A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, OBSERVER-BLINDED STUDY TO ASSESS THE IMMUNOGENICITY, SAFETY, AND TOLERABILITY OF BIVALENT RLP2086 WHEN ADMINISTERED AS A 2-DOSE REGIMEN AND A FIRST-IN-HUMAN STUDY TO DESCRIBE THE IMMUNOGENICITY, SAFETY, AND TOLERABILITY OF A BIVALENT RLP2086-CONTAINING PENTAVALENT VACCINE (MENABCWY) IN HEALTHY SUBJECTS>=10 TO <26 YEARS OF AGE
Phase: PHASE3
Conditions: Meningococcal Vaccine
Sponsor: Pfizer

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
B1971057
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PFIZER CONFIDENTIAL
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A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, OBSERVER-BLINDED 
STUDY TO ASSESS THE IMMUNOGENICITY, SAFETY, AND TOLERABILITY 
OF BIVALENT rLP2086 WHEN ADMINISTERED AS A 2-DOSE REGIMEN AND A 
FIRST-IN-HUMAN STUDY TO DESCRIBE THE IMMUNOGENICITY, SAFETY,
AND TOLERABILITY OF A BIVALENT rLP2086–CONTAINING PENTAVALENT 
VACCINE (MenABCWY) IN HEALTHY SUBJECTS ≥10 TO <26 YEARS OF AGE
Investigational Product Number:
PF-05212366
Investigational Product Name:
Neisseria meningitidis Serogroup B Bivalent 
Recombinant Lipoprotein 2086 Vaccine
(Bivalent rLP2086)
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
2016-004421-17
Protocol Number:
B1971057
Phase:
3
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.
CCI

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
B1971057
Final Protocol Amendment 2, 09 July 2019
PFIZER CONFIDENTIAL
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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 2
09 July 2019

Added edits included in the administrative letters dated 
13 July 2018, 18 February 2019, and 29 March 2019.

Opened enrollment in Stage 2 to ACWY-experienced 
subjects in addition to ACWY-naïve subjects. This is based 
on the recommendation from the Centers for Disease 
Control and Prevention (CDC) Advisory Committee on 
Immunization Practices (ACIP) to obtain data on the 
persistence of the immune response after 2 doses of 
MenABCWY as well as on the safety and immunogenicity 
of the booster response in individuals who had previously 
received an ACWY-containing vaccine.

Moved the booster dose safety endpoints from secondary to 
primary safety endpoints. These changes were made in 
consideration of a potential schedule that would include a 
booster for adolescents Safety of the booster dose was,
therefore, reprioritized to a primary safety endpoint.

Moved some immunogenicity endpoints (related to 
persistence evaluation) from secondary to exploratory 
endpoints. As booster responses were not previously 
assessed for MenABCWY, certain secondary 
immunogenicity endpoints for persistence and booster 
response were reconsidered and deemed more appropriate as 
exploratory endpoints.

Removed the 1:4 endpoint for ACWY strains for the 
persistence and booster endpoints. As the ACWY assay 
qualification had established that the lower limit of 
quantitation (LLOQ) could not be qualified at the start of the 
study, but subsequently qualified prior to unblinding with 
the LLOQ ≥1:8 for all 4 serogroups, the 1:4 titer was 
uninterpretable and therefore removed from analysis.

Added LLOQs for the ACWY strains. This was added 
because the LLOQ was established during assay 
qualification.

Updated the grading for redness and swelling in the mild and 
moderate categories in Table 7 to be consistent with the 
analyses performed in Stage 1.
Amendment 1
23 August 2017

Addition of edits included in the administrative letter dated 
24 February 2017.

Increase in Visit 6 and 7 windows to allow additional time 
for unblinding of all subjects prior to Visit 6 completion.

Increase in the volume of the subset blood draws at Visits 1, 
2, and 4 from 50 to 100 mL to support assay development.  
The volume of blood drawn will depend on the consent 
obtained.

Addition of a subset of subjects having a 100-mL blood 
draw at Visit 11 rather than 20 mL.

Correction in Section 3.1 of the duration of Stage 1 
participation for subjects in the ACWY-naive stratum.

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
B1971057
Final Protocol Amendment 2, 09 July 2019
PFIZER CONFIDENTIAL
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Document
Version Date
Summary of Changes and Rationale

Clarification of laboratory testing personnel blinding status 
in Section 5.3.

Clarification added to Sections 9.5.2 and 9.6 as to what the 
primary analysis population is for MnB and MenA/C/W/Y 
responses.

Addition of an optional blood draw of 50 mL of whole blood 
at Visit 4 at designated sites. Several changes were made 
throughout this protocol amendment to adjust blood volumes 
collected at Visit 4 and to modify language in order to allow 
whole blood sample testing for exploratory purposes. 
Additional exploratory analyses will be performed on study 
samples to augment vaccine assay development.
Original Protocol
16 January 2017
N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).  

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................9
PROTOCOL SUMMARY.......................................................................................................10
Objectives and Endpoints...............................................................................................11
Study Design ..................................................................................................................15
Investigational Products .................................................................................................17
Statistical Methods .........................................................................................................17
SCHEDULE OF ACTIVITIES................................................................................................19
1. INTRODUCTION ...............................................................................................................24
1.1. Mechanism of Action/Indication.............................................................................24
1.2. Background and Rationale ......................................................................................24
1.2.1. Background of Disease and Medical Need.................................................24
1.2.2. Prior Clinical Experience............................................................................26
1.2.2.1. Bivalent rLP2086 (Trumenba) ..................................................26
1.2.2.2. Nimenrix (MenACWY-TT) ......................................................27
1.2.3. MenA, MenC, MenW, and MenY Functional Antibody Assays as a 
Surrogate of Efficacy.......................................................................................28
1.2.4. Study Rationale...........................................................................................29
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................29
3. STUDY DESIGN.................................................................................................................37
3.1. Approximate Duration of Subject Participation......................................................40
3.2. Approximate Duration of Study..............................................................................40
3.3. Approximate Number of Subjects...........................................................................40
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................40
4.1. Inclusion Criteria.....................................................................................................41
4.2. Exclusion Criteria....................................................................................................41
4.3. Criteria for Temporarily Delaying Vaccine Administration...................................43
4.4. Criteria for Temporarily Delaying Blood Collection..............................................43
4.5. Lifestyle Requirements ...........................................................................................43
4.5.1. Contraception..............................................................................................43

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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4.6. Sponsor’s Qualified Medical Personnel..................................................................44
5. INVESTIGATIONAL PRODUCTS ...................................................................................45
5.1. Allocation to Investigational Product......................................................................45
5.2. Blinding of Site Personnel.......................................................................................46
5.3. Blinding of the Sponsor...........................................................................................46
5.4. Blinding of the Pilot Cohort....................................................................................46
5.5. Breaking the Blind ..................................................................................................47
5.5.1. Planned Unblinding ....................................................................................47
5.6. Subject Compliance.................................................................................................47
5.7. Investigational Product Supplies.............................................................................47
5.7.1. Dosage Form(s) and Packaging..................................................................47
5.7.2. Preparation and Dispensing........................................................................48
5.8. Administration.........................................................................................................48
5.9. Investigational Product Storage ..............................................................................49
5.10. Investigational Product Accountability.................................................................50
5.10.1. Destruction of Investigational Product Supplies ......................................50
5.11. Concomitant Treatment(s).....................................................................................51
5.11.1. Prohibited During the Study.....................................................................51
5.11.2. Permitted During the Study ......................................................................51
5.11.3. Prior Treatment.........................................................................................52
5.11.4. Prohibited Prior Treatments......................................................................52
6. STUDY PROCEDURES .....................................................................................................52
6.1. Informed Consent Process.......................................................................................52
6.2. Stage 1.....................................................................................................................53
6.2.1. Visit 1 (Day 1): Vaccination 1....................................................................53
6.2.2. Visit 2 (28 to 42 Days After Visit 1), Post–Vaccination 1 Blood 
Draw.................................................................................................................56
6.2.3. Visit 3 (173 to 194 Days After Visit 1): Vaccination 2..............................57
6.2.4. Visit 4 (28 to 42 Days After Visit 3), Post–Vaccination 2 Blood 
Draw.................................................................................................................59
6.2.5. Visit 5 (168 to 196 Days After Last Vaccination), Telephone Contact......61

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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6.2.6. Visit 6 (After Study Unblinding and Prior to Transition to Stage 2) 
Telephone Contact ...........................................................................................61
6.3. Stage 2.....................................................................................................................62
6.3.1. Visit 7 (336 to 694 Days After Visit 3), Antibody Persistence Blood 
Draw 1..............................................................................................................62
6.3.2. Visit 8 (700 to 756 Days After Visit 3), Antibody Persistence Blood 
Draw 2..............................................................................................................63
6.3.3. Visit 9 (1064 to 1120 Days After Visit 3), Antibody Persistence 
Blood Draw 3...................................................................................................63
6.3.4. Visit 10 (1428 to 1484 Days After Visit 3): Booster Vaccination .............64
6.3.5. Visit 11 (28 to 42 Days After Visit 10), Postbooster Blood Draw.............66
6.3.6. Visit 12 (168 to 196 Days After Booster Vaccination), Final 
Telephone Contact ...........................................................................................67
6.4. Unscheduled Visits..................................................................................................68
6.5. Subject Withdrawal.................................................................................................68
7. ASSESSMENTS..................................................................................................................70
7.1. Pregnancy Testing...................................................................................................70
7.2. Biological Samples..................................................................................................70
7.2.1. Immunogenicity..........................................................................................71
7.2.2. Serum Bactericidal Assays .........................................................................71
7.2.2.1. MenB Serum Bactericidal Assays.............................................72
7.2.2.2. MenA, MenC, MenW, and MenY Serum Bactericidal 
Assays................................................................................................73
7.2.3. Exploratory Assays.....................................................................................73
7.3. Safety.......................................................................................................................74
7.4. Electronic Diary ......................................................................................................75
7.4.1. Local Reactions ..........................................................................................76
7.4.1.1. Redness and Swelling................................................................76
7.4.1.2. Pain............................................................................................76
7.4.2. Systemic Events..........................................................................................77
7.4.2.1. Temperature ..............................................................................77
7.4.2.2. Other Systemic Events ..............................................................77
7.4.3. Use of Antipyretic Medication ...................................................................78

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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7.5. Pilot Cohort Safety Assessments.............................................................................78
8. ADVERSE EVENT REPORTING......................................................................................78
8.1. Requirements...........................................................................................................78
8.1.1. Additional Details on Recording Adverse Events on the CRF...................79
8.1.2. Eliciting Adverse Event Information..........................................................80
8.1.3. Withdrawal From the Study Due to Adverse Events (See Also the 
Subject Withdrawal Section) ...........................................................................80
8.1.4. Time Period for Collecting AE/SAE Information......................................80
8.1.4.1. Reporting SAEs to Pfizer Safety...............................................81
8.1.4.2. Recording Nonserious AEs and SAEs on the CRF...................81
8.1.5. Causality Assessment .................................................................................82
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ..................82
8.2. Definitions...............................................................................................................82
8.2.1. Adverse Events...........................................................................................82
8.2.2. Abnormal Test Findings .............................................................................83
8.2.3. Serious Adverse Events ..............................................................................83
8.2.4. Research-Related Injury .............................................................................84
8.2.5. Hospitalization............................................................................................85
8.3. Severity Assessment................................................................................................86
8.4. Special Situations ....................................................................................................87
8.4.1. Protocol-Specified Serious Adverse Events...............................................87
8.4.2. Potential Cases of Drug-Induced Liver Injury............................................87
8.4.3. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................89
8.4.3.1. Exposure During Pregnancy......................................................89
8.4.3.2. Exposure During Breastfeeding ................................................90
8.4.3.3. Occupational Exposure .............................................................90
8.4.4. Medication Errors and Lack of Efficacy ....................................................91
8.4.4.1. Medication Errors......................................................................91
8.4.4.2. Lack of Efficacy........................................................................92
8.5. Medical Device Complaint Reporting Requirements .............................................92
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................92

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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9.1. Sample Size Determination.....................................................................................92
9.2. Immunogenicity Analyses.......................................................................................94
9.2.1. Analysis of the Primary Immunogenicity Objective ..................................94
9.2.2. Analyses of the Secondary Objectives .......................................................95
9.2.3. Analyses of Exploratory Objectives ...........................................................99
9.3. Demographic and Baseline Characteristics...........................................................101
9.4. Safety Analyses.....................................................................................................101
9.4.1. Analysis for Safety and Reactogenicity....................................................101
9.5. Analysis Populations.............................................................................................101
9.5.1. Full Analysis Set.......................................................................................101
9.5.2. Per-Protocol Analysis Set.........................................................................101
9.6. Modified Intent-to-Treat (mITT) Population ........................................................102
9.7. Safety Analysis Set................................................................................................103
9.8. Analysis Timing ....................................................................................................104
9.9. Data Monitoring Committee .................................................................................104
10. QUALITY CONTROL AND QUALITY ASSURANCE...............................................104
11. DATA HANDLING AND RECORD KEEPING ...........................................................105
11.1. Case Report Forms/Electronic Data Record .......................................................105
11.2. Record Retention.................................................................................................105
12. ETHICS............................................................................................................................106
12.1. Institutional Review Board/Ethics Committee....................................................106
12.2. Ethical Conduct of the Study ..............................................................................106
12.3. Subject Information and Consent........................................................................106
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .........................................................................................................................108
13. DEFINITION OF END OF TRIAL.................................................................................108
13.1. End of Trial in a Member State...........................................................................108
13.2. End of Trial in All Other Participating Countries...............................................108
14. SPONSOR DISCONTINUATION CRITERIA ..............................................................108
15. PUBLICATION OF STUDY RESULTS........................................................................108
15.1. Communication of Results by Pfizer ..................................................................108
15.2. Publications by Investigators ..............................................................................109

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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16. REFERENCES ................................................................................................................111
LIST OF TABLES
Table 1.
Stage 1 Study Design................................................................................38
Table 2.
Stage 2 Study Design................................................................................39
Table 3.
Investigational Product Administration Schedule ....................................49
Table 4.
Validated hSBA LODs and LLOQs for the 4 Primary MenB Strains......72
Table 5.
Qualified hSBA LODs and LLOQs for the 10 Secondary MenB 
Strains .......................................................................................................73
Table 6.
Qualified hSBA LODs and LLOQs for the ACWY Strains.....................73
Table 7.
Grading of Redness and Swelling.............................................................76
Table 8.
Grading of Pain.........................................................................................77
Table 9.
Severity Scale for Fever............................................................................77
Table 10.
Grading of Other Systemic Events ...........................................................77
Table 11.
Summary of Adverse Event Collection....................................................81
Table 12.
Overall Power to Meet the Primary Objectives........................................93
Table 13.
Probabilities of Detecting AEs at Specified Incidences ...........................94
Table 14.
Highlights of the Analyses for the Secondary Immunogenicity 
Objectives – Stage 1 .................................................................................96
Table 15.
Highlights of the Analyses for the Secondary Immunogenicity 
Objectives –Persistence ............................................................................98
Table 16.
Highlights of the Analyses for the Secondary Immunogenicity 
Objectives – Booster.................................................................................98
Table 17.
Analyses for the Exploratory Immunogenicity Objectives – Stages 
1 and 2.......................................................................................................99

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
B1971057
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PFIZER CONFIDENTIAL
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PROTOCOL SUMMARY
Background and Rationale
Neisseria meningitidis is an obligate human pathogen that colonizes the upper respiratory 
tract and in some individuals can cause serious, life-threatening disease.  Under certain 
instances that are not well understood, N meningitidis is capable of invading the human host, 
leading to bacteremia, which then manifests as life-threatening invasive meningococcal 
disease (IMD).  Five (5) N meningitidis serogroups (groups A, B, C, W, and Y) currently 
cause virtually all IMD globally.  In the United States, meningococcal disease is primarily 
caused by groups B, C, and Y, which are responsible for approximately 64% of disease 
across all ages.
Temporal variations in IMD incidence occur naturally.  In industrialized countries, disease 
rates range from 0.1 cases per 100,000 individuals during endemic periods to 5 to 15 or more 
cases per 100,000 individuals during prolonged epidemics.  In the United States, prevention 
of meningococcal disease through vaccination has been focused on routine immunization of 
adolescents and also individuals identified at increased risk of disease due to either medical 
or situational factors. 
Results from Phase 2 Study B1971012, a randomized, single-blind, multicenter trial 
conducted in Europe comparing the safety and immunogenicity of bivalent recombinant 
lipoprotein 2086 vaccine (bivalent rLP2086) administered using various 2- and 3-dose 
schedules, demonstrated the safety and immunogenicity of bivalent rLP2086 administered on 
a 2-dose 0- and 6-month schedule; these results supported the licensure of bivalent rLP2086
(Trumenba) in the United States under Accelerated Approval (AA) regulations.  As part of 
the AA approval, a Phase 3 postmarketing commitment is required to confirm the data 
observed in Phase 2.  This study will fulfill the Food and Drug Administration (FDA)
postapproval requirement (PAR) to verify and describe the clinical benefit of a 2-dose 
schedule for the use of bivalent rLP2086 administered at Months 0 and 6 in healthy subjects 
10 years to <26 years of age.
In the United States, it is recommended to routinely immunize 11- to 12-year-olds with a 
meningococcal group A, C, W, and Y conjugate vaccine (MenACWY) (as a single dose), 
followed by the addition of a booster vaccination at 16 years of age. The recommendation 
and use of meningococcal vaccines differ in other regions. Monovalent meningococcal 
group C vaccines have been used in a number of ex-US countries and continue to be 
administered in response to increases in disease (eg, Italy). In the United Kingdom, there has 
been an increase in group W disease, and a campaign has started to vaccinate adolescents 
with quadrivalent meningococcal conjugate vaccines (ie, MenACWY). France has also seen 
recent group B outbreaks and has responded with local (as opposed to national) vaccination 
campaigns to manage the outbreaks.
Recommendations remain complicated for preventive immunization against IMD due to the 
different age groups targeted for MenACWY and N meningitidis group B (MnB) vaccination, 
the dosing regimens for the different vaccines, and regional differences. Currently, no 

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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combination pentavalent (containing groups A, B, C, W, and Y) meningococcal vaccine is 
available.
Development and licensure of a pentavalent vaccine for the prevention of IMD due to groups
A, B, C, W, and Y would allow for optimization of the current schedules, offer the possibility 
of using a single vaccine to meet the current recommendations, and offer a comprehensive
approach to prevent meningococcal disease against all 5 disease-causing N meningitidis 
groups (A, B, C, W, and Y).
Pfizer intends to develop a pentavalent meningococcal vaccine (N meningitidis group A, B, 
C, W, and Y vaccine [MenABCWY]) by combining bivalent rLP2086 and Nimenrix®
(meningococcal polysaccharide groups A, C, W-135, and Y tetanus toxoid conjugate vaccine 
[MenACWY-TT]).  This study is primarily designed to fulfill the FDA PAR to verify the 
clinical benefit of a 2-dose schedule for the use of bivalent rLP2086 administered at 
Months 0 and 6 in healthy subjects 10 years to <26 years of age.  This study will also 
describe the safety, tolerability, and immunogenicity of MenABCWY, and describe the 
immune response to groups A, C, W, and Y following administration of MenABCWY, or 
bivalent rLP2086 and a meningococcal group A, C, W-135, and Y conjugate vaccine
(MenACWY-CRM).
Objectives and Endpoints
Primary Immunogenicity Objective:
Primary Immunogenicity Endpoints:

To assess the immune response induced by 
bivalent rLP2086 as measured by serum 
bactericidal assay using human complement 
(hSBA) performed with 4 primary MnB test 
strains, 2 expressing a lipoprotein 2086 (LP2086)
subfamily A protein and 2 expressing an LP2086 
subfamily B protein, measured 1 month after the 
second vaccination, in the bivalent rLP2086 arms 
(Group 2 and 4 subjects) combined. 
Five (5) coprimary endpoints are defined for the 
primary objective; they are defined for hSBA 
performed with each of the 4 primary test strains: 
PMB80 (A22), PMB2001 (A56), PMB2948 (B24), 
and PMB2707 (B44).

One (1) of the 5 coprimary endpoints is the 
composite endpoint defined as the proportion of 
subjects achieving an hSBA titer lower limit of 
quantitation (LLOQ; 1:16 for A22 and 1:8 for 
A56, B24, and B44) for all 4 primary test strains 
combined, 1 month after the second vaccination 
in the bivalent rLP2086 arms (Group 2 and 4 
subjects) combined. 

Four (4) of the coprimary endpoints are defined 
as the proportion of subjects achieving at least a 
4-fold increase in hSBA titer from baseline to 
1 month after the second vaccination in the 
bivalent rLP2086 arms (Group 2 and 4 subjects) 
combined for each of the 4 primary test strains.

For subjects with a baseline hSBA titer below 
the limit of detection (LOD, or an hSBA titer of 
<1:4), a 4-fold response is defined as an hSBA 
titer of 1:16 or the LLOQ (whichever titer is 
higher).

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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
For subjects with a baseline hSBA titer of 
LOD (ie, hSBA titer of 1:4) and < LLOQ, a 
4-fold response is defined as an hSBA titer of 
4 times the LLOQ.

For subjects with a baseline hSBA titer of 
LLOQ, a 4-fold response is defined as an 
hSBA titer of 4 times the baseline titer.
Primary Safety Objectives:
Primary Safety Endpoints:

To describe the safety profile of bivalent rLP2086, 
as measured by local reactions, systemic events, 
adverse events (AEs), serious adverse events 
(SAEs), newly diagnosed chronic medical 
conditions, medically attended AEs, and 
immediate AEs, following Vaccinations 1 and 2 in 
the bivalent rLP2086 arms (Group 2 and 4 
subjects) combined.
The following endpoints will be described after 
Vaccinations 1 and 2 in the bivalent rLP2086 arms 
(Group 2 and 4 subjects) combined.

Percentage of subjects reporting local reactions 
(pain, redness, and swelling) and by severity 
within 7 days after each vaccination visit.

Percentage of subjects reporting systemic events 
(fever, vomiting, diarrhea, headache, fatigue, 
chills, muscle pain other than muscle pain at any 
injection site, and joint pain) and by severity 
within 7 days after each vaccination visit. 

Percentage of subjects reporting the use of 
antipyretic medication within 7 days after each 
vaccination visit. 

Percentage of subjects with at least 1 SAE during 
the following time periods:

30 Days after each vaccination.

30 Days after any vaccination.

During the Stage 1 vaccination phase (from 
the first study vaccination [Visit 1] through 
1 month after the second study vaccination 
[Visit 4]).

During the Stage 1 follow-up phase (from 
1 month after the second study vaccination 
[Visit 4] through 6 months after the second 
study vaccination [Visit 5]).

Throughout Stage 1 (from the first study 
vaccination [Visit 1] through 6 months after 
the second study vaccination [Visit 5]).

Percentage of subjects with at least 1 medically 
attended AE occurring during the following time 
periods:

30 Days after each vaccination.

30 Days after any vaccination.

During the Stage 1 vaccination phase (from 
the first study vaccination [Visit 1] through 
1 month after the second study vaccination 
[Visit 4]).

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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
During the Stage 1 follow-up phase (from 
1 month after the second study vaccination 
[Visit 4] through 6 months after the second 
study vaccination [Visit 5]).

Throughout Stage 1 (from the first study 
vaccination [Visit 1] through 6 months after 
the second study vaccination [Visit 5]).

Percentage of subjects with at least 1 newly 
diagnosed chronic medical condition occurring 
during the following time periods:

30 Days after each vaccination.

30 Days after any vaccination.

During the Stage 1 vaccination phase (from 
the first study vaccination [Visit 1] through 
1 month after the second study vaccination 
[Visit 4]).

During the Stage 1 follow-up phase (from 
1 month after the second study vaccination 
[Visit 4] through 6 months after the second 
study vaccination [Visit 5]).

Throughout Stage 1 (from the first study 
vaccination [Visit 1] through 6 months after 
the second study vaccination [Visit 5]).

Percentage of subjects with at least 1 AE 
occurring during the following time periods:

30 Days after each vaccination.

30 Days after any vaccination.

During the Stage 1 vaccination phase (from 
the first study vaccination [Visit 1] through 
1 month after the second study vaccination 
[Visit 4]).

Percentage of subjects reporting at least 1 
immediate AE after each vaccination.

Subject days missing school or work because of 
AEs during the Stage 1 vaccination phase (Visit 1
though Visit 4).

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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PFIZER CONFIDENTIAL
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
To describe the safety profile of MenABCWY, as 
measured by local reactions, systemic events, 
AEs, SAEs, newly diagnosed chronic medical 
conditions, medically attended AEs, and 
immediate AEs, after the booster vaccination. 

To describe the safety profile of bivalent rLP2086, 
as measured by local reactions, systemic events, 
AEs, SAEs, newly diagnosed chronic medical 
conditions, medically attended AEs, and 
immediate AEs, after the booster vaccination.
The following endpoints will be described after the 
booster vaccination in Groups 1 through 4:

Percentage of subjects reporting local reactions 
(pain, redness, and swelling) and by severity 
within 7 days after the booster vaccination.

Percentage of subjects reporting systemic events 
(fever, vomiting, diarrhea, headache, fatigue, 
chills, muscle pain other than muscle pain at any 
injection site, and joint pain) and by severity 
within 7 days after the booster vaccination. 

Percentage of subjects reporting the use of 
antipyretic medication within 7 days after the 
booster vaccination. 

Percentage of subjects with at least 1 SAE during 
the following time periods:

During the booster vaccination phase (from 
the booster vaccination [Visit 10] through 
1 month after the booster vaccination [Visit 
11]). 

During the booster follow-up phase (from 
1 month after the booster vaccination 
[Visit 11] through 6 months after the booster 
vaccination [Visit 12]).

From the booster vaccination (Visit 10) 
through 6 months after the booster vaccination 
(Visit 12).

Percentage of subjects with at least 1 medically 
attended AE occurring during the following time 
periods:

During the booster vaccination phase (from 
the booster vaccination [Visit 10] through 
1 month after the booster vaccination [Visit 
11]).

During the booster follow-up phase (from 
1 month after the booster vaccination [Visit 
11] through 6 months after the booster 
vaccination [Visit 12]).

From the booster vaccination (Visit 10) 
through 6 months after the booster vaccination 
(Visit 12).

Percentage of subjects with at least 1 newly 
diagnosed chronic medical condition occurring 
during the following time periods:

During the booster vaccination phase (from 
the booster vaccination [Visit 10] through 1 
month after the booster vaccination [Visit 11]).

During the booster follow-up phase (from 
1 month after the booster vaccination [Visit 
11] through 6 months after the booster 

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
B1971057
Final Protocol Amendment 2, 09 July 2019
PFIZER CONFIDENTIAL
Page 15
vaccination [Visit 12]).

From the booster vaccination (Visit 10) 
through 6 months after the booster vaccination 
(Visit 12).

Percentage of subjects with at least 1 AE 
occurring during the following time periods:

During the booster vaccination phase (from 
the booster vaccination [Visit 10] through 1 
month after the booster vaccination [Visit 11]).

Percentage of subjects reporting at least 1 
immediate AE after the booster vaccination.

Subject days missing school or work because of 
AEs.
Study Design
This is a Phase 3, randomized, active-controlled, observer-blinded multicenter trial in which 
approximately 1590 subjects will be randomly assigned to receive either MenABCWY and 
placebo (saline), or bivalent rLP2086 and MenACWY-CRM.  All subjects will be naive to 
any meningococcal group B vaccine prior to enrollment. Randomization will be stratified by 
prior vaccination history; approximately 795 ACWY-naive subjects and 795 
ACWY-experienced (having received 1 prior dose of a vaccine containing 1 or more ACWY 
groups 4 years prior to the date of randomization) subjects will be enrolled.
Randomization will also be stratified by geographic region.  Approximately 1320 subjects 
from US investigative sites and 270 subjects from ex-US countries will be randomized.  
Regional stratification will ensure sufficient population representation. 
The study will be conducted in 2 stages as shown below.  In order to support assay 
development, a subset of up to approximately 600 subjects 18 to 25 years of age will have up 
to 100 mL, rather than 20 mL, of blood drawn at Visits 1, 2, and 4.  Additionally, at 
designated sites, an additional optional whole blood sample of approximately 50 mL will be 
obtained at Visit 4 from up to approximately 30 subjects 18 to 25 years of age.  This sample 
will be used for exploratory purposes.
Subjects from both ACWY-naïve and ACWY-experienced strata will participate in Stage 2
(approximately 132 subjects from each of Groups 1 and 3 and approximately 65 subjects
from each of Groups 2 and 4).  Stage 1 will be observer-blinded and Stage 2 will be 
open-label.

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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Stage 1 Study Design
Vaccination 1
Post–
Vaccination 
1 Blood 
Draw
Vaccination 
2
Post–
Vaccination 
2 Blood 
Draw
Safety 
Telephone 
Call
Telephone 
Call
Approximate 
Month
0
1
6
7
12
Visit Number 1
2
3
4
5
6
ACWY-
Naive 
Subjects
Group 1a
(n=265)
MenABCWY + 
saline
MenABCWY
Group 2 
(n=530)
Bivalent rLP2086 + 
MenACWY-CRM
Bivalent 
rLP2086
Blood Draw
for serum 
collection
20 mL
(or up to 100 mL in 
subset)
20 mL
(or up to 
100 mL in 
subset)
20 mL
20 mL
(or up 
to100 mL in 
subset)
ACWY-
Experienced 
Subjects
Group 3a
(n=265)
MenABCWY + 
saline
MenABCWY
Group 4 
(n=530)
Bivalent rLP2086 + 
MenACWY-CRM
Bivalent 
rLP2086
Blood Draw
for Serum
Collection
20 mL
(or up to 100 mL in 
subset)
20 mL
(or up to 
100 mL in 
subset)
20 mL
20 mL
(or up to 
100 mL in 
subset)
Subjects 18 
to 25 years 
of age (naïve 
or 
experienced)
Optional 
Blood Draw 
for Whole 
Blood 
Collection
50 mL
a.
Pilot cohort subjects will be assigned to either Group 1 or 3, but will receive only MenABCWY at Vaccination 1. Pilot 
cohort subjects will not receive saline at Vaccination 1.
Stage 2 Study Design
Antibody 
Persistence
Booster Vaccination
Postbooster Blood 
Draw
Safety 
Telephone 
Call
Approximate Month 18-42
54
55
60
Visit Number
7-9
10
11
12
ACWY-
Naive 
Subjects
Group 1 (n ~132)
MenABCWY
Group 2 (n ~65)
Bivalent rLP2086 + 
MenACWY-CRM
ACWY-
Experienced 
Subjects
Group 3 (n ~132)
MenABCWY
Group 4 (n ~65)
Bivalent rLP2086 + 
MenACWY-CRM
Blood Draw for 
Serum Collection
20 mL × 3
20 mL
20 mL
(or up to 100 mL in 
subset)

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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PFIZER CONFIDENTIAL
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Investigational Products
For this study, the investigational products are bivalent rLP2086 (Trumenba), MenABCWY
(consisting of MenACWY-TT [Nimenrix] and bivalent rLP2086 [Trumenba]), 
MenACWY-CRM (Menveo), and placebo.  Any reference to normal saline or placebo refers 
to a solution containing 0.85% sodium chloride and water for injection. The placebo solution 
is also referred to as “saline” throughout the protocol.
Statistical Methods
Both hypothesis testing and estimation will be performed.  The hypothesis-testing component 
will address the need to confirm the immunogenicity of bivalent rLP2086 administered at 
Months 0 and 6 in all subjects 10 through 25 years of age, using prespecified criteria for the 
primary MnB immunogenicity endpoints. Safety of bivalent rLP2086 administered at 
Months 0 and 6 will also be described. Immunogenicity and safety information for the 
MenABCWY arms will be described.
Hypothesis testing will be performed on the 5 coprimary MnB endpoints in all subjects,
which includes a 4-fold rise from baseline in hSBA titers for each of the 4 primary strains 
and the composite response (hSBA titer LLOQ for all 4 primary strains combined) 1 month 
after the second vaccination.  If the lower limit of the 2-sided 95% confidence interval 
exceeds each of the target lower limit of the confidence interval (LCI) values, the study’s
primary objective will be met.
The study sample size is mainly based on hypothesis-testing criteria to verify the clinical 
benefit of a 2-dose schedule for the use of bivalent rLP2086 administered at Months 0 and 6 
in healthy subjects 10 years to <26 years of age. With 900 evaluable subjects in Group 2 and 
Group 4, the primary objectives (based on all 5 primary endpoints) will be met with a power 
of 95.2% as shown in the table below.
Overall Power to Meet the Primary Objectives
Primary Endpoint 
Test Strain 
(Variant)
LCI Criteria 
Study B1971012 0-
and 6-Month 
Responses With 95% 
Confidence Interval 
(%)a
Number of 
Evaluable 
Subjects
Power
hSBA titer fold rise 4 
from baseline
PMB80
(A22)
LL of 95%
CI >75%
82.3
(76.3, 87.3)
900
99.97%
PMB2001 (A56)
LL of 95%
CI >85
90.1
(85.1, 93.8)
900
99.60%
PMB2948 (B24)
LL of 95%
CI >55
64.5
(57.4, 71.1)
900
99.99%
PMB2707 (B44)
LL of 95%
CI >60
66.0
(58.9, 72.6)
900
95.7%
Composite response
(hSBA titer LLOQ 
for all of 4 primary 
strains combined)
LL of 95%
CI >65
72.9
(65.9, 79.1)
900
99.92%

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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Final Protocol Amendment 2, 09 July 2019
PFIZER CONFIDENTIAL
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Overall Power to Meet the Primary Objectives
Primary Endpoint 
Test Strain 
(Variant)
LCI Criteria 
Study B1971012 0-
and 6-Month 
Responses With 95% 
Confidence Interval 
(%)a
Number of 
Evaluable 
Subjects
Power
Overall power
95.2%
Abbreviations: hSBA = serum bactericidal assay using human complement; LCI = lower limit of the confidence 
interval; LL = lower limit; LLOQ = lower limit of quantitation.
a.
The power calculation was based on Study B1971012 with a vaccine schedule of 0 and 6 months.
Assuming ~85% evaluable subjects, ~1060 subjects should be enrolled to receive bivalent 
rLP2086 and MenACWY-CRM.
An additional 530 subjects will be enrolled in the MenABCWY-MenABCWY regimen, 
which will allow a probability of 93.0% to observe at least 1 AE with a true incidence of
0.5%.
A total of 1590 subjects will therefore be enrolled into this study.  The randomization will be 
performed separately for ACWY-naive and ACWY-experienced subjects.  Equal numbers of 
subjects will be recruited into each stratum.

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent rLP2086; subfamily A and B; E coli])
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SCHEDULE OF ACTIVITIES
The Schedule of Activities table provides an overview of the protocol visits and procedures.  Refer to the Study Procedures and 
Assessments sections of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed on the Schedule of Activities table, in order to 
conduct evaluations or assessments required to protect the well-being of the subject.
Stage 1
Visit ID
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit Description
Vaccination 1
Post–
Vaccination 1 
Blood Draw
Vaccination 2
Post–
Vaccination 2 
Blood Draw
Telephone 
Contact
Telephone 
Contact
Approximate Month
0
1
6
7
6 Months After 
Last Study 
Vaccination
Visit Window
Day 1
28 to 42 Days 
After Visit 1
173 to 194 
Days After 
Visit 1
28 to 42 Days 
After Visit 3
168 to 196 Days 
After Visit 3
After Study 
Unblinding 
and Before 
Transition to 
Stage 2a
Informed consent 
X
Informed consent for optional blood draw for whole blood collectionb
X
Review eligibility criteria
X
Demography
X
Confirm continued eligibilityc
X
X
X
Medical history and physical examination
X
Record previous PRP-OMP vaccinations
X
Record any previous meningococcal vaccinations
X
Record use of antipyretics and other pain medications received on the 
day prior to vaccination
X
X
Urine pregnancy test for female subjects
X
X
Oral temperature
X
X
Randomization
X

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent rLP2086; subfamily A and B; E coli])
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Stage 1
Visit ID
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit Description
Vaccination 1
Post–
Vaccination 1 
Blood Draw
Vaccination 2
Post–
Vaccination 2 
Blood Draw
Telephone 
Contact
Telephone 
Contact
Approximate Month
0
1
6
7
6 Months After 
Last Study 
Vaccination
Visit Window
Day 1
28 to 42 Days 
After Visit 1
173 to 194 
Days After 
Visit 1
28 to 42 Days 
After Visit 3
168 to 196 Days 
After Visit 3
After Study 
Unblinding 
and Before 
Transition to 
Stage 2a
Obtain blood sample(s) for serum collectiond
20 mL
(up to 100 mL 
in subset)
20 mL
(up to 100 mL 
in subset)
20 mL
(20 mL in 
subset)
20 mL
(up to 100 mL 
in subset)
Additional optional blood draw for whole blood collectione
50 mL
Investigational product administration and observationf
X
X
Record nonstudy vaccinations
X
X
X
X
Provide subject with an e-diary, caliper, measuring tape/ruler, and 
thermometer, if necessary
X
X
Review and collect e-diary
X
X
Assess reactogenicity and record use of antipyretic medicationg
Days 1 to 7
Days 1 to 7
Provide the subject with a contact card
X
Provide the subject with a memory aid
X
Complete Study Visit/Telephone Contact AE Checklisth
X
X
X
X
Record concomitant medications used to treat AEs
X
X
X
X
X
(S)AE collection appropriate for the visiti
X
X
X
X
X
Notification of Stage 2 participation
X
Abbreviations: e-diary = electronic diary; PRP-OMP = polyribosylribitol phosphate oligosaccharide of Haemophilus influenzae type b conjugated to outer 
membrane protein.
a.
Visit 6 must be conducted prior to Visit 7.
b.
Applicable only at designated sites. This consent relating to the whole blood sample may be obtained at prior visits if appropriate.  
c.
Ensure that the subject continues to be eligible for the study, and continues to comply with contraception requirements, as appropriate.

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent rLP2086; subfamily A and B; E coli])
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Stage 1
Visit ID
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit Description
Vaccination 1
Post–
Vaccination 1 
Blood Draw
Vaccination 2
Post–
Vaccination 2 
Blood Draw
Telephone 
Contact
Telephone 
Contact
Approximate Month
0
1
6
7
6 Months After 
Last Study 
Vaccination
Visit Window
Day 1
28 to 42 Days 
After Visit 1
173 to 194 
Days After 
Visit 1
28 to 42 Days 
After Visit 3
168 to 196 Days 
After Visit 3
After Study 
Unblinding 
and Before 
Transition to 
Stage 2a
d.
Subject participation in the subset will be voluntary for subjects 18 to 25 years of age, and the volume of blood drawn (either 50 or 100 mL) will depend on 
the consent obtained.
e.
Applicable only for subjects at designated sites who have given consent for this additional blood draw.
f.
Observe the subject for at least 30 minutes (or longer as per local practice) after the investigational product administration for any acute reactions.
g.
Between visits, review the e-diary data online at frequent intervals.  Contact the subject in order to obtain stop dates for any local reactions, systemic events, 
or use of antipyretic medication that were ongoing on the last day that the e-diary was completed.
h.
Checklist includes questions regarding newly diagnosed chronic medical conditions, medically attended adverse events, and missed days of school or work, 
as well as about neuroinflammatory and autoimmune conditions, such as transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.
i.
Please refer to protocol Section 8.1.4.

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent rLP2086; subfamily A and B; E coli])
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Stage 2
Visit ID
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Visit 12
Visit Description
Antibody 
Persistence 
Blood Draw 1
Antibody 
Persistence 
Blood Draw 2
Antibody 
Persistence 
Blood Draw 3
Booster 
Vaccination
Postbooster 
Blood Draw
Telephone Contact
Approximate Month
18
30
42
54
55
6 Months After 
Booster Vaccination
Visit Window
336 to 694
Days After 
Visit 3
700 to 756 
Days After 
Visit 3a
1064 to 1120
Days After 
Visit 3
1428 to 1484
Days After 
Visit 3
28 to 42 Days 
After Visit 10
168 to 196 Days 
After Visit 10
Informed consent
X
Confirm continued eligibilityb
X
X
X
X
X
New medical history and physical examination
X
Urine pregnancy test for female subjects
X
Oral temperature
X
Obtain blood sample 
20 mL
20 mL
20 mL
20 mL
20 mL
(up to 100 mL in 
subset)
Record use of antipyretics and other pain medications 
received on the day prior to vaccination
X
Investigational product administration and observationc
X
Record nonstudy vaccinations
X
X
X
X
X
Provide subject with an e-diary, caliper, measuring 
tape/ruler, and thermometer, if necessary
X
Review and collect e-diary
X
Assess reactogenicity and record use of antipyretic 
medicationd
Day 1 to 7
Provide the subject with a memory aid
X
Complete Study Visit/Telephone Contact AE Checkliste
X
X

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent rLP2086; subfamily A and B; E coli])
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Final Protocol Amendment 2, 09 July 2019
PFIZER CONFIDENTIAL
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Stage 2
Visit ID
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Visit 12
Visit Description
Antibody 
Persistence 
Blood Draw 1
Antibody 
Persistence 
Blood Draw 2
Antibody 
Persistence 
Blood Draw 3
Booster 
Vaccination
Postbooster 
Blood Draw
Telephone Contact
Approximate Month
18
30
42
54
55
6 Months After 
Booster Vaccination
Visit Window
336 to 694
Days After 
Visit 3
700 to 756 
Days After 
Visit 3a
1064 to 1120
Days After 
Visit 3
1428 to 1484
Days After 
Visit 3
28 to 42 Days 
After Visit 10
168 to 196 Days 
After Visit 10
Record concomitant medications used to treat AEs
X
X
X
X
X
X
(S)AE collection appropriate for the visitf
X
X
X
X
X
X
Abbreviation: e-diary = electronic diary.
a.
Visit 7 and Visit 8 should be conducted within no less than 30 days of each other. If Visit 7 cannot be conducted within the protocol-defined visit window, 
Visit 7 can be omitted and Visit 8 performed directly.
b.
Ensure that the subject continues to be eligible for the study, and continues to comply with contraception requirements, as appropriate.
c.
Observe the subject for at least 30 minutes (or longer as per local practice) after the investigational product administration for any acute reactions.
d.
Between visits, review the e-diary data online at frequent intervals.  Contact the subject in order to obtain stop dates for any local reactions, systemic events, 
or use of antipyretic medication that were ongoing on the last day that the e-diary was completed.
e.
Checklist includes questions regarding newly diagnosed chronic medical conditions, medically attended adverse events, and missed days of school or work, 
as well as about neuroinflammatory and autoimmune conditions, such as transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.
f.
Please refer to protocol Section 8.1.4.

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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PFIZER CONFIDENTIAL
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1. INTRODUCTION
1.1. Mechanism of Action/Indication
Bivalent recombinant lipoprotein 2086 vaccine (bivalent rLP2086; Trumenba®) is indicated 
for active immunization to prevent invasive disease caused by Neisseria meningitidis 
group B.  Bivalent rLP2086 is approved for use in individuals 10 through 25 years of age.
Pfizer intends to develop a pentavalent meningococcal vaccine (N meningitidis group A, B, 
C, W, and Y vaccine [MenABCWY]) by combining bivalent rLP2086 and Nimenrix®
(meningococcal polysaccharide groups A, C, W-135, and Y tetanus toxoid conjugate vaccine 
[MenACWY-TT]). The target indication for the candidate pentavalent vaccine is active 
immunization to prevent invasive disease caused by N meningitidis groups A, B, C, W, and 
Y in individuals 10 through 25 years of age.
1.2. Background and Rationale
1.2.1. Background of Disease and Medical Need
N meningitidis is an obligate human pathogen that colonizes the upper respiratory tract and in 
some individuals can cause serious, life-threatening disease.  Transmission with
N meningitidis is via contact with droplets from the upper respiratory tract, typically resulting 
in colonization and asymptomatic carriage in otherwise healthy individuals.  Under certain 
instances that are not well understood, N meningitidis is capable of invading the human host, 
leading to bacteremia, which then manifests as life-threatening invasive meningococcal 
disease (IMD).1  Twelve (12) serogroups of N meningitidis have been identified based on 
structural differences in their polysaccharide capsule.  Five (5) of these groups (A, B, C, W, 
and Y) currently cause virtually all IMD globally.2,3
Temporal variations in IMD incidence occur naturally.  In industrialized countries, disease 
rates range from 0.1 cases per 100,000 individuals during endemic periods to 5 to 15 or more 
cases per 100,000 individuals during prolonged epidemics.3,4,5,6 In Europe, meningococcal 
disease has been declining in general over the past decade.  This decline can be attributed, in 
part, to the introduction of meningococcal group C conjugate vaccine programs; however,
IMD caused by N meningitidis group B (MnB) has also declined. In 2007, overall 
meningococcal rates were 3.76 per 100,000 in Ireland and 2.50 per 100,000 in the United 
Kingdom but had decreased to 1.99 in Ireland and 1.66 in the United Kingdom by 2011.5,6
While IMD is at a historic low in the United States,7 the Centers for Disease Control and 
Prevention (CDC) estimates that in 2014 approximately 450 cases of meningococcal disease 
occurred, resulting in a disease incidence nationally of 0.14 per 100,000 individuals.8  In the 
United States, meningococcal disease is primarily caused by groups B, C, and Y, which are 
responsible for approximately 64% of disease across all ages.8  Higher rates of 
meningococcal disease due to groups B and C are seen in younger individuals, whereas 
disease due to group Y tends to occur in older individuals.8
Results from Phase 2 Study B1971012, a randomized, single-blind, multicenter trial 
conducted in Europe comparing the safety and immunogenicity of bivalent rLP2086 
administered using various 2- and 3-dose schedules, demonstrated the safety and 

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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PFIZER CONFIDENTIAL
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immunogenicity of bivalent rLP2086 administered on a 2-dose 0- and 6-month schedule; 
these results supported the licensure of bivalent rLP2086 in the United States under 
Accelerated Approval (AA) regulations.  As part of the AA approval, a Phase 3 
postmarketing commitment is required to confirm the data observed in Phase 2.  This study 
will fulfill the Food and Drug Administration (FDA) postapproval requirement (PAR) to 
verify and describe the clinical benefit of a 2-dose schedule for the use of bivalent rLP2086 
administered at Months 0 and 6 in healthy subjects 10 years to <26 years of age.
In the United States, prevention of meningococcal disease through vaccination has been 
focused on routine immunization of adolescents and also individuals identified at increased 
risk of disease due to either medical or situational factors. In the United States it is 
recommended to routinely immunize 11- to 12-year-olds with a meningococcal group A, C, 
W, and Y conjugate vaccine (MenACWY) (as a single dose), followed by the addition of a 
booster vaccination at 16 years of age.9,10,11 In addition to these age-based recommendations
for meningococcal vaccines, there are recommendations in place to vaccinate at-risk 
individuals aged 2 months to 55 years for meningococcal groups A, C, W, and Y and 
10 years for meningococcal group B (MenB).10,12
The recommendation and use of meningococcal vaccines differ in other regions. Monovalent 
meningococcal group C vaccines have been used in a number of ex-US countries and 
continue to be administered in response to increases in disease (eg, Italy).13 In the United 
Kingdom, there has been an increase in group W disease, and a campaign has started to 
vaccinate adolescents with quadrivalent meningococcal vaccines.14,15 The United Kingdom
is one of only a limited number of countries to recommend Bexsero in the infant 
population.16 Over the past 10 years there have been outbreaks of meningococcal diseases 
recorded in Europe in varied settings, including kindergarten classes, nursery schools, and a 
family cluster.17,18,19,20 France has also seen recent group B outbreaks and has responded 
with local (as opposed to national) vaccination campaigns to manage the outbreaks.21
Recommendations remain complicated for preventive immunization against IMD due to the 
different age groups targeted for MenACWY and MnB vaccination, the dosing regimens for 
the different vaccines, and regional differences. Currently, no combination pentavalent 
(containing groups A, B, C, W, and Y) meningococcal vaccine is available. Development 
and licensure of a pentavalent vaccine for the prevention of IMD due to groups A, B, C, W, 
and Y would allow for optimization of the current schedules in terms of convenience to 
patient and healthcare providers to prevent meningococcal disease in those considered at 
increased risk. A pentavalent vaccine would also offer the possibility of using a single 
vaccine to meet the current recommendations and the ability to simplify the interpretation of
the schedule for vaccine providers. For example, in countries where MenACWY is 
recommended at 11 years of age, followed by a MenACWY booster approximately 5 years 
later, use of a pentavalent vaccine could address the recommendation for quadrivalent 
vaccination while also confer protection against MenB disease.
Meningococcal disease epidemiology is dynamic, and fluctuations in the prevalence of
different groups are observed. Examples such as the increase in group W observed in the

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United Kingdom and South America14,22 illustrate the need for a comprehensive approach to
prevent meningococcal disease both in terms of vaccine characteristics and implementation
of any recommendations. Development of a safe and immunogenic pentavalent vaccine
would support these aims.
1.2.2. Prior Clinical Experience
1.2.2.1. Bivalent rLP2086 (Trumenba)
Bivalent rLP2086 is composed of 2 recombinant lipidated factor H binding protein (fHBP) 
variants from MnB, one from fHBP subfamily A and one from subfamily B (A05 and B01, 
respectively).
Bivalent rLP2086 was approved on 29 October 2014, under 21 Code of Federal Regulations 
(CFR) 601 Subpart E - Accelerated Approval of Biological Products for Serious or 
Life-Threatening Illnesses, for active immunization of individuals aged 10 through 25 years 
to prevent invasive disease caused by meningococcal group B.
Approval of bivalent rLP2086 was based on demonstration of safety and a serological 
correlate that showed in Phase 2 studies the induction of serum bactericidal activity against 
4 group B strains that are representative of the prevalent US strains. These were measured 
using serum bactericidal assays using human complement (hSBAs). As a requirement of 
licensure, Phase 3 studies were conducted to confirm the safety and immune responses 
associated with the 3-dose schedule. As of 21 January 2016, it is estimated that 21,607 
subjects have participated in the bivalent rLP2086 clinical development program: 11,436 
subjects were exposed to bivalent rLP2086.  A total of 4145 subjects received bivalent 
rLP2086 in combination with the following: diphtheria, tetanus, and acellular pertussis,
Haemophilus influenzae type b, and hepatitis B virus vaccine combined with inactivated 
poliomyelitis virus vaccine (DTaP-Hib-HBV+IPV)/Prevnar(32); dTaP-IPV (372); 
quadrivalent human papillomavirus vaccine (HPV4) (992); quadrivalent meningococcal 
polysaccharide conjugate (MCV4)/tetanus, diphtheria, and acellular pertussis (Tdap) vaccine
(884); or saline (1865). In addition, 417 subjects are currently receiving blinded therapy, and 
5609 subjects have received control. The total unit distribution in the United States from 
launch through 21 January 2016 is approximately 210,380 doses.
Results from 11 Phase 1, 2, and 3 completed clinical trials concluded that robust functional 
and broadly protective immune responses were observed in individuals receiving bivalent 
rLP2086 on the 2-dose 0- and 6-month schedule in Phase 2 Study B1971012, and on a 3-dose 
schedule in the Phase 3 program (0-, 2-, and 6-month schedule), as measured in hSBAs that 
used MnB strains (4 primary or 10 additional) that were prospectively selected to represent 
the diversity of the target antigen fHBP.  Each primary and each additional strain expressed 
fHBPs that were heterologous (to vaccine) fHBP variants.
Preliminary results of a persistence-of-immunity and booster study, B1971033, show that 
persistence of immunity following any of the 2- and 3-dose primary bivalent rLP2086 series 
schedules utilized in Study B1971012 follows similar patterns over 4 years.  Of note, 4-year 
persistence immunity data were comparable following a 2-dose 0- and 6-month or 3-dose 0-,

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2-, and 6-month primary bivalent rLP2086 series.  Similarly, the immune response following 
a booster dose with bivalent rLP2086 4 years after the primary bivalent rLP2086 series 
resulted in high hSBA titers, irrespective of whether subjects received a 2-dose or 3-dose 
primary bivalent rLP2086 series.  hSBA titers observed following the booster vaccination are 
higher than those seen 1 month following a 2- or 3-dose primary bivalent rLP2086 series.
Clinical studies also demonstrated that bivalent rLP2086 may be coadministered with MCV4, 
Tdap, HPV4, and dTap-IPV vaccines, which may facilitate introduction of bivalent rLP2086 
into national immunization programs. In addition, a consistent favorable safety and 
reactogenicity profile supports the use of bivalent rLP2086 to prevent invasive MnB disease 
in individuals 10 years of age and older in the European Union (EU).
1.2.2.2. Nimenrix (MenACWY-TT)
Nimenrix is composed of capsular polysaccharides from each of the A, C, W, and Y groups
of N meningitidis conjugated to tetanus toxoid.
Nimenrix was first approved in the EU on 20 April 2012 via the centralized procedure and is 
currently marketed in 67 countries. Nimenrix is not presently licensed in the United States, 
though there is an open investigational new drug application (IND) (BB-IND 13278). 
Licensure outside of the United States was based on safety and demonstration of 
immunologic noninferiority (based mainly on comparing proportions of subjects with serum 
bactericidal assay using rabbit complement [rSBA] titers of at least 1:8) to licensed 
meningococcal vaccines. Immunogenicity was measured using rSBA or hSBAs.
In the EU, Nimenrix is indicated for active immunization of individuals from the age of 
12 months and above against IMD caused by N meningitidis groups A, C, W-135, and Y.
The cumulative number of subjects who have received Nimenrix within GlaxoSmithKline 
(GSK)-sponsored interventional studies is estimated to be 13,533 subjects in primary study 
groups and 992 in booster study groups (note that some subjects from booster study groups 
also participated in primary study groups). Additionally, 1991 subjects in primary study 
groups have received treatment that is still blinded to the GSK/Pfizer study team. Finally, 
1219 subjects enrolled in the clinical development program for Nimenrix were vaccinated 
with a MenACWY-TT formulation other than the one that is currently on the market. 
Information on exposure is sourced from the clinical trial databases as of 19 October 2015.
Since launch in the EU to 30 September 2015, it is estimated that 2,953,217 doses of 
Nimenrix have been distributed. As vaccination with Nimenrix consists of 1 dose per subject 
in accordance with the local recommendations and assuming compliance with the 
vaccination schedule, the postmarketing exposure to Nimenrix is estimated to be 2,953,217 
individuals.
The immunogenicity studies conducted in subjects from 12 months of age and above
demonstrate that 1 dose of MenACWY-TT induces a response that is similar to or higher 
than the response induced by licensed meningococcal vaccines used as control, and that the

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vaccine is able to induce an immunologic memory against the 4 meningococcal groups in 
individuals vaccinated as toddlers 12 to 14 months of age, historically an age group that is 
not responsive to meningococcal polysaccharide vaccines. Follow-up studies demonstrate 
that persistence of the responses elicited by the vaccine is similar or higher than persistence 
of those elicited by the licensed meningococcal polysaccharide vaccines Meningitecand 
Mencevaxwhen assessed using the GSK rSBA. A variation is under review to extend the 
age indication to 6 weeks of age.
1.2.3. MenA, MenC, MenW, and MenY Functional Antibody Assays as a Surrogate of 
Efficacy
Meningococcal clearance from the bloodstream is primarily by complement-mediated 
bacteriolysis, and an effective complement system is critical for resistance against infections 
caused by N meningitidis. Individuals with complement deficiencies have an increased risk 
of developing meningococcal disease.23,24 The in vivo complement-mediated bacteriolysis of 
meningococcus is mimicked by the in vitro serum bactericidal assay (SBA), a functional 
serological assay shown to be the surrogate of protection for meningococcal disease.25
For meningococcal group C conjugate vaccines, postlicensure efficacy estimates in the 
United Kingdom demonstrated that a cutoff of 1:8 in the rSBA was the most consistent with 
observed efficacy at 4 weeks after vaccination.26  The established correlate of protection for 
the SBA-MenC assay using human serum as the exogenous complement source is a titer 
1:4.25,27 Even though no correlate of protection has been established for meningococcal 
groups A, W, and Y,28 it is common practice to extend the 1:8 cutoff for rSBA using 
meningococcal groups A, W, and Y (rSBA-MenA, rSBA-MenW, and rSBA-MenY) and the 
1:4 cut-off for hSBA-MenA, hSBA-MenW, and hSBA-MenY.25,29
hSBA responses have been used routinely as surrogates of efficacy and as the basis for 
licensure of MnB vaccines.30,31 Outer membrane vesicle (OMV) vaccines have been 
deployed in some countries in response to outbreaks caused by specific epidemic MnB 
strains,32 and large-scale efficacy studies with OMV vaccines have been conducted in Cuba, 
Brazil, Chile, Norway, and New Zealand.33,34,35,36,37,38  In each instance, a relationship 
between responses measured by hSBA and protection from MnB disease was demonstrated39
with a 1:4 cutoff for hSBA MnB as the correlate of protection.25,27,40
Use of hSBA in clinical trials of MenABCWY is scientifically reasonable as a surrogate of 
vaccine efficacy and necessary, because a traditional trial with an efficacy endpoint is not 
feasible because of the low incidence of meningococcal disease, <1/100,000 in the United 
States and Europe,7,40,41 meaning that extremely large numbers of subjects (>100,000) would 
be required to support a statistically significant assessment.

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1.2.4. Study Rationale
The study design is described in Section 3. This is a Phase 3 study to verify and describe the 
clinical benefit of a 2-dose schedule for the use of bivalent rLP2086 administered at 
Months 0 and 6 in healthy subjects 10 years to <26 years of age.
This study will also describe the safety, tolerability, and immunogenicity of MenABCWY, 
and describe the immune response to groups A, C, W, and Y following administration of 
MenABCWY, or bivalent rLP2086 and a meningococcal group A, C, W-135, and Y 
conjugate vaccine (MenACWY-CRM).
Pfizer considers the available information from prior studies with MenACWY-TT
(PF-06866681) and bivalent rLP2086 (PF-05212366) sufficient to support an expectation of 
a favorable benefit-risk profile for this study using MenABCWY (PF-06886992).
Additional information for this compound (MenABCWY) may be found in the single 
reference safety document (SRSD), which for this study is the MenABCWY investigator’s 
brochure (IB).  Additional information for bivalent rLP2086 may be found in the SRSD, 
which for this study is the IB for bivalent rLP2086.  The SRSD for the comparator agent 
MenACWY-CRM is the Menveo US package insert.
Refer to the most recent version of the MenABCWY IB for a summary of findings from 
nonclinical studies that potentially have clinical significance and from clinical studies that are 
relevant to this study.  Also refer to the most recent version of the MenABCWY IB for a 
summary of the known and potential risks and benefits, if any, to human subjects.
Refer to the most recent version of the Menveo US package insert for a summary of the 
known and potential risks and benefits, if any, to human subjects.
2. STUDY OBJECTIVES AND ENDPOINTS
Subjects having received a vaccine containing 1 or more ACWY groups prior to enrollment 
will be randomized in the ACWY-experienced stratum but, for the purposes of A, C, W, and 
Y analyses, will be considered A, C, W, Y-naive or -experienced based on what group(s) 
were present in the prior ACWY-containing vaccine.
The secondary strain immunogenicity objective is based on hSBA results from subjects in 
Groups 2 and 4 using 10 test strains expressing the following variants:  A29, A06, A12, A07, 
A15, A19, B16, B09, B03, and B15. Three (3) subsets of study subjects will be selected for 
this analysis. Each subset will be used to assess the response to 3 or 4 of the 10 secondary
test strains in addition to the 4 primary test strains.

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Primary Immunogenicity Objective:
Primary Immunogenicity Endpoints:

To assess the immune response induced by bivalent 
rLP2086 as measured by hSBA performed with 4 
primary MnB test strains, 2 expressing an LP2086 
subfamily A protein and 2 expressing an LP2086 
subfamily B protein, measured 1 month after the 
second vaccination, in the bivalent rLP2086 arms 
(Group 2 and 4 subjects) combined.
Five (5) coprimary endpoints are defined for the primary
objective; they are defined for hSBA performed with each of 
the 4 primary test strains: PMB80 (A22), PMB2001 (A56), 
PMB2948 (B24), and PMB2707 (B44).

One (1) of the 5 coprimary endpoints is the composite 
endpoint defined as the proportion of subjects achieving 
an hSBA titer lower limit of quantitation (LLOQ; 1:16 
for A22 and 1:8 for A56, B24, and B44) for all 4 primary 
test strains combined, 1 month after the second 
vaccination in the bivalent rLP2086 arms (Group 2 and 4 
subjects) combined. 

Four (4) of the coprimary endpoints are defined as the 
proportion of subjects achieving at least a 4-fold increase 
in hSBA titer from baseline to 1 month after the second 
vaccination in the bivalent rLP2086 arms (Group 2 and 4 
subjects) combined for each of the 4 primary test strains.
For subjects with a baseline hSBA titer below the limit 
of detection (LOD, or an hSBA titer of <1:4), a 4-fold 
response is defined as an hSBA titer of 1:16 or the 
LLOQ (whichever titer is higher).
For subjects with a baseline hSBA titer of LOD 
(ie, hSBA titer of 1:4) and < LLOQ, a 4-fold 
response is defined as an hSBA titer of 4 times the 
LLOQ.
For subjects with a baseline hSBA titer of LLOQ, a 
4-fold response is defined as an hSBA titer of 4 times 
the baseline titer.
Primary Safety Objectives:
Primary Safety Endpoints:

To describe the safety profile of bivalent rLP2086, as 
measured by local reactions, systemic events, 
adverse events (AEs), serious adverse events (SAEs), 
newly diagnosed chronic medical conditions, 
medically attended AEs, and immediate AEs,
following Vaccinations 1 and 2 in the bivalent 
rLP2086 arms (Group 2 and 4 subjects) combined.
The following endpoints will be described after Vaccinations 1 
and 2 in the bivalent rLP2086 arms (Group 2 and 4 subjects)
combined.

Percentage of subjects reporting local reactions (pain, 
redness, and swelling) and by severity within 7 days after 
each vaccination visit.

Percentage of subjects reporting systemic events (fever, 
vomiting, diarrhea, headache, fatigue, chills, muscle pain 
other than muscle pain at any injection site, and joint 
pain) and by severity within 7 days after each vaccination
visit.

Percentage of subjects reporting the use of antipyretic 
medication within 7 days after each vaccination visit. 

Percentage of subjects with at least 1 SAE during the 
following time periods:

30 Days after each vaccination.

30 Days after any vaccination.

During the Stage 1 vaccination phase (from the first 
study vaccination [Visit 1] through 1 month after the 
second study vaccination [Visit 4]).

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
During the Stage 1 follow-up phase (from 1 month 
after the second study vaccination [Visit 4] through 
6 months after the second study vaccination [Visit 5]).

Throughout Stage 1 (from the first study vaccination 
[Visit 1] through 6 months after the second study 
vaccination [Visit 5]).

Percentage of subjects with at least 1 medically attended 
AE occurring during the following time periods:

30 Days after each vaccination.

30 Days after any vaccination.

During the Stage 1 vaccination phase (from the first 
study vaccination [Visit 1] through 1 month after the 
second study vaccination [Visit 4]).

During the Stage 1 follow-up phase (from 1 month 
after the second study vaccination [Visit 4] through 6 
months after the second study vaccination [Visit 5]).

Throughout Stage 1 (from the first study vaccination 
[Visit 1] through 6 months after the second study 
vaccination [Visit 5]).

Percentage of subjects with at least 1 newly diagnosed 
chronic medical condition occurring during the following 
time periods:

30 Days after each vaccination.

30 Days after any vaccination.

During the Stage 1 vaccination phase (from the first 
study vaccination [Visit 1] through 1 month after the 
second study vaccination [Visit 4]).

During the Stage 1 follow-up phase (from 1 month 
after the second study vaccination [Visit 4] through 
6 months after the second study vaccination [Visit 5]).

Throughout Stage 1 (from the first study vaccination 
[Visit 1] through 6 months after the second study 
vaccination [Visit 5]).

Percentage of subjects with at least 1 AE occurring during 
the following time periods:

30 Days after each vaccination.

30 Days after any vaccination.

During the Stage 1 vaccination phase (from the first 
study vaccination [Visit 1] through 1 month after the 
second study vaccination [Visit 4]).

Percentage of subjects reporting at least 1 immediate AE 
after each vaccination.

Subject days missing school or work because of AEs 
during the Stage 1 vaccination phase (Visit 1 though 
Visit 4).

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
To describe the safety profile of MenABCWY, as 
measured by local reactions, systemic events, AEs, 
SAEs, newly diagnosed chronic medical conditions, 
medically attended AEs, and immediate AEs, after 
the booster vaccination.

To describe the safety profile of bivalent rLP2086, as 
measured by local reactions, systemic events, AEs, 
SAEs, newly diagnosed chronic medical conditions, 
medically attended AEs, and immediate AEs, after 
the booster vaccination.
The following endpoints will be described after the booster
vaccination in Groups 1 through 4:

Percentage of subjects reporting local reactions (pain, 
redness, and swelling) and by severity within 7 days after 
the booster vaccination.

Percentage of subjects reporting systemic events (fever, 
vomiting, diarrhea, headache, fatigue, chills, muscle pain 
other than muscle pain at any injection site, and joint pain) 
and by severity within 7 days after the booster vaccination. 

Percentage of subjects reporting the use of antipyretic 
medication within 7 days after the booster vaccination. 

Percentage of subjects with at least 1 SAE during the 
following time periods:

During the booster vaccination phase (from the 
booster vaccination [Visit 10] through 1 month after 
the booster vaccination [Visit 11]).

During the booster follow-up phase (from 1 month 
after the booster vaccination [Visit 11] through 
6 months after the booster vaccination [Visit 12]).

From the booster vaccination (Visit 10) through 
6 months after the booster vaccination (Visit 12).

Percentage of subjects with at least 1 medically attended 
AE occurring during the following time periods:

During the booster vaccination phase (from the booster 
vaccination [Visit 10] through 1 month after the 
booster vaccination [Visit 11]).

During the booster follow-up phase (from 1 month 
after the booster vaccination [Visit 11] through 
6 months after the booster vaccination [Visit 12]).

From the booster vaccination (Visit 10) through 
6 months after the booster vaccination (Visit 12).

Percentage of subjects with at least 1 newly diagnosed 
chronic medical condition occurring during the following 
time periods:

During the booster vaccination phase (from the booster 
vaccination [Visit 10] through 1 month after the 
booster vaccination [Visit 11]).

During the booster follow-up phase (from 1 month 
after the booster vaccination [Visit 11] through 
6 months after the booster vaccination [Visit 12]).

From the booster vaccination (Visit 10) through 
6 months after the booster vaccination (Visit 12).

Percentage of subjects with at least 1 AE occurring during 
the following time periods:

During the booster vaccination phase (from the booster 
vaccination [Visit 10] through 1 month after the 
booster vaccination [Visit 11]).

Percentage of subjects reporting at least 1 immediate AE 
after the booster vaccination.

The number of days missed, school or work, by the subject
because of AEs after the booster vaccination.

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Secondary Immunogenicity Objectives:
Secondary Immunogenicity Endpoints:

To describe the immune response induced by bivalent 
rLP2086 as measured by hSBA performed with 4 
primary MnB test strains, 2 expressing an LP2086 
subfamily A protein and 2 expressing an LP2086 
subfamily B protein, measured 1 month after the 
second vaccination, in the bivalent rLP2086 arms
(Group 2 and 4 subjects) combined.

Proportions of subjects with hSBA titers LLOQ, 1:4, 
1:8, 1:16, 1:32, 1:64, and 1:128 for each of the 4 
primary MenB test strains at Visit 4.

hSBA geometric mean titers (GMTs) for each of the 4 
primary MnB test strains at Visit 4.

To describe the MenB immune response as measured 
by hSBA performed with secondary MenB test strains 
measured 1 month after the second vaccination in 
Groups 2 and 4 combined.
The secondary immunogenicity endpoints for the subsets 
tested with the additional hSBA test strains are as follows:

Proportions of subjects with hSBA titers LLOQ (1:16 
for A06, A12, and A19 and 1:8 for A07, A15, A29, B03, 
B09, B15, and B16) for each of the secondary test strains 
1 month after the second vaccination.

Proportions of subjects with hSBA titers 1:4, 1:8, 
1:16, 1:32, 1:64, and 1:128 for each of the secondary 
test strains 1 month after the second vaccination.

hSBA GMTs for each of the secondary test strains 
1 month after the second vaccination.

To describe the immune response induced by 1 dose 
of MenABCWY compared to the immune response 
induced by 1 dose of MenACWY-CRM, as measured 
by hSBA performed with ACWY test strains, in 
ACWY-naive and ACWY-experienced subjects 
separately.
Proportions of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW, and hSBA-MenY titers 1:8 (or LLOQ, 
whichever is higher) at Visit 2.
Proportions of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW, and hSBA-MenY titers 1:4, 1:8, 1:16, 
1:32, 1:64, and 1:128 at Visit 2.
hSBA GMTs for each of the ACWY test strains at Visit 2.

To describe the immune response induced by 2 doses 
of MenABCWY compared to the immune response 
induced by 1 dose of MenACWY-CRM, as measured 
by hSBA performed with ACWY test strains, in 
ACWY-naive and ACWY-experienced subjects 
separately.
Proportions of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW, and hSBA-MenY titers 1:8 (or LLOQ, 
whichever is higher) at Visit 4 in Groups 1 and 3 and at 
Visit 2 in Groups 2 and 4. 
Proportions of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW, and hSBA-MenY titers 1:4, 1:8, 1:16, 
1:32, 1:64, and 1:128 at Visit 4 in Groups 1 and 3 and 
Visit 2 in Groups 2 and 4.
hSBA GMTs for each of the ACWY test strains at Visit 4 in 
Groups 1 and 3 and Visit 2 in Groups 2 and 4.

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
To describe the immune response induced by 
MenABCWY compared to the immune response 
induced by bivalent rLP2086, as measured by hSBA 
performed with 4 primary MnB test strains, 2 
expressing an LP2086 subfamily A protein and 2 
expressing an LP2086 subfamily B protein, measured 
1 month after the second vaccination in the ACWY-
naive and ACWY-experienced subjects combined.

Proportions of subjects who achieve the 5 MnB endpoints 
1 month after the second vaccination, which are defined 
for hSBA performed with each of the 4 primary test 
strains: PMB80 (A22), PMB2001 (A56), PMB2948 (B24), 
and PMB2707 (B44), as detailed below:

One (1) of the 5 endpoints is the composite endpoint 
defined as the proportion of subjects achieving an 
hSBA titer LLOQ (1:16 for A22 and 1:8 for A56, 
B24, and B44) for all 4 primary test strains combined, 
1 month after the second vaccination. 

Four (4) of the endpoints are defined as the proportion 
of subjects achieving at least a 4-fold increase in hSBA 
titer from baseline to 1 month after the second 
vaccination for each of the 4 primary test strains.

For subjects with a baseline hSBA titer below the 
LOD (ie, an hSBA titer of <1:4), a 4-fold response 
is defined as an hSBA titer of 1:16 or the LLOQ 
(whichever titer is higher).

For subjects with a baseline hSBA titer of LOD 
(ie, hSBA titer of 1:4) and < LLOQ, a 4-fold 
response is defined as an hSBA titer of 4 times 
the LLOQ.

For subjects with a baseline hSBA titer of 
LLOQ, a 4-fold response is defined as an hSBA 
titer of 4 times the baseline titer.

Proportions of subjects with hSBA titers LLOQ, 1:4, 
1:8, 1:16, 1:32, 1:64, and 1:128 for each of the 4 
primary MenB test strains at Visit 4.  

hSBA GMTs for each of the 4 primary MnB test strains at 
Visit 4.

To describe the immune response induced by 
MenABCWY compared to the immune response 
induced by MenACWY-CRM and bivalent rLP2086,
as measured by hSBA performed with ACWY test 
strains and 4 primary MenB test strains, 2 expressing 
an LP2086 subfamily A protein and 2 expressing an 
LP2086 subfamily B protein, at blood sampling time 
points prior to the booster vaccination (Stage 1).

Proportions of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW, and hSBA-MenY titers 1:8 (or LLOQ, 
whichever is higher) at Visits 1 and 3, in the ACWY-naive 
and ACWY-experienced subjects separately.

Proportions of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW, and hSBA-MenY titers 1:4, 1:8, 1:16, 
1:32, 1:64, and 1:128 at Visits 1 and 3, in the ACWY-
naive and ACWY-experienced subjects separately.

hSBA GMTs for each of the ACWY test strains at Visits 1
and 3, in the ACWY-naive and ACWY-experienced 
subjects separately.

Proportions of subjects with hSBA titers LLOQ1:4, 
1:8, 1:16, 1:32, 1:64, and 1:128 for each of the 4 
primary MenB test strains at Visits 1 and 3, in the ACWY-
naive and ACWY-experienced subjects combined.  

hSBA GMTs for each of the 4 primary MenB test strains 
at Visits 1 and 3, in the ACWY-naive and 
ACWY-experienced subjects combined. 

To describe the immune response induced by 
MenABCWY compared to the immune response 
induced by MenACWY-CRM and bivalent rLP2086,
as measured by hSBA performed with ACWY test 
strains and 4 primary MenB test strains, 2 expressing 
an LP2086 subfamily A protein and 2 expressing an 
LP2086 subfamily B protein, at blood sampling time 

Proportions of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW, and hSBA-MenY titers 1:8 (or LLOQ, 
whichever is higher) at Visits 7, 8, 9, and 10, in the 
ACWY-naive and ACWY-experienced subjects 
separately.

Proportions of subjects with hSBA titers LLOQ for each 

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rLP2086; subfamily A and B; E coli])
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points prior to the booster vaccination (Stage 2).
of the 4 primary MenB test strains at Visits 7, 8, 9, and 10, 
in the ACWY-naive and ACWY-experienced subjects 
combined.  

To describe the immune response induced by 
MenABCWY, as measured by hSBA performed with 
ACWY and 4 primary MnB test strains, 1 month 
after a booster vaccination in Groups 1 and 3.

Proportions of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW, and hSBA-MenY titers 1:8 (or LLOQ, 
whichever is higher) at Visit 11 in Groups 1 and 3,
separately. 

Proportions of subjects with hSBA titers LLOQ for each 
of the 4 primary MenB test strains at Visit 11, in Groups 1 
and 3 combined. 

To describe the immune response induced by 
bivalent rLP2086, as measured by hSBA performed 
with 4 primary MnB test strains, 2 expressing an 
LP2086 subfamily A protein and 2 expressing an 
LP2086 subfamily B protein, measured 1 month after 
the booster vaccination in Groups 2 and 4.

Proportions of subjects with hSBA titers LLOQ for each 
of the 4 primary MenB test strains at Visit 11, in Groups 2 
and 4 combined. 
Secondary Safety Objectives:
Secondary Safety Endpoints: 

To describe the safety profile of MenABCWY, as 
measured by local reactions, systemic events, AEs, 
SAEs, newly diagnosed chronic medical conditions, 
medically attended AEs, and immediate AEs, after 
Vaccinations 1 and 2 in the ACWY-naive and 
ACWY-experienced subjects separately. 
The following endpoints will be described after Vaccinations 1 
and 2 in Groups 1 and 3:

Percentage of subjects reporting local reactions (pain, 
redness, and swelling) and by severity within 7 days after 
each vaccination visit.

Percentage of subjects reporting systemic events (fever, 
vomiting, diarrhea, headache, fatigue, chills, muscle pain 
other than muscle pain at any injection site, and joint pain) 
and by severity within 7 days after each vaccination visit. 

Percentage of subjects reporting the use of antipyretic 
medication within 7 days after each vaccination visit. 

Percentage of subjects with at least 1 SAE during the 
following time periods:

30 Days after each vaccination.

30 Days after any vaccination.

During the Stage 1 vaccination phase (from the first 
study vaccination [Visit 1] through 1 month after the 
second study vaccination [Visit 4]).

During the Stage 1 follow-up phase (from 1 month 
after the second study vaccination [Visit 4] through 
6 months after the second study vaccination [Visit 5]).

Throughout Stage 1 (from the first study vaccination 
[Visit 1] through 6 months after the second study 
vaccination [Visit 5]).

Percentage of subjects with at least 1 medically attended 
AE occurring during the following time periods:

30 Days after each vaccination.

30 Days after any vaccination.

During the Stage 1 vaccination phase (from the first 
study vaccination [Visit 1] through 1 month after the 
second study vaccination [Visit 4]).

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rLP2086; subfamily A and B; E coli])
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
During the Stage 1 follow-up phase (from 1 month 
after the second study vaccination [Visit 4] through 
6 months after the second study vaccination [Visit 5]).

Throughout Stage 1 (from the first study vaccination 
[Visit 1] through 6 months after the second study 
vaccination [Visit 5]).

Percentage of subjects with at least 1 newly diagnosed 
chronic medical condition occurring during the following 
time periods:

30 Days after each vaccination.

30 Days after any vaccination.

During the Stage 1 vaccination phase (from the first 
study vaccination [Visit 1] through 1 month after the 
second study vaccination [Visit 4]).

During the Stage 1 follow-up phase (from 1 month 
after the second study vaccination [Visit 4] through 
6 months after the second study vaccination [Visit 5]).

Throughout Stage 1 (from the first study vaccination 
[Visit 1] through 6 months after the second study 
vaccination [Visit 5]).

Percentage of subjects with at least 1 AE occurring during 
the following time periods:

30 Days after each vaccination.

30 Days after any vaccination.

During the Stage 1 vaccination phase (from the first 
study vaccination [Visit 1] through 1 month after the 
second study vaccination [Visit 4]).

Percentage of subjects reporting at least 1 immediate AE 
after each vaccination.

The number of days missed, school or work, by the subject
because of AEs after vaccination.
Exploratory Objectives:
Exploratory Endpoints:

To describe the immune response induced by 
MenACWY-CRM as measured by hSBA performed 
with ACWY test strains, 1 month after a booster 
vaccination in Groups 2 and 4.

Proportion of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW, and hSBA-MenY titers 1:8 (or LLOQ, 
whichever is higher) at Visit 11, in Groups 2 and 4 
separately.

To describe the immune response induced by bivalent 
rLP2086 as measured by hSBA performed with 4 
primary MnB test strains, 2 expressing an LP2086 
subfamily A protein and 2 expressing an LP2086 
subfamily B protein, measured 1 month after the first 
vaccination, in the bivalent rLP2086 arms (Group 2 
and 4 subjects) combined.

Proportion of subjects who achieve the 5 MnB endpoints 
at Visit 2.

Proportions of subjects with hSBA titers LLOQ, 1:4, 
1:8, 1:16, 1:32, 1:64, and 1:128 for each of the 4 
primary MenB test strains at Visit 2. 

hSBA GMTs for each of the 4 primary MnB test strains at 
Visit 2.

To further describe the immune response induced by 
MenABCWY compared to the immune response 
induced by MenACWY-CRM and bivalent rLP2086,
as measured by hSBA performed with ACWY test 
strains and 4 primary MenB test strains, 2 expressing 
an LP2086 subfamily A protein and 2 expressing an 
LP2086 subfamily B protein, at blood sampling time 
points prior to the booster vaccination (Stage 2).

Proportions of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW, and hSBA-MenY titers 1:8, 1:16, 
1:32, 1:64, and 1:128 at Visits 7, 8, 9, and 10, in the 
ACWY-naive and ACWY-experienced subjects 
separately.

hSBA GMTs for each of the ACWY test strains at Visits 
7, 8, 9, and 10, in the ACWY-naive and 
ACWY-experienced subjects separately.

Proportions of subjects with hSBA titers 1:4, 1:8, 
1:16, 1:32, 1:64, and 1:128 for each of the 4 primary 

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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MenB test strains at Visits 7, 8, 9, and 10, in the ACWY-
naive and ACWY-experienced subjects combined.  

hSBA GMTs for each of the 4 primary MenB test strains 
at Visits 7, 8, 9, and 10, in the ACWY-naive and ACWY-
experienced subjects combined. 

To further describe the immune response induced by 
MenABCWY, as measured by hSBA performed with 
ACWY and 4 primary MnB test strains, 1 month after 
a booster vaccination in Groups 1 and 3.

Proportions of subjects with hSBA-MenA, hSBA-MenC, 
hSBA-MenW, and hSBA-MenY titers 1:8, 1:16, 1:32, 
1:64, and 1:128 at Visit 11, in Groups 1 and 3 
separately.

hSBA GMTs for each of the ACWY test strains at 
Visit 11, in Groups 1 and 3 separately. 

Proportion of subjects who achieve the 5 MnB endpoints 
at Visit 11, in Groups 1 and 3 combined. 

Proportions of subjects with hSBA titers 1:4, 1:8, 1:16, 
1:32, 1:64, and 1:128 for each of the 4 primary MenB 
test strains at Visit 11, in Groups 1 and 3 combined.

hSBA GMTs for each of the 4 primary MnB test strains at 
Visit 11, in Groups 1 and 3 combined. 

To further describe the immune response induced by 
bivalent rLP2086, as measured by hSBA performed 
with 4 primary MnB test strains, 2 expressing an 
LP2086 subfamily A protein and 2 expressing an 
LP2086 subfamily B protein, measured 1 month after 
the booster vaccination in Groups 2 and 4.

Proportion of subjects who achieve the 5 MnB endpoints 
1 month after the booster vaccination, in Groups 2 and 4 
combined.

Proportions of subjects with hSBA titers 1:4, 1:8, 1:16, 
1:32, 1:64, and 1:128 for each of the 4 primary MenB 
test strains at Visit 11, in Groups 2 and 4 combined.

hSBA GMTs for each of the 4 primary MnB test strains at 
Visit 11, in Groups 2 and 4 combined.
3. STUDY DESIGN
This is a Phase 3, randomized, active-controlled, observer-blinded multicenter trial in which 
approximately 1590 subjects will be randomly assigned to receive either MenABCWY and 
placebo, or bivalent rLP2086 and MenACWY-CRM. All subjects will be naive to any
meningococcal group B vaccine prior to enrollment.
Randomization will be stratified by prior vaccination history; approximately 795 
ACWY-naive subjects and 795 ACWY-experienced (having received 1 prior dose of a 
vaccine containing 1 or more ACWY groups 4 years prior to the date of randomization) 
subjects will be enrolled.
Randomization will also be stratified by geographic region.  Approximately 1320 subjects 
from US investigative sites and 270 subjects from ex-US countries will be randomized.  
Regional stratification will ensure sufficient population representation.
Enrollment targets will also be adjusted to achieve appropriate representation by age
(subjects 10 to <18 years old and subjects 18 to <26 years old), age within ACWY strata, and 
ACWY strata within a geographic region. Additional details will be provided during pretrial 
assessment and site initiation visits.
The study will be conducted in 2 stages:

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
Stage 1: from study entry (Visit 1) through Visit 6.  See Table 1.  A pilot cohort 
consisting of 10 subjects 18 to <26 years of age will first be enrolled at selected site(s).  
These pilot cohort subjects will be assigned to either Group 1 or 3, and therefore will 
receive MenABCWY at Vaccination 1.  The sponsor will be unblinded to vaccine 
assignment for the pilot cohort. Seven (7) days after the last pilot cohort subject has 
received MenABCWY, 7-day electronic diary (e-diary) and AE data will be summarized
for review by the sponsor’s independent review committee (IRC).  No further enrollment 
will be permitted until review of these safety data is complete.  If the IRC finds the safety 
data from the pilot cohort acceptable, enrollment will be opened to all ages and 
randomization groups, and pilot cohort subjects will proceed through the study. During 
Stage 1, the sponsor will be blinded to vaccine assignment beyond completion of pilot 
cohort enrollment (Section 5.4).
In order to support assay development, a subset of up to approximately 600 subjects 18 to 
25 years of age will have up to 100 mL, rather than 20 mL, of blood drawn at Visits 1, 2,
and 4; and a subset of up to approximately 150 subjects 18 to 25 years of age will have 
up to 100 mL, rather than 20 mL, of blood drawn at Visit 11.  Subject participation in this 
subset will be voluntary, and the volume of blood drawn will depend on the consent 
obtained.  Stage 1 will be observer-blinded.
At designated sites, an additional optional whole blood sample of approximately 50 mL 
will be obtained at Visit 4 from up to approximately 30 subjects 18 to 25 years of age.  
This sample will be used for exploratory purposes.

Stage 2: from Months 18 to 60 (Visits 7 to 12). Subjects from both the ACWY-naïve and 
ACWY-experienced strata, approximately 132 from each of Groups 1 and 3 and 
approximately 65 from each of Groups 2 and 4, will participate in Stage 2.  Stage 1 will 
be observer-blinded and Stage 2 will be open-label.
Table 1.
Stage 1 Study Design
Vaccination 1
Post–
Vaccinatio
n 1 Blood 
Draw
Vaccination 2
Post–
Vaccination 
2 Blood 
Draw
Safety 
Telephone 
Call
Telephone 
Call
Approximate 
Month
0
1
6
7
12
Visit Number
1
2
3
4
5
6
ACWY-
Naive 
Subjects
Group 1a
(n=265)
MenABCWY + 
saline
MenABCWY
Group 2 
(n=530)
Bivalent 
rLP2086 + 
MenACWY-
CRM
Bivalent 
rLP2086
Blood Draw
for serum 
collection
20 mL
(or up to 100 mL 
in subset)
20 mL
(or up to 
100 mL in 
subset)
20 mL
20 mL
(or up to 
100 mL in 
subset)

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rLP2086; subfamily A and B; E coli])
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Table 1.
Stage 1 Study Design
Vaccination 1
Post–
Vaccinatio
n 1 Blood 
Draw
Vaccination 2
Post–
Vaccination 
2 Blood 
Draw
Safety 
Telephone 
Call
Telephone 
Call
ACWY-
Experienced 
Subjects
Group 3a
(n=265)
MenABCWY + 
saline
MenABCWY
Group 4 
(n=530)
Bivalent 
rLP2086 + 
MenACWY-
CRM
Bivalent 
rLP2086
Blood Draw
for Serum
Collection
20 mL
(up to 100 mL in 
subset)
20 mL
(up to
100 mL in 
subset)
20 mL
20 mL
(up to
100 mL in 
subset)
Subjects 18 to 
25 years of 
age (naïve or 
experienced)
Optional 
Blood Draw 
for Whole 
Blood 
Collection
50 mL
a.
Pilot cohort subjects will be assigned to either Group 1 or 3, but will receive only MenABCWY at 
Vaccination 1. Pilot cohort subjects will not receive saline at Vaccination 1. 
Table 2.
Stage 2 Study Design
Antibody
Persistence
Booster
Vaccination
Postbooster
Blood Draw
Safety
Telephone
Call
Approximate
Month
18-42
54
55
60
Visit Number
7-9
10
11
12
ACWY-Naive 
Subjects
Group 1(n ~132)
MenABCWY
Group 2 (n ~65)
Bivalent rLP2086 + 
MenACWY-CRM

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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Final Protocol Amendment 2, 09 July 2019
PFIZER CONFIDENTIAL
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Table 2.
Stage 2 Study Design
Antibody
Persistence
Booster
Vaccination
Postbooster
Blood Draw
Safety
Telephone
Call
Approximate
Month
18-42
54
55
60
Visit Number
7-9
10
11
12
ACWY-
Experienced 
Subjects
Group 3 (n ~132)
MenABCWY
Group 4 (n ~65)
Bivalent rLP2086 + 
MenACWY-CRM
Blood Draw for 
Serum Collection
20 mL × 3
20 mL
20 mL
(or up to 100 mL 
in subset)
In Stage 2, the total number subjects for Groups 1 and 3 combined will be approximately 264
and the total number of subjects for Groups 2 and 4 combined will be approximately 130.  
3.1. Approximate Duration of Subject Participation
Subjects will participate in Stage 1 for approximately 18 months.  This includes a telephone 
contact 6 months after the last Stage 1 study vaccination.  
Subject participation in Stage 2 will last for approximately 4 years.
The total study duration for subjects who complete Stage 2 will be approximately 5 years 
(60 months).
3.2. Approximate Duration of Study
This study will be completed in approximately 66 months.
3.3. Approximate Number of Subjects
Approximately 1590 subjects will be randomized to participate in this study.  Subjects 
withdrawn from the study will not be replaced, regardless of the reason for withdrawal.
Approximately 394 subjects may continue into Stage 2. Subjects from both ACWY-naïve 
and ACWY-experienced strata, approximately 132 from each of Groups 1 and 3 and 
approximately 65 from each of Groups 2 and 4, will participate in Stage 2.  Stage 1 will be 
observer-blinded and Stage 2 will be open-label.  
4. SUBJECT ELIGIBILITY CRITERIA
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate.  All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular subject is suitable for this protocol.

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PFIZER CONFIDENTIAL
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Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study.
4.1. Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Evidence of a personally signed and dated informed consent document (ICD) indicating 
that the subject (or parent(s)/legal guardian) has been informed of all pertinent aspects of 
the study.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures.
3. Male and female subject aged 10 and <26 years, at the time of randomization.
4. Subjects who have never received a prior dose, or who have received not more than 
1 prior dose no sooner than 4 years prior to the date of randomization, of a vaccine 
containing 1 or more ACWY groups.  Written confirmation of ACWY vaccination 
history should be obtained prior to randomization; however, if written ACWY 
vaccination history is not available, history obtained verbally from the subject 
(or parent(s)/legal guardian) is acceptable, if deemed reliable by the investigator.
5. Available for the entire study period and can be reached by telephone.
6. Healthy subject as determined by medical history, physical examination, and judgment of 
the investigator.
7. Male and female subjects of childbearing potential must agree to use a highly effective 
method of contraception throughout Stage 1 (through the follow-up telephone contact at 
Month 12), and from Visit 10 (booster vaccination) to Visit 11.  A subject is of 
childbearing potential if, in the opinion of the investigator, he/she is biologically capable 
of having children and is sexually active.
8. Negative urine pregnancy test for all female subjects.
4.2. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Previous vaccination with any meningococcal group B vaccine or any purely 
polysaccharide (nonconjugate) meningococcal vaccine.  Written vaccination history 
should be obtained prior to randomization; however, if written vaccination history is not 
available, history obtained verbally from the subject (or parent(s)/legal guardian) is 
acceptable, if deemed reliable by the investigator.

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rLP2086; subfamily A and B; E coli])
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PFIZER CONFIDENTIAL
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2. Previous vaccination with >1 dose of a vaccine containing 1 or more ACWY group.
3. Subjects having received 1 prior dose of a vaccine containing 1 or more ACWY group
<4 years prior to the date of randomization.
4. A previous anaphylactic reaction to any vaccine or vaccine-related component.
5. Subjects receiving any allergen immunotherapy with a nonlicensed product or receiving 
allergen immunotherapy with a licensed product and are not on stable maintenance doses.
6. Bleeding diathesis or condition associated with prolonged bleeding time that would 
contraindicate intramuscular injection.
7. A known or suspected defect of the immune system that would prevent an immune 
response to the vaccine, such as subjects with congenital or acquired defects in B-cell 
function, those receiving chronic systemic (oral, intravenous, or intramuscular) 
corticosteroid therapy, or those receiving immunosuppressive therapy.  Subjects in the 
United States with terminal complement deficiency are excluded from participation in 
this study. Please refer to the study reference manual (SRM) for additional details.
8. History of microbiologically proven disease caused by Neisseria meningitidis or 
Neisseria gonorrhoeae.
9. Significant neurological disorder or history of seizure (excluding simple febrile seizure).
10. Receipt of any blood products, including immunoglobulin, within 6 months before the 
first study vaccination.
11. Current chronic use of systemic antibiotics.
12. Participation in other studies involving investigational drug(s) within 28 days prior to 
study entry and/or during study participation.
13. Any neuroinflammatory or autoimmune condition, including, but not limited to, 
transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.
14. Other acute or chronic medical or psychiatric condition including recent (within the past 
year) or active suicidal ideation or behavior or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the subject inappropriate for entry into this study.
15. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or subjects 
who are Pfizer employees, including their family members, directly involved in the 
conduct of the study.

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rLP2086; subfamily A and B; E coli])
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16. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female 
subjects of childbearing potential who are unwilling or unable to use a highly effective 
method of contraception as outlined in Section 4.5.
4.3. Criteria for Temporarily Delaying Vaccine Administration
The following conditions are temporary or self-limiting and a subject may be vaccinated 
once the conditions have resolved and the subject is eligible for vaccination:
1. Current febrile illness (temperature 38.0C [100.4F]) or other acute illness within 
48 hours before investigational product administration.
2. Subject has received a nonlive vaccine (or intramuscular/sublingual allergen 
immunotherapy) within 14 days, or live vaccine within 28 days, before investigational 
product administration.
3. Subject has received a vaccine containing all or individual antigens included in Tdap 
vaccine within the previous 28 days.
4. Subject is less than 5 days into a course of systemic antibiotic therapy.
5. Subject has received systemic (oral, intravenous, or intramuscular) corticosteroid therapy 
within the previous 28 days.
If a subject meets any delay criteria for vaccination, all study procedures, including blood 
sample collection relating to that visit, should be delayed until the day of vaccination.  Blood 
samples must always be collected prior to vaccination.
4.4. Criteria for Temporarily Delaying Blood Collection
The following condition is temporary or self-limiting and blood may be drawn once the 
condition has resolved and the subject is eligible for blood collection:
1. Subject has received systemic antibiotic therapy within the last 5 days.
4.5. Lifestyle Requirements
4.5.1. Contraception
All fertile male subjects and female subjects who are of childbearing potential who are, in the 
opinion of the investigator, sexually active and at risk for pregnancy with their partner(s) 
must agree to use a highly effective method of contraception consistently and correctly 
throughout Stage 1 (through the follow-up telephone contact at Month 12), and from Visit 10
(booster vaccination) to Visit 11.  The investigator or his or her designee, in consultation 
with the subject, will confirm that the subject has selected an appropriate method of 
contraception for the individual subject from the permitted list of contraception methods 
(see below) and will confirm that the subject has been instructed in its consistent and correct 
use.

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rLP2086; subfamily A and B; E coli])
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At time points indicated in the Schedule of Activities, the investigator or designee will 
inform the subject of the need to use highly effective contraception consistently and correctly 
and document the conversation and the subject’s affirmation in the subject’s chart (subjects
need to affirm their consistent and correct use of at least 1 of the selected methods of 
contraception).  In addition, the investigator or designee will instruct the subject to call 
immediately if the selected contraception method is discontinued or if pregnancy is known or 
suspected in the subject or the partner.
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following:
1. Established use of hormonal methods of contraception associated with inhibition of 
ovulation (eg, oral, inserted, injected, implanted, transdermal), provided the subject or 
male subject’s female partner plans to remain on the same treatment throughout the entire 
study and has been using that hormonal contraceptive for an adequate period of time to 
ensure effectiveness.
2. Correctly placed copper-containing intrauterine device (IUD).
3. Male condom or female condom used WITH a separate spermicide product (ie, foam, gel, 
film, cream, or suppository). For countries where spermicide is not available or condom 
plus spermicide is not accepted as highly effective contraception, this option is not 
appropriate.
4. Male sterilization with absence of sperm in the postvasectomy ejaculate.
5. Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label).
NOTE: Sexual abstinence, defined as completely and persistently refraining from all 
heterosexual intercourse (including during the entire period of risk associated with the study 
treatments) may obviate the need for contraception ONLY if this is the preferred and usual 
lifestyle of the subject.
4.6. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the SRM.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card.  The contact card contains, 
at a minimum, protocol and investigational product identifiers, subject study numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study.

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The contact number can also be used by investigator staff if they are seeking advice on 
medical questions or problems; however, it should be used only in the event that the 
established communication pathways between the investigator site and the study team are not 
available. It is therefore intended to augment, but not replace, the established communication 
pathways between the investigator site and the study team for advice on medical questions or 
problems that may arise during the study. The contact number is not intended for use by the 
subject directly, and if a subject calls that number, he or she will be directed back to the 
investigator site.
5. INVESTIGATIONAL PRODUCTS
For the purposes of this study, and per International Council for Harmonisation (ICH)
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33).
For this study, the investigational product(s) to be provided are:

Bivalent rLP2086 (bivalent rLP2086 and meningococcal group B vaccine [Trumenba]
may be used interchangeably)

MenABCWY, consisting of:
o
Bivalent rLP2086 
o
MenACWY-TT (Nimenrix)

MenACWY-CRM (Menveo)

Placebo (normal saline).  Any reference to normal saline or placebo refers to a solution 
containing 0.85% sodium chloride and water for injection. The placebo solution is also 
referred to as “saline” throughout the protocol.
The investigational products will be provided by the sponsor to each study site.  Study 
vaccines will be packed into kits and labeled as investigational product in accordance with 
current guidelines and applicable local and legal regulatory requirements.  Investigational 
product kits will be labeled with a unique dispensable unit (DU) or container number.
Subjects will receive investigational products at each of the vaccination visits (Visits 1, 3,
and 10) according to Table 1 and Table 2.
5.1. Allocation to Investigational Product
Allocation of subjects to vaccine groups will proceed through the use of an interactive 
response technology (IRT) system that is accessible 24 hours a day, 365 days a year.  Having 

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logged in, the site personnel (study coordinator or specified designee) will be required to 
enter or select certain information including but not limited to the user’s identification (ID) 
and password, protocol number, the subject number, if the subject should be considered 
ACWY naive or experienced, and the date of birth of the subject.  The site personnel will 
then be provided with a subject randomization number and DU or container number.  The 
randomization number and the date on which the randomization number was assigned will be 
recorded on the case report form (CRF).  Once subject numbers, DU numbers, and 
randomization numbers have been assigned, they cannot be reassigned.  The IRT system will 
provide a confirmation report containing the subject randomization number and DU or 
container number assigned.  The confirmation report must be stored in the site’s files.
The study-specific IRT reference manual will provide the contact information and further 
details on the use of the IRT system. 
5.2. Blinding of Site Personnel
In this observer-blinded study, the study staff dispensing, preparing, and administering the 
vaccine will be unblinded.  All other study and site personnel, including the investigator, 
investigator staff, subjects, and subjects’ parent(s)/legal guardian, will be blinded to 
investigational product assignments during Stage 1.  In particular, the individuals who 
evaluate subject safety will be blinded during Stage 1.  Because the study vaccines are 
different in physical appearance, the study vaccine syringes will be administered in a manner 
that prevents the study subjects from identifying the vaccine type based on its appearance.
The responsibility of the unblinded dispenser and administrator must be assigned to an 
individual or individuals who will not participate in the evaluation of any study subjects.  
Contact between the unblinded dispenser and study subjects and unblinded administrator and 
study subjects should be kept to a minimum.  The remaining site personnel must not know 
investigational product assignments.
5.3. Blinding of the Sponsor
Those study team members who are involved in ensuring that protocol requirements for 
investigational product preparation, handling, allocation, and administration are fulfilled at 
the site will be unblinded for the duration of the study (eg, unblinded study manager, 
unblinded clinical research associate). An unblinded clinician who is not a direct member of 
the study team will review unblinded protocol deviations.  All other study team members and 
all laboratory testing personnel performing serology assays will remain blinded to vaccine 
assigned/received throughout Stage 1 of the study to Visit 5. All laboratory testing personnel 
performing serology assays will also remain blinded to visit number throughout Stage 1 of 
the study.
5.4. Blinding of the Pilot Cohort
Depending on prior ACWY vaccination history, pilot cohort subjects will be assigned to 
either Group 1 or 3, and therefore will receive MenABCWY at Vaccination 1.  For these 

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subjects only, the subjects, study personnel at the investigational site, and study personnel at 
the sponsor will be unblinded to vaccine assignment during Stage 1.
5.5. Breaking the Blind
At the initiation of the study, the study site will be instructed on the method for breaking the 
blind.  The method will be either a manual or an electronic process.  Blinding codes should 
only be broken in emergency situations for reasons of subject safety.
In case of an emergency, when knowledge of the investigational product assignment is 
required for the medical management of an individual subject, it may be unblinded.  The 
investigator must notify a member of the study team immediately after determining that it is 
necessary to unblind the assignment.  The investigator must also indicate in source 
documents that the blind was broken and provide the date and reason for breaking the blind.  
Any AE or SAE associated with breaking the blind must be recorded and reported as 
specified in this protocol.
5.5.1. Planned Unblinding
Pfizer will release unblinding information to the investigators after all subjects have 
completed Visit 5 and will inform the investigators prior to Visit 7 which subjects may be 
invited to progress to Stage 2.  Additional information is included in the SRM.
The booster vaccination will be open-label.
5.6. Subject Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
5.7. Investigational Product Supplies
5.7.1. Dosage Form(s) and Packaging
Bivalent rLP2086 is a 0.5-mL dose supplied as a prefilled syringe and formulated to contain 
60 µg each of a purified subfamily A and a purified subfamily B rLP2086 protein, 0.15 M 
sodium chloride, 2.8 molar ratio polysorbate 80, and 0.25 mg of Al3+ as aluminum phosphate 
(AlPO4) in 10 mM histidine-buffered saline at pH 6.0.
MenACWY-TT is supplied as a single-dose vial containing lyophilized powder to be 
reconstituted for injection. The vaccine is formulated on the basis of purified capsular 
polysaccharide content and the amount of protein carrier is dependent on the 
polysaccharide-to-protein ratio. The vaccine is nonadjuvanted and preservative-free. The 
quantitative composition of the lyophilized vaccine is shown in the Nimenrix IB.
MenACWY-TT will be reconstituted with bivalent rLP2086 as detailed in the investigational 
product (IP) manual, and 0.5 mL of the resultant MenABCWY will be administered via 
intramuscular injection.  The final MenABCWY composition includes rLP2086 subfamily A 
and B proteins formulated at 120 µg/mL/subfamily, purified capsular polysaccharides of 

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N meningitidis types A, C, W, and Y at concentration of 10 µg/mL/type conjugated to tetanus 
toxoid at ratios of ~1:3, ~1:3, ~1:1.5, and ~1:1.3, respectively, in 10 mM histidine and 
1.2 mM Tris buffer containing 150 mM sodium chloride, 0.5 mg/mL aluminum as AlPO4, 
0.035 mg/mL polysorbate 80, and 56 mg/mL sucrose.
Menveo is supplied in 2 vials that must be combined prior to administration: the MenA 
lyophilized conjugate vaccine component is reconstituted with the meningococcal group C, 
Y, and W-135 (MenCYW-135) liquid conjugate vaccine component immediately before 
administration as a 0.5-mL intramuscular injection.
The placebo is sterile normal saline solution for injection and will be administered as a 
0.5-mL intramuscular injection.
5.7.2. Preparation and Dispensing
See the IP manual or appropriate package inserts for instructions on how to prepare the 
investigational products for administration.  Investigational product should be prepared and 
dispensed by an unblinded, appropriately qualified, and experienced member of the study 
staff (eg, physician, nurse, physician’s assistant, practitioner, or pharmacist) as allowed by 
local, state, and institutional guidance.  The investigational product will be administered to 
subjects who are blinded.
5.8. Administration
Standard vaccination practices must be observed and vaccine must not be injected into blood 
vessels.  Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices.
Administration of investigational products should be performed by an appropriately 
qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced member of the 
study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local, state, and institutional guidance.
Because the study vaccines are different in physical appearance, the study vaccine syringes 
will be administered in a manner that prevents the study subjects from identifying the vaccine 
type based on its appearance.
Investigational product administration details will be recorded on the CRF.
Table 3 below describes the administration details for each vaccine. Each vaccine will be 
administered as a 0.5-mL dose in the upper deltoid muscle of the left or right arm.

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Table 3.
Investigational Product Administration Schedule
Investigational Product
Group(s)
Visit(s)
Upper Deltoid Muscle 
Injection Location
MenABCWY
1 and 3
1, 3, 10
Left arm
Placebo (normal saline) a
1 and 3
1
Right arm
Bivalent rLP2086
2 and 4
1, 3, 10
Left arm
MenACWY-CRM
2 and 4
1, 10
Right arm
a.
Pilot cohort subjects will be assigned to either Group 1 or 3, but will receive only MenABCWY at 
Vaccination 1. Pilot cohort subjects will not receive saline at Vaccination 1.
MenABCWY is administered intramuscularly by injecting 0.5 mL into the upper deltoid 
muscle of the left arm at Visits 1, 3, and 10 (Groups 1 and 3).
Placebo is administered intramuscularly by injecting 0.5 mL into the upper deltoid muscle of 
the right arm at Visit 1 (Groups 1 and 3); pilot cohort subjects will not receive placebo at 
Vaccination 1. 
Bivalent rLP2086 is administered intramuscularly by injecting 0.5 mL into the upper deltoid 
muscle of the left arm at Visits 1, 3, and 10 (Groups 2 and 4).
MenACWY-CRM is administered intramuscularly by injecting 0.5 mL into the upper deltoid 
muscle of the right arm at Visits 1 and 10 (Groups 2 and 4).
In the event of a product quality complaint, please refer to Section 8.5.
5.9. Investigational Product Storage
The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational products, including any comparator and/or marketed products, are stored in a 
secured area with controlled access under required storage conditions and in accordance with 
applicable regulatory requirements.
Investigational products should be stored in their original containers and in accordance with 
the labels.
See the IP manual and package insert(s) for storage conditions of the products 
(eg, MenABCWY) once reconstituted.
Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products).  This should 
be captured from the time of investigational product receipt throughout the study.  Even for 

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continuous-monitoring systems, a log or site procedure that ensures active evaluation for 
excursions should be available.  The intent is to ensure that the minimum and maximum 
temperature is checked each business day to confirm that no excursion occurred since the last 
evaluation and to provide the site with the capability to store or view the minimum/maximum 
temperature for all nonworking days upon return to normal operations. The operation of the 
temperature-monitoring device and storage unit (for example, refrigerator), as applicable, 
should be regularly inspected to ensure they are maintained in working order.
Any excursions from the product label storage conditions should be reported to Pfizer upon 
discovery. The site should actively pursue options for returning the product to the storage 
conditions described in the labeling, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer.
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides permission to use the investigational product.  It will not be considered a 
protocol deviation if Pfizer approves the use of the investigational product after the 
temperature excursion. Use of the investigational product prior to Pfizer approval will be 
considered a protocol deviation. Specific details regarding information the site should report 
for each excursion will be provided to the site.
Receipt of materials, door opening and closing, and other routine handling operations where 
the products are briefly out of the temperature range described in the labeling are not 
considered excursions.
5.10. Investigational Product Accountability
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be 
accounted for using a drug accountability form/record.
5.10.1. Destruction of Investigational Product Supplies
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site). If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
Unused investigational product may be destroyed according to procedures and local 
environmental regulations after all investigational product accountability documentation has 
been completed, unless there are regulatory requirements for this to be returned.  Empty 
investigational product containers may be destroyed after the sponsor has performed 
accountability.  Only outer containers are used to perform accountability while syringes and 
vials are discarded at the point of use.  Investigational product return must be documented on 
the accountability log.

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5.11. Concomitant Treatment(s)
The name and date of administration of any nonstudy vaccine (or allergen immunotherapy) 
given from the signing of the ICD up to Visit 11 will be recorded on the CRF.
The name, start and stop dates, and route of administration for concomitant medications 
(prescription and nonprescription) used to treat an AE (excluding events recorded only in the 
e-diary) from the signing of the ICD to Visit 12 will be recorded in the CRF.
The name, start and stop dates, and route of administration of antipyretic and other pain 
medications received by the subject on the day prior to investigational product administration
will be recorded in the CRF.
5.11.1. Prohibited During the Study

Receipt of any blood products, including immunoglobulin.

Nonstudy meningococcal vaccines or vaccines containing 1 or more ABCWY group are 
prohibited throughout the course of the study.

Nonlive or live nonstudy vaccines are not permitted within 14 and 28 days, respectively, 
of any study vaccination.

Vaccine containing all or individual antigens included in Tdap vaccine are not permitted 
within 28 days of any study vaccination.

Intramuscular/sublingual allergen immunotherapy is not permitted within 14 days of any 
study vaccination.

Systemic (oral, intravenous, or intramuscular) corticosteroid therapy within 28 days of 
any study vaccination.
5.11.2. Permitted During the Study

Nonstudy vaccines used in the event of a disease outbreak or pandemic are allowed.  
However, while prioritizing standard clinical care, efforts should be made not to 
administer nonstudy vaccines within 14 days (for nonlive vaccines) or 28 days (for live 
vaccine) as specified below.

Nonstudy vaccines (other than any meningococcal vaccines or vaccines containing 1 or 
more ABCWY group, or vaccines containing all or individual antigens included in Tdap
vaccine) that are part of recommended immunization schedules are allowed anytime 
during the study but should not be administered within 14 days (for nonlive vaccines) and 
28 days (for live vaccines) of study vaccine administration.  Please refer to Section 5.11.1
restrictions on administration on meningococcal vaccines or vaccines containing 1 or 
more ABCWY group, and on administration of all or individual antigens included in
Tdap vaccines.

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
Antipyretic medication may be administered.

A local anesthetic may be used at the site of the blood draw.

Topical antibiotics are permitted.

Topical and inhaled corticosteroids are permitted.
5.11.3. Prior Treatment
If the subject is known to have ever received a polyribosylribitol phosphate oligosaccharide 
of Haemophilus influenzae type b conjugated to outer membrane protein (PRP-OMP) 
vaccine, the name of the vaccine and date of administration will be recorded on the CRF.  
Please refer to the SRM for a list of PRP-OMP–containing vaccines that are or have been 
commercially available.
If the subject has received any prior meningococcal vaccines or vaccines containing 1 or 
more ACWY group, the trade name (if known) and date of administration will be recorded 
on the CRF.  Please refer to the SRM for a list of ACWY-containing vaccines that are or 
have been commercially available.  Written confirmation of ACWY vaccination history 
should be obtained prior to randomization; however, if written ACWY vaccination history is 
not available, history obtained verbally from the subject (or parent(s)/legal guardian) is 
acceptable, if deemed reliable by the investigator.
If the subject has received antipyretic and other pain medications on the day prior to 
investigational product administration at Visit 1, the name, start and stop dates, and route of
administration of the medication will be recorded on the CRF.
5.11.4. Prohibited Prior Treatments
The following are prohibited:

Receipt of any blood products, including immunoglobulin, within 6 months before the 
first study vaccination.
6. STUDY PROCEDURES 
6.1. Informed Consent Process
The investigator or authorized designee is responsible for obtaining written informed consent 
for each subject enrolled prior to any study procedures.  Each signature on the ICD must be 
personally dated by the signatory.  A copy of the signed and dated ICD will be given to the 
subject.  The subject’s source documents must reflect that informed consent was obtained 
before participation in the study.
For subjects who have not reached the legal age of majority and are not legally able to 
provide informed consent, the investigator or authorized designee is responsible for obtaining 
written informed consent from the parent(s)/legal guardian.  In addition, a study-specific 

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assent form will be provided to the subject (age dependent on local requirements). It is to be 
understood as the child’s will to participate in a study after having received age-appropriate 
information and is sometimes also referred to as “knowing agreement.”  It is understood that 
wherever informed consent is used in this document, this also applies to assent for minor 
subjects.
If a subject reaches the age at which he or she is legally able to provide consent during the 
study, consent must be obtained. Since the subject is no longer a minor, the parent/legal 
guardian consent is no longer valid.  References in this protocol and other study documents 
to parent/legal guardian responsibility should be understood to be the direct responsibility of 
study subjects rather than parent/legal guardian after the subject has reached the legal age of 
majority.
6.2. Stage 1
6.2.1. Visit 1 (Day 1): Vaccination 1
In the case of temporary delay of vaccination, procedures and assessments below will be 
redone or reconfirmed, as applicable, on the day of vaccination.

Obtain written informed consent, and assent if appropriate, before performing 
study-specific procedures.  The date of informed consent will be recorded on the CRF.

Record the subject’s demographic information (including date of birth, sex, race, and 
ethnicity).

Record the presence of chronic conditions and/or medical history of significance, 
including relevant surgical procedures and cardiac medical history.

Record previous PRP-OMP vaccinations as described in the Prior Treatment section 
(Section 5.11.3).

Record any prior meningococcal vaccines or vaccines containing 1 or more ACWY 
groups as described in the Prior Treatment section (Section 5.11.3).

Record any antipyretics and other pain medications received by the subject on the day 
prior to investigational product administration as described in Section 5.11.3.

Perform physical examination evaluating any clinically significant abnormalities within 
the following body systems: general appearance; skin; head, eyes, ears, nose, throat;
heart; lungs; abdomen; extremities; neurological; musculoskeletal; and lymph nodes; 
including worsening of medical history conditions.  Results must be recorded on source 
documents and the CRF.  Findings from a physical examination conducted as part of 
standard routine care and before informed consent may be used for purposes of the study 
only if the examination was performed no more than 2 days before vaccination.  A brief 
examination must be performed on the day of vaccination to document that no change in 
health has occurred in the interim.

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
On the day of vaccination, perform a urine pregnancy test on female subjects.  A negative 
pregnancy test result is required before the subject may receive the investigational 
product.

On the day of and before vaccination, measure and record the subject’s oral temperature.

Ensure that all of the inclusion criteria, none of the exclusion criteria, and none of the 
temporary delay criteria are met.

If a subject is eligible for the study, randomize the subject to 1 of the 4 groups using an 
interactive voice response system (IVRS), interactive Web-based response system 
(IWRS), or an equivalent system.

On the day of and before vaccination, collect a blood sample (approximately 20 mL) 
from the subject.  Alternatively, for subjects who have consented to participate in the
subset, depending on the consent obtained:

Collect approximately 50 mL of blood, or

Collect approximately 100 mL of blood.  
Collect the blood sample only if the subject is eligible for vaccination on the same day.

For all subjects apart from the pilot cohort: The unblinded administrator administers a 
single 0.5-mL intramuscular injection of either MenABCWY (Groups 1 and 3) or 
bivalent rLP2086 (Groups 2 and 4) into the upper deltoid muscle of the left arm; and 
either MenACWY-CRM (Groups 2 and 4) or saline (Groups 1 and 3) into the upper 
deltoid muscle of the right arm.  The time of investigational product administration will 
be recorded on the CRF.
o
For pilot cohort subjects: the unblinded administrator administers a single 0.5-mL 
intramuscular injection of MenABCWY into the upper deltoid muscle of the left arm. 
The time of investigational product administration will be recorded on the CRF. Pilot 
cohort subjects will not receive placebo at Vaccination 1.

Observe the subject for at least 30 minutes (or longer as per local practice) after the 
investigational product administration for any acute reactions.  Record any AEs observed 
during the 30-minute observation period, these AEs are defined as immediate AEs 
(Section 8).

Record AEs as described in the AE Reporting Requirements section (Section 8) and the 
Schedule of Activities.  Time of onset will be recorded for any AEs that occur on the 
same day as investigational product administration.

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.11).

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
Issue a subject e-diary and provide instruction on its completion.  Ask the parent(s)/legal 
guardian or subject to complete the e-diary from Day 1 to Day 7 after vaccination. Day 1 
is the day of vaccination.

Issue a caliper, measuring tape/ruler, and a digital thermometer and provide instructions 
on their use.

Measuring tape/ruler data must be collected by the parent(s)/legal guardian for minor 
subjects.  All data must be recorded in the e-diary by the parent(s)/legal guardian for 
minor subjects.

Ask the parent(s)/legal guardian or the subject to use the caliper to measure the maximum 
diameter of redness and swelling at the left arm injection site each day for the 7 days after 
study vaccination and record in the e-diary as described in Section 7.4.

Ask the parent(s)/legal guardian or the subject to contact the investigator immediately if 
the subject experiences a severe redness or swelling (>20 caliper units) at the left arm 
injection site, a fever 39.0C (102.1F), or a severe headache within 7 days after 
vaccination, as an unscheduled visit should be arranged (Section 6.4).
o
If the reaction exceeds the maximum size the caliper is able to measure (>21 caliper 
units, Section 7.4.1), the parent(s)/legal guardian or the subject should also use the 
measuring tape/ruler to measure the maximum diameter of redness and/or swelling at 
the injection site, and report this immediately to the investigator. 
o
Ask the parent(s)/legal guardian or subject to report the maximum diameter of the 
redness and/or swelling at the injection site to the investigator daily until the reaction 
becomes 21 caliper units.

Provide the subject with a contact card (Section 4.6).

Ask the parent(s)/legal guardian or the subject to contact the investigator immediately if 
any significant illness or hospitalization occurs.

Schedule an appointment for the next study visit and confirm that it is scheduled within 
the time window per protocol.

Remind the parent(s)/legal guardian or subject to bring the e-diary to the next study visit.

Complete the source documents.

Complete the CRF and update the investigational product accountability records.
Between visits, review the e-diary data online at frequent intervals. Contact the 
parent(s)/legal guardian or the subject to obtain stop dates for any local reactions, systemic 
events, or use of antipyretic medication that were ongoing on the last day that the e-diary was 

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completed.  The stop dates should be documented in the source documents and the 
information entered into the CRF at the next study visit of the subject.
6.2.2. Visit 2 (28 to 42 Days After Visit 1), Post–Vaccination 1 Blood Draw

Ensure that the subject continues to be eligible for the study, and continues to comply 
with contraception requirements detailed in Section 4.5.

Ensure that the subject continues to meet none of the withdrawal criteria as described in 
Section 6.5 and none of the temporary delay of blood draw criteria as described in 
Section 4.4.

Collect the subject’s e-diary.

Review the subject’s e-diary data since the previous visit and follow up on any ongoing 
reactogenicity or use of antipyretic medication.

Complete the Study Visit/Telephone Contact AE Checklist to:
o
Inquire whether the subject had any newly diagnosed chronic medical conditions 
since the last visit.  Inquire whether the subject had any of the following related to an 
AE since the last visit: hospitalizations, visits to other medical facilities, medication 
use, or missed days of school or work.  Please refer to the SRM for additional details.
o
Inquire about neuroinflammatory and autoimmune conditions, such as transverse 
myelitis, uveitis, optic neuritis, and multiple sclerosis. Please refer to the SRM for 
additional details.

Record AEs as described in the AE Reporting Requirements section (Section 8) and the 
Schedule of Activities.

Review AEs that were ongoing since the previous visit and record their end dates or 
confirm that they are still continuing.

Record nonstudy vaccinations as described in the Concomitant Treatment(s) section 
(Section 5.11).

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.11).

Collect a blood sample (approximately 20 mL). Alternatively, for subjects who have 
consented to participate in the subset, depending on the consent obtained:

Collect approximately 50 mL of blood, or

Collect approximately 100 mL of blood.

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
Ask the parent(s)/legal guardian or the subject to contact the investigator immediately if 
any significant illness or hospitalization occurs.

Schedule an appointment for the next visit and confirm that it is scheduled within the 
time window per protocol.

Complete the source documents.

Complete the CRFs.
6.2.3. Visit 3 (173 to 194 Days After Visit 1): Vaccination 2
In the case of temporary delay of vaccination, procedures and assessments below will be 
redone or reconfirmed, as applicable, on the day of vaccination.

Ensure that the subject continues to be eligible for the study, and continues to comply 
with contraception requirements detailed in Section 4.5.

Ensure that the subject continues to meet none of the withdrawal criteria as described in 
Section 6.5 and none of the temporary delay of vaccination or blood draw criteria as 
described in Section 4.3 and Section 4.4.

Complete the Study Visit/Telephone Contact AE Checklist to:
o
Inquire whether the subject had any newly diagnosed chronic medical conditions 
since the last visit.  Inquire whether the subject had any of the following related to an 
AE since the last visit: hospitalizations, visits to other medical facilities, medication 
use, or missed days of school or work.  Please refer to the SRM for additional details.
o
Inquire about neuroinflammatory and autoimmune conditions, such as transverse 
myelitis, uveitis, optic neuritis, and multiple sclerosis.  Please refer to the SRM for
additional details.

Record AEs as described in the AE Reporting Requirements section (Section 8) and the 
Schedule of Activities.  Time of onset will be recorded for any AEs that occur on the 
same day as investigational product administration.

Review AEs that were ongoing from the previous visit and record their end dates or 
confirm that they are still continuing.

Record nonstudy vaccinations as described in the Concomitant Treatment(s) section 
(Section 5.11).

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.11).

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
Record any antipyretics and other pain medications received by the subject on the day 
prior to investigational product administration as described in Section 5.11.

On the day of and before vaccination, collect a blood sample (approximately 20 mL) 
from the subject.  Collect the blood sample only if the subject is eligible for vaccination 
on the same day.

On the day of vaccination, perform a urine pregnancy test on female subjects.  A negative 
pregnancy test result is required before the subject may receive the investigational 
product.

On the day of and before vaccination, measure and record the subject’s oral temperature.

The unblinded administrator administers a single 0.5-mL intramuscular injection of either 
MenABCWY (Groups 1 and 3) or bivalent rLP2086 (Groups 2 and 4) into the upper 
deltoid muscle of the left arm.  The time of investigational product administration will be 
recorded on the CRF.

Observe the subject for at least 30 minutes (or longer as per local practice) after the 
investigational product administration for any acute reactions.  Record any AEs observed 
during the 30-minute observation period; these AEs are defined as immediate AEs 
(Section 8).

Issue a subject e-diary and provide instruction on its completion.  Ask the parent(s)/legal 
guardian or subject to complete the e-diary from Day 1 to Day 7 after vaccination. Day 1 
is the day of vaccination.

Issue a caliper, measuring tape/ruler, and a digital thermometer and provide instructions 
on their use.

Measuring tape/ruler data must be collected by the parent(s)/legal guardian for minor 
subjects.  All data must be recorded in the e-diary by the parent/legal guardian for minor 
subjects.

Ask the parent(s)/legal guardian or the subject to use the caliper to measure the maximum 
diameter of redness and swelling at the left arm injection site each day for the 7 days after 
study vaccination and record in the e-diary as described in Section 7.4.

Ask the parent(s)/legal guardian or the subject to contact the investigator immediately if 
the subject experiences a severe redness or swelling (>20 caliper units) at the left arm 
injection site, a fever 39.0C (102.1F), or a severe headache within 7 days after 
vaccination, as an unscheduled visit should be arranged (Section 6.4).
o
If the reaction exceeds the maximum size the caliper is able to measure (>21 caliper 
units, Section 7.4.1), the parent/legal guardian or the subject should also use the 

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measuring tape/ruler to measure the maximum diameter of redness and/or swelling at 
the injection site, and report this immediately to the investigator. 
o
Ask the parent(s)/legal guardian or subject to report the maximum diameter of the 
redness and/or swelling at the injection site to the investigator daily until the reaction 
becomes 21 caliper units.

Ask the parent(s)/legal guardian or the subject to contact the investigator immediately if 
any significant illness or hospitalization occurs.

Schedule an appointment for the next study visit and confirm that it is scheduled within 
the time window per protocol.

Ask the parent(s)/legal guardian or the subject to bring the e-diary to the next visit.

Complete the source documents. 

Complete the CRF and update the investigational product accountability records.
Between visits, review the e-diary data online at frequent intervals. Contact the 
parent(s)/legal guardian or the subject to obtain stop dates for any local reactions or systemic 
events, or use of antipyretic medication that were ongoing on the last day that the e-diary was 
completed.  The stop dates should be documented in the source documents and the 
information entered into the CRF at the next study visit of the subject.
6.2.4. Visit 4 (28 to 42 Days After Visit 3), Post–Vaccination 2 Blood Draw

Ensure that the subject continues to be eligible for the study, and continues to comply 
with contraception requirements detailed in Section 4.5.

Ensure that the subject continues to meet none of the withdrawal criteria as described in 
Section 6.5 and none of the temporary delay of blood draw criteria as described in 
Section 4.4.

Collect the subject’s e-diary.

Review the subject’s e-diary data since the previous visit and follow up on any ongoing 
reactogenicity or use of antipyretic medication.

Complete the Study Visit/Telephone Contact AE Checklist to:
o
Inquire whether the subject had any newly diagnosed chronic medical conditions 
since the last visit.  Inquire whether the subject had any of the following related to an 
AE since the last visit: hospitalizations, visits to other medical facilities, medication 
use, or missed days of school or work.  Please refer to the SRM for additional details.

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o
Inquire about neuroinflammatory and autoimmune conditions, such as transverse 
myelitis, uveitis, optic neuritis, and multiple sclerosis. Please refer to the SRM for 
additional details.

Record AEs as described in the AE Reporting Requirements section (Section 8) and the 
Schedule of Activities.

Review AEs that were ongoing since the previous visit and record their end dates or 
confirm that they are still continuing.

Record nonstudy vaccinations as described in the Concomitant Treatment(s) section 
(Section 5.11).

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.11).

Provide the parent(s)/legal guardian or the subject with a memory aid. Instruct the subject 
to use the memory aid between Visits 4 and 5 to remind him or her to review any 
significant illnesses, hospitalizations, newly diagnosed medical conditions, or visits to a 
medical facility with study site personnel. The memory aid is not a diary for the 
collection of reactogenicity.  Please refer to the SRM and Section 7.3 for additional 
details.

Collect a blood sample (approximately 20 mL).  Alternatively, for subjects who have 
consented to participate in the subset, depending on the consent obtained:

Collect approximately 50 mL of blood, or

Collect approximately 100 mL of blood.

At designated sites participating in collection of blood samples for exploratory purposes, 
the following additional procedures may be completed:
o
Obtain written informed consent from subjects agreeing to the additional blood 
sample.  This consent may be obtained at prior visits if appropriate.
o
Collect a whole blood sample of approximately 50 mL for exploratory testing.  The 
maximum amount of blood to be obtained at this visit is 150 mL.

Ask the parent(s)/legal guardian or the subject to contact the investigator immediately if 
any significant illness or hospitalization occurs.

Schedule a telephone contact and confirm that it is scheduled within the time window per 
protocol.

Complete the source documents.

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
Complete the CRFs.
6.2.5. Visit 5 (168 to 196 Days After Last Vaccination), Telephone Contact

This telephone contact should occur approximately 6 months after the last Stage 1 study 
vaccination; this contact should be attempted for all subjects who have received at least 
1 Stage 1 study vaccination, unless they have withdrawn consent.

Contact the parent(s)/legal guardian or the subject by telephone.

Complete the Study Visit/Telephone Contact AE Checklist to:
o
Inquire about SAEs, newly diagnosed chronic medical conditions, or AEs that 
resulted in evaluation at a medical facility since the last visit.  Please refer to the SRM 
for additional details.
o
Inquire about neuroinflammatory and autoimmune conditions, such as transverse 
myelitis, uveitis, optic neuritis, and multiple sclerosis. A checklist will be provided as 
a guide. Please refer to the SRM for additional details.

Report any SAEs to the sponsor as defined in Section 8.

Record AEs as described in the AE Reporting Requirements section (Section 8) and the 
Schedule of Activities.

Record nonstudy vaccinations as described in the Concomitant Treatment(s) section 
(Section 5.11).

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.11).

Review AEs that were ongoing since the previous visit and record their end dates or 
confirm that they are still continuing.

Complete the source documents.

Complete the CRFs.

Inform subjects from the ACWY-naive stratum to expect a telephone contact to confirm 
if they are able to participate in Stage 2.
6.2.6. Visit 6 (After Study Unblinding and Prior to Transition to Stage 2) Telephone 
Contact
Visit 6 will be conducted once the sponsor has informed the investigator if the subject may 
progress to Stage 2 (Section 5.5.1). Visit 6 must be conducted prior to Visit 7.

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
Notify the parent(s)/legal guardian or the subject by telephone if the subject may progress 
to Stage 2.

For subjects progressing to Stage 2, schedule an appointment for the next study visit and 
confirm that it is scheduled within the time window per protocol.
6.3. Stage 2
Subjects from both the ACWY-naïve and ACWY-experienced strata, approximately 132 
from each of Groups 1 and 3 and approximately 65 from each of Groups 2 and 4, will 
participate in Stage 2.  Stage 1 will be observer-blinded and Stage 2 will be open-label. 
Investigators will be informed if a subject can be screened for Stage 2 based on a randomly 
generated list of eligible subjects and a randomly generated backup list to allow for 
replacement of subjects who decline participation in Stage 2 or are deemed ineligible after 
screening at Visit 7.
Visit 7 and Visit 8 should be conducted within no less than 30 days of each other. If Visit 7 
cannot be conducted within the protocol-defined visit window, Visit 7 can be omitted and 
Visit 8 performed directly.
6.3.1. Visit 7 (336 to 694 Days After Visit 3), Antibody Persistence Blood Draw 1

Obtain written informed consent, and assent if applicable, before performing further 
study-specific procedures.  The date of informed consent will be recorded on the CRF.

Ensure that the subject continues to be eligible for the study, meets none of the 
withdrawal criteria as described in Section 6.5, and meets none of the temporary delay of 
blood draw criteria as described in Section 4.4.

Record nonstudy vaccinations as described in the Concomitant Treatment(s) section 
(Section 5.11).

Collect a blood sample (approximately 20 mL).

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.11).

Schedule an appointment for the next visit and confirm that it is scheduled within the 
time window per protocol.

Complete the source documents.

Complete the CRFs.

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6.3.2. Visit 8 (700 to 756 Days After Visit 3), Antibody Persistence Blood Draw 2

Ensure that the subject continues to be eligible for the study, meets none of the 
withdrawal criteria as described in Section 6.5, and meets none of the temporary delay of 
blood draw criteria as described in Section 4.4.

Record nonstudy vaccinations as described in the Concomitant Treatment(s) section 
(Section 5.11).

Collect a blood sample (approximately 20 mL).

Record any AEs and research-related injuries (RRIs) occurring within 48 hours after the 
Visit 7 blood draw as described in Section 8.

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.11).

Schedule an appointment for the next visit and confirm that it is scheduled within the 
time window per protocol.

Complete the source documents.

Complete the CRFs.
6.3.3. Visit 9 (1064 to 1120 Days After Visit 3), Antibody Persistence Blood Draw 3

Ensure that the subject continues to be eligible for the study, meets none of the 
withdrawal criteria as described in Section 6.5, and meets none of the temporary delay of 
blood draw criteria as described in Section 4.4.

Record nonstudy vaccinations as described in the Concomitant Treatment(s) section 
(Section 5.11).

Collect a blood sample (approximately 20 mL).

Record any AEs and RRIs occurring within 48 hours after the Visit 8 blood draw as 
described in Section 8.

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.11).

Schedule an appointment for the next visit and confirm that it is scheduled within the 
time window per protocol.

Complete the source documents.

Complete the CRFs.

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6.3.4. Visit 10 (1428 to 1484 Days After Visit 3): Booster Vaccination
In the case of temporary delay of vaccination, procedures and assessments below will be 
redone or reconfirmed, as applicable, on the day of vaccination.

Ensure that the subject continues to be eligible for the study, and continues to comply 
with contraception requirements detailed in Section 4.5.

Ensure that the subject continues to meet none of the withdrawal criteria as described in 
Section 6.5 and none of the temporary delay of vaccination or blood draw criteria as 
described in Section 4.3 and Section 4.4.

Record nonstudy vaccinations as described in the Concomitant Treatment(s) section 
(Section 5.11).

Record any antipyretics and other pain medications received by the subject on the day 
prior to investigational product administration as described in Section 5.11.

Record the presence of chronic conditions and/or medical history of significance, 
including relevant surgical procedures and cardiac medical history that have been 
diagnosed since Visit 1.

Perform physical examination evaluating any clinically significant abnormalities within 
the following body systems: general appearance; skin; head, eyes, ears, nose, throat;
heart; lungs; abdomen; extremities; neurological; musculoskeletal; and lymph nodes; 
including worsening of medical history conditions.  Results must be recorded on source 
documents and the CRF.  Findings from a physical examination conducted as part of 
standard routine care and before informed consent may be used for purposes of the study 
only if the examination was performed no more than 2 days before vaccination.  A brief 
examination must be performed on the day of vaccination to document that no change in 
health has occurred in the interim.

On the day of vaccination, perform a urine pregnancy test on female subjects.  A negative 
pregnancy test result is required before the subject may receive the investigational 
product.

On the day of and before vaccination, measure and record the subject’s oral temperature.

On the day of and before vaccination, collect a blood sample (approximately 20 mL) 
from the subject.  Collect the blood sample only if the subject is eligible for vaccination 
on the same day.

Administer a single 0.5-mL intramuscular injection of either MenABCWY (Groups 1
and 3) or bivalent rLP2086 (Groups 2 and 4) into the upper deltoid muscle of the left 
arm; and MenACWY-CRM (Groups 2 and 4) into the upper deltoid muscle of the right 
arm.  The time of investigational product administration will be recorded on the CRF.

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
Observe the subject for at least 30 minutes (or longer as per local practice) after the 
investigational product administration for any acute reactions.  Record any AEs observed 
during the 30-minute observation period; these AEs are defined as immediate AEs 
(Section 8).

Record AEs as described in the AE Reporting Requirements section (Section 8) and the 
Schedule of Activities.  Time of onset will be recorded for any AEs that occur on the 
same day as investigational product administration.

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.11).

Issue a subject e-diary and provide instruction on its completion.  Ask the parent(s)/legal 
guardian or subject to complete the e-diary from Day 1 to Day 7 after vaccination. Day 1 
is the day of vaccination.

Issue a caliper, measuring tape/ruler, and a digital thermometer and provide instructions 
on their use.

Measuring tape/ruler data must be collected by the parent(s)/legal guardian for minor 
subjects.  All data must be recorded in the e-diary by the parent/legal guardian for minor 
subjects.

Ask the parent(s)/legal guardian or the subject to use the caliper to measure the maximum 
diameter of redness and swelling at the left arm injection site each day for the 7 days after 
study vaccination and record in the e-diary as described in Section 7.4.

Ask the parent(s)/legal guardian or the subject to contact the investigator immediately if 
the subject experiences a severe redness or swelling (>20 caliper units) at the left arm 
injection site, a fever 39.0C (102.1F), or a severe headache within 7 days after 
vaccination, as an unscheduled visit should be arranged (Section 6.4).
o
If the reaction exceeds the maximum size the caliper is able to measure (>21 caliper 
units, Section 7.4.1), the parent/legal guardian or the subject should also use the 
measuring tape/ruler to measure the maximum diameter of redness and/or swelling at 
the injection site, and report this immediately to the investigator. 
o
Ask the parent(s)/legal guardian or subject to report the maximum diameter of the 
redness and/or swelling at the injection site to the investigator daily until the reaction 
becomes 21 caliper units.

Ask the parent(s)/legal guardian or the subject to contact the investigator immediately if 
any significant illness or hospitalization occurs.

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
Schedule an appointment for the next study visit and confirm that it is scheduled within 
the time window per protocol.

Remind parent(s)/legal guardian or subject to bring the e-diary to the next study visit. 
Complete the source documents.

Complete the CRF and update the investigational product accountability records.
Between visits, review the e-diary data online at frequent intervals. Contact the 
parent(s)/legal guardian or the subject to obtain stop dates for any local reactions, systemic 
events, or use of antipyretic medication that were ongoing on the last day that the e-diary was 
completed.  The stop dates should be documented in the source documents and the 
information entered into the CRF at the next study visit of the subject.
6.3.5. Visit 11 (28 to 42 Days After Visit 10), Postbooster Blood Draw

Ensure that the subject continues to be eligible for the study, and continues to comply 
with contraception requirements detailed in Section 4.5.

Ensure that the subject continues to meet none of the withdrawal criteria as described in 
Section 6.5 and none of the temporary delay of blood draw criteria as described in 
Section 4.4.

Collect the subject’s e-diary.

Review the subject’s e-diary data since the previous visit and follow up on any ongoing 
reactogenicity or use of antipyretic medication.

Complete the Study Visit/Telephone Contact AE Checklist to:
o
Inquire whether the subject had any newly diagnosed chronic medical conditions 
since the last visit.  Inquire whether the subject had any of the following related to an 
AE since the last visit: hospitalizations, visits to other medical facilities, medication 
use, or missed days of school or work.  Please refer to the SRM for additional details.
o
Inquire about neuroinflammatory and autoimmune conditions, such as transverse 
myelitis, uveitis, optic neuritis, and multiple sclerosis. Please refer to the SRM for 
additional details.

Record AEs as described in the AE Reporting Requirements section (Section 8) and the 
Schedule of Activities.

Review AEs that were ongoing since the previous visit and record their end dates or 
confirm that they are still continuing.

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
Record nonstudy vaccinations as described in the Concomitant Treatment(s) section 
(Section 5.11).

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.11).

Provide the parent(s)/legal guardian or the subject with a memory aid. Instruct the 
subject to use the memory aid between Visits 11 and 12 to remind him or her to review 
any significant illnesses, hospitalizations, newly diagnosed medical conditions, or visits 
to a medical facility with study site personnel. The memory aid is not a diary for the 
collection of reactogenicity.  Please refer to the SRM and Section 7.3 for additional 
details.

Collect a blood sample (approximately 20 mL).  Alternatively, for subjects who have 
consented to participate in the subset, collect approximately 100 mL of blood.  

Ask the parent(s)/legal guardian or the subject to contact the investigator immediately if 
any significant illness or hospitalization occurs. 

Schedule a final telephone contact and confirm that it is scheduled within the time 
window per protocol.

Complete the source documents.

Complete the CRFs.
6.3.6. Visit 12 (168 to 196 Days After Booster Vaccination), Final Telephone Contact

The final telephone contact should occur approximately 6 months after the booster 
vaccination; this contact should be attempted for all subjects who have received the 
booster vaccination, unless they have withdrawn consent.

Contact the parent(s)/legal guardian or the subject by telephone.

Complete the Study Visit/Telephone Contact AE Checklist to:
o
Inquire about SAEs, newly diagnosed chronic medical conditions, or AEs that 
resulted in evaluation at a medical facility since the last visit.  Please refer to the SRM 
for additional details.
o
Inquire about neuroinflammatory and autoimmune conditions, such as transverse 
myelitis, uveitis, optic neuritis, and multiple sclerosis. Please refer to the SRM for 
additional details.

Report any SAEs to the sponsor as defined in Section 8.

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
Record AEs as described in the AE Reporting Requirements section (Section 8) and the 
Schedule of Activities.

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.11).

Review AEs that were ongoing since the previous visit and record their end dates or 
confirm that they are still continuing.

Complete the source documents.

Complete the CRFs.
6.4. Unscheduled Visits
If the subject experiences a severe redness or swelling at the left arm injection site 
(>20 caliper units), a temperature 39.0C (102.1F), or a severe headache in the 7 days after 
vaccination, a study site visit should be arranged as soon as possible to assess the extent of 
the event.  The parent(s)/legal guardian or subject contact will be documented in the CRF.
If the reaction exceeds the maximum size the caliper is able to measure (>21 caliper units, 
Section 7.4.1), ensure the parent(s)/legal guardian or subject has also measured the maximum 
diameter of the redness and/or swelling at the injection site using the measuring tape/ruler 
provided.  Ask the parent(s)/legal guardian or subject to report the maximum diameter of the 
redness and/or swelling at the injection site daily until the reaction becomes 21 caliper 
units.  Record these measurements in the CRF.
At an unscheduled visit, the subject’s oral temperature should be measured and the symptom 
that prompted the visit should be assessed by a medically qualified member of the study staff.  
Findings will be recorded on the CRF.  If the subject experiences any unsolicited AEs, these 
should be recorded on the AE CRF.
If the unscheduled visit does not take place following subject report of fever 39.0C, severe 
redness/swelling, or severe headache, the reason must be documented in the CRF 
(for example, reaction no longer present or e-diary entry error).
For the purpose of assessments performed during unscheduled visits, a medically qualified 
member of the study staff is a study physician or a study nurse, as applicable to the 
investigator’s local practice.
6.5. Subject Withdrawal
The investigator and/or sponsor may withdraw a subject from the study if deemed 
appropriate at any time.  Eligibility criteria as listed under inclusion criteria (refer to 
Section 4.1) and exclusion criteria (refer to Section 4.2) should be taken into consideration 
when determining if a subject must be withdrawn from the study. The investigator is not 

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required to repeat the physical examination completed at Visit 1 or 10, unless clinically 
indicated.
Reasons why a subject may discontinue or be withdrawn from the study may include, but are 
not limited to, AEs (including any neuroinflammatory and autoimmune conditions, such as 
transverse myelitis, uveitis, optic neuritis, and multiple sclerosis), parent(s)/legal guardian or 
subject request, investigator request, death, discontinuation of the study by the sponsor, 
protocol violation, and being lost to follow-up.  Subjects who have received investigational 
product will not be replaced.
An effort must be made to determine why a subject fails to return for the necessary visits or 
is withdrawn from the study.  Information detailing the circumstances leading to the 
withdrawal of a subject from the study, as well as the date of withdrawal, will be recorded on 
the study outcome CRF.
The decision to withdraw a subject from the study should be discussed with the sponsor.  
Every attempt must be made to collect all prompted reactogenicity data, AEs, or SAEs 
following each vaccination.  Any AEs or SAEs that are continuing at the time of withdrawal 
from the study must be followed until the events have subsided, until values have returned to 
baseline, or, in case of permanent impairment, until the condition stabilizes.  When a subject 
discontinues or is withdrawn from the study, the investigator will notify the sponsor.
For subjects who withdraw during Stage 1, when possible, the investigator will perform the 
procedures indicated for the next visit, provide the subject with a memory aid, and complete 
Visit 5 (telephone contact) if the subject has received at least 1 study vaccination.
For subjects who withdraw during Stage 2 between Visit 6 and the booster vaccination, 
follow up on AEs as indicated above.
For subjects who withdraw during Stage 2 after having received the booster vaccination, 
when possible, the investigator will perform the procedures indicated for the next visit, 
provide the subject with a memory aid, and complete Visit 12 (final telephone contact).
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety (see also 
Withdrawal From the Study Due to Adverse Events [Section 8.1.3]) or behavioral reasons, or 
the inability of the subject to comply with the protocol-required schedule of study visits or 
procedures at a given study site.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  All attempts to contact the subject and information received during contact attempts 
must be documented in the subject’s medical record.  In any circumstance, every effort 
should be made to document subject outcome, if possible.  The investigator should inquire 
about the reason for withdrawal, request that the subject return for a final visit, if applicable, 
and follow up with the subject regarding any unresolved AEs.

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If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test. In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the subject. When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible. The 
study team will be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
7.1. Pregnancy Testing
For the purposes of pregnancy testing in this study, all female subjects are considered to be 
of childbearing potential.
For female subjects of childbearing potential, a urine pregnancy test, with sensitivity of at 
least 25 mIU/mL, will be performed immediately before administration of each vaccine dose.  
A negative pregnancy test result is required before the subject may receive the investigational 
product.  Pregnancy tests may also be repeated if requested by institutional review boards 
(IRBs)/ethics committees (ECs) or if required by local regulations.  In the case of a positive 
confirmed pregnancy, the subject will be withdrawn from administration of investigational 
product but may remain in the study.
7.2. Biological Samples
Serum and whole blood samples will be used only for scientific research.  Each sample will 
be labeled with a code so that the laboratory personnel testing the samples will not know the 
subject’s identity.  Samples that remain after performing assays outlined in the protocol may 
be stored by Pfizer. Unless a time limitation is required by local regulations or ethical 
requirements, the samples will be stored for up to 15 years after the end of the study and then 
destroyed.
If allowed by the informed consent document, stored samples may be used for additional 
testing to better understand the immune responses to the vaccine(s) under study in this 
protocol, to inform the development of other products, and/or for vaccine-related assay work 
supporting vaccine programs.  No testing of the subject’s genetic material will be performed.

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A mechanism (eg, ICD addendum) will be established that enables testing of serum samples 
obtained during the study to assess for the preexistence of select AEs reported during study 
participation.
The subject/parent/legal guardian may request that his or her or child’s samples, if still 
identifiable, be destroyed at any time; however, any data already collected from those 
samples will still be used for this research.  The biological samples may be shared with other 
researchers as long as confidentiality is maintained and no testing of the subject’s genetic 
material is performed.
7.2.1. Immunogenicity
To facilitate immunogenicity analyses, subjects will have approximately 20 mL of blood 
collected as shown in Table 1 and Table 2.  In order to support assay development, a subset 
of up to approximately 600 subjects 18 to 25 years of age will, depending on the consent 
obtained, have up to 100 mL, rather than 20 mL, of blood drawn at Visits 1, 2, and 4; and a 
subset of up to approximately 150 subjects 18 to 25 years of age will have up to 100 mL, 
rather than 20 mL, of blood drawn at Visit 11.
Sample collection, storage, and shipping information can be found in the SRM.
Serum samples should be processed and stored as indicated in the SRM.  All serum samples 
should be stored in an upright position in a laboratory-grade manual-defrost freezer that does 
not undergo freeze-thaw cycles and where ice must be removed manually. A frost-free 
freezer must not be used, as the continuous freeze-thaw cycles of such freezers may affect the 
integrity of the samples.  The freezer must maintain a temperature of -15C or colder.
It is the responsibility of the investigator(s) (or designee) to record daily freezer temperature 
readings (working days only), to maintain a daily temperature log for the freezer, and to alert
the sponsor of any deviations. Deviations from storage requirements, including any actions 
taken, must be documented and reported to the sponsor. Guidance on temperature 
monitoring and procedures for the review of temperature deviations will be provided in the 
SRM.
7.2.2. Serum Bactericidal Assays
For assessment of the immune response, functional antibodies will be analyzed in hSBAs 
with meningococcal group A, B, C, W, and Y strains. The hSBA measures antibodies in 
human sera that result in complement-dependent killing of the target meningococcal strain.
Sera obtained from subjects at all time points as shown in Table 1 and Table 2 will be used in 
these assays.  All MenA, MenC, MenW, and MenY assays and MenB assays using the 10 
secondary MnB test strains will be qualified before any testing is performed. All MenB 
assays using the 4 primary MnB test strains will be validated before any testing is performed.
SBAs will be conducted at one or both of the following laboratories:

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
Pfizer Vaccine Research-High Throughput Clinical Testing, 401 N Middletown Road, 
Pearl River, NY 10965, USA

Pharmaceutical Product Development, Inc, Bioanalytical Laboratories, 2244 Dabney 
Road, Richmond, VA 23230, USA
7.2.2.1. MenB Serum Bactericidal Assays
For assessment of the immune response to bivalent rLP2086 and the B component of 
MenABCWY, 4 primary MnB test strains, PMB80 (A22), PMB2001 (A56), PMB2948 
(B24), and PMB2707 (B44), will be used in the hSBAs for determination of the 
immunogenicity endpoints in this study.
Validated hSBA LODs and LLOQs for the 4 primary strains are shown below.
Table 4.
Validated hSBA LODs and LLOQs for the 4 Primary MenB Strains
Strain Variant
LOD
LLOQ
A22
1:4
1:16
A56
1:4
1:8
B24
1:4
1:8
B44
1:4
1:8
Abbreviations:  hSBA = serum bactericidal assay using human complement; 
LLOQ = lower limit of quantitation; LOD = limit of detection; MenB = Neisseria meningitidis group B.
Ten (10) secondary test strains will be used to perform hSBA testing so that at least 150
(125 from US investigative sites and 25 from other investigative sites) evaluable 
post-Vaccination 2 hSBA results are available for each secondary test strain. The hSBA 
assays for the 10 secondary test strains will be performed on up to 750 subjects (up to 
600 subjects from US investigative sites and up to 150 subjects from other investigative sites,
as described in Step 2 below) from Groups 2 and 4, combined.
Step 1: The 10 secondary test strains will be allocated across the 3 subsets. The first 2 subsets 
will each include 3 secondary test strains and the last subset will include 4 secondary test 
strains.
Step 2: Once all subjects have completed enrollment (Visit 1), the independent statistical 
center (ISC; a statistical team not involved in the conduct of the study) will randomly 
allocate up to 600 US subjects (up to 200 per subset) and up to 150 subjects (up to 50 per 
subset) from other investigative sites from Groups 2 and 4 across the 3 subsets.
Among the Group 2 and 4 subjects, a maximum of 8 test strains (up to 4 additional test 
strains and 4 primary test strains) may be tested.
Stage 1 sera obtained prior to the first vaccination with bivalent rLP2086 and 1 month after 
the second vaccination with bivalent rLP2086 (Visit 4) will be used for hSBA testing on the 
10 secondary test strains.

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hSBAs have been qualified for the 10 secondary test strains.
Qualified hSBA LODs and LLOQs for the 10 secondary strains are shown below.
Table 5.
Qualified hSBA LODs and LLOQs for the 10 Secondary MenB Strains
Strain Variant
LOD
LLOQ
A29
1:4
1:8
A06
1:4
1:16
A12
1:4
1:16
A07
1:4
1:8
A15
1:4
1:8
A19
1:4
1:16
B16
1:4
1:8
B09
1:4
1:8
B03
1:4
1:8
B15
1:4
1:8
Abbreviations:  hSBA = serum bactericidal assay using human complement; 
LLOQ = lower limit of quantitation; LOD = limit of detection; MenB = Neisseria meningitidis group B.
7.2.2.2. MenA, MenC, MenW, and MenY Serum Bactericidal Assays
For assessment of the immune response to MenACWY-CRM and the ACWY components of 
MenABCWY, test strains specific for each of the ACWY groups (A [PMB277], 
C [PMB3204], W [PMB 6270], and Y [PMB3385]) will be used in the hSBAs for 
determination of the immunogenicity endpoints in this study. The qualified LLOQs and 
LODs for the ACWY test strains are as follows:
Table 6.
Qualified hSBA LODs and LLOQs for the ACWY Strains
Strain Variant
LOD
LLOQ
Men A
1:4
1:8
Men C
1:4
1:8
Men W
1:4
1:8
Men Y
1:4
1:8
Abbreviations:  hSBA = serum bactericidal assay using human complement; 
LLOQ = lower limit of quantitation; LOD = limit of detection; MenB = Neisseria meningitidis group B.
7.2.3. Exploratory Assays
At designated sites, an additional optional whole blood sample of approximately 50 mL will 
be obtained at Visit 4 from subjects who have consented to this.  This sample will be used for 
exploratory purposes.

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7.3. Safety
Any subject who receives at least 1 dose of investigational product will be included in the 
evaluation for safety.  The following safety parameters will be assessed as described in the 
Study Procedures section (Section 6) and Schedule of Activities:

Physical examination.

Reactogenicity: solicited local reactions and systemic events, including fever.

Use of antipyretic medication.

Unsolicited AEs and SAEs.
A medical history will be obtained and a physical examination will be performed on all 
subjects at Visit 1 to establish a baseline, and at Visit 10 prior to the booster vaccination.  
When taking the medical history and performing the physical examination, particular care 
must be taken to note any neuroinflammatory and autoimmune conditions, such as transverse 
myelitis, uveitis, optic neuritis, and multiple sclerosis.  Significant medical history and 
observations from the physical examination will be documented on the CRF.  In addition, a 
urine pregnancy test will be performed on all female subjects.
The safety parameters include reactogenicity, ie, both local reactions and systemic events that 
occur in the 7 days (Days 1 to 7) after investigational product administration.  These 
prompted e-diary events are:

Local reactions at the site of investigational product administration (redness, swelling, 
and pain).

Systemic events (fever, vomiting, diarrhea, headache, fatigue, chills, muscle pain other 
than muscle pain at the injection site, and joint pain).
Local reactions, systemic events, and use of antipyretic medication associated with vaccine 
administration will be collected using an e-diary.  For events that resolve after Day 7, the end
date will be collected in the symptoms resolved date CRF.  If a subject does not complete the 
e-diary for 7 days, end dates of local reactions, systemic events, or antipyretic medication use
that were ongoing on the last day the e-diary was completed by the subject will be collected 
on the symptoms resolved date CRF.
Immediate AEs, defined as AEs occurring within the first 30 minutes after investigational 
product administration, will be assessed and documented on the AE CRF. The time of onset 
will be recorded for any AEs that occur on the same day as investigational product 
administration.
Medically attended AEs and newly diagnosed chronic medical conditions will also be 
assessed throughout the study and documented on the appropriate AE CRF.  A medically 

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attended AE is defined as a nonserious AE that results in an evaluation at a medical facility.  
A newly diagnosed chronic medical condition is defined as a disease or medical condition, 
not previously identified, that is expected to be persistent or otherwise long-lasting in its 
effects.
AEs (serious and nonserious), newly diagnosed chronic medical conditions, and visits to 
other medical facilities will be assessed at study visits as specified in the Schedule of 
Activities and reported as defined in Section 8.  AE-related hospitalizations, visits to other 
medical facilities, medication use, and days of school or work missed will be collected and 
recorded in the AE CRF.  Hospitalizations and visits to medical facilities not associated with 
an AE, such as elective hospitalizations, healthcare visits for preventive care, or routine 
physical examinations, will not be collected.  Non–AE-related concomitant medications and 
days of school or work missed not associated with an AE will not be collected.  A Study 
Visit/Telephone Contact AE Checklist will be used as a guide, will be completed at each 
scheduled study visit/telephone contact, and will be included in the source documentation.  
Please refer to the SRM for details.
Subjects will be given a memory aid at Visit 4 and Visit 11. The memory aid will be used to 
remind subjects to review any significant illnesses, hospitalizations, newly diagnosed 
medical conditions, or visits to a medical facility with study site personnel. Subjects may use 
the memory aid as needed during the telephone contact at Visit 5 and Visit 12 to prompt 
recall of events.  These may be used to assist in reporting and discussion of events with study 
staff, but these memory aids will not be considered source documents and will not be 
collected at study visits.  Only information collected by study staff as part of a study visit or 
telephone contact (Visit 5 or 12) will be included in the source documents and entered into 
the CRF.
In addition, AEs and SAEs will be collected as defined in Section 8.
7.4. Electronic Diary
An e-diary will be issued based on a personal digital assistant or equivalent technology, and 
used to monitor and record the subject’s local reactions, systemic events, and use of 
antipyretic medication for 7 days after each vaccination.  Grading scales for local reactions 
and systemic events are based on US FDA Guidance for Industry, Toxicity Grading Scale for 
Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.42  
The e-diary allows recording of these assessments only within a fixed time-window, thus 
providing the accurate representation of the subject’s experience at that time.
For local reactions and systemic events that resolve after Day 7, the end date will be 
collected on the CRF.  If the e-diary is not completed for 7 days, the end dates of local 
reactions, systemic events, or antipyretic medication use that occurred during the 7 days will 
be collected on the CRF.  The investigator or designee should contact the parent(s)/legal 
guardian or subject in order to obtain stop dates for any solicited reactions or other solicited 
data ongoing on the last day that the e-diary was completed.

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Data reported on the e-diary will be transferred electronically to the e-diary vendor (a trusted 
third party), where they will be available for review by investigators at all times via an 
Internet-based portal.  At intervals agreed upon between the vendor and Pfizer, these data 
will be transferred electronically into Pfizer’s database for analysis and reporting.  These data 
do not need to be reported by the investigator on the CRF.
Investigators will be required to review the e-diary data online at frequent intervals to 
evaluate subject compliance and as part of the ongoing safety review.
7.4.1. Local Reactions
Local reactions (redness, swelling, and pain) at the site of investigational product 
administration will be recorded daily for 7 days (Days 1 to 7) after each vaccination.  Only 
local reactions at the site of investigational product administration on the left arm will be 
recorded.
7.4.1.1. Redness and Swelling
Redness and swelling will be measured and recorded in caliper units (range: 1 to 21+), and 
then categorized as none, mild, moderate, or severe based on the scale given in Table 7
below.  Each caliper unit represents 0.5 cm.  A caliper will be issued with instructions for 
measuring any redness or swelling at the injection site.  The caliper will be used to measure 
and to report the largest diameter of a local reaction.  In the event that a caliper measurement 
is between 2 values, the higher value should be reported.  The measurements will then be 
recorded in the e-diary.
In the event the reaction exceeds the maximum size the caliper is able to measure 
(>21 caliper units), the parent(s)/legal guardian or subject will also measure the maximum 
diameter of the redness and/or swelling at the injection site using the measuring tape/ruler 
provided and report this immediately to the investigator.  The parent(s)/legal guardian or 
subject will report the maximum diameter of the redness and/or swelling at the injection site 
to the investigator daily until the reaction becomes 21 caliper units.  These measurements 
will be recorded in the CRF.
Table 7.
Grading of Redness and Swelling
None
0 to 2.0 cm (0 to 4 caliper units)
Mild
>2.0 to 5.0 cm (5 to 10 caliper units)
Moderate
>5.0 to 10.0 cm (11 to 20 caliper units)
Severe
>10.0 cm (>20 caliper units)
7.4.1.2. Pain
If the subject experiences injection site pain, the pain will be graded using the scale in 
Table 8.  The assessment will then be recorded in the e-diary.

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Table 8.
Grading of Pain
Mild
Does not interfere with activity
Moderate
Interferes with activity
Severe
Prevents daily activity
7.4.2. Systemic Events
7.4.2.1. Temperature
A digital thermometer will be given to the parent(s)/legal guardian or the subject with 
instructions on how to measure the subject’s oral temperature at home.  Oral temperature will 
be collected at in the evening daily for 7 days (Day 1 to Day 7) after each vaccination, and at 
any time during the 7 days when fever is suspected.  The highest temperature for each day 
will be recorded in the e-diary.  Fever is defined as temperature of 38.0C (100.4F).
Temperature will be measured and recorded to 1 decimal place and then categorized 
according to the severity scale in Table 9:
Table 9.
Severity Scale for Fever
Temperature 38.0C to 38.4C (100.4F to 101.1F)
Temperature 38.5C to 38.9C (101.2F to 102.0F)
Temperature 39.0C to 40.0C (102.1F to 104.0F)
Temperature >40.0C (>104.0F)
7.4.2.2. Other Systemic Events
The e-diary will be used to record the presence of other systemic events, including vomiting, 
diarrhea, headache, fatigue, chills, muscle pain other than muscle pain at the injection site, 
and joint pain daily for 7 days (day 1 to day 7) after each vaccination, using the scales in 
Table 10.
Table 10.
Grading of Other Systemic Events
Grade 1 (Mild)
Grade 2 (Moderate)
Grade 3 (Severe)
Vomiting
1 to 2 times in 24 hours
>2 times in 24 hours
Requires IV hydration
Diarrhea
2 to 3 loose stools in 
24 hours
4 to 5 loose stools in 
24 hours
6 or more loose stools in 
24 hours
Headache
Does not interfere with 
activity
Some interference with 
activity
Prevents daily routine 
activity
Fatigue
Does not interfere with 
activity
Some interference with 
activity
Prevents daily routine 
activity
Chills
Does not interfere with 
activity
Some interference with 
activity
Prevents daily routine 
activity
Muscle pain (other than 
muscle pain at the injection 
site)
Does not interfere with 
activity
Some interference with 
activity
Prevents daily routine 
activity

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Table 10.
Grading of Other Systemic Events
Grade 1 (Mild)
Grade 2 (Moderate)
Grade 3 (Severe)
Joint pain 
Does not interfere with 
activity
Some interference with 
activity
Prevents daily routine 
activity
Abbreviation: IV = intravenous.
7.4.3. Use of Antipyretic Medication
The use of antipyretic medication will be recorded in the e-diary daily during the active 
safety observation periods (Day 1 to Day 7) for each vaccination.
7.5. Pilot Cohort Safety Assessments
After Vaccination 1, 7-day e-diary and AE data will be collected for each pilot cohort 
subject.  These safety data from the pilot cohort will be reviewed by the sponsor’s IRC to
determine if the safety, reactogenicity, and tolerability profile of MenABCWY is satisfactory 
and supports further enrollment into the study.
The external data monitoring committee (EDMC) will not participate in the decision whether 
or not to open enrollment further after review of the pilot cohort safety data, but will 
participate in review of safety data from this study as detailed in the EDMC charter
(Section 9.7).
8. ADVERSE EVENT REPORTING
8.1. Requirements
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report Form 
to Pfizer Safety.  These requirements are delineated for 3 types of events: (1) SAEs; (2) 
nonserious AEs; and (3) exposure to the investigational product under study during 
pregnancy or breastfeeding, and occupational exposure.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the investigational 
product under study during 
pregnancy or breastfeeding, and 
occupational exposure
None
Exposure during pregnancy, 
exposure via breastfeeding, 
occupational exposure (regardless of 
whether associated with an AE)
All observed or volunteered events regardless of vaccine group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs.

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Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information.  This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
If the investigator is aware of an SAE with an onset on the day of investigational product 
administration or during the calendar day following investigational product administration, 
the investigator must contact the Pfizer study physician directly immediately after sending 
the SAE report form to Pfizer as described above. The investigator must also contact the 
Pfizer study physician directly as soon as possible after becoming aware of an AE that 
required medical attention that began on the day of investigational product administration or 
during the calendar day following investigational product administration.  These procedures 
do not replace any of the standard AE reporting requirements. Additional information 
regarding such events and the reporting requirements are included in the SRM.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see Serious Adverse Events [Section 8.2.3] below).  In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.  
This information is more detailed than that recorded on the CRF.  In general, this will include 
a description of the event in sufficient detail to allow for a complete medical assessment of 
the case and independent determination of possible causality.  Any information relevant to 
the event, such as concomitant medications and illnesses, must be provided.  In the case of a 
subject death, a summary of available autopsy findings must be submitted as soon as possible 
to Pfizer Safety.  Any pertinent additional information must be reported on the CT SAE 
Report Form; additional source documents (eg, medical records, CRF, laboratory data) are to 
be sent to Pfizer Safety ONLY upon request.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.1.1. Additional Details on Recording Adverse Events on the CRF
All events detailed in the table above will be recorded on the AE page(s) of the CRF.  It 
should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 

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terminology and the same AE term should be used on both the CRF and the CT SAE Report 
Form for reporting of SAE information.
8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study subject/parent(s)/legal guardian.  In addition, each study 
subject/parent(s)/legal guardian will be questioned about the occurrence of AEs in a 
nonleading manner.
8.1.3. Withdrawal From the Study Due to Adverse Events (See Also the Subject 
Withdrawal Section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF.
When a subject withdraws from the study because of an SAE, the SAE must be recorded on 
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section (Section 8.1) above.
8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each subject begins from the time the subject/parent(s)/legal guardian provides 
informed consent, which is obtained before the subject’s participation in the study (ie, before 
undergoing any study-related procedure and/or receiving investigational product), through 
and including Visit 4, and from Visit 10 to Visit 11.
At Month 12 (Visit 5: telephone contact), the parent(s)/legal guardian or subject will be 
contacted by telephone to inquire about SAEs, newly diagnosed chronic medical conditions,
or AEs that resulted in evaluation at a medical facility since Visit 4.  These events must be 
recorded in the CRF and the event must be followed.
At Month 60 (Visit 12: final telephone contact), the parent(s)/legal guardian or subject will 
be contacted by telephone to inquire about SAEs, newly diagnosed chronic medical 
conditions, or AEs that resulted in evaluation at a medical facility since Visit 11.  These 
events must be recorded in the CRF and the event must be followed.
At Visits 7, 8, and 9, the site will inquire about any AEs, as well as RRIs (Section 8.2.4), for 
events occurring during the 48-hour period after each blood draw.  These events must be 
recorded in the CRF and the event must be followed.
AE collection is summarized in Table 11.

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Table 11.
Summary of Adverse Event Collection
Visits 1-4
Visit 5
Visit 6
Visits 7-9
Visits 10-11
Visit 12
Approximate 
Month
0-7
12
18-42
54-55
60
Nonserious AEs ICD through 
and including 
Visit 4
Within 48 
hours of blood 
draw
From Visit 10
to Visit 11
SAEs
ICD through 
and including 
Visit 4
Since Visit 4
Nonactive SAE collection 
period
From Visit 10
to Visit 11
Since Visit 11
MAEs
ICD through 
and including 
Visit 4
Since Visit 4
From Visit 10
to Visit 11
Since Visit 11
NDCMCs
ICD through 
and including 
Visit 4
Since Visit 4
From Visit 10
to Visit 11
Since Visit 11
RRIs
Within 48 
hours of blood 
draw
Abbreviations: ICD = informed consent document; MAE = medically attended adverse event; 
NDCMC = newly diagnosed chronic medical condition; RRI = research-related injury.
For subjects who are screen failures, the active collection period ends when screen failure 
status is determined.
8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.
SAEs occurring in a subject after the active collection period has ended are reported to Pfizer 
Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
8.1.4.2. Recording Nonserious AEs and SAEs on the CRF
During the active collection period, both nonserious AEs and SAEs are recorded on the CRF.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.

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8.1.5. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
nonserious); the investigator must record the causal relationship on the CRF, and report such 
an assessment in accordance with the SAE reporting requirements, if applicable.  An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the investigational product caused or contributed to an AE; generally the facts 
(evidence) or arguments to suggest a causal relationship should be provided.  If the 
investigator does not know whether or not the investigational product caused the event, then 
the event will be handled as “related to investigational product” for reporting purposes, as 
defined by the sponsor.  If the investigator's causality assessment is “unknown but not 
related” to investigational product, this should be clearly documented on study records.
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
8.2. Definitions
8.2.1. Adverse Events
An AE is any untoward medical occurrence in a study subject administered a product or 
medical device; the event need not necessarily have a causal relationship with the treatment 
or usage.  Examples of AEs include, but are not limited to:

Abnormal test findings;

Clinically significant signs and symptoms;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:

Drug overdose;

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
Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.
8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention; and/or

Test result leads to a change in study dosing (outside of any protocol-specified dose
adjustments) or discontinuation from the study, significant additional concomitant drug 
treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
recording as an AE.
8.2.3. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

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
Results in congenital anomaly/birth defect.
Or that is considered to be:

An important medical event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
Medical device complaints may meet the SAE reporting requirement criteria (see Medical 
Device Complaint Reporting Requirements [Section 8.5]).  An incident is any malfunction 
(ie, the failure of a device to meet its performance specifications or to perform as intended; 
performance specifications include all claims made in the labeling for the device) that, 
directly or indirectly, might lead to or might have led to the death of a subject, or user, or of 
other persons, or to a serious deterioration in their state of health.
A serious injury that can cause a serious deterioration in state of health can include:

A life-threatening illness, even if temporary in nature;

A permanent impairment of a body function or permanent damage to a body structure; 

A condition necessitating medical or surgical intervention to prevent the above 2 bulleted 
items;
Examples: clinically relevant increase in the duration of a surgical procedure; a condition 
that requires hospitalization or significant prolongation of existing hospitalization;

Any indirect harm as a consequence of an incorrect diagnostic or in vitro diagnostic 
device test results when used within the manufacturer’s instructions for use;

Fetal distress, fetal death, or any congenital abnormality or birth defects.
8.2.4. Research-Related Injury
Should a subject, in the investigator’s opinion, suffer a medically important research related 
injury caused by their participation in the study, the designated Pfizer clinician or medical 
monitor must be notified immediately.

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A medically important research related injury is any untoward medical occurrence that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Medical and scientific judgment is exercised in determining whether an injury is an 
important medical event.  An important medical event may not be immediately 
life-threatening and/or result in death or hospitalization.  However, if it is determined that the 
event may jeopardize the subject or may require intervention to prevent one of the other 
outcomes listed in the definition above, the important medical event should be reported as a 
research-related injury.
An investigator may be requested by the designated Pfizer clinician or medical monitor to 
obtain specific additional follow-up information in an expedited fashion.  In general, this will 
include a description of the injury in sufficient detail to allow for a complete medical 
assessment of the case and independent determination of possible causality.  Information on 
other possible causes of the event, such as concomitant treatments, vaccines, and/or illnesses 
must be provided.  In the case of a subject death, a summary of available autopsy findings 
must be submitted as soon as possible to Pfizer or its designated representative.
8.2.5. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

Skilled nursing facilities;

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
Nursing homes;

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE.  Examples include:

Admission for treatment of a preexisting condition not associated with the development 
of a new AE or with a worsening of the preexisting condition (eg, for workup of a 
persistent pretreatment laboratory abnormality);

Social admission (eg, subject has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline
documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE.  For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE.
8.3. Severity Assessment
GRADE 
If required on the AE page of the CRF, the investigator will use the adjectives MILD, 
MODERATE, or SEVERE to describe the maximum intensity of the AE. For purposes of 
consistency, these intensity grades are defined as follows:
1
MILD
Does not interfere with subject's usual function.
2
MODERATE
Interferes to some extent with subject's usual function.
3
SEVERE
Interferes significantly with subject's usual function.
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.

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8.4. Special Situations
8.4.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections, and will be handled as SAEs in 
the safety database.
8.4.2. Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some subjects, transaminase elevations are a harbinger of a more 
serious potential outcome.  These subjects fail to adapt and therefore are "susceptible" to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury 
(DILI).  Subjects who experience a transaminase elevation above 3 times the upper limit of 
normal (× ULN) should be monitored more frequently to determine if they are an “adaptor” 
or are “susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to assess LFTs because a subject 
presents with clinical signs/symptoms, such LFT results should be managed and followed as 
described below.
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same lab sample).  
In rare instances, by the time TBili elevations are detected, AST/ALT values might have 
decreased.  This occurrence is still regarded as a potential DILI.
Therefore, abnormal elevations in either AST OR ALT in addition to TBili that meet the 
criteria outlined below are considered potential DILI (assessed per Hy’s law criteria) cases
and should always be considered important medical events, even before all other possible 
causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the subject’s 
individual baseline values and underlying conditions.  Subjects who present with the 
following laboratory abnormalities should be evaluated further as potential DILI (Hy’s law) 
cases to definitively determine the etiology of the abnormal laboratory values:

Subjects with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value >2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available;

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
For subjects with baseline AST OR ALT OR TBili values above the ULN, the following 
threshold values are used in the definition mentioned above, as needed, depending on 
which values are above the ULN at baseline:
o
Preexisting AST or ALT baseline values above the normal range: AST or ALT values 
>2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is smaller).
o
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches >3 × ULN 
(whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The subject should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili, laboratory tests should 
include albumin, creatine kinase (CK), direct and indirect bilirubin, gamma-glutamyl 
transferase (GGT), prothrombin time (PT)/international normalized ratio (INR), total bile 
acids, alkaline phosphatase and acetaminophen drug and/or protein adduct levels.  
Consideration should also be given to drawing a separate tube of clotted blood and an 
anticoagulated tube of blood for further testing, as needed, for further contemporaneous 
analyses at the time of the recognized initial abnormalities to determine etiology.  A detailed 
history, including relevant information, such as review of ethanol, acetaminophen (either by 
itself or as a coformulated product in prescription or over-the-counter medications), 
recreational drug, supplement (herbal) use and consumption, family history, sexual history, 
travel history, history of contact with a jaundiced person, surgery, blood transfusion, history 
of liver or allergic disease, and potential occupational exposure to chemicals, should be 
collected.  Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging 
(eg, biliary tract) may be warranted.
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.

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8.4.3. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and 
Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.4.3.1. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an EDP occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;
o
An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has 
been exposed to chemotherapeutic products).

A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed during 
his partner’s pregnancy.
If a subject or subject’s partner becomes or is found to be pregnant during the subject’s 
treatment with the investigational product, the investigator must report this information to 
Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, regardless of 
whether an SAE has occurred.  In addition, the investigator must submit information 
regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a subject 
reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or 
spillage) to Pfizer Safety using the EDP supplemental form.  This must be done irrespective 
of whether an AE has occurred and within 24 hours of awareness of the exposure.  The 
information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).

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If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the investigational product.
Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the subject with the Pregnant Partner Release of Information Form 
to deliver to his partner.  The investigator must document in the source documents that the 
subject was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.3.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.4.3.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a subject enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.

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8.4.4. Medication Errors and Lack of Efficacy
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors and lack of efficacy.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report Form to 
Pfizer Safety Within 24 Hours of 
Awareness
Medication errors and lack of 
efficacy
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
8.4.4.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong subject, or at the wrong time, or at the wrong dosage strength.
Medication errors include:

Medication errors involving subject exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the participating subject.
Other examples include but are not limited to:

The administration of expired investigational product.

The administration of an incorrect investigational product.

The administration of an incorrect dosage.

Administration of an investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined prior to administration by the 
sponsor that the investigational product under question is acceptable for use.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.

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8.4.4.2. Lack of Efficacy
Lack of efficacy in an approved indication should be reported as an SAE to Pfizer Safety.
8.5. Medical Device Complaint Reporting Requirements
All medical device complaints, regardless of whether the medical device complaint is 
associated with an AE, will be recorded on the applicable pages within the CRF.  This 
includes potential incidents or malfunctions associated with the use of a medical device 
product.  An incident or malfunction is an event that might have led to death or serious 
deterioration in health, or if it occurred again might lead to death or serious deterioration in 
health.
Pfizer is to be notified of all medical device complaints within 24 hours of the investigator’s 
awareness of the event.
Please note, no unblinded investigational product information should be entered on the 
medical device complaint CRF when reporting medical device complaints.  Please refer to 
the IP manual for further details regarding reporting medical device complaints.
9. DATA ANALYSIS/STATISTICAL METHODS
Methodology for summary and statistical analyses of the data collected in this study is 
outlined here and will be further detailed in a statistical analysis plan (SAP). The SAP may 
modify what is outlined in the protocol where appropriate (however, any major modifications 
of the primary endpoint definitions or their analyses will also be reflected in a protocol 
amendment) and will be finalized before data unblinding in Stage 1.
9.1. Sample Size Determination
Both hypothesis testing and estimation will be performed.  The hypothesis-testing component 
will address the need to confirm the immunogenicity of bivalent rLP2086 administered at 
Months 0 and 6 in all subjects 10 through 25 years of age, using prespecified criteria for the 
primary MnB immunogenicity endpoints.  Safety of bivalent rLP2086 administered at 
Months 0 and 6 will also be described.  Immunogenicity and safety information for the 
MenABCWY arms will be described.
Hypothesis testing will be performed on the 5 coprimary MnB endpoints in all subjects, 
which will include a 4-fold rise from baseline in hSBA titers for each of the 4 primary strains 
and the composite response (hSBA titer LLOQ for all 4 primary strains combined) 1 month 
after the second vaccination.  If the lower limit of the 2-sided 95% confidence interval (CI) 
exceeds each of the target lower limit of the confidence interval (LCI) values, the study’s
primary objective will be met.
The null hypothesis will be that the true proportion of subjects is less than or equal to the 
target LCI criterion for 1 or more primary endpoints.  The alternate hypothesis is that the true 
proportion of subjects for each of the primary immunogenicity endpoints exceeds the target 
LCI.

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Hypothesis testing will be performed by calculating 2-sided 95% CIs on each of the 5 MnB 
endpoints limited to Groups 2 and 4 in which ACWY-naive and ACWY-experienced cohorts 
will be combined.  The Clopper-Pearson method will be used to calculate the CIs for the 
proportions.  If the LCI exceeds the corresponding target LCI for each strain and the 
composite, then the null hypothesis will be rejected.
The study sample size is mainly based on hypothesis-testing criteria to verify the clinical 
benefit of a 2-dose schedule for the use of bivalent rLP2086 administered at Months 0 and 
6 in healthy subjects 10 years to <26 years of age in both Group 2 and Group 4. Given the 
observed response proportions from Study B1971012 for each endpoint, with 900 evaluable 
subjects, the primary objective based on all 5 primary endpoints will be met with a power of 
95.2% (Table 12).  Furthermore, with 748 evaluable subjects from US sites, the LCI criteria 
for the primary objective will also be met with a power of 89.9%. For the global study, 
assuming that ~85% of enrolled subjects qualify for the evaluable immunogenicity 
population, ~1060 subjects should be enrolled to receive bivalent rLP2086 and 
MenACWY-CRM.  This assumes that every subject has sufficient sera for the 4 hSBAs.
Table 12.
Overall Power to Meet the Primary Objectives
Primary Endpoint 
Test Strain 
(Variant)
LCI Criteria 
Study B1971012 0-
and 6-Month 
Responses With 95% 
Confidence Interval 
(%)a
Number of 
Evaluable 
Subjects
Power
hSBA titer fold rise 
4 from baseline
PMB80
(A22)
LL of 95% CI 
>75%
82.3
(76.3, 87.3)
900
99.97%
PMB2001 (A56)
LL of 95%
CI >85
90.1
(85.1, 93.8)
900
99.60%
PMB2948 (B24)
LL of 95%
CI >55
64.5
(57.4, 71.1)
900
99.99%
PMB2707 (B44)
LL of 95%
CI >60
66.0
(58.9, 72.6)
900
95.7%
Composite response
(hSBA titer 
LLOQ for all 4 
primary strains 
combined)
LL of 95%
CI >65
72.9
(65.9, 79.1)
900
99.92%
Overall power
95.2%
Abbreviations: hSBA = serum bactericidal assay using human complement; LCI = lower limit of the confidence 
interval; LL = lower limit; LLOQ = lower limit of quantitation.
a.
The power calculation was based on Study B1971012 with a vaccine schedule of 0 and 6 months.
An additional 530 subjects will be enrolled in the MenABCWY-MenABCWY regimen.  
Assuming 85% evaluable subjects, there will be 450 evaluable subjects in this regimen. 
These subjects will be further split between ACWY-naive and ACWY-experienced strata.

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Given 530 subjects receiving at least 1 dose of MenABCWY, the probability of observing at 
least 1 AE will be 93.0% with a true incidence of 0.5% (see Table 13).
Table 13.
Probabilities of Detecting AEs at Specified Incidences
Sample Size
True Incidence of AE
Probability of at Least 1 AE
530
0.01%
5.2%
530
0.10%
41.2%
530
0.25%
73.5%
530
0.50%
93.0%
530
1.00%
99.5%
A total of 1590 subjects will therefore be enrolled into this study.  The randomization will be 
performed separately for ACWY-naive and ACWY-experienced subjects.  Equal numbers of 
subjects will be recruited into each stratum.
9.2. Immunogenicity Analyses
Subjects having received a vaccine containing 1 or more ACWY groups prior to enrollment 
will be randomized in the ACWY-experienced stratum but, for the purposes of group A, C, 
W, and Y analyses, will be considered A, C, W, Y-naive or -experienced based on what 
group(s) were present in the prior ACWY-containing vaccine.
For the calculation of GMTs, hSBA results below LLOQ will be set as ½ of LLOQ (see 
Table 4 and Table 5).  Two (2)-sided 95% CIs will be provided for all proportions and 
GMTs.
Exact 2-sided 95% CIs will be compiled using the Clopper-Pearson method for any 
proportions of subjects with hSBA titers cutoff or LCI criteria.
Geometric means will be obtained by log transformation of titers, averaging the transformed 
values, then exponentiating the results.  Ninety-five percent CIs will also be obtained for the 
geometric means.  The CIs will be calculated in the log scale with reference to the 
appropriate t-distribution.  Then the lower and upper limits will be exponentiated.
9.2.1. Analysis of the Primary Immunogenicity Objective
The assessment of the MnB immune response induced by bivalent rLP2086 will be 
performed by compiling the proportions of subjects (point estimate) in the bivalent rLP2086
+ MenACWY-CRM vaccine groups (Group 2 – ACWY-naive and 
Group 4 – ACWY-experienced) for each MnB coprimary endpoint, along with the exact 
2-sided 95% CI for each endpoint. The primary endpoints are defined as a 4-fold rise from 
baseline in hSBA titer as follows:

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
For subjects with a baseline hSBA titer below the LOD (or an hSBA titer of <1:4), a 
4-fold response is defined as an hSBA titer of 1:16 or the LLOQ (whichever titer is 
higher).

For subjects with a baseline hSBA titer of LOD (ie, hSBA titer of 1:4) and < LLOQ, a 
4-fold response is defined as an hSBA titer of 4 times the LLOQ.

For subjects with a baseline hSBA titer of LLOQ, a 4-fold response is defined as an 
hSBA titer of 4 times the baseline titer.
The composite endpoint defined as

the proportion of subjects achieving an hSBA titer LLOQ (1:16 for A22 and 1:8 for 
A56, B24, and B44) for all 4 primary test strains combined.
If each of the LCIs meets or exceeds the associated target LCI (Table 12), then the null 
hypothesis will be rejected, and the study objective in terms of the immunogenicity will be
met.
The evaluation for all 5 primary endpoints will also be performed for US subjects only.
9.2.2. Analyses of the Secondary Objectives
The MnB immune response induced by 2 doses of bivalent rLP2086 will be described by 
compiling results for Groups 2 and 4.
The MnB immune response induced by 2 doses of MenABCWY (combined Groups 1 and 3) 
compared to the immune response induced by 2 doses of bivalent rLP2086 (combined 
Groups 2 and 4) will be described.
The ACWY immune response induced by 1 dose of MenABCWY compared to the immune 
response induced by 1 dose of MenACWY-CRM will be analyzed for the ACWY-naive and 
ACWY-experienced subjects separately.
The ACWY immune response induced by 2 doses of MenABCWY compared to the immune 
response induced by 1 dose of MenACWY-CRM will be analyzed for the ACWY-naive and 
ACWY-experienced subjects separately.
Prior to the booster vaccination, the immune response induced by MenABCWY compared to 
the immune response induced by MenACWY-CRM and bivalent rLP2086 will be described 
for ACWY test strains in ACWY-naive and ACWY-experienced subjects separately, and for
MnB strains for the ACWY-naive and ACWY-experienced subjects combined, at each of the 
blood sample time points.
The following tables highlight the analyses for the evaluation of the secondary objectives for 
immunogenicity (all the analyses are descriptive).

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Table 14.
Highlights of the Analyses for the Secondary Immunogenicity Objectives –
Stage 1
Vaccine Group
Analysis Time Point
Strain
Analysis
Bivalent rLP2086 +
MenACWY-CRM 
(Groups 2 and 4 
combined)
1 Month after the second dose 
of bivalent rLP2086 (Visit 4)
PMB80 (A22), PMB2001
(A56), PMB2948 (B24), 
PMB2707 (B44)
Proportion of subjects 
with hSBA titer LLOQ 
for each strain
Proportion of subjects 
with hSBA titer 1;4, 
1;8, 1;16, 1;32, 1;64, 
1;128 for each strain
hSBA GMTs for each 
strain
Baseline and 1 month after the 
second dose of bivalent 
rLP2086 (Visit 1 and Visit 4)
Each secondary MenB test 
strain (see Table 5)
Proportion of subjects 
with hSBA titer LLOQ
Proportion of subjects 
with hSBA titer 1:4, 
1:8, 1:16, 1:32, 1:64, 
1:128 
hSBA GMTs
MenABCWY 
(ACWY-naive and 
ACWY-experienced
groups separately)
MenACWY-CRM 
(ACWY-naive and 
ACWY-experienced
groups separately)
1 Month after the first dose of 
MenABCWY (Visit 2) for 
Groups 1 and 3
1 Month after the first dose of 
MenACWY-CRM (Visit 2)
for Groups 2 and 4
hSBA-MenA, 
hSBA-MenC, 
hSBA-MenW, 
hSBA-MenY
Proportion of subjects 
with hSBA-MenA/C/W/Y
titer 1:8 (or LLOQ, 
whichever is higher)
Proportion of subjects 
with hSBA-MenA/C/W/Y
titer 1:4, 1:8, 1:16, 
1:32, 1:64, 1:128 
hSBA-MenA/C/W/Y 
GMTs
MenABCWY 
(ACWY-naive and 
ACWY-experienced 
groups separately)
MenACWY-CRM 
(ACWY-naive and 
ACWY-experienced
groups separately)
1 Month after the second dose 
of MenABCWY (Visit 4)
1 Month after the first dose of 
MenACWY-CRM (Visit 2)
hSBA-MenA, 
hSBA-MenC, 
hSBA-MenW, 
hSBA-MenY
Proportion of subjects 
with hSBA-MenA/C/W/Y 
titer 1:8 (or LLOQ, 
whichever is higher) 
Proportion of subjects 
with hSBA-MenA/C/W/Y
titer 1:4, 1:8, 1:16, 
1:32, 1:64, 1:128 
hSBA-MenA/C/W/Y 
GMTs

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Table 14.
Highlights of the Analyses for the Secondary Immunogenicity Objectives –
Stage 1
Vaccine Group
Analysis Time Point
Strain
Analysis
MenABCWY 
(ACWY-naive and 
ACWY-experienced 
groups combined)
1 Month after the second dose 
of MenABCWY (Visit 4)
PMB80 (A22), PMB2001
(A56), PMB2948 (B24), 
PMB2707 (B44)
Composite response 
(proportion of subjects 
achieving an hSBA titer 
LLOQ for all 4 strains)
Proportion of subjects 
achieving at least a 4-fold 
increase in hSBA titer 
from baseline for each of 
the 4 strains 
Proportion of subjects 
with hSBA titer LLOQ 
for each strain
Proportion of subjects 
with hSBA titer 1:4, 
1:8, 1:16, 1:32, 1:64, 
1:128 for each strain
hSBA GMTs for each 
strain
MenABCWY 
(ACWY-naive and 
ACWY-experienced 
groups separately)
Bivalent rLP2086 + 
MenACWY-CRM 
(ACWY-naive and 
ACWY-experienced 
groups separately)
Before and after MenABCWY 
or MenACWY-CRM +
bivalent rLP2086 at Visits 1
and 3 
hSBA-MenA, 
hSBA-MenC, 
hSBA-MenW, 
hSBA-MenY
Proportion of subjects 
with hSBA-MenA/C/W/Y 
titer 1:8 (or LLOQ,
whichever is higher)
Proportion of subjects 
with hSBA-MenA/C/W/Y
titer 1:4, 1:8, 1:16, 
1:32, 1:64, 1:128 
hSBA-MenA/C/W/Y 
GMTs
MenABCWY 
(ACWY-naive and 
ACWY-experienced 
groups combined)
Bivalent rLP2086 + 
MenACWY-CRM 
(ACWY-naive and 
ACWY-experienced 
groups combined)
Before and after MenABCWY 
vaccination at Visits 1 and 3 
PMB80 (A22), PMB2001
(A56), PMB2948 (B24), 
PMB2707 (B44)
Proportion of subjects 
with hSBA titer LLOQ 
for each strain
Proportion of subjects 
with hSBA titer 1:4, 
1:8, 1:16, 1:32, 1:64, 
1:128 for each strain
hSBA GMTs for each 
strain
Abbreviations: GMT = geometric mean titer; hSBA = serum bactericidal assay using human complement; 
LLOQ = lower level of quantitation; MenA, MenB, MenC, MenW, and MenY = Neisseria meningitidis groups 
A, B, C, W, and Y.

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Table 15.
Highlights of the Analyses for the Secondary Immunogenicity Objectives –
Persistence
Vaccine Group
Analysis Time Point
Strain
Analysis
MenABCWY (ACWY-
naive and ACWY-
experienced groups 
separately)
Bivalent rLP2086 + 
MenACWY-CRM 
(ACWY-naive and 
ACWY-experienced 
groups separately)
At Visits 7, 8, and 9, and 
before booster vaccination 
at Visit 10
hSBA-MenA, 
hSBA-MenC, 
hSBA-MenW, 
hSBA-MenY
Proportion of subjects 
with hSBA-MenA/C/W/Y 
titer 1:8 (or LLOQ, 
whichever is higher)
MenABCWY (ACWY-
naive and ACWY-
experienced groups 
combined)
Bivalent rLP2086 + 
MenACWY-CRM 
(ACWY-naive and 
ACWY-experienced 
groups combined)
At Visits 7, 8, and 9, and 
before booster vaccination 
at Visit 10
PMB80 (A22), PMB2001
(A56), PMB2948 (B24), 
PMB2707 (B44)
Proportion of subjects 
with hSBA titer ≥LLOQ 
for each strain
Abbreviations: GMT = geometric mean titer; hSBA = serum bactericidal assay using human complement; 
LLOQ = lower level of quantitation; MenA, MenB, MenC, MenW, and MenY = Neisseria meningitidis groups 
A, B, C, W, and Y.
Table 16.
Highlights of the Analyses for the Secondary Immunogenicity Objectives –
Booster
Vaccine Group
Analysis Time Point
Strain
Analysis
MenABCWY (Groups 1
and 3 combined in Stage 
2)
1 Month after the booster 
dose of MenABCWY 
(Visit 11)
PMB80 (A22), PMB2001
(A56), PMB2948 (B24), 
PMB2707 (B44)
Proportion of subjects 
with hSBA titer LLOQ 
for each MnB strain
MenABCWY (Groups 1
and 3 separately in Stage 
2)
1 Month after the booster 
dose of MenABCWY 
(Visit 11)
hSBA-MenA, 
hSBA-MenC, 
hSBA-MenW, 
hSBA-MenY
Proportion of subjects 
with 
hSBA-MenA/C/W/Y titer 
1:8 (or LLOQ, 
whichever is higher)
Bivalent rLP2086 + 
MenACWY-CRM 
(Groups 2 and 4 
combined in Stage 2)
1 Month after the booster 
dose of bivalent rLP2086 
+ MenACWY-CRM 
(Visit 11)
PMB80 (A22), PMB2001
(A56), PMB2948 (B24), 
PMB2707 (B44)
Proportion of subjects 
with hSBA titer LLOQ 
for each strain
Abbreviations: GMT = geometric mean titer; hSBA = serum bactericidal assay using human complement; 
LLOQ = lower level of quantitation; MenA, MenB, MenC, MenW, and MenY = Neisseria meningitidis groups 
A, B, C, W, and Y; MnB = Neisseria meningitidis group B.

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9.2.3. Analyses of Exploratory Objectives
The table below outlines the exploratory analysis for immunogenicity.
Table 17.
Analyses for the Exploratory Immunogenicity Objectives – Stages 1 and 2
Vaccine Group
Analysis Time Point
Strain
Analysis
Bivalent rLP2086 + 
MenACWY-CRM 
(ACWY-naive and 
ACWY-experienced 
groups combined: Groups
2 and 4 in Stage 1)
1 Month after the first 
dose of bivalent rLP2086
+ MenACWY-CRM 
(Visit 2)
PMB80 (A22), PMB2001
(A56), PMB2948 (B24), 
PMB2707 (B44)
Composite response 
(proportion of subjects 
achieving an hSBA titer 
LLOQ for all 4 strains)
Proportion of subjects 
achieving at least a 4-fold 
increase in hSBA titer 
from baseline for each of 
the 4 MnB strains 
Proportion of subjects 
with hSBA titer LLOQ 
for each MnB strain
Proportion of subjects 
with hSBA titer 1:4, 
1:8, 1:16, 1:32, 1:64, 
1:128 for each MnB 
strain
hSBA GMTs for each 
MnB strain
Bivalent rLP2086 +
MenACWY-CRM 
(Groups 2 and 4 separately 
in Stage 2)
1 Month after the booster 
dose of bivalent rLP2086
+ MenACWY-CRM 
(Visit 11)
hSBA-MenA, 
hSBA-MenC, 
hSBA-MenW, 
hSBA-MenY
Proportion of subjects 
with hSBA-MenA/C/W/Y 
titer 1:8 (or LLOQ,
whichever is higher)
MenABCWY (Groups 1 
and 3 separately)
Bivalent rLP2086 + 
MenACWY-CRM 
(Groups 2 and 4 
separately)
At Visits 7, 8, and 9, and 
before booster vaccination 
at Visit 10
hSBA-MenA, 
hSBA-MenC, 
hSBA-MenW, 
hSBA-MenY
Proportion of subjects 
with hSBA-MenA/C/W/Y
titer 1:8, 1:16, 1:32, 
1:64, 1:128 
hSBA-MenA/C/W/Y 
GMTs
MenABCWY (Groups 1 
and 3 combined)
Bivalent rLP2086 + 
MenACWY-CRM 
(Groups 2 and 4 
combined)
At Visits 7, 8, and 9, and 
before booster vaccination 
at Visit 10
PMB80 (A22), PMB2001
(A56), PMB2948 (B24), 
PMB2707 (B44)
Proportion of subjects 
with hSBA titer 1:4, 
1:8, 1:16, 1:32, 1:64, 
1:128 for each strain
hSBA GMTs for each 
strain

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Table 17.
Analyses for the Exploratory Immunogenicity Objectives – Stages 1 and 2
Vaccine Group
Analysis Time Point
Strain
Analysis
MenABCWY (Groups 1
and 3 combined in
Stage 2)
1 Month after the booster 
dose of MenABCWY 
(Visit 11)
PMB80 (A22), PMB2001
(A56), PMB2948 (B24), 
PMB2707 (B44)
Composite response 
(proportion of subjects 
achieving an hSBA titer 
LLOQ for all 4 MnB
strains)
Proportion of subjects 
achieving at least a 4-fold 
increase in hSBA titer 
from baseline for each of 
the 4 MnB strains 
Proportion of subjects 
with hSBA titer 1:4, 
1:8, 1:16, 1:32, 1:64, 
1:128 for each MnB 
strain
hSBA GMTs for each 
MnB strain
MenABCWY (Groups 1
and 3 separately in
Stage 2)
1 Month after the booster 
dose of MenABCWY 
(Visit 11)
hSBA-MenA, 
hSBA-MenC, 
hSBA-MenW, 
hSBA-MenY
Proportion of subjects 
with hSBA-MenA/C/W/Y
titer 1:8, 1:16, 1:32, 
1:64, 1:128 
hSBA-MenA/C/W/Y 
GMTs
Bivalent rLP2086 + 
MenACWY-CRM 
(Groups 2 and 4 combined 
in Stage 2)
1 Month after the booster 
dose of bivalent rLP2086 
+ MenACWY-CRM (Visit 
11)
PMB80 (A22), PMB2001
(A56), PMB2948 (B24), 
PMB2707 (B44)
Composite response 
(proportion of subjects 
achieving an hSBA titer 
LLOQ for all 4 strains)
Proportion of subjects 
achieving at least a 4-fold 
increase in hSBA titer 
from baseline for each of 
the 4 strains
Proportion of subjects 
with hSBA titer 1:4, 
1:8, 1:16, 1:32, 1:64, 
1:128 for each strain
hSBA GMTs for each 
strain
Abbreviations: GMT = geometric mean titer; hSBA = serum bactericidal assay using human complement; 
LLOQ = lower level of quantitation; MenA, MenB, MenC, MenW, and MenY = Neisseria meningitidis groups 
A, B, C, W, and Y; MnB = Neisseria meningitidis group B.
The exploratory analysis to investigate the association of the primary strains and additional 
MenB testing strains, as well as a sensitivity analysis that may be performed for
immunogenicity in Stage 1, will be detailed in the SAP.

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9.3. Demographic and Baseline Characteristics
The following demographic characteristics will be descriptively summarized: sex, race, 
ethnicity, and age at first vaccination.  Medical history and baseline physical examination 
data will also be descriptively summarized.  Demographic characteristics will be summarized 
by cohort and by combined cohorts.  Demographic characteristics will also be compiled for 
subjects participating in Stage 2.
9.4. Safety Analyses
9.4.1. Analysis for Safety and Reactogenicity
The proportion of subjects reporting local reactions at the investigational product 
administration sites and systemic events within the 7-day period after each vaccination will 
be descriptively summarized by group.  Two (2)-sided 95% CIs based on the 
Clopper-Pearson method will be presented with the proportions.  Severities of local reactions 
and systemic events reported after each vaccination will also be descriptively summarized by 
vaccine group.  Local reactions will be summarized only for the left arm, which is the 
MenABCWY or bivalent rLP2086 injection site.
The proportion of subjects reporting the use of antipyretic medication for Days 1 to 7 will be 
compiled for each vaccine group after each vaccination.
All AEs and SAEs will be categorized according to the latest version of the Medical 
Dictionary for Regulatory Activities (MedDRA).  A medically attended AE is defined as a 
nonserious AE that results in an evaluation at a medical facility.  A newly diagnosed chronic 
medical condition is defined as a disease or medical condition not previously identified that 
is expected to be persistent or otherwise long-lasting in its effects.  AEs, SAEs, medically 
attended AEs, and newly diagnosed chronic medical conditions will be summarized by 
vaccine group.
All of the analyses will be performed for each ACWY stratum as well as for the combined 
strata.  Safety analyses may also be summarized by other demographic variables.
Detailed analyses for each safety endpoint will be addressed in the SAP.
9.5. Analysis Populations
9.5.1. Full Analysis Set
The full analysis set will be referred to as the intent-to-treat (ITT) population.
9.5.2. Per-Protocol Analysis Set 
The per-protocol analysis set will be referred to as the evaluable immunogenicity population,
which is the primary population for the primary objective assessments and for the analyses of 
the secondary endpoints related to MnB strains in Stage 1.

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All randomized subjects who are included in the Stage 1 modified intent-to-treat (mITT)
population as well as who meet the following criteria will be included in the Stage 1 
evaluable immunogenicity population:
1. Were randomized to the study group of interest.
2. Were eligible, ie, fulfilling all of the inclusion criteria and none of the exclusion criteria.
3. Received all investigational products as randomized.
4. Had blood drawn for assay testing within the required time frames at Months 0 (Visit 1: 
before Vaccination 1) and 7 (Visit 4: 1 month after the second vaccination: window 
28-42 days).
5. Had as least 1 valid and determinate MenB assay result after the second vaccination.
6. Had no important protocol deviations. An important protocol deviation is a protocol 
deviation that, in the opinion of the sponsor’s global medical monitor, would materially 
affect assessment of immunogenicity, eg, subject receipt of a prohibited vaccine or 
medication that might affect immune response or a medication error with suspected 
decrease in potency of the vaccine.
An evaluable immunogenicity population for booster response will be used for booster 
immunogenicity analysis, which includes subjects who were eligible for the study (ie, met all 
Stage 1 and booster stage eligibility criteria), received a booster dose as intended (same 
vaccine as they received in Stage 1), had blood drawn for assay testing within the required 
time frame at Month 55 (Visit 11), and had a valid and determinate MenB or MenA/C/W/Y 
assay result after the booster dose, as well as no major protocol violations as determined by 
the sponsor’s global medical monitor. This population will be referred to as the booster
evaluable immunogenicity population.
9.6. Modified Intent-to-Treat (mITT) Population
All randomized subjects who have at least 1 valid and determinate MenB or MenA/C/W/Y
assay result available at any time point from Visit 1 to Visit 4 will be included in the mITT 
population for Stage 1. This will be the primary immunogenicity population for the analyses
of the secondary endpoints related to ACWY endpoints in Stage 1.
The mITT population for Stage 2 is defined as all subjects who signed informed consent at 
Visit 7 and who have at least 1 valid and determinate MenB or MenA/C/W/Y assay result 
available in Stage 2.
The mITT populations will be used for the evaluation of the primary, secondary, and 
exploratory immunogenicity endpoints, and subjects will be analyzed according to the 
investigational product to which they were randomized. Endpoints to assess antibody 
persistence will include subjects in the Stage 2 mITT population.

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Subjects included in the sentinel cohort will be included in the Stage 1 mITT population for 
immunogenicity analyses.
A booster mITT immunogenicity population will also be defined for supportive analyses for 
booster endpoints. This population will consist of subjects who received a booster 
vaccination and who have any booster immunogenicity data.
9.7. Safety Analysis Set
The safety population will be used for all safety analyses. The safety population for Stage 1 
will include all subjects who have received at least 1 dose of investigational product during 
Stage 1 and for whom safety data are available. The safety population for Stage 2 will 
include all subjects who received the booster vaccination and for whom safety data are 
available. For the safety analysis, subjects will be analyzed according to the investigational 
product received. Additionally, a persistence safety population will include all subjects who 
signed the informed consent to participate in Stage 2.
Separate safety populations will be defined for each vaccination visit and follow-up phase: 
Vaccination 1, Vaccination 2, follow-up phase for Stage 1, booster vaccination visit, and 
follow-up phase for Stage 2. These populations are detailed below.
1. Vaccination 1 safety population: This population will include all subjects who received
the first dose of investigational product (MenABCWY + saline or bivalent rLP2086 + 
MenACWY-CRM) at Visit 1, and for whom safety information from Visit 1 to before
Visit 3 is available.
2. Vaccination 2 safety population: This population will include all subjects who received
the second dose of investigational product (MenABCWY or bivalent rLP2086) at Visit 3, 
and for whom safety information from Visit 3 up to and including Visit 4 is available.
3. Follow-up safety population for Stage 1: This population will include all subjects who 
received at least 1 dose of investigational product and for whom safety information is 
available from after Visit 4 up to and including Visit 5. Subjects who received the wrong 
investigational product and are followed for 6 months for safety will not be included in 
this population.
4. Booster vaccination safety population: This population will include all subjects who 
received the booster dose of investigational product (MenABCWY or bivalent rLP2086) 
at Visit 10, and for whom safety information from Visit 10 up to and including Visit 11 is 
available.
5. Follow-up safety population for Stage 2: This population will include all subjects who 
received the booster dose of investigational product and for whom safety information is 
available from after Visit 11 up to and including Visit 12. Subjects who received the 
wrong investigational product and are followed for 6 months for safety will not be 
included in this population.

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9.8. Analysis Timing
No formal interim analyses are planned for this study.
The study database will be unblinded after the last subject has completed the Visit 5 
telephone contact.
Analyses will be completed after Stage 1 and after Stage 2. The Stage 1 analyses will 
include immunogenicity analyses up to and including the post–Vaccination 2 blood draw 
(approximately 1 month after Vaccination 2) and safety assessments up to and including the 
Visit 5 telephone contact (approximately 6 months after Vaccination 2).
The Stage 2 analyses (persistence and booster analyses) will include all data collected after 
Visit 5 through the end of the study.
After unblinding following the completion of Stage 1 (through Visit 5) and testing the 
hypothesis associated with the primary immunogenicity objective, interim summaries of 
immunogenicity and safety data may be generated. The alpha level (confidence level of 95% 
CIs) will not be adjusted for these descriptive summaries.
9.9. Data Monitoring Committee
This study will use an EDMC.  The ISC will provide unblinded safety reports to the EDMC
for review.  Safety data will be reviewed by the EDMC throughout the study and no type I 
error will be adjusted for the multiple looks at the data.
The EDMC will be responsible for ongoing monitoring of the safety of subjects in the study 
according to the charter. The recommendations made by the EDMC to alter the conduct of 
the study will be forwarded to Pfizer for final decision.  Pfizer will forward such decisions, 
which may include summaries of aggregate analyses of endpoint events and of safety data 
that are not endpoints, to regulatory authorities, as appropriate.
Please see the EDMC charter for further details.
10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and GCPs are being followed.  The monitors may review source documents to 
confirm that the data recorded on CRFs are accurate.  The investigator and institution will 
allow Pfizer monitors/auditors or its agents and appropriate regulatory authorities direct 
access to source documents to perform this verification.  This verification may also occur 
after study completion.
During study conduct and/or after study completion, the investigator site may be subject to 
review by the IRB/EC, and/or to quality assurance audits performed by Pfizer, or companies 
working with or on behalf of Pfizer, and/or to inspection by appropriate regulatory 
authorities.

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The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the investigator site for the inspection and will allow Pfizer or its
agent, whenever feasible, to be present during the inspection.  The investigator site and 
investigator will promptly resolve any discrepancies that are identified between the study 
data and the subject's medical records.
The investigator will promptly provide copies of the inspection findings to Pfizer or its agent.  
Before response submission to the regulatory authorities, the investigator will provide Pfizer 
or its agents with an opportunity to review and comment on responses to any such findings.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true. Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry.
In most cases, the source documents are the hospital or the physician subject chart.  In these 
cases, data collected on the CRFs must match the data in those charts.
In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.
11.2. Record Retention
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, CRFs and hospital records), all original signed 

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informed consent/assent documents, copies of all CRFs, safety reporting forms, source 
documents, and detailed records of treatment disposition, and adequate documentation of 
relevant correspondence (eg, letters, meeting minutes, and telephone call reports).  The 
records should be retained by the investigator according to the ICH guidelines, according to 
local regulations, or as specified in the clinical study agreement (CSA), whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or an independent third party arranged by Pfizer.
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board/Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent/assent documents, and other relevant documents, 
eg, recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
Helsinki.
12.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where
required by law.
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 

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numbering system provided by Pfizer in order to de-identify study subjects. The investigator
site will maintain a confidential list of subjects who participated in the study, linking each 
subject’s numerical code to his or her actual identity.  In case of data transfer, Pfizer will 
maintain high standards of confidentiality and protection of subjects’ personal data consistent 
with applicable privacy laws.
The informed consent/assent documents and any subject recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws.
The informed consent/assent documents used during the informed consent process and any 
subject recruitment materials must be reviewed and approved by Pfizer, approved by the 
IRB/EC before use, and available for inspection.
The investigator must ensure that each study subject, or his or her parent(s) or legal guardian 
if a minor, is fully informed about the nature and objectives of the study and possible risks 
associated with participation.
Whenever consent is obtained from a subject’s parent(s) or legal guardian, the subject’s 
assent (affirmative agreement) must subsequently be obtained when the subject has the 
capacity to provide assent, as determined by the IRB/EC.  If the investigator determines that 
a subject’s decisional capacity is so limited he/she cannot reasonably be consulted, then, as 
permitted by the IRB/EC and consistent with local regulatory and legal requirements, the 
subject’s assent may be waived with source documentation of the reason assent was not 
obtained.  If the study subject does not provide his or her own consent, the source documents
must record why the subject did not provide consent (eg, minor, decisionally impaired adult), 
how the investigator determined that the person signing the consent was the subject’s legally 
acceptable representative, the consent signer’s relationship to the study subject (eg, parent, 
spouse), and that the subject’s assent was obtained or waived.  If assent is obtained verbally,
it must be documented in the source documents.
A study-specific assent form will be provided to pediatric subjects as required by local 
regulations.  It is to be understood as the adolescent's will to participate in a trial after having 
received age-appropriate information and is sometimes also referred to as "knowing 
agreement."  If the study includes minor subjects who reach the age of majority during the 
study, as recognized under local law, they must reconsent as adults to remain in the study. If 
the enrollment of emancipated minors is permitted by the study age criteria, the IRB/EC, and 
local law, they must provide documentation of legal status to give consent without the 
permission of a parent or legal guardian.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject or parent(s) or legal guardian and the subject’s assent, when 
applicable, before any study-specific activity is performed, unless a waiver of informed 
consent has been granted by an IRB/EC. The investigator will retain the original of each 
subject's signed consent/assent document.

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12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in a Member State 
End of trial in a Member State of the European Union is defined as the time at which it is 
deemed that a sufficient number of subjects have been recruited and completed the study as 
stated in the regulatory application (ie, clinical trial application [CTA]) and ethics application 
in the Member State.  Poor recruitment (recruiting less than the anticipated number in the 
CTA) by a Member State is not a reason for premature termination but is considered a 
normal conclusion to the study in that Member State.
13.2. End of Trial in All Other Participating Countries
End of trial in all other participating countries is defined as last subject last visit (LSLV).
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of
bivalent rLP2086, MenACWY-TT, and/or MenABCWY at any time.
If a study is prematurely terminated, Pfizer will promptly notify the investigator.  After 
notification, the investigator must contact all participating subjects and the hospital pharmacy 
(if applicable) immediately.  As directed by Pfizer, all study materials must be collected and 
all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.

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www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  US 
Basic Results are submitted for posting within 1 year of the primary completion date (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final subject was examined or received an intervention for 
the purposes of final collection of data for the primary outcome, whether the clinical study 
concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product.  However, 
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed. If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.

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If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI will reference that primary publication. However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at 
all participating sites, the investigator is free to publish separately, subject to the other 
requirements of this section.
For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues.

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30. Bexsero prescribing information. 
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CM431447.pdf. Accessed 14 September 2016.
31. Trumenba prescribing information. 
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CM421139.pdf. Accessed 14 September 2016.
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rLP2086; subfamily A and B; E coli])
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35. Milagres LG, Ramos SR, Sacchi CT, et al. Immune response of Brazilian children to a 
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PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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Appendix 1. Abbreviations
This following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AA
Accelerated Approval
ACIP
Advisory Committee on Immunization Practices
AE
adverse event
AlPO4
aluminum phosphate
ALT
alanine aminotransferase
AST
aspartate aminotransferase
bivalent rLP2086
bivalent recombinant lipoprotein 2086 vaccine (Trumenba)
CDC
Centers for Disease Control and Prevention
CFR
Code of Federal Regulations
CI
confidence interval
CK
creatine kinase
CRF
case report form
CRM
cross-reactive material
CSA
clinical study agreement
CT
clinical trial
CTA
clinical trial application
DILI
drug-induced liver injury
DTaP, dTaP
diphtheria, tetanus, and acellular pertussis vaccine
DU
dispensable unit
EC
ethics committee
e-diary
electronic diary
EDMC
external data monitoring committee 
EDP
exposure during pregnancy
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration (United States)
fHBP
factor H binding protein
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMT
geometric mean titer
GSK
GlaxoSmithKline
HBV
hepatitis B virus
Hib
Haemophilus influenzae type b 
HPV4
quadrivalent human papillomavirus vaccine
hSBA
serum bactericidal assay using human complement
hSBA-MenA
serum bactericidal assay using human complement to measure activity against 
Neisseria meningitidis group A 

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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Abbreviation
Term
hSBA-MenA/C/W/Y
serum bactericidal assay using human complement to measure activity against 
Neisseria meningitidis group A, group C, group W, and/or group Y
hSBA-MenC
serum bactericidal assay using human complement to measure activity against 
Neisseria meningitidis group C 
hSBA-MenW
serum bactericidal assay using human complement to measure activity against 
Neisseria meningitidis group W 
hSBA-MenY
serum bactericidal assay using human complement to measure activity against 
Neisseria meningitidis group Y 
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IMD
invasive meningococcal disease
IND
investigational new drug application
INR
international normalized ratio
IP
investigational product
IPV
inactivated poliomyelitis virus
IRB
institutional review board
IRC
independent review committee 
IRT
interactive response technology
ISC
independent statistical center
ITT
intent-to-treat
IUD
intrauterine device
IVRS
interactive voice response system
IWRS
interactive Web-based response system
LCI
lower limit of the confidence interval
LFT
liver function test
LLOQ
lower limit of quantitation
LOD
limit of detection
LP2086
lipoprotein 2086
LSLV
last subject last visit 
MCV4
quadrivalent meningococcal polysaccharide conjugate 
MedDRA
Medical Dictionary for Regulatory Activities
MenA
Neisseria meningitidis group A 
MenABCWY
Neisseria meningitidis group A, B, C, W, and Y vaccine
MenACWY
meningococcal groups A, C, W, and Y conjugate vaccine
MenA/C/W/Y
Neisseria meningitidis group A, group C, group W, and/or group Y
MenACWY-CRM
meningococcal group A, C, W-135, and Y conjugate vaccine (Menveo)
MenACWY-TT
meningococcal polysaccharide groups A, C, W-135, and Y tetanus toxoid conjugate 
vaccine (Nimenrix)
MenB
Neisseria meningitidis group B 
MenC
Neisseria meningitidis group C 

PF-05212366 (Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine [Bivalent 
rLP2086; subfamily A and B; E coli])
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Abbreviation
Term
MenCYW-135
meningococcal group C, Y, and W-135
MenW
Neisseria meningitidis group W 
MenY
Neisseria meningitidis group Y 
mITT
modified intent-to-treat
MnB
Neisseria meningitidis group B
N/A
not applicable
OMV
outer membrane vesicle
PAR
postapproval requirement
PCD
primary completion date
PI
principal investigator
PRP-OMP
polyribosylribitol phosphate oligosaccharide of Haemophilus influenzae type b 
conjugated to outer membrane protein
PT
prothrombin time
rLP2086
recombinant lipoprotein 2086
RRI
research-related injury
rSBA
serum bactericidal assay using rabbit complement
rSBA-MenA
serum bactericidal assay using rabbit complement to measure activity against 
Neisseria meningitidis group A
rSBA-MenC
serum bactericidal assay using rabbit complement to measure activity against 
Neisseria meningitidis group C
rSBA-MenW
serum bactericidal assay using rabbit complement to measure activity against 
Neisseria meningitidis group W
rSBA-MenY
serum bactericidal assay using rabbit complement to measure activity against 
Neisseria meningitidis group Y
SAE
serious adverse event
SAP
statistical analysis plan
SBA
serum bactericidal assay
SRM
study reference manual
SRSD
single reference safety document
TBili
total bilirubin
Tdap
tetanus, low-dose diphtheria, and low-dose acellular pertussis
ULN
upper limit of normal
US
United States

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