: 
Schematic diagram of the VS9_77 study design. 
Day l 
Day 4 
Day 6 
Day15 
Day 29 
Day 91 
Day 181 
Blood draw 
(all subjects) 
Blood draw 
(50% of 
Blood draw 
(50% of 
Safety 
Phone call 
Blood draw 
(allsubjects) 
Safety 
Phone 
Safety 
Phone call 
Menveo 
subjects) 
subjects) 
call 
Study 
tennination 
Number of Subjects planned: Approximately 700 subjects are planned for enrollment 
into this study, approximately 300 subjects who previously received Menveo (Menveo- 
Menveo group), 300 subjects who previously received Menactra (Menactra-Menveo 
group) and 100 meningococcal vaccine-naive subjects (Naive group). Assuming a 10% 
drop-out rate that should provide approximately 630 evaluable subjects. 
Study Populati on and Su bject Char acte1istics: The list of inclusion and exclusion 
criteria is included in protocol section 4, Selection of Study Population. 
Study Procedures: The study includes three clinic visits, one vaccination, three blood 
draws, and threesafety phone calls for each subject. All studyprocedures associated 
with the pre-vaccination, vaccination, post-vaccination, unscheduled and study 
termination visit are described in section 5.0. 
Study Vaccines: 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
GlaxoSmithKline Meningococcal MenAC\1VY - CRl "\1 vacc in e (M en veo): 
Meningococcal (groups A, C, Wand Y)oligosaccharide diphtheria CRM-197 conjugate 
vaccine is supplied as a vial contain 10 µg of serogroup A oligosaccharides and 5 µg of 
serogroups C, W and Y oligosaccharides, conjugated to Corynebacterium diphtheriae 
CRM191 protein. Overall injection volume of 0.5 mL. 
The vaccine will be administered intramuscularly, preferably in the deltoid area of the 
non-dominant arm. 
P1i mary Endpoint(s): 
Immunogenicity Endpoints: 
The following measures will be summarized for the pooled (Menveo-Menveo and 
Menactra-Menveo) group. 
1. Percentage of subjects with hSBA seroresponse1 against N. meningitidis serogroups 
A, C, Wand Y at Day29. 
SecondaryEndpoints: 
Immunogenicity endpoints: 
The following measures will be summarized for Menveo-Menveo, Menactra-Menveo, 
Naive and the pooled (Menveo-Menveo and Menactra-Menveo) groups unless 
otherwise noted: 
1. Percentage of subjects with hSBA titer 8 against N. meningitidis serogroups A, C, 
Wand Y at Day 1, Day 4, Day 6 and Day 29; 
2. Percentages of subjects with hSBA seroresoonse against N. meninf!itidis sero!!I'ouos 
 
 
1 Seroresponse is defined as: a) post-vaccination hSBA 8 for subjectswitha pre-vaccination hSBA <4; b) 
for subjects with a pre-vaccinationhSBA ' an increase of at least four timesthe pre-vaccinationhSBA. 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
A, C, Wand Y at Day4, Day 6 and Day 29 (Day 29 Except the pooled group); 
3. hSBAGMfs againstN. meningitidis serogroupA, C, Wand YatDay 1, Day4, Day 
6 andDay29; 
4. Ratios ofhSBA GMTs at Day 1, Day 4, Day 6 and Day29 (between study groups). 
5. Ratios ofhSBA GMfs at Day 4, Day 6, and Day 29 compared to Day 1 (within 
study groups). 
Safety endpoints: 
Safety of the study vaccine will be assessed in the pooled vaccine group (Menveo­ 
Menveo and Menactra-Menveo) and the vaccine-naive group in terms of the frequency 
(percentage) of reported adverse events including: 
1. Any unsolicited AEs reported within 30 minutes after vaccination; 
2. Solicited local and systemic AEs reported from Day 1 (6 hours) through Day 7 after 
vaccination; 
3. Other indicators of reactogenicity(e.g. use of analgesics / antipyretics, body 
temperature) within 7 days after vaccination; 
4. All unsolicited AEs reported from Day 1 through Day 29 after vaccination; 
5. Medically-attended AEs, AEs leading to withdrawal and SAEs reported from Day 1 
through Day 181 (during the entire studyperiod). 
Statistical Analyses: 
P1i mary Immunogenicity Objective 
The primary population for the analysis of sufficient immune response is the Full 
Analysis Set (FAS), and will consist of pooled data from the Menveo-Menveoand 
Menactra-Menveo group (n=540 evaluable). 
To demonstrate immune response sufficiency after MenACWY-CRM booster vaccine 
administration, the lower limit of the one-sided 97.5% Confidence Interval (CI) for 
percentage of subjects with hSBA seroresponse against eaciI of serogroups A, C, W and 
Y must be !!reater than 80% (in the pooled !!l'OUP of subjects who received 
, 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59- 77 
Gene1ic name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
vaccination with Menveo or Menactra) 
Hypothesis: 
Null hypothesis 
Alternative hypothesis 
P, s 0.80 
P, > 0.80 
Where: P., is the population seroresponse rate for the pooled Menveo-Menveoand 
Menactra-Menveo group; i = 1,2,3,4 refer to serotypes A, C, Wand Y respectively. 
Sample Size: 
Statistical power was estimated based onobserved data from study V59Pl3El , where 
seroresponse rates at one-month post booster dose of MenACWY-CRM ranged from: 
97% (90%-100%)to 100% (95%-100%) for serogroupA; 93% (85%-98%)for 
serogroup C; 91% (82%-97%)to 93% (84%-98%) forserogroup W; and 90% (80%- 
96%) to 93% (84%-98%) forserogroup Y among subjects primed with MenACWY- 
CRM or Menactra in the three years preceding the study. 
Assuming the true seroresponse rates in the pooled group range from 90% to 97% 
(alternativehypothesis) for each serotype, a sample size of n=540 will have at least 96% 
power to show sufficiency of immune response to a booster dose of MenACWY-CRM 
in the pooled group, compared with a pre-specified reference seroresponse of 80% (null 
hypothesis) using an exact test with 0.025 one-sidedsignificance level When taking a 
10% dropout rate into account, N=600 previously vaccinated subjects have to be 
enrolled in the study. Calculations have been done with nQuery Advisor (Version 7.0). 
Tab le 3: 
 Stati stical Power to Tes t for Sufficiency of Immune Response 
Given a Range of True Seroreponse Rates for Evaluable 
Sample Size of 540 subjects 
Serotype 
T111e Serores po nse Rate 
Powel' 
A 
0.97 
0.99 
C 
0.93 
0.99 
w 
0.91 
0.99 

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Name of Sponsor: 
GlaxoSmithKline 
Vaccines 
Protocol number: 
V59- 77 
Gene1i c name of study vaccine(s): 
Meningococcal (groups A, C, W, and Y) 
oligosaccharide diphtheria CRM-197 
conjugate vaccine 
y 
0.90 
0.99 
Total Power 
0.96 
Interim Analysis: No interim analysis is planned for this study. 
Data Monito1i ng Committee: No DMC will be utilized for the study. 

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Table 4 
Time and Events Table 
 
Visit Type 
Study period 
Study Day 
Visit Window (Days) 
Visit Number 
Clinic Visit 
Clinic Visit 
Phone Call Clinic Visit Phone Call Clinic Visit 
Phone Call Phone Call 
Screening 
Treatment 
Tre.itment 
Treatment 
Treatment Treatment 
Follow-up 
Follow-up 
1 
3, 5 
4/6• 
15 
29 
91 
181 
-5 
to 1 
0 
2 days (- 
1/+l ), 4 
da ys (0/+2) 
after vacc 
3/5 days 
(-1/+l ) 
after vacc 
14 days 
(-2/+2) 
after vacc 
28days 
(- 7/+14) 
after vacc 
90days 
(-14/+14) 
aftel' vacc 
180 days 
(-14/+14) 
after vacc 
Pre- 
vacc.ination 
1 
N/A 
2 
3 
4 
5 
6 
Study Event 
References 
Study Treatment 
Vaccination (vacc) 
Section 5.2 
X 
Screening and 
Safety 
Informed Consent" 
Section 5.1.1 
X 
Medical History 
Section 5.1.2 
X 
Physical Exam 
Sections 5.1.2 
and 5 .3.1 
X 
x< 
X 
X 
Pregnancy Test 
Sections 3.5 and 
5 .1.2 
X 
x< 
Exclusion/Inclusion 
Criteria 
Section4 
X 
Randomization 
Section 5.1.4 
x< 
30 Minutes Post 
InjectionAssessment 
Section 5.2.1 
X 

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Visit Type 
Study period 
Study Day 
Visit Window (Days) 
Visit Number 
Clinic Visit 
Clinic Visit PhoneCall Clinic Visit Phone Call Clinic Visit Phone Call PhoneCall 
Screening 
Treatment Tre.itment 
Treatment Treatment Treatment 
Follow-up 
Follow-up 
1 
3, 5 
4/6• 
15 
29 
91 
181 
-5 
to 1 
0 
2 days (- 
1/+l ), 4 
days(0/+2) 
after vacc 
3/5 da)'S 
(-1/+l ) 
after vacc 
14 days 
(-2/+2) 
after vacc 
28days 
(-7/+14) 
after vacc 
90days 
(-14/+14) 
aftel' vacc 
180 days 
(-14/+14) 
after vacc 
Pre- 
vacc.ination 
1 
NIA 
2 
3 
4 
5 
6 
Study Event 
References 
SubjectDiary 
Dispensed with 
Training 
Section 5.2.1 
X 
SubjectDiary 
Reminder Call 
Section 5.2.2 
xi 
xi 
Subject Diary 
Reviewed and 
Collected 
Section 5.3.1 
X 
Assess Unsolicited 
AEs 
Section 7.1 
X 
X 
X 
X 
Assess SAEs 
Section 7.1.4 
X 
X 
X 
X 
X 
X 
Assess for medically 
attended AEs and 
AEs leading to 
withdrawal 
Sections 7.I.4.I 
and7.1.3 
X 
X 
X 
X 
X 
X 
Assess relevant 
medications/ 
vaccinations 
Sections5.1.2 
and 6.5 
X 
X 
X 
X 
X 
X 
X 

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Visit Type 
Study period 
Study Day 
Visit Window (Days) 
Visit Number 
Clinic Visit 
Clinic Visit PhoneCall Clinic Visit Phone Call Clinic Visit 
Phone Call Phone Call 
Screening 
Treatment Tre.itment 
Treatment Treatment Treatment 
Follow - up 
Follow - up 
1 
3, 5 
4/6• 
15 
29 
91 
181 
-5 
to 1 
0 
2 days (- 
1/+l ), 4 
da ys (0/+2) 
after vacc 
3/5 da)'S 
(-1/+l ) 
after vacc 
14 days 
(-2/+2) 
after vacc 
28days 
(-7/+14) 
after vacc 
90days 
(-14/+14) 
aftel' vacc 
180 days 
(-14/+14) 
after vacc 
Pre- 
vacc.ination 
1 
NIA 
2 
3 
4 
5 
6 
Study Event 
I References 
Imm unogenicity 
Serology blooddraw  I 
Section 3.5 
X" 
X 
X 
Study C-0mp lerion 
Pt·ocedure 
StudyTennination' I 
Section 5.5 
X 
Notes : 
• Subject will berandomized into a blood draw schedule in a I:I ratio. Thesecond clinic visit will occur at Day 4 OR Day 6. 
b Confirm consent fonn(s) signed prior to any procedures. 
' Procedure to be performed prior to vaccination 
d  If the clinicvisit at Day 4 is overlapping with thespecified window of the Day 3 reminder call.the Day  3 reminder call may be omitted. 
If the clinic visit at Day 6 is overlapping with the specified window of the Day 5 reminder call, the Day 5 reminder call may beomitted. 
• Subjects who tenninate thestudy early are recommended to complete certainstudy-relatedprocedures. See section 5.5 for  further details. 

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LIST OF ABBREVIATIONS 
 
ACIP 
AE 
CI 
CBER 
CRM 
CRO 
EC 
eCRF 
EDC 
FAS 
FDA 
GCP 
GMR 
GMT 
GSK 
hSBA 
IB 
ICF 
ICH 
 
IM 
IRB 
LSLV 
MedDRA 
pp 
Ref. 
SAE 
soc 
SOP 
Advisory Committee on Imm1mziation Practices 
Adverse Event 
Confidence Inteival 
Center for Biologics Evaluation and Research 
Cross Reactive material 
Contract Research Organization 
Ethics Committee 
Electronic Case Report Form 
ElectronicData Capture 
Full Analysis Set 
Food and Drug Administration 
Good Clinical Practices 
Geometric Mean Ratio Geometric 
Mean Titer GlaxoSmithKline 
Vaccines Human Serum 
Bactericidal Assay Investigator' s 
Brochure 
Informed Consent Form 
International Conference on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use 
Intramuscular 
Institutional Review Board 
Last Subject Last Visit 
Medical Dictionary for Regulatory Activities 
Per Protocol 
Reference 
Serious Adverse Event 
System Organ Class 
Standard Operating Procedure 

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l. 
BACKGROUl''-D M 'D RATIONALE 
 
1.1 
Background 
 
Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis worldwide, 
capable of causing outbreaks and epidemics of invasive disease. Meningococcal disease is 
associated with high morbidity and mortality even among patients who receive early 
antibiotic treatment. Most cases of invasive disease worldwide are caused by serogroups 
A, B, C, W and Y. 
 
The quadrivalent meningococcal oligosaccharide diphtheria CRM-197 conjugate vaccine 
(MenACWY-CRM; Menveo, GSK Vaccines) is approved for active immunization of 
individuals from 2 months through 55 years of age in the United States. As of February 
2015, more than 30,000 of subjects have been exposed to MenACWY-CRMvaccine in 
completed clinical studies and more than 24 million doses of the vaccine have been 
distributed globally. 
 
The US Advisory Committee on Immunization Practices (ACIP) recommends routine 
vaccination with a quadrivalent conjugated meningococcal vaccine for adolescents at 11- 
12 yearsof age with a booster dose administered 5 years later. While a substantial body of 
data exists showing a robust immune response and good antibody persistence after a 
single dose of MenACWY-CRM in adolescents, the response to a booster dose of 
MenACWY-CRM in this age group has only been evaluated in 2 clinical studies with 
limited number of subjects. 
 
A robust anamnestic immune response to a booster dose of Menveo vaccine administered 
at approximately 5 years after previous vaccination with the same vaccine or a licensed 
meningococcal polysaccharide vaccine (Menomune®) was demonstrated in the phase 2 
clinical study V59P6El . Hightiters of bactericidal antibodies against the vaccine 
serogroups were achieved at 7 and 30 days after booster dose in MenACWY-CRM­ 
primed subjects. However, the number of subjects included in this study was relatively 
small (N=101, including 50 subjects who received a booster dose after the primary 
MenACWY-CRM vaccination). 
 
In the phase 3b clinical study V59Pl3 El , a booster dose of MenACWY-CRM was given 
3 years after primary vaccination with either MenACWY-CRM or Menactra®(a 
meningococcal diphtheria toxoid-conjugated MenACWY vaccine, MenACWY-D) in 
adolescents. A booster dose was able to substantially increase antibody titers against all 4 
serogroups irrespective of the priming vaccine. Again, only small number of subjects 
(N=160) received the MenACWY-CRM booster, (83 who received primary MenACWY­ 
CRM and 77 who received MenACWY-D). 

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In the light of the current ACIP recommendation for a booster dose of MenACWY-CRM, 
there exists a need to evaluate the response to a MenACWY-CRM booster given at - 5 
years after primary vaccination in meningococcal-vaccineprimed adolescents. Generation 
of this data would also be of relevance in outbreak management and vaccination of 
travelers to endemic areas. 
 
1.2 
Rationale 
 
The purpose/aim of this study is to assess the safety and antibody response to vaccination 
with a booster dose ofMenveo given 4-6 years after primary vaccination and the response 
to a single dosegiven to vaccine-naive subjects, and to describe the immune response 
over time after a singledose of Menveo, dministi>red to su b j ects previous ly vaccinated 
with Menveo or Menactra or to vaccine-naive subjects. The inclusion of vaccine-naive 
subjects in a separate study arm is to enable comparison of the rapidity and magnitude of 
an anamnestic response to a booster dose (in primed individuals) or the primary response 
to a first dose(in naive individuals) of MenACWY-CRM. 

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2. 
OBJECTIVES 
 
2.1 
Plimary Objective(s) 
 
Plimary Immunogeoicity Objective(s) 
 
1. To demonstrate a sufficient immune response following a single dose of MenACWY­ 
CRM (Menveo) vaccine, given to subjects who previously received Menveo or 
Menactra, as measured by the percentage of subjects with hSBA seroresponse against 
N. m.eningitidis serogroups A, C, W and Y at Day 29 after vaccination 
Criteria to demonstrate immune response sufficiency: The immune response will be 
considered as sufficient if the lower limit of the one-sided 97.5% CI for percentage of 
subjects with hSBA seroresponse against serogroups A, C, Wand Y is greater than 
80% (in pooled group of subjects who received primary vaccination with Menveo or 
Menactra). 
 
2.2 
Seco nd a r y O bjec ti ve(s) 
 
Seco nd a r y I m m un oge nicity O bjec ti ve(s) 
 
1. To compare the immunogenicityof a single dose of MenACWY-CRM vaccine, 
between subjects who previously received Menveo, subjects who previously received 
Menactra and vaccine-naive individuals, as measured by the percentage of subjects 
withhSBA titer ;,:8, with hSBA seroresponse, and hSBA GMTs against N. 
meningitidis serogroups A, C, W and Y at Day 29 after vaccinat ion 
2. To compare the immune responses over time following a single dose of MenACWY­ 
CRM vaccine, between subjects who previously received Menveo, subjects who 
previously received Menactra and vaccine-naive individuals, as measured by the 
percentage of subjects with hSBA titer 8 and hSBA GMTs against N. meningitidis 
serogroups A, C, Wand Y at Day 1, Day 4, Day 6, and Day 29 after vaccination . 
3. To assess persistence of bactericidal antibodies against serogroups A, C, Wand Y at 
approximately 4-6 years after the primary vaccinat ion with Menveo and after the 
primary vaccination with Menactra in comparison with naturally-acquired level in 
vaccine-naive individuals, as measured by the percentage of subjects with hSBA titer 
8 and hSBA GMTs at Day 1. 
4. 
 
Secondary Safety Objective(s) 

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1. To assess reactogenicityandsafety of MenACWY-CRMvaccine when administered 
to subjects who previously received Menveo or Menactra and vaccine-naive 
individuals. 
2.3 
Explor atory Objective(s) 
There are no exploratoryobjectives. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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3. 
STUDY DESIGN 
 
3.1 
Overview of Study Design 
This is a phase 3b, controlled, open-labe multi-center studyto evaluate safety and 
immunogenicityof MenACWY-CRM after a single vaccination in healthy individuals 
who were vaccinated with Menveo or Menactra 4 to 6 years ago and in vaccine-naive 
individuals 
Study population: Approximately 700 healthy subjects 15 through 55 years of age willbe 
enrolled in the study. 
Duration of the study: The duration of this studyis approximately 6 months per subject. 
 
Written informed consent and, as applicable according to local guidelines, written assent 
willbeobtained before conducting anystudy-specificprocedures. 
 
Vaccination schedule: All subjects will receive a single dose of MenACWY-CRM at Day 
1. 
 
Study groups: 
 
Group Menveo-Menveo: approximately 300 subjects, who were vaccinated with a single 
dose ofMenveo 4 to 6 years ago, will receive one dose of MenACWY-CRM. 
 
Group Menactra-Menveo approximately 300 subjects, who were vaccinated with a single 
dose of Menactra 4 to 6 years ago, willreceive one doseof MenACWY-CRM. 
 
Group Naive: approximately 100 subjects equally enrolled across all clinical sites, who 
have not received any meningococcal vaccination, willreceive one dose of MenACWY­ 
CRM. 
 
Randomization / Stratification: 
Within each study group, subjects willberandomized into one of two different blood 
draw schedules according to a 1:1 ratio, described as follows: 
• 
Subjects getting blood draws at Day 1, Day 4 and Day 29. 
• 
Subjects getting blood draws at Day 1, Day 6 and Day 29. 
 
For a schematic overview, see Table 1 
 
 
 
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Table 3.1-1: Schematic diagram of the VS9_77 study gro ups 
 
Vacd ne History 
Vaccination in cwTent 
study 
Blood draw schedule 
Menveo 
N=300 
Menveo 
Blood draw Day I, 4, 29 (N=150) 
Blood draw Day I, 6, 29 (N= l 50) 
Menactra 
N=300 
Menveo 
Blood draw Day I, 4, 29 (N=150) 
Blood draw Day I, 6, 29 (N= l 50) 
Vaccine-Naive 
N=IOO 
Menveo 
Blood draw Day 1, 4, 29 (N=50) 
Blood draw Day 1, 6, 29 (N=50) 
 
Blinding· open-label study. 
 
Blood sanmles: Three (3) blood samples of approximately 10 mL each will be collected 
according to the blood draw schedule in Table 3.1.1. 
Data collection: Electronic Case Reporting Form (eCRF). 
 
Study clinic visits: Three (3) clinic visits at Day I, Day 4 or Day 6 and Day 29 are 
planned for eachsubject. 
 
Reminder Phone calls: Two (2) reminder phone calls willbe conducted at Day 3 and Day 
S after the study vaccination to remind the subject/ legal guardian to complete the diary 
card. 
 
Safety phone calls: Three (3) safety phone calls (at Day IS, Day 91 and Day 181) will be 
conducted to collect any medically-attendedAEs, AEs leading to withdrawal, SAEs, 
related medications and any vaccinations. In addition, all unsolicited AEs and related 
medications occurring after the vaccination will be collected during the safety call at Day 
IS. The Day 181 Safety Phonecall will also serve as the termination visit. 
 
Solicited Adverse Events (injection site pain, erythema, induration, fatigue, headache, 
myalgia, arthralgia, loss of appetite, nausea, chills and fever) occurring on the day of 
vaccination and the following six days (Day 1 through Day 7) willbe recorded daily 
using a Diary Card for all subjects. 
 
Unsolicited AEs occurring within 28 days after studyvaccination will be collected. 
Qualified site staffwillinterview the subject by phone approximately 14 days after 
vaccination and in person at the studysite approximately 28 days after studyvaccination 
to assess the occurrence of any unsolicited AEs. 
 
 
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Medically-attended AEs AEs leading to stuqy withdrawal and SAEs will be collected 
during the entire study period. These data will be captured by interviewing the subject 
and/or subjects' parents / guardian (as applicable) during the sitevisits and phone calls 
and by review of available medical records. Subjects and/or parents / guardian will be 
encouraged to call the site in the event of any medically-attendedAEs or any AEs which 
theyperceive as being of concern during the entire study period. 
 
Table 3.1-2: 
Schematic diagram of the V59_77 study design 
 
Day l 
Da y 4 
Da y 6 
Da y 15 
Da y 29 
Da y 91 
Da y 181 
Blood draw 
(all subjects) 
Blood draw 
(50¾ of 
Blood draw 
(50% of 
Safety 
Phone call 
Blood draw 
(all subjects) 
Safety 
Phone 
SafetyPhone 
call 
Menveo 
subjects) 
subjects) 
call 
Study 
termination 
 
3.2 
Study Period 
 
Each subject should expect to participate in the study for 6 months, from the time of 
enrolment through the last study visit. 
 
3.3 
Blinding Prncedures 
 
The trialis designed as an open-label study. 
 
3.4 
Data Collection 
3.4.l 
Data Collected from Subjects 
 
The following data will be collected from each subject over the duration of their study 
participation: 
• 
Demographic Information. 
• 
Adverse Events. 
• 
Medical History. 
• 
Concomitant Medications/Vaccination.s 
• 
Information on the blood samples. 
 
All data collected must only be identified using the Subject ID, as described in section 
S.1.4, Randomization. 
 
 
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3.4.2 
Tools Used for Data Collection 
 
Data willbe recorded in the Subject Diary and collected on electronic Case Report Forms 
(eCRFs). 
 
Subj ect Diar y 
 
Paper Diaries (pDiaries), hereafter referred to as Subject Diaries will be the onlysource 
document allowed for solicited localand systemic adverse events (including body 
temperature measurements), starting after the initial, 30minute post-vaccination period at 
the clinic. The following additional rules apply to documentation of safety information 
collected in the Subject Diary. 
 
The Investigator or delegated staff should monitor the Subject's Diary status throughout 
the study for compliance and anysolicited local and systemic adverse events that were of 
concern to the subject. 
 
• 
No corrections or additions to the information recorded by the subject or 
parent(s)/legalguardian(s) within the Subject Diary willbe allowed after it is 
delivered to the site. 
• 
Any blank or illegible fields on the Subject Diary must be described as missing in the 
eCRF. 
 
Case R ep01t F or ms 
This study utilizes electronic Case Report Forms (eCRFs) to collect study-related data 
from each subject. A qualified site staff member(s) is required to enter subject data in the 
eCRFs in English based on the medical information available in each subject' s source 
record. 
 
Data should be entered into the eCRF in a timely fashion following each subject' s clinic 
visit,study procedure, or phone call. Each subject's eCRF casebook will be compared 
withthe subject's source records by a GSK-approved study monitor (or designee) over 
the duration of the study in order to ensure data collection accuracy. 
 
 
 
 
 
 
 
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The following additional rules apply to documentation of Subject Diary information 
collected in the eCRFs: 
• 
The site must enter all readable entries in the Subject Diary into the eCRF, including 
those values that may be biologically implausible (e.g. bodytemperature: 400°C). 
• 
Any illegible or implausible data should be reviewed with the subject and/or 
parent(s)/legal guardian(s). If an underlying solicited or unsolicited adverse event is 
 
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described on review with the subject, this should be described in the source document 
and reported as an unsolicited adverse event in the Adverse Event eCRF (e.g., if the 
subject above confinns body temperature of 40°C on the day in which body 
temperature: 400°C was written into his/her Subject Diary, this fever of 40°C should 
be recorded in the Adverse Event eCRF). 
• 
Any newly described safety infonnation (including a solicited adverse event) nrust not 
be written into the Subject Diary andnrust be described in the study file as a verbally 
reported adverse event. Any adverse event reported in this fashion must be described 
as an unsolicited adverse event and therefore entered on the Adverse EventeCRF. 
3.5 
Collection of Clinical Specimens 
The following clinical specimens are required to be collected from each subject in this 
study: 
• Blood. 
• Urine for pregnancy testing (As per routine practice, specimens willbetested at each 
site). 
Processing of a specimen should be completed bya qualified site member and in 
accordance with the study-specificClinical Specimen Laboratory Manual. Testing of 
serum specimens willbe performed by a GSK or a designated laboratory. Refer to the 
study-specific Clinical Specimen Laboratory Manual for additional details. 
 
Blood Specimens 
Approximately 10 mL sample of blood willbedrawn from all subjects at visit Day 1 
before vaccination, and at visit Day 4 or Day 6 and Day 29. The blood volume willnot 
exceed 10mL at each time point in order to provide the necessary serum volume 
(approximately half of the blood draw volume) for the serology assays. 
The blood will be used for immunological assays. See section 7, Assessments for 
additional details. 
The total amount of blood collected over the study period per subject will be 
approximately 30mL. 
 
 
 
 
 
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Urine willbe collected for pregnancy testing in females of child bearing potential. Urine 
will becollected at visit Day 1 before vaccination and the results recorded in the source 
document and eCRF. 
 
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3.6 
Stopping/Pausing Guidelines 
There are no predetermined stopping rules in this study. Subjects may be withdrawn from 
the study according to investigator discretion as described in section 3.8, Premature 
Withdrawal from Study. 
 
3.7 
Data Monit01ing Co mmittee 
No DMC will be utilized for the study. 
3.8 
Premature \Vithdrawal from Study 
 
Subjects may withdraw at any time, or be dropped from the study at the discretion of the 
investigator should any untoward effects occur and/or for safetyreasons. In addition, a 
subject may be withdrawn by the investigator or the Sponsor if he/she violates the study 
plan or for administrative reasons. The investigator or study coordinator nrust notify the 
Sponsor immediately when a subject has been withdrawn due to an adverse event. 
 
The circumstances above are referred to as premature withdrawal from the study, and the 
reason for premature withdrawal should be clearly documented and detailed in the source 
documentation. The investigator should make every attempt to evaluate the subject's 
safety, including resolution of ongoing AEs, at the time of premature withdrawal. If a 
subject wants to withdraw from the study before or prior to the last planned study visit, 
the subject will be asked to be followed for safety for the duration of the study. When a 
subject withdraws, or is withdrawn, from the study, the procedures described in section 
S.5.1, Early Termination Visit should be completed if possible. 
 
The reasons for premature withdrawal from the study include: Adverse event, death, 
withdrawal of consent, lost to follow-up, administrative reason, and protocol deviation. 
These reasons are described in greater detail below. 
AdverseEvent 
 
For anysubject withdrawn from study participation prior to the planned Study 
Termination Visit, it is important to determine if an AE was associated with the reason for 
discontinuing the study. This AE nrust be identified on the AE eCRF page by indicating 
"Withdrawn from study due to AE". Any ongoing AEs at the time of studywithdrawal 
must be followed until resolution or stabilization 
 
 
 
 
 
 
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Death 
For anysubject withdrawn from study participation due to death, this should be noted on 
the StudyTennination eCRF page and the associated SAE that led to the death must be 
reported. 
\ Vith drawal of consent 
 
The subject and/or parent(s)/legal guardian(s) can withdraw consent for participation in 
the study at any time without penalty or loss of benefit to which the subject is otherwise 
entitled. Reason for early termination should be deemed as "withdrawal of consent'' if the 
subject withdraws from participation due to a non-medical reason (i.e., reason other than 
AE). If the subject and/or parent(s)/legal guardian(s) intends to withdraw consent from 
the study, the investigatorshould clarify if the subject will withdrawcompletely from the 
study or if the subject willcontinue study participation forsafety, or a subset of other 
study procedures. If the subjectrequests complete withdrawal from the study, no further 
study interventions will be performed with the subject. 
If a subject and/or parent(s)/legalguardian(s) withdraws consent but does not revoke the 
HIPAA authorization, the Sponsor will have fullaccess to the subject' s medical records, 
including tennination visit information. If a subject and/or parent(s)/legal guardian(s) 
revokes only the HIP AA authorization, the Sponsor will have fullaccess to all of the 
subject's medical records prior to the date and time of written revocation. 
 
Lo st to Follow-Up 
For subjects who fail to show up for final visits (clinic or telephone contacts), or for three 
consecutive visits, study staff are encouraged to make at least three documented attempts 
to contact the subject by telephone and at least one documented written attempt to contact 
the subject and/or parent(s)/legal guardian(s) to encourage the completion of study 
termination procedures. These efforts to contact the subject should be recorded in the 
source document. The termination date for the subject to be captured on the Study 
Tennination eCRF page is the date of the last successful contact (clinic visit or telephone) 
withthe subject. 
 
Administrative Reason 
 
Examples for subjects withdrawn from the study due to administrativereason can include: 
Sponsor decision to terminate the study, subject discontinuation for insurance issues, 
moving, no time, etc. This reason should be noted in the StudyTennination eCRF page 
and any ongoing AEs at the time of studywithdrawal should be followed until 
resolution/stabilization,if possible. 
 
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If the clinical study is prematurely tenninated by the Sponsor, the investigator is to 
promptly inform the study subjects and local EC/IRB and should assure appropriate 
therapy and follow up for the subjects. All procedures and requirements pertaining to the 
archiving of study documents should be followed. All other study materials (study 
medication/vaccines, etc.) must be returned to the Sponsor. 
 
For subjects who are withdrawn from the study due to receipt of an excluded 
medication/vaccination or due to significant protocol non-compliance, this reason should 
be noted in the StudyTermination eCRF page. 
 
Protocol Deviation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. In general, subjects associated with protocol deviations 
may remain in the study unless continuation in the study jeopardizes the subject' s health, 
safety, or rights. 
 
Investigatorswill apply due diligence to avoid protocol deviations. Under no 
circumstances should the investigator contact GSK or its agents, if any, monitoring the 
study to request approval of a protocol deviation, as no authorized deviations are 
permitted. If the investigator feels a change to the protocol would improve the conduct of 
the studythis must be considered a protocol amendment, and unless such an amendment 
is agreed upon by GSK and approved by the IRB/EC and health authorities it cannot be 
implemented. 
 
Any subject who becomes pregnant during the study, despite the protocol requirement for 
adequate contraception should be encouraged to continue participating in the study for 
safety follow-up only. The site must complete a Pregnancy Report CRF (initial report) as 
soon as possible after learning of pregnancy occurrence (see section 7.1.6, Pregnancies 
for further details). If the subject withdraws fromthe study for any of  the above 
categories except death, the sitewill obtain permission from the subject to continue to 
remain in contact with her until the outcome of the pregnancy is known, evenif the 
outcome is not known until after the subject reaches the end of follow-up period. 
 
3.9 
End of Study 
 
Most clinical trials intended to support the efficacy/immunogenci ityand safety of an 
Investigational Product proceed to fullcompletion of planned sample size accrual. 
Evaluation of the primary and/or secondary immunogenicity/efficacyobjectives requires 
the testing of biological samples from the study subjects, which can only be completed 
after all samples are collected. The last samples for the analysis of the primary and/or 
 
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secondary objectives will be taken at the last clinic visit, Day 29. For the purpose of this 
protocol, end of study is defined as the completion of the testing of such biological 
samples, to be achieved no later than 8 months after collection of the last biological 
sample at Day 29 visit. 
 
If the completion of testing occurs prior the completion of the Last Subject Last Visit 
(LSLV) the latter date defines the end of study visit. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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4. 
SELECTION OF STUDY POPULATION 
 
4.1 
Inclusion C1iteria 
 
In order to participate in this study, all subjectsmust meet ALL of the inclusion criteria 
described. 
 
1. Individuals of IS through SS years of age on the day of informed consent or assent. 
2. Individuals who received Menveo 4 to 6 years prior to enrollment at an age of 11 
years or older (Menveo-Menveo group) 
OR 
Individuals who received Menactra 4 to 6 years prior to enrollment at an age of 11 
years or older (Menactra-Menveo group) 
OR 
Individuals who have not received any previous meningococcal vaccine (Naive 
group). 
3. Individuals who have voluntarily given written informed consent or assent after the 
nature of the study has been explained according to local regulatory requirements, 
prior to study entry. If the subject is under age 18 at the tinie of enrollment, the 
parent(s)l1egalguardian(s) of the subject should have voluntarily given written 
informed consent. 
 
4. Individuals who can comply with study procedures including follow-up2 
S. Males 
Or 
Females of non-ciiildbearingpotential3 
Or 
 
 
2 A subject and/or parent(s)/Jegal guardian(s) is/are considered to be compliant if the Investigator judges 
thatthesubjectwill completetheSubject Diary and return for all thefollow-up visitsscheduled in the 
study. 
3 A female is considered to be of non-childbearingpotential prior to menarcheand after natural or induced 
menopause. Natural menopause is recognized to have occuned after 12 consecutive months of amenorrhea 
for which thereis nootherobvious pathological or physiologicalcause. Induced menopause is recognized 
tohave occurred after hysterectomy, after bilateral oophorecotmy, or iatrogenic ablation of ovarian 
ftmction. 
 
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Females of childbearing potential who are using aneffective birth control method4 
which they intendto use for at least 30 days after the last study vaccination. 
4.2 
Exclusion Crite1i a 
 
Each subject must not have: 
1. History of any meningococcal vaccine administration other thanthe single 
vaccination given at 4 to 6 years ago (Menveo-Menveoand Menactra-Menveo 
groups) 
OR 
History of any meningococcal vaccine administration (Naive group) 
2. Current or previous, confirmed or suspected disease caused by N. meningitidis. 
3. Household contact with and/or intimate exposure to an individual with any laboratory 
confirmed N. meningitidis infection within 60 days prior to study vaccination. 
4. Progressive, unstable or uncontrolled clinical conditions. 
S. Hypersensitivity, including allergy, to any component of vaccines, medicinal products 
or medical equipment whose use is foreseen in this study. 
6. Clinical conditions representing a contraindication to intramiscular vaccination (IM) 
and blood draws. 
7. Abnormal function of the immune system resulting from: 
a. Clinical conditions. 
b. Systemic administration of corticosteroids (PO/IV/IM) for more than 14 
consecutive days within 90 days prior to study vaccination. 
c. Administration of antineoplastic and immunomodulating agents or radiotherapy 
within 90 days prior to study vaccination. 
 
 
 
 
 
 
 
 
 
 
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4 The following birth control methods areconsidered effective: 
Abstinence 
Hormonal contraceptive(such asoral,injection, transdennal patch, implant) if used for at least 30 
days prior to informed consent 
Diaphragm preferably with spermicide, tubal occlusion device 
Intrauterine device (IUD) 
Tubal ligation 
Male par1ner using condom preferably with spermicide 
Male par1ner having been vasectomized at least six months prior toinformed consent 
 
 
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8. Received immunoglobulins or any blood products within 180 days prior to informed 
consent. 
9. Received systemic antibiotic treatment within 3 days prior to study vaccination or 
blood draw. 
10. Received an investigational or non-registeredmedicinal product within 30 days prior 
to study vaccination . 
11. Study personnel as an immediate family or household member. 
12. Individuals who have received any other vaccines within 7 days (for inactivated 
vaccines) or 14 days (for live vaccines) prior to vaccination in this study or who are 
planning to receive any vaccine within 28 days from the study vaccination. 
13. Individuals who have experienced a moderate or severe acute infection and/or fever 
defined as a temperature 38°C (100.4°F) within 3 days prior to study vaccination. 
14. Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the subject due to participation in the study. 
 
 
4.3 
C1ite1ia for De.lay of Vaccina tion and/or Blood Sam pling 
 
There may be instances when individuals meet all eligibility criteria for vaccination yet 
have a transient clinical circumstance which may warrant delay of vaccination: body 
temperature elevation [ 38.0° C 
100 .4° F) within 3 days prior to intended study 
vaccination], systemic antibiotic treatment within 3 days prior to study vaccination or 
blood draw. Under such circumstances, a subject may be considered eligible for study 
enrolment after the appropriate window for delay has passed and inclusion/exclusion 
criteria have been rechecked, and if the subject is confirmed to be eligible. 
 
There is a clinical circumstance that warrants delay of blood collection for 
immunogenicityassessments in this study. This situation is listed below. In the event that 
a subject meets this criterion for delay of blood collection, blood collection may proceed 
once the window for delay has passed. 
 
Subject has received a dose of systemic antibiotics less than 3 days before the intended 
blood collection. 
 
 
 
 
 
 
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5. 
STUDY PROCEDURES 
 
The sections that follow provide an overview of the procedures that are to be followed in 
enrolling, evaluating, and following subjects who participate in this clinical study. Visits 
can be either clinic visits or safety follow-up telephone calls, as specified in the Table 
below and in the Time and Events Table4. 
 
Table 5-1 
Study Procedures 
 
Visit Category 
Procedures 
Pre-vaccinationClinic Visit(s) 
Section 5.1 describes ptocedures to befollowed 
prior to study vaccination: informed consent/assent, 
screening, enrolment, andrandomization 
VaccinatiooClinic Visit(s) 
Section 5.2 describes ptocedures to befollowed 
during each clinic visit involvingvaccination: 
vaccination, post-vaccination ptocedures, and post- 
vaccination reminders 
Post-vaccination Visit(s) 
Section 5.3 describes follow-up clinic visits and 
safety follow-up calls 
Unscheduled Visit(s) 
Section 5.4 describes possible procedures to be 
followed at unscheduled clinic visit 
Study Termination Visit 
Section 5.5 describes ptocedures to befollowed at 
the last study visit for a subject (may include early 
termination visit) 
 
5.1 
Pre-vaccination Clinic Visit(s) 
 
This section describes the procedures that must be performed for each potential subject 
prior to vaccination, including obtaining informed consent/assent, screening, enrolment 
and randomization. 
5.1.l 
Informed Consent/Assent 
 
"Informed consent" is the voluntary agreement of an individual or his/her legal 
guardian(s) to participate in research. Consent must be given with free willof choice, and 
without undue inducement. The individual must have sufficient knowledge and 
understanding of the nature of the proposed research, the anticipated risks and potential 
benefits, and the requirements of the research to be able to make an informed decision. 
 
 
 
 
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"Assent" is a term used to express willingness to participate in research by persons who 
are by definition too young to give informed consent but who are old enough to 
understand the proposed research in general, its expected risks and possible benefits, and 
 
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theactivities expected of them as subjects. Assent by itself is not sufficient, however. If 
assent is given, informed consent must still be obtained fromthe subject's parent(s) or 
legal guardian(s). Local laws define who constitutes a "child," and such definitions dictate 
whether or not a person can legally consent to participate in a protocol (Levine 1988). 
 
Infonned consent of the parent(s)/legal guardian(s) and assent of subject following local 
!RB/EC guidance must be obtained before conducting any study-specific procedures (i.e., 
all of the procedures described in the protocol). The process of obtaining informed 
consent and assent should be documented in the subject source document in addition to 
maintaining a copy of the signed and dated informed consent. Additional specifics 
regarding the informed consent and assent processes are located in section 13.2, Infonned 
Consent Procedures. 
If a subject and/or parent(s)/legalguardian(s) is unable to read, an impartial witness 
should be present during the entire informed consent and assent discussion. An impartial 
witness is defined as a person who is independent from study conduct, who cannot be 
unfairly influenced by those involved with the study, who attends the informed consent 
process if the subject or the subject's legally acceptable representative cannot read, and 
who reads the informed consent form and any other written information supplied to the 
subject. After the written informed consent form and any other written information to be 
provided to subjects, is read and explained to the subject and/or parent(s)/legal 
guardian(s) and after the subject and/or parent(s)/legal guardian(s) has verbally consented 
to the subject's participation in the study and, if capable of doing so, has signed and 
personally dated the informed consent form, the witness should sign and personally date 
the consent form. By signing the consent form, the witness attests that the information in 
the consent form and any other written information was accurately explained to, and 
apparently understood by, the subject and/or parent(s)/legal guardian(s) and that informed 
consent was freely given by the subject and/or parent(s)/legal guardian(s). 
 
5.1.2 
Screening 
 
After an individual has consented to participate in the study and infonned consent/assent 
is signed, that individual will be given a unique Screening Number manually created by 
the investigator. The subject' s unique Screening Number will be documented in the 
Screening and Enrolment log. The eligibility of the subject will be determined based on 
the inclusion and exclusion criterialisted in section 4, Selection of Study Population and 
evaluated during this screening procedure. 
 
Prior to study enrolment, demographic data will be collected from the subject, including: 
date of birth, gender, race, ethnicity, prior vaccination against meningitis. 
 
 
 
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Medical history willalso be collected, including but not limited to any medical history 
that may be relevant to subject eligibility for study participation such as prior 
vaccinations, concomitant medications, and previous and ongoing illnesses or injuries. 
Relevant medical history can also include any medical history that contributes to the 
understanding of an adverse event that occurs during study participation, if it represents 
an exacerbation of an underlying disease/pre-existingproblem. 
 
Review of systems is a structured interview that queries the subject and/or parent(s)/legal 
guardian(s) as to any complaints the subject has experienced across each organ system 
This will be performed before enrolment and used to guide physical examination. 
 
If applicable, prior and concomitant medications or vaccinations taken prior to start of 
study should be collected (refer to section 6.5, Prior and Concomitant Medications and 
Vaccines for further details). 
 
Collect vital signs (heart rate, blood pressure, and temperature (preferably taken orally). 
Measure height and weight. 
Perform pregnancy testing in women of childbearing potential (refer to section 3.5, 
Collection of Clinical Specimens for additional information) 
A general physical examination is to be performed by a qualified health care practitioner. 
"Qualified health care practitioner" refers to any licensed health care professional who is 
permitted by institutional policy to perform physical examinations and who is identified 
within the Study Staff Signature Log. 
 
The data collected through study assessments listed above willbewritten in the source 
document (see section 9.1, Source Documentation). Should the physical assessment 
reveal any abnormal values or events, these must be documented in the CRF Adverse 
Events Form 
 
Prior to vaccination, approximately 10 mL of blood will bedrawn from all subjects for 
the immunological testing see section 3.5, Collection of Clinical Specimens. 
 
In the event that the individual is determined ineligible for studyparticipation, he/she is 
considered a screen failure. The reason for screen failure must be documented in the 
Screening and Enrolment log. If the individual is determined to be eligible for the study, 
he/she willbeenrolled into the study. 
5.1.3 
Em·olment 
 
After signing the informed consent/assent fonn, if an individual is determined to be 
eligible for study participation, the investigator will emoll the subject. 
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5.1.4 Randomization 
 
Upon entering subject demographic data in IRT, the systemwill assign a 7 digit subject 
ID number consisting of the 3 digit site number and 4 digit order of randomization at the 
site. Access to IRT can be obtained by the site staffeither via web or telephone (as back 
up). The Subject ID will be the subject' s unique identification number for all CRFs and 
associated study documentation that will be used for duration of the study. After 
randomization, the Screening Number ceases to be used and remains in the Screening and 
Enrolment Log only.: During the randomization transaction in IRT Subjects will be 
assigned a kit number for Menveo vaccination and will be randomized to a blood draw 
schedule (1:1 according to previous vaccination status).The list of randomization 
assignments is produced by the IRT service provider and approved by GSK 
Randomization Office according to applicable GSK Standard Operating Procedure (SOP). 
 
IRT will also be used to ensure adequate and appropriate distribution of enrolment of 
naivesubjects across all sites. Further details may be found in study-specific plans, for eg, 
the IRT User Manual and the Randomization Configuration Document. 
 
If for any reason, after signing the infonned consent form (ICF), the subject who is 
eligible and enrolled fails to be randomized, this is called a randomization failure and the 
early termination studyprocedures nrust be applied. The reason for all randomization 
failures should be recorded in the Screening and Enrolment Log and in the source 
document as specified in the Source Data Agreement (SDA). The information on subjects 
who are randomization failures should be kept distinct from subjects who are screen 
failures, as described in section 5.1.2, Screening. 
 
If for any reason, after randomization the subject fails to undergo treatment, this is an 
Early Termination and the reason should be recorded in source document as specified in 
the SDA. The information on these Early Termination subjects should be kept distinct in 
the source documentation from randomization failures. 
 
Within each study group, subjects will be randomized into one of two different blood 
draw schedules according to a 1:1 ratio, described as follows: 
• 
Subjects getting blood draws at Day 1, Day 4 and Day 29. 
• 
Subjects getting blood draws at Day 1, Day 6 and Day 29. 
 
If for any reason, after enrolment the subject fails to undergo treatment/study procedures 
this is an Early Termination and the reason should be recorded in source document as 
specified in the Source Data Agreement (SDA). The information on these Early 
Termination subjects should be kept distinct in the source documentation from subjects 
who are screen failures, as described in section 5.1.2, Screening. 
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5.2 
Vaccination Clinic Visit 
 
The first vaccination will be performed on Day 1. 
 
For studies which have visits for concomitant vaccinations or treatments, see section 6.5, 
Prior and Concomitant Medications and Vaccines for those visit procedures. 
 
Ensure all blood samples are taken p1ior to the vaccination. 
 
After completing the pre-vaccination procedures on day 1, administer the vaccine to the 
subject according to the procedures described in section 6.3, Vaccine Preparation and 
Administration. Observe the blinding procedures described in section 3.3, Blinding 
Procedures. 
 
Prior to administrationof study vaccination, confirm that the subject does not meet any 
criteria for delaying additional study vaccinations as described in section 4, Selection of 
Study Population. 
5.2.1 
Post-vaccination Procedures 
 
The following post-vaccination procedures will be performed on day 1. 
 
• 
After vaccination, the subject will be observed for at least 30 minutes including 
observation for unsolicited adverse events, solicited adverse events, and body 
temperature measurement. Record all safetydata collected during this time in the 
subject's source document. 
• 
A Subject Diary will be used in this studyto document solicited adverse events. The 
Subject Diary is the only source for collection of these data; therefore, it is critical that 
the subject completes the Subject Diary correctly. The subject should be trained on 
how and when to complete eaclJ field of the Subject Diary. 
• 
The subject and/or parent(s)/legal guardian(s) should be trained on how to self­ 
measure localsolicited adverse events. The measurement of solicited local adverse 
events is to be performed using the ruler provided by the site. 
• 
The subject and/or parent(s)/legal guardian(s) should be instructed how to perform 
bodytemperature measurement using the thermometer provided by the site. If the 
subject feels unusually hot or cold during the day, the subject and/or parent(s)/legal 
guardian(s) should check body temperature. If the subject has fever, the highest body 
temperature observed that dayshould be recorded in the Subject Diary. 
Subject Diary training should be directed at the individual(s) who will perform the 
measurements of adverse events and who will enter the information into the Subject 
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Diary. This individual may not be the subject and/or parent(s)/legal guardian(s), but if a 
person other than the subject and/or parent(s)/legal guardian(s) enters infonnation into the 
Subject Diary, this person's identity must be documented in the Subject Diary or subject' s 
source record. Any individual that makes entries into the Subject Diary must receive 
training on completion of the Subject Diary at the time of the visit. Tilis training must be 
documented in the subject's source record. 
 
The same individual should complete the Subject Diary throughout the course of the 
study. 
 
• 
The site should schedule the next study activity clinic visit on Day 4 or Day 6 
depending to which blood draw schedule subject was randomized to with the subject 
and/or parent(s)/legalguardian(s). 
 
The subject and/or parent(s)/legal guardian(s) will be reminded to complete the Subject 
Diary and to contact the site if there are any questions, and to contact the siteimmediately 
(or as soon as the subject is medically stable) if the subject has a medical condition that 
leads to a hospitalization or an emergency room visit or to a visit to/by a doctor or is of 
concern. 
5.2.2 
Post-vaccination Reminders 
 
Reminder calls or alerts are not intended to be an interview for collection of safety data. If 
the subject and/or parent(s)/legal guardian(s) wishes to describe safety infonnation, this 
information should only be collected by a healthcare professional at the site, and the 
safety data described must be written down in the subject's medical chart. 
 
Subject Diary Reminder Calls 
 
Subject Diary reminder calls will be performed on day 3 and day S. The purpose of this 
callis to remind the subject and/or parent(s)/legal guardian(s) about completion of the 
Subject Diary. The call follows the Subject Diary Reminder Telephone Call Script 
provided to the site. The subject and/or parent(s)/legalguardian(s) should be reminded to 
contact the site via the telephone number provided in the informed consent to discuss 
medical questions. If the clinic visit at Day 4 or Day 6 overlaps with the specified window 
of the Day 3 or Day S reminder call, the Day 3/Day S reminder call maybe omitted. 
5.3 
Post-vaccination Visit(s) 
 
Post-vaccinationvisits will be performed on Day 4 or Day 6according to the blood draw 
schedule to which subject was randomized and Day 29. 
 
 
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5.3.l Follow-up Clinic Visit.(s) 
 
Fo llow -up clinic visits willbeperformed on Day 4 or Day 6 according to the blood draw 
schedule to which subject was randomized and on Day 29.During the follow-up clinic 
visit: 
 
• 
Subject Diary will be reviewed at Day 29. No changes to the infonnation recorded 
within the Subject Diary are permissible. For details on the Subject Diary see sections 
3.4.2, Tools Used for Data Collection and 5.2.1, Post-vaccination Procedures. The 
subject and/or parent(s)/legal guardian(s) willbeinterviewed to determine if any 
unsolicited adverse events occurred and if any concomitant medications or vaccines 
were taken/received in the time since the last clinic visit. This interview willfollowa 
script which willfacilitate the collection of relevant safety information. The 
healthcare professional reviewing these data willdiscuss the symptoms (if any) 
reported by the subject and willdetermine if any additional diagnoses and/or adverse 
events are present. Adverse events reported by the subject and/or parent(s)/legal 
guardian(s) at this follow-up clinic visit must be recorded in the subject's source 
documentand on an Adverse Events CRF, as specified in section 7.1, Safety 
Assessment, and not written on the script used for the interview. 
• 
Performa brief symptom-directed physical examination if necessary according to 
symptoms the subject has reported. This is a physical examination that willinclude an 
examination of organ systems that are relevant to the investigator based on review of 
the subject's reported adverse events, concomitant medication use. This assessment 
may include: measurement of vital signs, body temperature and a check of general 
appearance. The physical assessment must be performed by the investigator or 
designee of the investigator, who is qualified to perform a physical assessment in 
accordance with their institutional policy. Corresponding information is documented 
in the subject' s source document and CRF(s). 
• 
Collect a blood sample (see section 3.5, Collection of Clinical Specimens for 
additional information). 
 
The site should schedule the next study activity safety call withthe subject and/or 
parent(s)/legal guardian(s). 
 
The subject and/or parent(s)/legal guardian(s)] willreceive a written reminder of the next 
planned study activity. The subject and/or parent(s)/legal guardian(s) will bereminded to 
contact the site if there are any questions and to contact the siteimmediately (or as soon 
as the subject is medically stable) if the subject has a medical condition that leads to a 
hospitalizationor an emergency roomvisit. 
 
 
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5.3.2 Safety Follow-upCalls 
 
Safety follow-up call will be performed on Day 1S, Day 91 and Day 181. 
 
Safety follow-up calls are calls made to the subject by a healthcare  professional 
designated on the site log. These calls will follow a script which will facilitate the 
collection of relevant safety information. The subject and/or parent(s)/legalguardian(s) 
will be inteIViewed according to the script, and information related to unsolicited adverse 
events (only at Day 1S), serious adverse events (SAEs),  medically attended adverse 
events, AEs leading to withdrawal and concomitant medications or vaccinations 
associated with those events will be reviewed. All safety information described by the 
subject must be written down in a designated location within the source document and not 
written on the script used for the telephone call. 
 
Thesite should schedule the next study activity with the subject and/or parent(s)/legal 
guardian(s). 
 
The subject and/or parent(s)/legal guardian(s) will be reminded to contact the site if there 
are any questions and to contact the site immediately (or as soon as the subject is 
medically stable) if the subject has a medical condition that leads to a hospitalizationor 
an emergency room visit. 
5.4 
Unscheduled Visits 
 
Unscheduled visits are not expected within this protocol. 
 
5.5 
Study Termination Visit 
 
The study termination visit willoccur on Day 181. The termination visit will be a 
telephone call. The date of termination is the date of the last contact (clinic visit or 
telephonecall) in which the subject's health status was assessed or, in cases where the 
subject does not agree to any further safety follow-up, it is the date consent is withdrawn. 
This date should be recorded on the termination CRF page. For visit procedures to be 
performed for a subject whose planned study participation ends prematurely, please see 
section S.S.1, Early Termination Visit. 
During the telephone call, the following procedures will be performed: inteIView of 
subject and/or parent(s)/legal guardian(s) to collect medically attended adverse events, 
AEs leading to withdrawal, SAEs, as well as inteIView of subject and/or parent(s)/legal 
guardian(s) to collect concomitant medications/ vaccinations associated with those events. 
All safety information described by the subject nrust be written down in a designated 
 
 
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location within the source document and not written on the script used for the telephone 
call. 
The site will review with the subject and/or parent(s)/legal guardian(s) the plan of when 
infonnation relating to the subject's participation in the study may be available (e.g., 
study results, treatment assignments). It will also be discussed how infonnation relating to 
the subject' s participation in the study will be shared with the subject's healthcare 
provider, if the subject and/or parent(s)/legalguardian(s) chooses to share this 
infonnation. 
 
The site willcomplete the tennination CRF page and this will mark the completion of the 
subject's participation in the study. 
5.5.1 E ar ly T ermin ati on Visit 
 
When a subject is withdrawn from treatment or withdraws from the study, the investigator 
will notifythe Sponsor and, when possible, will perform the procedures listed below. The 
reason(s) for the early tennination will be included in the subject' s source documentation. 
If the EarlyTermination Visit is a telephone call, collect as much infonnation as possible. 
Early Termination Visits include subjects who were randomized but not treated. 
 
At the clinic visit or during the telephone call, the following procedures willbe 
performed: interview of subject and/or parent(s)/legal guardian(s) to collect adverse 
events, medically attended adverse events, AEs leading to withdrawal, SAEs, interview of 
subject and/or parent(s)/legalguardian(s) to collect concomitant medications/ 
vaccinations. 
The site will review with the subject and/or parent(s)/legal guardian(s) the plan of when 
infonnation relating to the subject's participation in the study may be available  (e.g., 
study results, treatment assignments). It will also be discussed how information relating to 
the subject' s participation in the study will be shared with the subject's healthcare 
provider, if the subject and/or parent(s)/legalguardian(s)  chooses to  share this 
infonnation. 
 
The sitewillcomplete the termination CRF page and this will mark the completion of the 
subject's participation in the study. 
 
 
 
 
 
 
 
 
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6. 
TREATME1''TOF SUBJECTS 
 
All vaccines associated with this study are to be stored separately from other vaccines and 
medications in a secure location under appropriate storage conditions with temperature 
monitoring. All vaccines associated with this study must be checked for expiration 
date p1i or to use . Expired vaccines must not be administered to subjects. 
 
6.1 
Study Vaccine(s) 
 
The term 'study vaccine ' refers to those vaccines provided by the Sponsor, which will be 
evaluated as part of the study objectives. The study vaccines specific to this study are 
described below. The study vaccines specific to this study is the MenACWY-CRM 
vaccine (Menveo® , GSK)  . 
 
The Meningococcal ACWY conjugate vaccine is obtained by extemporaneous mixing 
just before injection of the lyophilized MenA-CRM component with the MenCWY-CRM 
fullliquid vaccine. The pharmaceutical form is Powder and solution for solution for 
injection. Menveo® is provided as vial/vial presentation. MenA lyophilised conjugate 
component (glass vial) and MenCWY liquid conjugate component (glass vial). After 
reconstitution, MenACWY-CRM will have the following composition per O.S mL of 
injectable solution (SeeTable 6.1-1): 
 
Table 6.1-1: MenAC\VY-CR"l\1 Composition 
 
Nameof Ingr edient 
Unit and/ol' Percentage Fol'mula 
(Dose 0.5 mL) 
D1111gSubstances 
CRM191-MenA conjug;ite 
10 µg MenA,16.7- 33.3µgCRM191 
CRM191-MenCconjug;ite 
5 µgMenC, 7.1 - 12.5 µg CRM197 
CRM191-MenWconjugate 
5 µg MenW, 3.3-  8.3µgCRM191 
CRM191-MenYconjug;ite 
5 µg MenY, 5.6- 10 µgCRM197 
Sodium chloride 
4.5mg 
Excipients 
Sucrose 
12.5 mg 
Sodium phosphate buffer 
Sodium dihydrogen phosphate 
Disodium hydrogen phosphate dehydrate 
!OmM 
2.5mM 
7.5mM 
Potassium dihydrogen phosphate 
5mM 
Water for Injection 
q.s 0.5 mL 
VolumeofFormulation 
0.6mL 

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Name of Ingredient 
Unit and/ol' Percentage Fol'mula 
(Dose 0.5 mL) 
Appearance 
Colotless tolight yellow 
Vaccine Presentation 
Asingle dose of two vials 
One 0.5 mL dose ofMenACWY will be administered by intranruscular (IM) injection in 
the deltoid area of non-dominant arm (preferably.) 
 
For more detailed information, refer to the latest version of Investigator Brochure and 
SPC for Menveo® , which are included in the investigator site file. 
6.2 
Non-Study Vaccines 
Not applicable. 
6.3 
Vaccine Pr epa rntion and Administra tion 
The investigator or designee will beresponsible for oversightof the administration of 
vaccine to subjects enrolled in the study according to the procedures stipulated in this 
study protocol All vaccines will be administered onlyby personnel who are qualified to 
perform that function under applicable local laws and regulationsfor the specific study 
site. 
All studyvaccines to be administered to the subjects must be stored in a safe and locked 
place with no access by unauthorized personnel. 
The study vaccines will be stored at the defined temperature range (i.e. +2 to +8 C). The 
storage temperature of the vaccines will bemonitored daily with temperature monitoring 
devices and willberecorded. 
Any temperature deviation, i.e. temperature outside the range (+2 to +8°C), must be 
reported to the sponsor as soon as detected. Following the exposure to such a temperature 
deviation, vaccines will not be used until written approval has been given by the sponsor. 
The study vaccine should be allowed to reach room temperature before administration, 
according to local vaccination practice. 
MenACWY-CRM (Menveo) vaccine is prepared by aseptically withdrawing all fluid 
fromthe vial containing the MenCWY-CRM liquid conjugate component and injecting 
the liquid into the vial containing the MenA-CRM lyophilized portion. Invert and shake 
the vial well until the vaccine is dissolved. The finalmixed vaccine is then ready for 
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Detailed vaccine preparation and administration instructions will be provided to 
investigators in the Protocol Ancillary Document prior to study start. 
PRECAUTIONS TO BE OBSERVED IN ADMINISTERINGSTUDY VACCINE: 
 
Prior to vaccination, subjects must be determined to be eligible for studyvaccination and 
it must be clinically appropriate in the judgment of the investigator to vaccinate. 
Eligibilityfor vaccination prior to first study vaccine dministration is detennined by 
evaluating the entry criteria outlined in protocol sections 4.1, Inclusion Criteria and 4.2, 
Exclusion Criteria. 
 
Eligibility for non-study vaccines should be determined by the investigator, pending the 
review of the package insert of the relevant vaccine. 
Study vaccines should not be dministered to individuals with known hypersensitivity to 
any component of the vaccines. 
 
Standard immunization practices are to be observed and care should be taken to 
administer the injection: intramuscularly. Before administering vaccine, the vaccination 
site is to be disinfected with a skin disinfectant (e.g., 70% alcohol). Allow the skin to dry. 
DO NOT inject intravascularly. 
 
As with all injectable vaccines, trained medical personnel and appropriate medical 
treatment should be readily available in case of anaphylactic reactions following vaccine 
administration. For example, epinephrine 1:1000, diphenhydramine, and/or other 
medications for treating anaphylaxis should be available. 
6.4 
Vaccine Adminish·ation En or or Overdose of Vaccine 
 
Vaccine administration error is defined as receiving a dose of studyvaccine that was not 
reconstituted as instructed or administered by a different route from the intended route of 
administration. An overdose of studyvaccine (whether accidental or intentional) is 
defined when a dosage higher than the recommended dosage is administered in one dose 
of study vaccine. 
 
Any vaccine administrationerror or overdose of study vaccine detailed in this protocol 
must be reported as an adverse event, and if the vaccine dministration error or overdose 
is associated with a serious adverse event, it must be reported as such within 24 hours to 
the Sponsor. 
 
 
 
 
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6.5 
Plior and Concomitant Medications and Vaccines 
All medicatoi ns, vaccines and blood products taken or received by the subject within 30 
days prior to the start of the study are to berecorded on the Prior and Concomitant 
Medications CRF. 
In addition, the following are considered prior medications for this protocol: all 
medication/vaccines described in theinclusion and exclusion criteria of this protocol 
including: 
 
• Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive 
days within 90 days prior to study vaccination; 
• 
Administration of antineoplastic anrl iroro1momodulating agents or radiotherapy 
within 90 days prior to study vaccination; 
• Tmmnnnglobulins or anyblood products within 180 days prior to informed consent; 
• Systemic antibiotic treatment within 3 days prior to study vaccination or blood draw; 
• Any investigationalor non-registered medicinal product within 30 days prior to study 
vaccination; 
• Administration of vaccines within 7 days (for inactivated vaccines) or 14 days (for 
live vaccines) prior to vaccination in this study or who are planning to receive any 
vaccine within 28 days fromthe studyvaccination. 
Use of analgesics/antipyreticsto prevent or treat solicitedAEs will be captured in the 
Subject Diary from day 1-7 following each vaccination. Medications taken for 
prophylaxis arethose intended to prevent the onset of symptoms. Medications taken for 
treatment are intended to reduce or eliminate the presence of symptoms that are present. 
Concomitant medications include all prescription and non-prescription medications 
(including vaccines) taken by/administeredto the subject during the 30 days after study 
vaccination andmust be documented on the Concomitant Medications CRF. Mineral 
supplementsand vitamins are not considered concomitant medications. 
When recording concomitant medications/vaccine,sthey should be checked against the 
study entry and continuation criteria in section 4, Selection of Study Population to ensure 
that the subject should be enrolled/continue in the study. 
Concomitant medication dministered for treatment of AEs with medically-attended 
visits, AEs leading to study withdrawal andSAEs must be documented during the entire 
study period. 

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Any vaccine not foreseen in the studyprotocol in the period starting at Day1 and ending 
at Day 181 must be recorded in the eCRF. 
6.6 
Vaccine Supply, Labeling, Storage and Tracking 
The Sponsor willensure the following 
• Supply the study vaccine(s). 
• Appropriate labeling of allstudyvaccines provided that complies with the legal 
requirements of each country where the study is to be performed. 
The investigator must ensure the following: 
 
• Acknowledge receipt of the study vaccines bya designatedstaff member at the site, 
including: 
Confirmation that the vaccines were received in good condition 
Confirmation to the Sponsor of the temperature range during shipment from the 
Sponsor to the investigator's designatedstorage location 
Confirmation by the Sponsor that the vaccines are authorized for use. 
• Proper storage of the studyvaccines, including: 
Storage in a secure, locked, temperature-controlled location. 
Proper storage according to the instructions specified on the labels. 
Appropriate record keeping and inventory of the study vaccines, including regular 
documentation of adequate storage temperature. 
• Appropriate use of the study vaccines, including: 
Not use of vaccines prior to receipt of authorization for use fromthe Sponsor. 
Use only in accordance with the approved protocol 
Proper handling, including confirmation that the vaccine has not expired prior to 
administration. 
• Appropriate documentation of administrationof vaccines to study subjects including: 
- Date, dosage, batch/lot numbers, expiration dates , unique identifying numbers 
assigned to subjects and study vaccines, and time of vaccine administration. This 
information will bemaintained in an accountability log that will be reviewed by 
the site monitor. 

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- Reconciliation of all vaccines received from the Sponsor. Reconciliation is 
defined as mairitaioiog records of which and how many vaccines were received, 
which vaccines were administered to subjects, which vaccines were destroyed at 
the site, and which vaccines were returned to the Sponsor, as applicable. 
- Proper adherence to the local institutional policy with respect to destruction of 
study vaccines. 
• 
Complete record keeping of vaccine use, wastage, return or destruction, including 
documentation of 
Copy of the site's procedure for destruction of hazardous material. 
Number of doses destroyed, date of destruction, destruction code (if available), 
method of destruction, and name of individual performing destruction. 
Vaccines that have been stored differently from the manufacturer's indications must not 
be used unless the Sponsor provides written authorization for use. In the event that the use 
cannot be authorized, the Sponsor will make every effort to replace the vaccine supply. 
All vaccines used in conjunction with this protocol must be stored separately from normal 
hospital/practicestocks to prevent unintentional use of study vaccines outside of the 
clinical study setting. 
 
Monitoring of vaccine accountability will be performed by the study monitor during site 
visits and at the completion of the study. 
 
At the conclusion of the study, and as appropriate during the course of the study, the 
investigator must ensure that all unused studyvaccines, packaging and supplementary 
labels are destroyed locally (upon approval fromSponsor) or returned to the Sponsor or to 
the Depot for destruction. 

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7. 
ASSESSMENTS 
 
7.1 
Safety Assessment 
The measures of safety used in this study areroutine clinical procedures. They include a 
close vigilance for, and stringent reporting of, selected local and systemic adverse events 
routinely monitored in vaccine clinical studies as indicators of reactogenicity. 
An adverse event (AE) is defined as anyuntoward medical occurrence in a subject or 
clinical investigation subject administered a pharmaceutical product at any dose that does 
not necessarily have to have a causal relationship withthis treatment. Therefore, an AE 
can be any unfavorable and unintended sign (including an abnonnal laboratory finding, 
for example), symptom, or disease temporally associated with the use of an 
investigational product, whether or not considered related to the investigational product. 
This definition includes intercurrent illnesses or injuries and exacerbation of pre-existing 
conditions. 
The period of observation for AEs extends fromthe time the subject signs informed 
consent until he or she completes the specified safety follow-up period of 180 days or 
terminates the study early (whichever comes first). AEs occurring after the informed 
consent form is signed but prior to receiving studyvaccine/productwill be documented as 
an adverse event and recorded within source document. However, any AEs occurring 
prior to receipt of anystudyvaccine will be analyzed separately from" treatment 
emergent'' AEs (AEs occurring after dministration of the first study vaccine). 
Adverse events are collectedas either solicited or unsolicited adverse events. Solicited 
events arederived from organized data collection systems, such as Subject Diaries or 
interview. 
7.1.1 Solicited Adverse Events 
 
The term"reactogenicity'' refers to solicited signs and symptoms ("solicited adverse 
events") occurring in the hours and days following a vaccination, to be collected by the 
subject and/or parent(s)/legalguardian(s) for 7 consecutive days, using a pre-defmed 
Subject Diary. 
The following solicited adverse events are included in the Subject Diary. Each adverse 
event is to be assessed using the scoring system reported in parentheses below: 
 
 
 
 
 
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SolicitedLocal Adverse Events 
Injectionsite pain, erythema, induration, Solicited Systemic Adverse Events 
Fatigue, headache, myalgia, arthralgia, loss of appetite, nausea, chills and fever. 
Table 7.1.1-1 
Severity grading for solicitedlocal and systemic AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fever is defined and measured by a body temperature 38.0°C(100.4F). Route of 
temperature measurement is preferably oral. 
 
Other Indicators of Reactogenicity: 
• 
Use of analgesics / antipyretics for prophylaxis (Days 1-7) 
• 
Use of analgesics / antipyretics for treatment (Days 1-7) 
• Body temperature, described in degrees Celsius and summarized by route of 
measurement and in 05°C increments from 36.·o c . 
The study staff must review the data entered into the Subject Diary as described in section 
3.4.2, Tools Used for Data Collection and section S.3.1, Follow-up Clinic Visit(s). 
 
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]',fild 
Moderate 
Se.vel'e 
Pain 
No inteiference with 
dailyactivity 
Inteiferes with daily 
activity 
Prevents daily activity 
Erythema 
25-50mm 
51- IOOmm 
> l OOmm 
lnduration 
25-50 mm 
51- IOOmm 
> l OOmm 
Fatigue 
No inteiference with 
dailyactivity 
Inteifereswith daily 
activity 
Prevents daily activity 
Headache 
No inteiference with 
activity 
Inteifereswith daily 
activity 
Prevents daily activities 
Myalgia 
No inteiference with 
activity 
Inteifereswith daily 
activity 
Prevents daily activities 
Arthralgja 
No inteiference with 
activity 
Interfereswith daily 
activity 
Prevents daily activities 
Loss ofappetite 
Eating less than usual 
with no effect on normal 
activity 
Eating less thanusual / 
inteifered with normal 
activity 
Not eating at all 
Nausea 
No inteiference with 
dailyactivity 
Inteiferes with daily 
activity 
Prevents daily activity 
Chills 
No inteiference with 
activity 
Inteiferes with daily 
activity 
prevents daily activities 

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Note: Anysolicited adverse event that meets any of the following criteria must be entered 
into subjects' source document (see section 9.1, Source Documentation) and also as an 
adverse event on the Adverse Event CRF: 
 
• 
Solicited local or systemic adverse event that continues beyond day7 after 
vaccination. 
• 
Solicited local or systemic adverse event that leads to a visit to a healthcare provider 
(medically attended adverse event, see section 7.1.3, Evaluation of Adverse Events). 
• Solicited local or systemic adverse event leading to thesubject withdrawing fromthe 
study or the subject being withdrawn from the study by the investigator (adverse event 
leading to withdrawal, see section 7.1.3, Evaluation of Adverse Events). 
• Solicited local or systemic adverse event that otherwise meets the definition of a 
serious adverse event (see section 7.1.4, Serious Adverse Events). 
7.1.2 UnsolicitedAdverse Events 
An unsolicited adverse event is an adverse event that was not solicited using a Subject 
Diary and that was spontaneously communicated bya subject and/or parent(s)/legal 
guardian(s) who has signed the informed consent. 
Potential unsolicited AEs may be medically attended (defined as symptoms or illnesses 
requiring hospitalization, or emergency room visit, or visit to/by a health care provider), 
or were of concern to the subject and/or parent(s)/legal guardian(s). In case of such 
events, subjects and/or parent(s)/legal guardian(s) will be instructed to contact the site as 
soon as possible to report the event(s). The detailed information about the reported 
unsolicited AEs willbe collected by the qualified site personnel during the interview and 
will be documented in the subject's records. 
 
Unsolicited AEs that arenot medically attended nor perceived as a concern by subjects 
and/or parent(s)/legal guardian(s) will be collected during interview with the subject 
[and/or parent(s)/legalguardian(s) and by review of available medical records at the next 
visit (see section 5.3, Post-vaccination Visit(s). 
7.1.3 Evaluation of Adverse Events 
Everyeffort should be made by the investigator to evaluate safety information reported by 
a subject for an underlying diagnosis and to capture this diagnosis as the event in the AE 
page. In other words, the practice of reporting only symptoms (e.g., " cough" or "ear 
pain") are better reported according to the underlying cause (e.g., "asthma exacerbation" 
or "otitismedia"). 
 
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The severity of events reported on the Adverse Events CRF willbe determined by the 
investigator as: 
 
Mild: 
Moderate: 
Severe: 
transient with no limitation in normal daily activity. 
somelimitation in normal daily activity. 
unable to perform normal daily activity. 
 
The relationship of the studytreatment to an AE will be determined by the investigator 
based on the following definitions: 
 
1. Not Related 
The AE is not related to an investigational vaccine if there is evidence that clearly 
indicates an alternative explanation. If the subject has not received the vaccine, the timing 
of the exposure to the vaccine and the onset of the AE are not reasonably related in time, 
or other facts, evidence or arguments exist that reasonably suggest an alternative 
explanation, then the AE is not related. 
2. Possibly Related 
 
The administrationof the investigational vaccine and AE are considered reasonably 
related in time and the AE could be explained by exposure to the investigational vaccine 
or by other causes. 
 
3. Probably Related 
 
Exposure to the investigational vaccine and AE are reasonably related in time and no 
alternative explanation has been identified. 
 
The relationship of the studytreatment to an unsolicited AE will be determined by the 
investigator. 
 
Note: solicited AEs will not be evaluated for relationship to studytreatment. Grading for 
severity of solicited local and systemic AEs is described in section 7.1.1, Solicited 
Adverse Events. 
 
Adverse events will also be evaluated by the investigator for the co-existence of any of 
the other following conditions : 
 
• 
"Medically attended adverse event": an adverse event that leads to a visit to a 
healthcare provider. 
• 
AEs leading to withdrawal: adverse events leading to study or vaccine withdrawal. 
 
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If solicited or unsolicited adverse events have been reported and the subject and/or 
parent(s)/legalguardian(s)] indicated that the symptoms required medical attendance or 
were of concern, the subject and/or parent(s)/legalguardian(s) must be contacted for 
further information. 
When the subject and/or parent(s)/legal guardian(s) is contacted for any of these reasons, 
the contact must be documented in thesubject's source documentation. 
All AEs, regardless of severity, willbe monitored until resolution or until the investigator 
assesses them as chronic or stable. All subjects experiencing AEs - whether considered 
associated with the use of the study vaccine or not - must bemonitored until symptoms 
subside and any abnormal laboratory values have returned to baseline, or until there is a 
satisfactory explanation for the changes observed, or until death, in which case a full 
pathologist's report should be supplied, if possible. The investigator'sassessment of 
ongoing Adverse Events at the time of each subject's last visit should be documented in 
the subject' s medical chart. 
7.1.4 Serious Adverse Events 
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any 
dose results in one or more of the following: 
• 
Death. 
• 
Is life-threatening (i.e., the subject was, in theopinion of the investigator, at 
immediate risk of death from the event as it occUITed); it does not refer to anevent 
which hypothetically might have caused death if it were more severe. 
• 
Required or prolonged hospitalization. 
• 
Persistent or significant disability/incapacity(i.e., the event causes a substantial 
disruption of a person's ability to conduct normal life functions). 
• 
Congenital anomaly/or birth defect. 
• 
An important and significant medical event that may not be immediately life 
threatening or resulting in death or hospitalization but, based upon appropriate 
medical judgment, may jeopardize the subject or may require intervention to prevent 
one of the other outcomes listed above. 
Adverse events which do not fall into these categories are defined as non-serious. 
It should be noted that a severe adverse event need not be serious in nature and that a 
serious adverse event need not, bydefiniiton,be severe. 

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Serious adverse events will be captured both on the Vaccines Serious Adverse Event 
(VSAE) form as well as on the AE CRF. All SAEs will be evaluated by the investigator 
for relationship of the event to studyvaccine. SAEs that are judgedto be possibly or 
probably related to the studyvaccine should be reported to the Sponsor as 
related/suspected events. 
 
The relationship of the studytreatment to an SAE will be determined by the investigator 
based on the following definitions: 
 
1. Related/suspected 
 
The SAE is judged by the investigator to be possibly or probably related to the study 
vaccine on the AE CRF page (see section7.1.3, Evaluation of Adverse Events). 
 
2. Not Related 
 
The SAE is not related if exposure to the study vaccine has not occurred, or the 
occurrence of the SAE is not reasonably related in time, or the SAE is considered 
unlikely to be related to use of the study vaccine, i.e., there are no facts (evidence) or 
arguments to suggest a causal relationship. 
 
The relationship of the studyvaccine to an SAE will be determined by the investigator. 
 
In addition, SAEs will be evaluated by the Sponsor or designee for "expectedness." An 
unexpected AE is one that is not listed in the cUITent Summary of Product Characteristics 
or the Investigator's Brochure or an event that is by nature more specific or more severe 
than a listed event 
 
In addition, a pre-existing event or condition that results in hospitalization should be 
recorded on the Medical History CRF. If the onset of an event occUITed before the subject 
entered the study (e.g., any pre-planned hospitalization for conditions like cosmetic 
treatments or for non-emergency routine visits for a pre-existing condition), the 
hospitalizationwould not lead to an AE being classified as serious unless, in the view of 
the investigator, hospitalization was prolonged as a result of participation in the clinical 
study or was necessary due to a worsening of the pre-existing condition. 
7.1.4.1 
Adverse Events of Special Interest 
Adverse Events of Special Interest (AESis) will not be assessed during the study. 

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7.1.S Methods for Recording Adverse Events and Se1ious Adverse Events 
 
Findings regarding Adverse Events must be reported on an Adverse Events CRF, as 
specified in section 7.1.1, Solicited Adverse Events, and on the VSAE form, if applicable, 
which is part of the Investigator Site File. All findings in subjects experiencing AEs nrust 
be reported also in the subject's source document. 
 
All SAEs which occur during the course of the study, whether considered to be associated 
withthe study vaccination or not, must be reported wi thin 24 hours of the site becoming 
awar e of the event to GSK or its designee. Specific instructions and contact details for 
collecting and reporting SAEs to GSK willbeprovided to the investigator. 
 
All SAEs are also to be documented on the Adverse Events CRF. Any medication or 
other therapeutic measures used to treat the AE will berecorded on the appropriate 
CRF(s) in addition to the outcome of the AE. 
 
After receipt of the initial report, representatives of GSK or its designee willcontact the 
investigator if it is necessary to obtain further information for assessment of the event. 
 
All SAEs must be reported by the investigator to his/her corresponding EC/ IRB 
applicable regulatory authorities in accordance with institutional policy/regulatory 
requirements and adequate documentation of this notification must be provided to the 
Sponsor. 
 
GSK or its designee must also comply with the applicable regulatory requirement(s) 
related to the reporting of suspected unexpected serious adverse vaccine reactions (also 
known as SUSARs) to the regulatory authority(ies) and the IRB/EC. If a SUSAR or other 
safety signal relating to use of one of the study vaccines is reported to GSK or its 
designee, the Sponsor willcommunicate the information to the investigator and the 
investigator will beresponsilbe forsubmitting this information to the EC/IRB and other 
relevant authorities. 
 
7.1.S. l 
Post-S tudy Even ts 
 
Any SAE that occurs outside of the protocol-specifiedfollow-up period and considered to 
be caused by the study vaccine nrust be reported to GSK or its designee. These SAEs will 
be processed by GSK or its designee as during the course of the study, until 1 month after 
Last Subject Last Visit (LSLV). Instructions and contact details for collecting and 
reporting these suspected SAEs will beprovided to the investigato.r 
 
 
 
 
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7.1.6 
Pregnancies 
 
To ensuresubjects' safety, each pregnancy in a subject after study vaccination must be 
reported to GSK or delegate within 72 hours of the site learning of its occurrence. If the 
subject agrees to submit this information, the pregnancy must be followed to determine 
outcome, including spontaneous or voluntary termination, details of the birth, and the 
presence or absence of any birth defects, congenital abnormalities, or maternal and/or 
newborn complications. This follow-up should occur even if intended duration of safety 
follow-up for the study has ended. 
 
Pregnancy data must be recorded on a Pregnancy Report CRF (initial report) and 
Pregnancy Follow-Up CRF (outcome report) and reported to GSK or delegate. 
Instructions and contact details for submitting the Pregnancy CRFs will be provided to the 
investigator. 
Any pregnancy outcome meeting the definition of a SAE (see section 7.1.4, Serious 
Adverse Events) must also be reported on the VSAE Report Form. 
 
7.1.7 
Safety La bora tory l\ lll eas ur em e n ts 
No safety laboratory measurements will be done in this study. 
 
7.2 
Efficacy Assessment 
This section is not applicable. This studyhas no efficacy measurements. 
 
7.3 
Immunogenicity Assessment 
 
The functional measure of immunogenicity used in this study, Serum Bactericidal Assay 
(SBA), is a measure of the ability of antibodies, in concert with human complement, to 
kill meningococci, and is widely used and generally recognized as the serological 
correlate of protection The key measures of irom1mogenicitywillbe the percentages of 
subjects with seroresponse
[ I J  , percentages of subjects who achieve hSBA titers  8  and, 
and the hSBA GMfs against serogroups A, C, W and Y reference strains 
 
These measurements willbe assessed in serology samples collected at Visit Day 1, 4 or 8 
and Day 29. The measures of immunogenicity used in this study are standard, i.e., widely 
 
 
[ I J S eroresponse to N. meningitidis serogroups A, C, W and Y is defined as: for subjects with a pre­ 
vaccination hSBA titer < 4, a post-vaccinationhSBA titer 2:8; for subjectswith a pre-vaccination hSBAtiter 
24: , an increase in hSBA titer of at least four times the pre-vaccinationtiter. 
 
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used and generally recognized as reliable, accurate, and relevant (able to describe the 
quality and extent of the immune response). 
All subjects will have a blood draw at Day I, before vaccination. Subsequent blood draws 
willbe at either Day 4 or Day 6 post vaccination, and at Day 29 post vaccination. 
Primary: 
Collected samples may be used in other assays, for test improvement or development of 
analytical methods related to the study vaccines or the disease under evaluation to allow a 
more reliable measurement of the vaccine response. Under these circumstances, 
additional testing on the samples may be performed by GSK outside the scope of the 
protocol Any sample testing willbe done in line with the consent of the individual 
subject's parent/ guardian. 
 
Testing willbe conducted by qualified and certified laboratories. All assays will be 
performed in GSK, Clinical Laboratory Sciences, or a delegate laboratory. 

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8. 
STATISTICAL CONSIDERATIONS 
 
8.1 
Endpoints 
8.1.1 
Plimai-y En dpoint(s) 
 
8.1.1.1 
P1im ary Safety Endpoint(s) 
 
There are no primary safety endpoints in this study. 
8.1.1.2 
P1imar y Efficacy Endpoint(s) 
 
There are no primary efficacy endpoints in this study. 
 
8.1.1.3 
P1imary Immunogenicity Endpoint(s) 
 
Thefollowing measure willbe summarized for the pooled (Menveo-Menveo and 
Menactra-Menveo) group 
 
1. Percentage of subjects with hSBA seroresponse5 against N. meningitidis 
serogroups A, C, W and Y at Day 29. 
8.1.2 
Secondary Endpoin t(s) 
 
8.1.2.1 
Secondar y Safety Endpoint(s) 
 
Safety of the study vaccine willbe assessed in the pooled vaccine group (Menveo­ 
Menveo and Menactra-Menveo) and the vaccine-naivegroup in teimsof the frequency 
(percentage) of reported adverse events including 
 
1. Any unsolicited AEs reported within 30 minutes after vaccination; 
2. Solicited local and systemic AEs reported from Day 1 (6 hours) through Day 7 
after vaccination; 
3. Other indicators of reactogenicity (e.g. use of analgesics/ antipyretics, body 
temperature) within 7 days after vaccination; 
4. All unsolicited AEs reported from Day 1 through Day 29 after vaccination; 
 
 
 
 
5 Seroresponse is defined as: a) post-vaccination hSBA?:8 for subjectswith a pre-vaccination hSBA <4; b) 
for subjects with a pre-vaccinationhSBA ?:4, an increase of at least four timesthe pre-vaccinationhSBA. 

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5. Medically-attendedAEs, AEs leading to withdrawal and SAEs reported from Day 
1 through Day 181 (entire study period). 
Adverse events will be coded using MedDRA preferred terms as applicable. 
 
8.1.2.2 
Secondar y Efficacy Endpoint(s) 
There are no secondary efficacy endpoints in this study. 
 
8.1.2.3 
Secondar y Immunogenicity Endpoint(s) 
The following measures will be nmmari:i:ed for Menveo-Menveo, Menactra-Menveo, 
Naive and the pooled (Menveo-Menveoand Menactra-Menveo)groups unless otherwise 
noted: 
 
1. Percentage of subjects with hSBA titer 8 against N. meningitidis serogroups A, C, 
Wand Y at Day 1, Day 4, Day6 and Day 29; 
2. Percentagesof subjectswith hSBA seroresponse against N. meningitidis 
serogroups A, C, Wand Y at Day 4, Day 6 and Day 29 (Day 29: Except the 
pooled group); 
3. hSBA GMfs againstN. meningitidis serogroup A, C, Wand Y at Day 1, Day 4, 
Day 6 and Day 29; 
4. Ratios of hSBA GMfs atDay 1, Day 4, Day 6 and Day 29 (between study 
groups). 
5. Ratios of hSBA GMfs atDay 4, Day6, and Day 29 compared to Day 1 (within 
study groups). 
8.1.3 
Explora tory Endpoint(s) 
 
8.1.3.1 
Exploratory Safety Endpoint(s) 
There are no exploratory safety endpoints in this study. 
 
8.1.3.2 
Exploratory Efficacy Endpoint(s) 
There are no exploratory efficacy endpoints in this study. 
 
8.1.3.3 
Exploratory Immunogenicity Endpoint(s) 
 
There are no exploratory immunogenicity endpoints in this study. 

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8.2 
Success C1iteria 
 
8.2.1 
Success C1iteria for P1imary Objective(s) 
 
8.2.1.1 
Success C1ite1ia for P1imary Safety Objective(s) 
There are no primary safety objectives in this study. 
8.2.1.2 
S uccess C1ite1ia for P1ima ry Efficacy O bjective(s) 
There are no primary efficacy objectives in this study. 
8.2.1.3 
Success C1ite1ia for P1imary Immunogenicity Objective(s) 
To demonstrate immune response sufficiency after MenACWY-CRM booster vaccine 
administration, the lower limit of the one-sided 97.S% Confidence Interval(CI) for 
percentage of subjects with hSBA seroresponse against each of serogroups A, C, Wand 
Y must be greater than 80% (in the pooled group of subjects who received primary 
vaccination with Menveo or Menactra). The threshold of80% was previously agreed for 
demonstration of immune response adequacy in other age groups (e.g. in infants, study 
VS9_36). 
 
8.2.1.3.1  Rationale for Combining the Menveo-Menveo and Menach·a-Menveo 
groups 
Table 8.2.1.3.1-1 shows excerpt of data from a previous study (VS9Pl3El) assessing the 
immunogenicityof a booster dose of Menveo among subjects who had previously been 
vaccinated with either Menveo or Menactra 3 years prior in another study (VS9P13) while 
subjects were 11-18 years old. The table shows almost identical seroreponse rates and 
95% Cls at one-month post-booster dose of Menveo for subjects previous vaccinated with 
Menveo and Menactra. This suggests that data from the two groups can be pooled or 
combined for analysis of seroresponse following a booster doseof Menveo as planned in 
the current studyVS9_77. 
 
 
 
 
 
 
 
 
 
 
 
 
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Table8.2.l.3.l -1: 
 hSBA Seroresponse at One Month Following the Booster at 3 
Years After Vaccination, by Serogroup - Booster- PP Population 
 
Vaccination 
ACWY/ACWY 
Gt·oup IV 
MenactJ"a/ A 
GroupV 
Y 
Difference' 
G1·onp IV - G1·onp V 
<I'. 
Q. 
:, eco  Overall Seroresponse 
e 
68 (97%) 
(90-100) 
70(100°/o) 
(95-100) 
(-3%) 
(-10-2) 
N=70 
N=70 
u 
Q. 
:, eco  Overall Seroresponse 
e 
66 (93%) 
65 (93%) 
(0%) 
(84-98) 
(84-98) 
(-9-10) 
N=71 
N=70 
Q. 
:, 
ee  Overall Seroresponse 
63 (91%) 
(82-97) 
64 (93%) 
(84-98) 
(-! %) 
(-11-8) 
N=69 
N=69 
> 
Q. 
:, 
.
ec.
o  Overall Seroresponse 
e "' 
63 (90%) 
(80-96) 
65 (93%) 
(84-98) 
(-3%) 
(-13-7) 
N=70 
N=70 
Source: Table 14.2.1.7 of Clinical Study Report for V59Pl3El; 'Data represented as (difference in %)( 95% 
CI of difference). 
 
 
8.2.2 
Success C1i teria for Secondar y Objective(s) 
 
8.2.2.1 
SuccessC1i te1i a for Secondary Safety Objective(s) 
 
There are no success criteria associated with the secondary safety objectives. 
 
8.2.2.2 
S uccess C1i te1i a for Secondary Efficacy Objective(s) 
There are no secondary efficacy objectives in this study. 

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8.2.2.3 
Success C1i te1i a for Secondary Immunogenicity Objective(s) 
 
There are no success criteria associated withthe secondary immunogenicity objectives in 
this study. 
 
8.3 
Analysis Sets 
8.3.l 
AllEnrolled Set 
 
All screened subjects who provide informed consent and provide demographic and/or 
baseline screening assessments, regardless of the subject's randomization and treatment 
status in the study, and received a SubjectID . 
8.3.2 All Exposed Set 
 
All subjects in the enrolied set who receive a study vaccination. 
 
8.3.3 Safety Set 
 
Solicited Safety Set (solicited local and systemic adverse events and other solicited 
adverse events) 
 
All subjects in the Exposed Set with any solicited adverse event data. 
Unsolicited Safety Set (unsolicited adverse events) 
All subjects in the Exposed Set with unsolicited adverse event data. 
Overall Safety Set 
All subjects who are in the Solicited Safety Set and/or Unsolicited SafetySet. 
 
Subjects will be analyzed as "treated" (i.e., according to the vaccine a subject received, 
rather than the vaccine to which the subject may have been randomized). 
 
8.3.4 Full AnalysisSet (FAS) Efficacy/l mmunogenicity Set 
Full AnalysisSet Immunogenicity 
FAS <Day 1) 
All subjects in the All Enrolled Set who: 
• 
are randomized; 

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• 
provide evaluable serum samples at Day 1 whose result is available for at least one 
serogroup. 
FAS (Day4) 
All subjects in the All Enrolled Set who: 
• 
are randomized; 
• 
receive the study vaccination; 
• 
provide evaluable serum samples at Day 1 whose result is available for at least one 
serogroup (except for hSBA titer 8, GMTs and between-group GMRs calculated at 
specific timepoints); and 
• 
provide evaluable serum samples at Day 4 whose result is available for at least one 
serogroup. 
FAS (Day6) 
 
All subjects in the All Enrolled Set who: 
• 
are randomized; 
• 
receive the study vaccination; 
• 
provide evaluable serum samples at Day 1 whose result is available for at least one 
serogroup (except for hSBA titer 8, GMTs and between-group GMRs calculated at 
specific timepoints); 
• 
provide evaluable serum samples at Day 6 whose result is available for at least one 
serogroup. 
FAS (Day29) 
All subjects in the All Enrolled Set who: 
• 
are randomized; 
• 
receive the study vaccination; 
• 
provide evaluable serum samples at Day 1 whose result is available for at least one 
serogroup (except for hSBA titer 8, GMTs and between-group GMRs calculated at 
specific timepoints); 
• 
provide evaluable serum samples at Day 29 whose result is available for at least one 
serogroup. 
In case of vaccination error, subjects in the FAS sets will be analyzed " as randomized" 
(i.e., according to the vaccine a subject was designated to receive, which may be different 
fromthe vaccine the subject actually received). 

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8.3.S 
Per Protocol (PP) Set Efficacy/l mmunogenicity Set 
A PPS willbedefined for each FAS described in the previous Section with additional 
criteria specified below. 
All subjects in the FAS Immunogenicitywho 
• 
Correctly receive the study vaccine (i.e., receive the vaccine to which the subjects is 
randomized and at the scheduled time points). 
• 
Have no protocol deviations leadingto exclusion (see section 8.3.8, Protocol 
Deviations) as defined prior to unblinding / analysis. 
• 
Are not excluded due to other reasons defmed prior to unblinding or analysis (see 
section 8.3.8, Protocol Deviations) 
 
Examples for subjects excluded due to other reasons than protocol deviations are: 
Subjects who withdrew informed consent. 
8.3.6 
Other Analysis Sets 
 
There are no other analysis sets used in this study. 
 
8.3.7 
Subgroups 
Using the FAS (Day 29), the analyses of the primary objectives willbereplicated by 
center; gender; and race. 
8.3.8 
Protocol Deviations 
 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. A protocol deviation may be a reason to remove data from 
an analysis set at the time of analysis. CSR-reportable protocol deviations will bedefined 
as exclusionary fromthe analysis according to protocol objectives and endpoints, which 
will bespecified in the statistical analysis plan. In some cases exclusion of data may be 
due to a reason other than a protocol deviation, e.g. early termination. 
 
8.4 
Statistical Analysis Plan 
 
8.4.1 
Analysis of Demographic and Baseline Characteristics 
 
Descriptive statistics (mean, standard deviation, median, minimum and maximum) for 
age, height and weight at enrolment willbecalculated overall and by study group. 

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Distributions of subjects by sex and ethnic origin will be summarized overall and by 
study group. 
 
8.4.2 
Analysis of Primary Objective(s) 
 
8.4.2.1 
Analysis of Primary Safety Objective(s) 
There are no primary safety objectivesin this study. 
8.4.2.2 
Analysis of Primary Efficacy Objective(s) 
There are no primary efficacy objectives in this study. 
8.4.2.3 
Analysis of Primary Immunogenicity Objective(s) 
 
8.4.2.3.1 
Statistical Hypotheses 
Null hypothesis: 
P, :;; 0,8 0 
 
Alternative hypothesis: 
P, > 0 .80 
Where: P, is the population seroresponse rate for the pooled Menveo-Menveo and 
Menactra-Menveo group; i =,1 2, 3 4 refer to serogroup A, C, Wand Y respectively. The 
level of significance is fixed at one-sided 0.02S. 
 
8.4.2.3.2 
Analysis Sets 
 
The analysis population to be used for the primary objectives is the FAS (Day 29) Set. 
Analyses of primary objectives willbe repeated on the PPS (Day 29) to assess robustness 
of results. 
 
8.4.2.3.3 
Statistical Methods 
General 
Missing immunogenicityvalues are assumed MCAR (Missing Completely At Random) 
and therefore may not contain information that impact the result of the analysis (i.e., not 
informative). Imputation methods will therefore not be used. 
 
Overall significance level for all hypothesis tests is one-sided a = 2.5%. 
 
 
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Seroresponse (Day 29) 
Seroresponse is defined as: a) post-vaccination hSBA titer 8forsubjects with a pre­ 
vaccination hSBA titer <4; b) forsubjects with a pre-vaccination hSBA titer 4, an 
increase of at least four times the pre-vaccination hSBA. 
For each ACWY serogroup, the percentage of subjects withseroresponse willbe 
computed, along with associated two-sided 95%Clopper-Pearson Cls. 
Further details of the statistical methods will be provided in the SAP. 
8.4.3 
Analysis of Secondary Objective(s) 
8.4.3.1 
Analysis of Secondary Safety Objective(s) 
8.4.3.1.1 
Analysis of Extent of Exposur e 
Subjects will be analyzed to the extent that they were exposed to study vaccines and 
according to the available safety data for the subject during any study period. Subjects 
who withdraw early or who are lost to follow-up will be removed from the summary table 
denominator for the time period in which they have no available safety data collected. 
8.4.3.1.2 
Analysis of Solicited Local,Systemic and Other Adverse Events 
 
All solicited adverse events will be summarized according to defined severity grading 
scales. 
Frequencies and percentages of subjects experiencing each adverse event willbe 
presented for each symptom severity. Summary tables showing theoccurrence of any 
localor systemic adverse event overall and at each time point will also be presented. 
Post-vaccinationsolicited adverse events reported from Day 1 to Day 7 willbe 
summarized for the intervals Day 1 (6 hours) - Day 3, Days 4-7, Day 1 (6 hours) - Day 7 
by maximal severity and by study group. Separate analyses will be performed for 
solicited AEs reported 30 minutes after vaccination. Theseverity of solicited local 
adverse events, including injection-site erythema and induration, will be categorized 
based on linear measurement: None (0-24 mm), Mild (25-50 mm), Moderate (51-100 
mm), Severe (> 100mm). 
Injection site pain and systemic reactions, including fatigue, headache, myalgia, 
arthralgia, chills, nausea, loss of appetite, occurring up to 7 days after each vaccination 
will be summarized according to "mild", "moderate" or "severe". 
 
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Each solicited local and systemic adverse event will also be further summarized as "none" 
versus ''anY'. 
Use of antipyreticsand analgesics will be summarized by frequency, by type of use 
(prophylactic versus treatment) and percentage of subjects reporting use. 
Body teJl1)erature will be summarized separately according to the 3 schemes described 
below and will be broken down according to route of measurement: 
• 
by O.S °C increments from 36.0°Cup to ,::40°C; 
• 
by 1°C increments: <36.0, 36.0-36.9, 37.0-37.9, 38.0-38.9, 39.0-39.9, ,::40°C; 
• 
According to different cut-offs (< versus ::::): 38 . 0 , 38 .S , 39 . 0 , 39.S , 40 .0 ° C . 
 
8 .4 .3 .1. 3 
An al ys i s o f U n so li cited Advene Events 
 
This analysis applies to all adverse events occurring during the study, judged either as 
probably related, possibly related, or not related to vaccination by the investigator, 
recorded in AE CRF, with a start date on or after the dateof first vaccination. AE starting 
prior to the first vaccination willonly be listed. The original verbatim terms used by 
investigators to identify adverse events in the CRFs will be mapped to preferred terms 
using the MedDRA dictionary. The adverse events will thenbe grouped by MedDRA 
preferred terms into frequency tables according to system organ class (SOC). 
 
All reported adverse events, as well as adverse events judged by the investigator as at 
least possibly related to study vaccine, willbe summarized according to SOC and 
preferred term within SOC. These summaries will be presented by study group and by 
interval of study observation. When an adverse event occurs more than once for a subject, 
the maximal severity and strongest relationship to the vaccine willbe counted. 
 
Separate summaries will be producedfor the following categories: 
• 
Adverse events that are possibly or probably related to vaccine 
• 
Unsolicited AEs reported within 30 minutes after vaccination 
• 
Unsolicited AEs reported within 30 days after vaccination 
• 
Adverse events leading to withdrawal 
• 
Adverse events leading to a medically attended visit 
• 
Serious adverse events 
Data listings of all adverse events will be provided by subject. In addition, adverse events 
in the categories above will be provided as listed data. 
 
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8.4.3.1.4 Statistical Hypotheses 
 
There are no statistical hypotheses associated with the secondary safety objectives. 
 
8.4.3.1.S Analysis Sets 
 
Analyses of solicited adverse events - and other solicited reactions - and unsolicited 
adverse events will be performed on the relevant safety sets. 
 
8.4.3.1.6 Statistical Methods 
 
For unsolicited adverse events, the entirestudy period will be divided into the following 
intervals: onset within30 minutes after vaccination , onse t within 28 days after 
vaccination; and from Day 1 through Day 181. For solicited adverse events, the solicited 
study period will be divided into intervals: from 6 hours through day 3; from day 4 
throughday 7; and from 6 hours through day 7. 
 
No imputation methods will be used to address missing safety data. 
 
SnmmariPS of safety will be presented using frequencies and percentages within each 
study group. No statistical comparisons among the studygroups with respect to any of the 
safety parameters will be performed. 
 
8.4.3.2 
Analysis of Seconda ry Efficacy O bjective(s) 
 
There are no secondary efficacy objectives associated with this study. 
 
8.4.3.3 
Analysis of Seconda ry I mmun ogenicity Objective(s) 
 
8.4.3.3.1 
Sta tistical Hypotheses 
 
Analyses related to the secondary immunogenicity objectives will be descriptive; no 
formal statistical tests will be performed. 
8.4.3.3.2 
Analysis Sets 
 
Analysesof secondary imm1mogenicity will be based on the FAS and repeated on the 
PPS. 
 
 
 
 
 
 
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8.4.3.3.3 
StatisticalMethods 
 
General 
The hSBA titers at each visit will be logarithmicallytransformed (baselO) to obtain 
approximately nonnally distributed data. 
 
For comparison of percentages and GMT ratios, unadjusted estimates will be obtained 
along with adjusted estimates from regression models to account for potential baseline 
imbalance between study groups. 
For eachN. meningitidis serogroup A, C, Wand Y, unadjustedGMTs will be calculated, 
withtheir associated two-sided 95% Cls, by exponentiating the corresponding log­ 
transformed means and their 95% Cls. Adjusted GMR.s will be obtained from Analysis of 
Covariance (ANCOVA) models. 
 
See section 8.4.2.3.3 for other relevant details. 
 
Seroresponse (Day 29) 
 
The percentage of subjects with seroresponse and associated two-sided 95% Clopper­ 
Pearson Cls will be computed by group (Menveo-Menveo, Menactra-Menveo, and Naive) 
and N. meningitidis serogroups A, C, W and Y test strains. Differences in percentages and 
associated 95% Cls between study groups will be calculated using the Miettinen & 
Nurminen score method. 
 
In a descriptive fushion - using the difference in percentages and 95% Cls - each of the 
previously vaccinated groups will be compared to the nai:Ve group . Also the two 
previously vaccinated study groups will be compared to each other. 
 
As sensitivity analyses, the difference in percentages will also be obtained from a log­ 
linear model adjusting for center and pre-vaccinationtiter. Please see SAP for technical 
details. 
 
 
 
 
 
 
 
 
 
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Percentage of Su bjects \Vith hSBA titere::8 (Da y I , Da y 4, Da y 6, and D ay 29) 
 
For each study group and in the pooled group, the percentage of subjects with hSBA titer 8 
andassociatedtwo-sided 95% Clopper-Pearson Cls will be computed by the N. 
meningitidis serogroups A, C, W and Y test strains on Day 1, Day 4, Day 6 and Day 29 
(as applicable, depending on blood draw schedule). 
Differences in percentages and associated 95% Cls between study groups will be 
calculated using the Miettinen & Nurminen score method. 
 
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In a descriptive fashion - using the difference in percentages and 95% Cls - the previously 
vaccinated groups (individually and pooled) will be compared to the naive group. Also 
the two previously vaccinated groups will be compared to each other. 
 
As sensitivity analyses, the difference in percentages will also be obtained from a log­ 
linear model adjusting for center and pre-vaccinationtiter. Please see SAP for technical 
details. 
 
Between-gr oup Ratios of Gl\ lll T s (Ad jus ted an d U na d ju sted) 
 
The between -group ratio ofhSBA GMTs and corresponding 95% CI, at each of Visit Day 
1 (Persistence), Day 4, Day 6 and Day 29 against each N. meningiti.dis serogroups A, C, 
W and Y test strains will be obtained by exponentiatingthe mean between-group 
differences in log-transformedtiters and the corresponding 95% Cls at each of the 
timepoints specified. 
Additionally, adjusted ratio of GMTs will be obtained fromANCOVA models including 
center and pre-vaccination titer as factors in the model. 
 
The previously vaccinated groups (individually and pooled) will be compared to the naive 
group at each timepoint - descriptively - using the ratios of GMTs. 
The two previously vaccinated groups will be compared at each timepoint using GMT 
ratios. 
\Vithin-gro up Ratios of Gl\ lll T s (Ad jus ted an d U na d ju sted) 
Within each study group and for each antigen/serotype, ratios of GMT will be calculated, 
as applicable, at: 
• 
Visit Day 4 versus at Visit Day 1; 
• 
Visit Day 6 versus at Visit Day 1; and 
• 
Visit Day 29 versus at Visit Day 1. 
 
The unadjusted GMRs and 95% Cis will be constructed by exponentiating the mean 
within-groupdifferences in log-transformed titers and the corresponding 95% Cls. 
Adjusted GMRs will be obtained from Analysis of Covariance (ANCOVA) models 
including center as factor in the model. Further details of the statistical methods will be 
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8.4.4 
Analysis of Explora tor y Objectives 
 
8.4.4.1 Analysis of Explora tor y Safety Objective(s) 
There are no exploratory safety objectivesin this study. 
8.4.4.2 
Analysis of Explorator y Efficacy Objective(s) 
There are no exploratory efficacy objectives in this study. 
8.4.4.3 
Analysis of Explora tor y Immunogeoicity Objective(s) 
There are no exploratory immunogenicityobjectives in this study. 
8.5 
Sam ple Size and Power Considera tions of P1imary Objectives 
Statistical power was estimated based on observed data from study V59Pl3El , where 
seroresponse rates at one-month post booster dose ofMenACWY-CRM ranged from 
97% (90%-100%) to 100% (95%-100%)for serogroup A, 93% (85%-98%) for serotype 
C; 91% (82%-97%) to 93% (84%-98%) for serogroup W; and 90% (80%-96%) to 93% 
(84%-98%) for serogroup Y among subjects printed with MenACWY-CRM or Menactra 
in the three years preceding the study. 
Assuming the trueseroresponse rates in the pooled group range from 90% to 97% 
(alternative hypothesis) for each serotype, a sample size of n=540will have at least 96% 
power to show sufficiency of immune response to a booster dose of MenACWY-CRM in 
the pooled group, compared with a pre-specified reference seroresponse of 80% (null 
hypothesis) using an exact test with 0.025 one-sided significance level. When taking a 
10% dropout rate into account, N=600 previously vaccinated subjects have to be enrolled 
in the study. Calculations have been done with nQuery Advisor (Version 7.0). 
 
Table 8.5-1: 
Sta tistical Power to Test for Sufficiency of Immune Response 
Given a Range of True Seroresponse Rates for Evaluable Sample 
Size of 540 subjects 
 
Serot}11e 
T111e Sero r es ponseRate 
Power 
A 
0.97 
0.99 
C 
0.93 
0.99 
w 
0.91 
0.99 
y 
0.90 
0.99 
Total Power 
0.96 
 
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8.6 
Interim Analysis 
No interim analysis of data from this studyis planned. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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9. 
SOURCE DOCUMENTATION, STUDY MONITORING AND AUDITING 
In order to ensure consistency across sites, study monitoring and auditing will be 
standardized and performed in accordance with the Sponsor's or delegated contract 
research organization' s (CRO) standard operating procedures and applicable regulatory 
requirements (e.g., FDA, EMA, and ICH guidelines). 
 
Prior to enrolment of the first study subject, GSK or delegate will traininvestigators 
and/or their study staff on the study protoco allapplicable studyprocedures, 
documentation practices and all electronic systems. CRFs supplied by the Sponsor must 
be completed for each randomized subject (see section 8.3.1, All Enrolled Set for 
definition of enrolled subject). Documentation of screened but not enrolled subjects must 
be maintained at the site and made available for review by the site monitor. Data and 
documents will be checked by the Sponsor and/or monitor. 
9.1 
Source Documentation 
 
Prior to the start of the study, the site staff participating in the study conduct will be 
instructed on what documents will be required for review as source documents. The kinds 
of documents that will serve as source documents will be agreed between Sponsor or 
delegate and investigator and designees and specified in the SDA prior to subject 
enrolment. 
 
In addition, source documentation must include all of the following: subject identification 
(on each page), eligibility and participation, proper informed consent procedures, dates of 
visits, adherence to protocol procedures, adequate reporting and follow-up of adverse 
events,: documentation of prior/concomitant medication/vaccines, study vaccine 
receipt/dispensing/return records, study vaccine administration information, any data 
collected by a telephone conversation with the subject and/or parent(s)/legal guardian(s) 
and date of completion and reason. 
 
 
 
 
 
 
 
 
 
 
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The subject and/or parent(s)/legal guardian(s) must also allow access to the subject's 
medical records. Each subject and/or the parent(s)/legal guardian(s) must be informed of 
this prior to the start of the study and consent for access to medical records may be 
required in accordance with local regulations. 
All safetydata reported by subjects must be written down in source documents prior to 
entry of the data into CRFs. If there are multiple sources of information (e.g., Subject 
Diary, verbal report of the subject, telephone contact details, medical chart) supporting 
the diagnosis of an adverse event, thesesources must be identified in the source 
documents, discrepancies between sources clarified, the ultimate diagnosis must be 
justified and written in the source documents, and this diagnosis must be captured in the 
 
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Adverse Event CRF (AE CRF). The AE CRFmust also capture which source(s) of 
infonnation were used to detennine the adverse event (e.g., subject recall, medical chart, 
Subject Diary). 
9.2 
Study Monitorin g, Auditing and Sow·ce Data Verification 
Prior to enrolment of the first study subject, GSK or its designee (e.g., a CRO) will 
develop a Clinical Monitoring Plan to specify how centralized and/or on-site monitoring, 
including clinical specimens reconciliation, will be performed for the study. Study 
progress will be monitored byGSK or its designee as frequently as necessary to ensure: 
• 
that the rights and well-beingof human subjects are protected, 
• 
the reported study data are accurate, complete, and verifiable from the source 
documents and 
• 
the conduct of the studyis in compliance with the cUITent approved 
protocol/amednment(s), GCP and applicable regulatory requirements. 
Contact details for the GSK teamor its designee involved in study monitoring will be 
provided to the investigator. Study data recorded on CRFs will be verified by checking 
the CRFentries against source documents in order to ensure data completeness and 
accuracy as required by study protocol. . 
Data verification may also be performed through a centralized review of data (e.g., 
checking for outliers or other anomalies). Additional documents such as the investigator 
site file, pharmacy records, and infonned consent documentation must also be available 
for review if requested. Arrangements for monitoring visits will be made in advance in 
accordance with the monitoring plan, except in case of emergency. 
The investigator and/or site staff must make source documents of subjects enrolled in this 
study available for inspection by GSK or its representative at the time of each monitoring 
visit and Sponsor audits, when applicable. These documents must also be available for 
inspection, verification and copying, as required by regulation,sbyofficials of the 
regulatory health authorities (e.g., FDA, EMA and others) and/or ECs/IRBs. The 
investigator and study site staff must comply with applicable privacy, data protection and 
medical confidentialitylaws for use and disclosure of infonnation related to the study and 
enrolled subjects. 
 
 
 
 
 
 
 
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10. 
DATA MANAGEME1''T 
10.1 
Data Enh·y and Management 
 
In this study, all clinical data (including, but not limited to, AE/SAEs, concomitant 
medications, medical history, and physical assessments), safety data, and immunogenicity 
data will be entered onto case report fonns (CRFs) in a timely fashion by the investigator 
and/or the investigator's dedicated site staff. Data entered onto CRFs are stored on a 
secure website. The data collected on this secure website are assimilated into an 
electronic data capture (EDC) system, which is compliant with Title 21 Part 11 policies of 
the Code of Federal Regulations (FDA 1997). The data system includes password 
protection and internal quality checks. The EDC system will be designed and validated by 
the Sponsor prior to activation for data entry by sites. The investigator or designated 
delegate nrust review data entered and electronicallysign the CRFs to verifytheir 
accuracy. 
 
Access to the EDC system for data entryor review will require training and distinct 
individual access code assignments to those site staffmembers who willbe entering study 
data and those involved in study oversight who may review study data. Data are collected 
within the EDC system, to which the Sponsor and site monitors have exclusively "read 
only" access. 
 
10.2 
Data Cla1ifi cation 
 
As part of the conduct of the trial, the Sponsor may havequestions about the data entered 
by the site, referred to as queries. The monitors and the Sponsor are the only parties that 
can generate a query. All corrections and clarifications will be entered into the EDC 
system and will be identified by the person entering the information, the reason for the 
change, as well as the time of the changes made. If changes are made to a previously and 
electronically signed CRF, the investigator must confirm and endorse the changes. 
 
10.3 
Data Protection 
 
GSK respects the subjects' rights to privacy and willensure the confidentiality of their 
medical information in accordance with all applicablelaws and regulations. 
 
 
 
 
 
 
 
 
 
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11. 
RECORD RETENTION 
 
Investigators must retain all study records required by GSK and by the applicable 
regulations in a secure and safe facility. The investigator must consult a GSK 
representativebefore disposal of any studyrecords, andmust notify the Sponsor of any 
change in the location, disposition, or custody of the study files. Essential documents 
must be retained for 1S years. "Essential documents" are defined as documents that 
individually and collectively permit evaluation of the conduct of a study and the quality 
of the data produced. These documents should be retained for a longer period, however, if 
required by the applicable national regulatory or institutional requirements. 
 
These principles of record retention will also be applied to the storage of immnoogenicity 
samples, provided that the integrity of the stored sample permits testing. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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12. 
USE OF Jll,'FORMATION AND PUBLICATION 
 
GSK assures that the key design elements of this protocol willbe posted in a publicly 
accessible database such as clinicaltrials.gov, and in compliance with cUITent regulations. 
 
GSK also assures that key results of this clinical study will be posted in a publicly 
accessible database within the required time-frame from theend of study as defined in 
section 3.9, End of Study. 
In accordance with standard editorial, ethical practices and cUITent guidelines of Good 
Publication Practice (Graf 2009), GSK will generally support publication of multicenter 
studies only in their entirety and not as individual center data. In this case, a coordinating 
investigator will be designated by mutual agreement prior to the start of the study. The 
coordinating investigator will also sign the clinical study report on behalf of the principal 
investigators (CPMP/EWP/2747/00). Authorship willbe determined by mutual agreement 
and in line with International Committee of Medical Journal Editors authorship 
requirements. Any fonnal publication of the studyin which contribution ofGSK 
personnel exceeded that of conventional monitoring will be considered as a joint 
publication by the investigator and the appropriate GSK personnel. 
 
Novartis must be notified of any intent to publish data collected from the study and prior 
approval from GSK must be obtained prior to submission for publication. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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13. 
ETIDCAL CONSIDERATIONS 
 
13.1 
Regulatory and Ethical Compliance 
The study will be conducted in compliance with the protocol, GCP and applicable 
regulatory requirement(s). 
 
This clinical study was designed and shall be implemented and reported in accordance 
withthe ICH HarmonizedTripartite Guidelines for GoodClinical Practice, with 
applicable local regulations including European Directive 2001/20/EC, US Code of 
Federal Regulations Title 21, and Japanese Ministry ofHealth, Labor, and Welfare, GSK 
codes on protection of human rights, and with the ethical principles laid down in the 
Declaration of Helsinki (European Council 2001, US Code of Federal Regulations, ICH 
1997). 
 
13.2 
Informed Consent Procedures 
 
Eligible subjects may only be included in the study after providing written informed 
consent or assent, as described in section 5.1.1, Informed Consent/Assent. Before the start 
of the study, the investigator will have the informed consent and any other materials that 
will be provided to the subjects reviewed and approved by the IRB/EC. This review and 
approval will be documented and stored with other studydocuments. The investigator or 
designee must fully inform the subject or legal guardian of all pertinent aspects of the 
study. A copy of the written informed consent will be given to the subject or the designee. 
The subject/designee must be allowed ample time to ask about the details of the study and 
to make a decision as to whether or not to participate in the study. The subject and/or legal 
guardian(s) must sign the consent form indicating their agreement to participate in the 
studybefore anystudy-related procedures are conducted. The informed consent process 
may be conducted up to 5 days prior to vaccination on Day I. If the subject and/or legal 
guardian(s) is unable to read and write, a witness must be present during the infonned 
consent discussion and at the time of informed consent signature. 
 
Prior to the start of the study, GSK will provide to investigators a proposed informed 
consent form that complies with the ICH GCP guideline and regulatory requirements and 
is considered appropriate for this study. Any changes to the proposed consent form 
suggested by the investigator must be agreed to by GSK before submission to the IRB/EC 
and a copy of the approved version must be provided to the GSK monitor after IRB/EC 
approval 
 
 
 
 
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Women of childbearing potential should be informed that taking the study medication 
may involve unknown risks to the fetus if pregnancy were to occur during the study and 
agree that in order to participate in the study they must adhere to the contraception 
 
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requirements indicated in the protocol for the duration of the study. If case of doubts on 
the ability of a subject to adhere to these requirements, that subject should not be allowed 
in the study 
Before the start of the study, the investigator willhave the informed assent, the informed 
consent, and any other materials that will be provided to the subject and/or parent(s)/legal 
guardian(s) reviewed and approved by the IRB/EC. This review and approval willbe 
documented and stored with other study documents. The investigator or designee must 
fully inform the subject and/or parent(s)/legalguardian(s) of all pertinent aspects of the 
study. A copy of the written informed consent and informed assent willbegiven to the 
subject and/or parent(s)/legalguardian(s). 
 
In addition, the investigator or designee should explain pertinent aspects of the study in an 
age appropriate manner to pediatric subjects who are eligible for informed assent in 
accordance with local policies. The subject and parent(s)/legalguardian(s) must be 
allowed ample time to ask about the details of the study and to make a decision as to 
whether or not to participate in the study. The subject and parent(s)/legal guardian(s) must 
sign the consent/assent forms indicating their agreement to participate in the study before 
any study-related procedures are conducted. If the subject and/or parent(s)/legal 
guardian(s) are unable to read and write, a witness must be present during the informed 
consent/assentdiscussion and at the time of informed consent/assentsignature. 
13.3 
Responsibilities of the Investiga tor a nd IRB/EC 
 
The protocol and the proposed informed consent form must be reviewed and approved by 
a properly constituted IRB/EC before study start. Properly constituted IRB/EC is defined 
in ICH Guideline for Good Clinical Practice E6 (RI), Section 3 (ICH 1997). A signed and 
dated statement that the protocol and informed consent have been approved by the 
IRB/EC must be given to GSK before study initiation. Prior to studystart and at any time 
the protocol is amended during studyconduct, the investigator is required to sign a 
protocol signature page confirming his/her agreement to conduct the study in accordance 
withthese documents and all of the instructions and procedures found in this protocol and 
to give access to all relevant data and records to GSK monitors, auditors, GSK Clinical 
Quality Assurance representatives, designated agents of Novartis, IRBs/ECs, and 
regulatory authorities as required. If an inspection of the clinical site is requested by a 
regulatory authority, the investigator must inform GSK immediately that thisrequest has 
been made. 
 
The investigator also responsible for the following: 
• 
Maintaining a list of appropriately qualified persons to whom the investigator has 
delegated significant study-related duties. 

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• 
Demonstrating the capability of recruiting the required number of suitable subjects 
within the recruitment period. 
• 
Demonstrating sufficient time and staffing to properly conduct and complete the study 
within the agreed study period. 
• 
Ensuring that all persons assisting with the study are adequately informed about the 
protoco the investigationalproduct(s,)and their study-relatedduties and functions 
• Ensuring that appropriately trained health care professionals are responsible for all 
study-related medical decisions and for ensuring appropriate medical care of subjects 
experiencing any adverse event related to the study. 
• 
If permission to do so is given by the subject and/or parent(s)/legalguardian(s), 
ensuring that the subject's primary healthcare provider is informed of the subject's 
participation in the study. 
The investigator should not implement any deviation from, or changes of the protocol 
without agreement by the Sponsor and prior review and documented approval/favourable 
opinion from theIRB/IEC of an amendment, except where necessary to eliminate an 
immediate hazard(s) to study subjects, or when thechange(s) involves only logistical or 
administrative aspects of the study (e.g., change in monitor(s), change of telephone 
nwnber(s)). In addition, the investigato,ror person designatedby the investigato,rshould 
document and explain any deviation from the approved protocol. 
 
The investigator may implement a deviation from, or a change of, the protocol to 
eliminate an immediate hazard(s) to study subjects without prior IRB/IEC 
approval/favourable opinion. As soon as possible, the implemented deviation or change, 
the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be 
submitted: 
(a) to theIRB/IEC for review and approval/favourable opinion, 
(b) to the Sponsor for agreement and, if required, 
(c) to the regulatory authority(ies). 
13.4 
Protocol Amendments 
An amendment is a written descriptionof change(s) to or formal clarification of a study 
protocol which may impact on the conductof the clinical study, potential benefit of the 
clinical study, or may affect subject safety, including changes of study objectives, study 
design, subject population, sample sizes, studyprocedures, or significant administrative 
aspects. An administrative change of a studyprotocol is a minor correction or 
clarificationthat has no significant impact on the waythe clinical study is to be conducted 

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and no effect on subject safety (e.g., change of telephone number(s), logistical changes.) 
Protocol amendments nrust be approved by GSK, health authorities where required, and 
the IRB/EC. In cases when the amendment is required in order to protect the subject 
safety, the amendment can be implemented prior to IRB/EC approval. Notwithstanding, 
the need for formal approval of a protocol amendmen,tthe investigator is expected to take 
any inunediate action required for the safety of anysubject included in this study, evenif 
this action represents a deviation from the protocol. In such cases, GSK should be notified 
of this action, the IRB/EC at the study site, and, if required bylocal regulations, the 
relevant health authority) should be informed within 10 working days. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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14. 
REFERENCE LIST 
Code of Federal Regulations (1997): Food and Drug Administration, U.S. Depar1ment of 
Health and Human Services: Title 21, Part 11: Electronic Records Electronic Signatures. 
Federal Register 62: 13464 
European Parliament (1995): Directive 95/46/EC of the European Parliament and of the 
Council of 4 April 2001. Official Journal of the European Communities. L 281/31-39 
European Parliament (2001): Directive 2001/20/EC of the European Parliament and of 
the Council of 4 April 2001. Official Journal of the European Communities. L 121/34-44 
Graf C, Battisti WP, Bridges D (2009). Good publication practice for communicating 
company Sponsored medical research: the GPP2 guidelines. BMJ; 339: b4330 
ICH (1997) ICH Harmonised Tripartite ICH Guideline for Good Clinical Practices E6 
(RI). Federal Register, 62 (90): 25691-25709 
 
ICH (1998) ICH Harmonised Tripartite ICH Guideline for Statistical Principles for 
Clinical Trials E9. Federal Register, 63 (179): 49583 
Levine RJ. (1988) Ethics and Regulations of Clinical Research. New Haven: Yale 
University Press. 
 
U.S. Depar1ment of Health and Human Services, Food and Drug Administration, CBER 
(2009): Guidance for Industry Patient-Reported Outcome Measures: Use in Medical 
Product Development to Support Labeling Claims 
 
59th World Medical Association General Assembly (October 2008) Declaration of 
Helsinki - Ethical Principles for Medical Research Involving Human Subjects. Seoul, 
Korea 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Date: Wednesday, 24 February 20 1,6 1 3:16 GMT 
Meaning: As an approver, I agree with the content and format of this document 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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