A PHASE 3 STUDY TO ASSESS THE PERSISTENCE OF HSBA RESPONSE UP TO 48 MONTHS AFTER COMPLETION OF A PRIMARY SERIES OF BIVALENT RLP2086, AND THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A BOOSTER DOSE OF BIVALENT RLP2086
Phase: PHASE3
Conditions: Meningococcal Infection
Sponsor: Pfizer

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 1
A PHASE 3 STUDY TO ASSESS THE PERSISTENCE OF hSBA RESPONSE UP TO 
48 MONTHS AFTER COMPLETION OF A PRIMARY SERIES OF BIVALENT 
rLP2086, AND THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 
BOOSTER DOSE OF BIVALENT rLP2086
Compound:
PF-05212366
Compound Name:
Neisseria meningitidis Serogroup B Bivalent 
Recombinant Lipoprotein 2086 Vaccine
(Bivalent rLP2086; subfamily A and B; 
E coli)
United States (US) Investigational New 
Drug (IND) Number:
13812
European Clinical Trials Database 
(EudraCT) Number: 
2011-005697-31
Universal Trial Number:
Not Applicable
Protocol Number:
B1971033
Phase:
3

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 5
Document
Version Date
Summary of Changes and Rationale

Added Section 7.1.2 on the Luminex assay 
for antigen detection for MCV4.

Added a confirmation that subjects’ consent 
should be obtained after they are no longer 
minors.
Protocol Amendment 1
21 Mar 2012
The purpose of this amendment is to add the 
benefit-risk assessment in the protocol.
Wording on biological samples has also been 
added.
Original protocol
14 Dec 2011
N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities, institutional review boards/ethics committees 
(IRBs/ECs), etc.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 6
ABBREVIATIONS
This is a list of abbreviations that may or may not be used in the protocol.
ACIP
Advisory Committee on Immunization Practices
AE
adverse event 
Al3+
aluminum
ALPO4
aluminum phosphate
ALT
alanine aminotransferase
AST
aspartate aminotransferase
bivalent rLP2086
bivalent recombinant lipoprotein 2086 vaccine
CDC
Centers for Disease Control and Prevention (United States)
CI
confidence interval 
CIOMS
Council for International Organizations of Medical Sciences
CRF
case report form
CSA
clinical study agreement
CTA
clinical trial application
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)
FDAAA
Food and Drug Administration Amendments Act of 2007
fHBP
factor H binding protein
GCP
Good Clinical Practice 
GMC
geometric mean concentration
GMT
geometric mean titer
HAV
hepatitis A virus
HPV
human papillomavirus
hSBA
serum bactericidal assay using human complement 
IB
investigator’s brochure
ICD
informed consent document 
ICH
International Council for Harmonisation 
IgG
immunoglobulin G
IMD
invasive meningococcal disease 
INR
international normalized ratio

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 7
IRB
institutional review board 
ISC
independent statistical center
IUD
intrauterine device
IVRS
interactive voice response system
IWRS
interactive Web-based response system
LFT
liver function test
LLOQ
lower limit of quantitation 
LP2086
lipoprotein 2086
LSLV
last subject last visit
MCV4
quadrivalent meningococcal polysaccharide conjugate
MedDRA
Medical Dictionary for Regulatory Activities 
mITT
modified intent-to-treat 
MnB
Neisseria meningitidis serogroup B 
N/A
not applicable
NDCMC
newly diagnosed chronic medical condition
OMV
outer membrane vesicle 
PCD
primary completion date
PS80
polysorbate 80
PT
prothrombin time
RCDC
reverse cumulative distribution curve
rLP2086
recombinant lipoprotein 2086 
RRI
research-related injury
SAE
serious adverse event 
SAP
statistical analysis plan 
SRM
study reference manual 
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
Tdap
tetanus, diphtheria, and acellular pertussis
ULN
upper limit of normal
US
United States

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 8
PROTOCOL SUMMARY
Background and Rationale
Neisseria meningitidis is a leading cause of bacterial meningitis in infants, adolescents, and 
young adults. In particular, N meningitidis serogroup B (MnB) is responsible for 
approximately two-thirds of the cases of observed meningococcal infections in Europe, with 
a case-fatality rate of 6% to 8% from 1999 to 2006. MnB disease accounts for approximately 
one-third of meningococcal cases seen in North America.
A recombinant, multicomponent MnB vaccine (Bexsero) is licensed in the European Union 
(EU), Canada, Australia, and Chile; and recommendations for use are under consideration in 
various countries. Trumenba® (bivalent recombinant lipoprotein 2086 vaccine), developed 
by Pfizer, has recently (October 2014) been approved in the United States for active 
immunization to prevent invasive disease caused by N meningitidis serogroup B, for use in 
individuals 10 through 25 years of age. The US Centers for Disease Control and 
Prevention’s Advisory Committee on Immunization Practices (ACIP) has assigned a 
Category B recommendation for administration of MnB vaccines for adolescents and young 
adults aged 16 to 23 years, with particular focus on the 16- to 18-year age group. A 
Category A recommendation was assigned for MnB vaccination of certain groups of persons 
at increased risk for serogroup B meningococcal disease, including for persons aged 
10 years during outbreaks of serogroup B meningococcal disease. Broad implementation of 
a safe and immunogenic vaccine against diverse MnB strains is anticipated to provide 
substantial improvement in prevention of this uncommon but severe bacterial infection and a 
reduction in the burden of disease.
Trumenba is targeted to a conserved, surface-exposed lipoprotein, lipoprotein 2086 
(LP2086), a meningococcal virulence factor that binds human factor H, and therefore is 
designated as factor H binding protein (fHBP). The LP2086 gene is present in 100% of MnB 
strains in Pfizer’s strain collection of more than 1800 strains isolated from patients with 
invasive disease in the United States and Europe. The lipoproteins segregate into 
2 antigenically and immunologically distinct subfamilies, A and B. Trumenba is a sterile 
suspension composed of 2 recombinant lipidated fHBP variants from MnB, 1 from fHBP 
subfamily A and 1 from subfamily B (A05 and B01, respectively).
This study was initiated in September 2012 to assess the longevity of immune responses in 
adolescents (aged 10 to <19 years at the time of entry into a primary study) following 
receipt of a vaccination regimen of 2 or 3 doses of bivalent rLP2086 in a primary study 
(a previously conducted Pfizer study using the final formulation of bivalent rLP2086). This 
study was amended in January 2015 to add a booster dose of bivalent rLP2086 at 
approximately 4 years following the final dose of the 2- or 3-dose primary bivalent rLP2086
vaccination series. The study was therefore divided into Stage 1 (4-year persistence of 
immune responses following receipt of a primary vaccination series) and the booster stage 
(follow-up through 12 months after booster vaccination). 

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 9
The study is now amended to further evaluate safety and immune responses up to 26 months 
following a single booster dose of bivalent rLP2086. The postbooster follow-up through 
26 months after booster vaccination is being conducted for a subset of booster stage subjects 
who previously received bivalent rLP2086 in a primary series of either a 0-, 2-, and 6-month 
or a 0- and 6-month schedule. The rationale for focusing on this subset of subjects is based 
on the fact that the 0-, 2-, and 6-month and the 0- and 6-month schedules are the dosing 
schedules approved by the Food and Drug Administration (FDA).
Objectives:
Primary Objectives
Stage 1

To describe the immunogenicity of bivalent rLP2086 as determined by serum 
bactericidal assay using human complement (hSBA) titers to 4 primary test strains at
approximately 6, 12, 18, 24, 36, and 48 months after the last dose (second or third 
dose) of bivalent rLP2086 or saline in the primary study (ie, a previously conducted 
Pfizer study using the final formulation and dose of bivalent rLP2086).
Booster Stage

To describe the immune response as measured by hSBA titers to 4 primary test strains 
1 month following the last vaccination with bivalent rLP2086 in the primary study, 
before the booster vaccination, and 1 month, 12 months, and 26 months after a single 
booster dose of bivalent rLP2086.
Primary Safety Objective (Booster Stage)

To evaluate the safety profile of bivalent rLP2086 as measured by the incidence of local 
reactions, systemic events, adverse events (AEs), serious adverse events (SAEs), newly 
diagnosed chronic medical conditions (NDCMCs), medically attended events, and 
immediate AEs following a booster vaccination of bivalent rLP2086.
Primary Endpoints
Stage 1

Proportion of subjects with hSBA titers ≥ lower limit of quantitation (LLOQ) for each 
of the 4 primary strains at each blood draw visit in Stage 1 (Visits 1-6). 
Booster Stage

Proportions of subjects with hSBA titers ≥ LLOQ for each of the 4 primary strains at 
1 month following the last vaccination received in the primary study, before the 
booster vaccination (Visit 6), and 1 month, 12 months, and 26 months (Visits 8, 10,
and 11) following booster vaccination. 

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 10
Primary Safety Endpoints (Booster Stage)

Percentages of subjects reporting local reactions via the electronic diary (e-diary) by type 
(pain at the injection site, redness, and swelling) and by severity after a booster 
vaccination of bivalent rLP2086. 

Percentages of subjects reporting systemic events via the e-diary by type (fever, 
vomiting, diarrhea, headache, fatigue, chills, muscle pain other than muscle pain at the 
injection site, and joint pain) and by severity after a booster vaccination of bivalent 
rLP2086. 

Percentage of subjects reporting the use of antipyretic medication via the e-diary after a 
booster vaccination of bivalent rLP2086.

Percentages of subjects with at least 1 AE occurring during the following time periods:

From Visit 7 to Visit 8

Percentages of subjects with at least 1 SAE during the following periods: 

From Visit 7 to Visit 8

From Visit 8 to Visit 9

From Visit 7 to Visit 9

Percentages of subjects with at least 1 NDCMC occurring during the following time 
periods:

From the 6-month safety telephone call in the primary study to Visit 6 (Stage 1)

From Visit 7 to Visit 8

From Visit 8 to Visit 10

From Visit 7 to Visit 10

From Visit 8 to Visit 11 (only subjects proceeding to Visit 11)

From Visit 7 to Visit 11 (only subjects proceeding to Visit 11)

Percentages of subjects with at least 1 medically attended event occurring during the 
following time periods:

From Visit 7 to Visit 8

From Visit 8 to Visit 9

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 11

From Visit 7 to Visit 9

Percentage of subjects reporting at least 1 immediate AE after receiving the booster dose 
of bivalent rLP2086.

Number of days subjects miss school or work because of AEs from Visit 7 through 
Visit 9.
Design
Stage 1 of the study (Visits 1-6) is designed to provide follow-up information on Pfizer 
Studies B1971010, B1971012, and B1971015, which used the final formulation and dose of 
bivalent rLP2086 (primary studies). In Stage 1, subjects will attend up to 6 study visits for 
collection of a 20-mL blood sample at each visit.
The booster stage of the study (Visits 7-11) is optional for eligible subjects at selected sites. 
Subjects who wish to participate in the booster stage must have completed Stage 1 and 
received all scheduled doses of bivalent rLP2086 in the primary study. 
Subjects will be required to sign a consent form to enter and participate in the booster stage
for Visits 7 to 10. Eligible subjects at selected sites will be asked to sign another consent 
form prior to participating in Visit 11, for a blood draw at 26 months after the booster 
vaccination. 
For consenting booster stage subjects, a booster dose of 120 µg of bivalent rLP2086 will be 
administered at Visit 7 and blood samples (20 mL per visit) will be collected for 
immunogenicity analysis 1 month, 12 months, and 26 months after the booster vaccination 
(Visits 8, 10, and 11).
Design Overview:
STAGE 1
BOOSTER STAGE
Visit 
purpose
Blood 
draw
Blood 
draw
Blood 
draw
Blood 
draw
Blood 
draw
Blood 
draw
Booster 
vaccinatio
n
Blood 
draw
6-Month 
telephone 
call
Blood 
draw
Blood 
draw
Visit 
number
1
2
3
4
5
6
7
8
9
10
11
Approximate 
month
6
12
18
24
36
48
48
1 Month 
after 
booster
6 Months 
after 
booster
12 
Months 
after 
booster
26
Months 
after 
booster
Vaccination
Bivalent 
rLP2086
Blood draw
20 mL 20 mL 20 mL
20 mL
20 mL
20 mL
20 mL
20 mL
20 mL

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 13
SCHEDULE OF ACTIVITIES
The schedule of activities (Table 1 to Table 3) 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, in order to conduct evaluations or assessments required to protect the 
well-being of the subject.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 14
Table 1.
Schedule of Activities – Stage 1
Visit Identifier
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit Window
6 Months
(150-240 Days) After 
Last Dose of Bivalent 
rLP2086, or After Last 
Injection of 
Investigational 
Product in Primary 
Studya
12 Months
(330-390 Days) After 
Last Dose of Bivalent 
rLP2086, or After Last 
Injection of 
Investigational 
Product in Primary 
Studya
18 Months
(510-570 Days) After 
Last Dose of Bivalent 
rLP2086, or After Last 
Injection of 
Investigational 
Product in Primary 
Studya
24 Months
(676-764 Days) After 
Last Dose of Bivalent
rLP2086, or After Last 
Injection of 
Investigational 
Product in Primary 
Studya
36 Months
(1036-1124 Days) After 
Last Dose of Bivalent 
rLP2086, or After Last 
Injection of 
Investigational 
Product in Primary 
Studya
48 Months
(1396-1484 Days) After 
Last Dose of Bivalent 
rLP2086, or After Last 
Injection of 
Investigational Product 
in Primary Studya
Informed consent
X
Xb
Confirm continued 
eligibility
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
Record any nonstudy 
vaccination
X
X
X
X
X
X
Blood samples for 
hSBAd
X
X
X
X
X
X
NDCMCs 
X
X
X
X
X
X
AEs and RRIs
48 Hours after visit
48 Hours after visit
48 Hours after visit
48 Hours after visit
48 Hours after visit
48 Hours after visit
a.
If the subject’s primary study vaccine assignment is known at the time of consent for Study B1971033, the visits in Study B1971033 should be scheduled 
relative to the last dose of bivalent rLP2086 in the primary study. If the subject’s primary study vaccine assignment is blinded at the time of consent for 
Study B1971033, the visits in Study B1971033 should be scheduled relative to the last injection of investigational product in the primary study.
b.
Consent may be obtained at Visit 2 if subjects are enrolled at Visit 2.
c.
Vital signs will include blood pressure, pulse rate, and temperature (oral). 
d.
Amount of blood collected is approximately 20 mL.
Abbreviations: AE = adverse event; hSBA = serum bactericidal assay using human complement; NDCMC = newly diagnosed chronic medical condition; 
RRI = research-related injury. 

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 15
Table 2.
Schedule of Activities – Booster Stage
Visit Identifier
Visit 7
Booster Vaccination 
Visit 8
Postvaccination 
Blood Draw 1
Visit 9
6-Month Telephone 
Contact
Visit 10
Postvaccination Blood 
Draw 2 
Visit 11
Postvaccination 
Blood Draw 3
Visit Window
48 Months
After Last Dose of 
Bivalent rLP2086 in 
Primary Studya
(1396-1484 Days After 
Last Dose of Bivalent 
rLP2086, and Within 42 
Days After Visit 6)
1 Month After Booster
(28-42 Days After Visit 
7)
6 Months After Booster
(168 to 196 Days After 
Visit 7)
12 Months After 
Booster
(330-390 Days After 
Visit 7)
26 Months After 
Booster
(750-810 Days After 
Visit 7)
Informed consentb
X
X
Review eligibility criteriac
X
X
Confirm continued eligibilityc
X
X
X
Vital signsd
Xe
X
X
X
Medical history
X
Physical examination
X
Urine pregnancy test (all female 
subjects)
X
Record any nonstudy vaccination and 
allergen immunotherapyf
Xe
X
X
X
X
Blood sampleg
X
X
X
IVRS/kit assignment
X
Investigational product administration 
and observation
X
Provide subject or parent/legal 
guardian with e-diary, caliper, 
measuring tape/ruler, and thermometer
X
Record concomitant medications used 
to treat AEs
X
X
X
X
X
Review e-diary
X

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 16
Table 2.
Schedule of Activities – Booster Stage
Visit Identifier
Visit 7
Booster Vaccination 
Visit 8
Postvaccination 
Blood Draw 1
Visit 9
6-Month Telephone 
Contact
Visit 10
Postvaccination Blood 
Draw 2 
Visit 11
Postvaccination 
Blood Draw 3
Visit Window
48 Months
After Last Dose of 
Bivalent rLP2086 in 
Primary Studya
(1396-1484 Days After 
Last Dose of Bivalent 
rLP2086, and Within 42 
Days After Visit 6)
1 Month After Booster
(28-42 Days After Visit 
7)
6 Months After Booster
(168 to 196 Days After 
Visit 7)
12 Months After 
Booster
(330-390 Days After 
Visit 7)
26 Months After 
Booster
(750-810 Days After 
Visit 7)
Collect e-diary
X
Record use of antipyretic medication in 
the e-diary
Day 1 to 7
Assess reactogenicity
Day 1 to 7
Provide the subject with a memory aid
X
Complete study visit/AE checklist
X
X
X
X
X
(S)AE collection appropriate for the 
visith
X
X
X
X
X
a.
Visit 7 may occur a maximum of 42 days after Visit 6.
b.
If a subject reaches the age at which he or she is able to provide legal consent during the study, the subject’s consent must be obtained.
c.
Subjects must satisfy all eligibility criteria for Stage 1 and the booster stage. In addition, subjects participating in Visit 11 must meet eligibility criteria for 
Visit 11.
d.
Vital signs will include blood pressure, pulse rate, and temperature (oral). 
e.
If Visits 6 and 7 do not occur on the same day, ensure that vital sign measurements and recording of nonstudy vaccinations are performed again at Visit 7.
f.
Nonstudy vaccination occurring from the final blood draw in the primary study until Visit 11. From Visit 7, this also includes allergen immunotherapy.
g.
Amount of blood collected is approximately 20 mL.
h.
Subject or subject’s parent(s)/legal guardian to report any AEs within 48 hours following Visit 10 and Visit 11.
Abbreviations: AE = adverse event; e-diary = electronic diary; IVRS = interactive voice response system; RRI = research-related injury; SAE = serious adverse 
event.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 18 April 2017
Page 17
Table 3.
Adverse Event Reporting Schedule
Stage 1
Booster Stage
AE Type
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
SAEa
Nonactive reporting of SAEs to the primary study
From booster stage ICD to Visit 9
Nonactive reporting of SAEs to 
the B1971033 study
NDCMCb
From 6-month telephone call in the primary study to Visit 11
MAE
From booster stage ICD to Visit 9
RRIc
48 Hours 
after 
blood 
draw
48 Hours 
after 
blood 
draw
48 
Hours 
after 
blood 
draw
48 
Hours 
after 
blood 
draw
48 
Hours 
after 
blood 
draw
48 
Hours 
after 
blood 
draw
48 Hours after 
blood draw
48 Hours after 
blood draw
AEd
48 Hours 
after 
blood 
draw
48 Hours 
after 
blood 
draw
48 
Hours 
after 
blood 
draw
48 
Hours 
after 
blood 
draw
48 
Hours 
after 
blood 
draw
48 
Hours 
after 
blood 
draw
All AEs from 
booster stage ICD 
to Visit 8
48 Hours 
after blood 
draw
48 Hours after 
blood draw
48 Hours after 
blood draw
Reactogenicity 
events
1-7 Days
a.
Events with an onset during Stage 1 will be reported under the primary study number. Events with an onset during the booster stage will be reported under 
Study B19710133. 
b.
Events with an onset after the 6-month follow-up telephone call in the primary study.
c.
Events reportable only within the first 48 hours following a blood draw.
d.
Events with an onset in Stage 1, or from Visit 8 to Visit 11, are reportable only within the first 48 hours following a blood draw. From Visit 7 to Visit 8, all 
AEs are reportable.
Abbreviations: AE = adverse event; ICD = informed consent document; MAE = medically attended event; NDCMC = newly diagnosed chronic medical 
condition; RRI = research-related injury; SAE = serious adverse event.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 18
TABLE OF CONTENTS
ABBREVIATIONS ...................................................................................................................6
LIST OF TABLES...................................................................................................................23
1. INTRODUCTION ...............................................................................................................24
1.1. Mechanism of Action/Indication.............................................................................24
1.2. Background and Rationale ......................................................................................24
1.2.1. Neisseria meningitidis Disease Background ..............................................24
1.2.2. Bivalent Recombinant Lipoprotein 2086 Vaccine .....................................25
1.2.3. Functional Antibody Assay as a Surrogate of Efficacy..............................25
1.2.4. Clinical Experience.....................................................................................26
1.2.5. Study Rationale...........................................................................................29
1.2.6. Risk and Benefits........................................................................................30
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................30
2.1. Objectives................................................................................................................30
2.1.1. Primary Objectives .....................................................................................30
2.1.2. Primary Safety Objective (Booster Stage)..................................................30
2.2. Endpoints.................................................................................................................31
2.2.1. Primary Endpoints ......................................................................................31
2.2.2. Primary Safety Endpoints (Booster Stage).................................................32
3. STUDY DESIGN.................................................................................................................34
3.1. Description ..............................................................................................................34
3.2. Approximate Duration of Subject Participation......................................................35
3.3. Approximate Duration of the Study........................................................................35
3.4. Approximate Number of Subjects...........................................................................35
4. SUBJECT SELECTION......................................................................................................35
4.1. Inclusion Criteria.....................................................................................................36
4.1.1. Stage 1 ........................................................................................................36
4.1.2. Booster Stage..............................................................................................36
4.1.2.1. Booster Stage Visits 7 to 10 ......................................................36
CCI
CCI

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 19
4.1.2.2. Booster Stage Visit 11...............................................................37
4.2. Exclusion Criteria....................................................................................................37
4.2.1. Stage 1 ........................................................................................................37
4.2.2. Booster Stage..............................................................................................38
4.3. Criteria for Temporarily Delaying Vaccine Administration during the 
Booster Stage.............................................................................................................39
4.4. Criteria for Temporarily Delaying Blood Collection..............................................39
4.5. Lifestyle Guidelines ................................................................................................40
4.6. Sponsor’s Qualified Medical Personnel..................................................................40
5. INVESTIGATIONAL PRODUCT......................................................................................41
5.1. Allocation to Investigational Product......................................................................41
5.2. Compliance..............................................................................................................42
5.3. Investigational Product Supplies.............................................................................42
5.3.1. Dosage Form and Packaging ......................................................................42
5.3.2. Preparation and Dispensing........................................................................42
5.4. Administration.........................................................................................................43
5.5. Investigational Product Storage ..............................................................................43
5.6. Investigational Product Accountability...................................................................44
5.7. Concomitant Treatment(s).......................................................................................44
5.8. Prohibited During the Study....................................................................................44
5.9. Permitted During the Study.....................................................................................45
5.10. Prior Treatment .....................................................................................................45
5.10.1. Prohibited Prior Treatments......................................................................45
6. STUDY PROCEDURES .....................................................................................................46
6.1. Informed Consent Process.......................................................................................46
6.2. Stage 1.....................................................................................................................46
6.2.1. Study Visit 1 – Serology Follow-up (6 Months [150-240 Days] After 
the Last Dose of Bivalent rLP2086 in the Primary Study, or After the 
Last Injection of Investigational Product in the Primary Study if 
Vaccine Assignment Is Blinded) .....................................................................46
6.2.2. Study Visit 2 – Serology Follow-up (12 Months [330-390 Days] 
After the Last Dose of Bivalent rLP2086 in the Primary Study, or After 
the Last Injection of Investigational Product in the Primary Study if 
Vaccine Assignment Is Blinded) .....................................................................47

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 20
6.2.3. Study Visit 3 – Serology Follow-up (18 Months [510-570 Days] 
After the Last Dose of Bivalent rLP2086 in the Primary Study, or After 
the Last Injection of Investigational Product in the Primary Study if 
Vaccine Assignment Is Blinded) .....................................................................47
6.2.4. Study Visit 4 – Serology Follow-up (24 Months [676-764 Days] 
After the Last Dose of Bivalent rLP2086 in the Primary Study, or After 
the Last Injection of Investigational Product in the Primary Study if 
Vaccine Assignment Is Blinded) .....................................................................48
6.2.5. Study Visit 5 – Serology Follow-up (36 Months [1036-1124 Days] 
After the Last Dose of Bivalent rLP2086 in the Primary Study, or After 
the Last Injection of Investigational Product in the Primary Study if 
Vaccine Assignment Is Blinded) .....................................................................48
6.2.6. Study Visit 6 – Serology Follow-up (48 Months [1396-1484 Days] 
After the Last Dose of Bivalent rLP2086 in the Primary Study, or After 
the Last Injection of Investigational Product in the Primary Study if 
Vaccine Assignment Is Blinded) .....................................................................49
6.3. Booster Stage...........................................................................................................50
6.3.1. Visit 7, Booster Vaccination of Bivalent rLP2086 (48 Months [1396-
1484 Days] After the Last Dose of Bivalent rLP2086 in the Primary 
Study, and within 42 Days After Visit 6) ........................................................50
6.3.2. Visit 8 (28 to 42 Days after Visit 7), Postvaccination Blood Draw 1 ........52
6.3.3. Visit 9 (168 to 196 Days after Visit 7), Safety Telephone Contact............53
6.3.4. Visit 10 (12 Months [330-390 Days] after Visit 7), Postvaccination 
Blood Draw 2...................................................................................................54
6.3.5. Visit 11 (26 Months [750-810 Days] after Visit 7), Postvaccination 
Blood Draw 3...................................................................................................55
6.4. Unscheduled Visits..................................................................................................56
6.5. Subject Withdrawal.................................................................................................56
7. ASSESSMENTS..................................................................................................................57
7.1. Immunogenicity ......................................................................................................58
7.1.1. Bivalent rLP2086 Serum Bactericidal Assay - Primary Test Strains.........58
7.1.2. Bivalent rLP2086 Serum Bactericidal Assay - Secondary Test 
Strains ..............................................................................................................58
7.2. Safety.......................................................................................................................59
7.3. Pregnancy Testing...................................................................................................60
7.4. Electronic Diary ......................................................................................................61
7.5. Local Reactions.......................................................................................................61

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 21
7.5.1. Injection Site Redness and Swelling...........................................................61
7.5.2. Injection Site Pain.......................................................................................62
7.6. Systemic Events ......................................................................................................62
7.6.1. Temperature................................................................................................62
7.6.2. Use of Antipyretic Medication ...................................................................63
7.6.3. Other Systemic Events................................................................................63
7.7. Risks and Benefits...................................................................................................63
8. ADVERSE EVENT REPORTING......................................................................................64
8.1. Adverse Events........................................................................................................64
8.2. Reporting Period .....................................................................................................64
8.2.1. Stage 1 ........................................................................................................65
8.2.2. Booster Stage..............................................................................................65
8.3. Definition of an Adverse Event...............................................................................65
8.4. Medication Errors....................................................................................................66
8.5. Abnormal Test Findings..........................................................................................67
8.6. Research-Related Injury..........................................................................................67
8.7. Serious Adverse Events...........................................................................................68
8.7.1. Protocol-Specified Serious Adverse Events...............................................69
8.7.2. Potential Cases of Drug-Induced Liver Injury............................................69
8.8. Hospitalization ........................................................................................................70
8.9. Severity Assessment................................................................................................71
8.10. Causality Assessment............................................................................................72
8.11. Exposure during Pregnancy ..................................................................................72
8.12. Occupational Exposure .........................................................................................73
8.13. Withdrawal Due to Adverse Events (See also the Section on Subject 
Withdrawal)...............................................................................................................74
8.14. Eliciting Adverse Event Information ....................................................................74
8.15. Reporting Requirements........................................................................................74
8.15.1. Serious Adverse Event Reporting Requirements .....................................74
8.15.2. Nonserious Adverse Event Reporting Requirements ...............................75
8.15.3. Medical Device Complaint Reporting Requirements...............................75
8.15.4. Sponsor’s Reporting Requirements to Regulatory Authorities ................75

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 22
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................76
9.1. Sample Size Determination.....................................................................................76
9.2. Immunogenicity Analysis .......................................................................................76
9.2.1. Analysis of Primary Endpoint ....................................................................76
9.3. Immunogenicity Analysis Populations....................................................................77
9.4. Analysis of Other Endpoints ...................................................................................77
9.5. Safety Analysis........................................................................................................78
9.6. Analysis Timing ......................................................................................................78
9.7. Data Monitoring Committee ...................................................................................79
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................79
11. BIOLOGICAL SAMPLES................................................................................................79
12. DATA HANDLING AND RECORD KEEPING .............................................................80
12.1. Case Report Forms/Electronic Data Record .........................................................80
12.2. Record Retention...................................................................................................80
13. ETHICS..............................................................................................................................81
13.1. Institutional Review Board (IRB)/Ethics Committee (EC)...................................81
13.2. Ethical Conduct of the Study ................................................................................81
13.3. Subject Information and Consent..........................................................................81
13.4. Subject Recruitment ..............................................................................................82
13.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................82
14. DEFINITION OF END OF TRIAL...................................................................................83
14.1. End of Trial in a Member State.............................................................................83
14.2. End of Trial in All Other Participating Countries.................................................83
15. SPONSOR DISCONTINUATION CRITERIA ................................................................83
16. PUBLICATION OF STUDY RESULTS..........................................................................83
16.1. Communication of Results by Pfizer ....................................................................83
16.2. Publications by Investigators ................................................................................84
17. REFERENCES ..................................................................................................................86
CCI

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 23
LIST OF TABLES
Table 1.
Schedule of Activities – Stage 1...........................................................................14
Table 2.
Schedule of Activities – Booster Stage ................................................................15
Table 3.
Adverse Event Reporting Schedule......................................................................17
Table 4.
Study Status as of April 2017...............................................................................27
Table 5.
Study Design Overview........................................................................................35
Table 6.
Grading of Redness and Swelling.........................................................................62
Table 7.
Grading of Pain.....................................................................................................62
Table 8.
Temperature Categories........................................................................................62
Table 9.
Grading of Other Systemic Events .......................................................................63
Table 10.
Severity Assessment Grade ..................................................................................71

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 24
1. INTRODUCTION
1.1. Mechanism of Action/Indication
The development program for the Pfizer investigational Neisseria meningitidis serogroup B 
(MnB) bivalent recombinant lipoprotein 2086 vaccine (bivalent rLP2086; subfamily A and 
B; Escherichia coli) is in support of licensure with an indication for active immunization to 
prevent invasive meningococcal disease (IMD) caused by MnB expressing either subfamily 
A or subfamily B factor H binding protein (fHBP) in adolescents and young adults, aged 10 
through 25 years.
1.2. Background and Rationale
1.2.1. Neisseria meningitidis Disease Background
N meningitidis is a leading cause of bacterial meningitis in infants, adolescents, and young 
adults. In particular, MnB is responsible for approximately two-thirds of the cases of 
observed meningococcal infections in Europe, with a case-fatality rate of 6% to 8% from 
1999 to 2006.1  MnB disease accounts for approximately one-third of meningococcal cases 
seen in North America.2   There is substantial morbidity among survivors, including 
neurological disability, limb loss, and hearing loss.1
The incidence rate of IMD varies with age, with a peak in infants and a peak in adolescents 
and young adults.3 The increased risk of disease in adolescents and young adults is believed 
to be due to a number of factors, including social behavior and crowding of susceptible 
individuals in classrooms and dormitories.4,5 Carriage rates are high in adolescents, and this 
age group may serve as a reservoir for transmission to younger age groups.6
After licensure of the first quadrivalent meningococcal conjugate vaccine (MCV4, 
MenACWY vaccine) in the United States in 2005, the Centers for Disease Control and 
Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) prioritized 
vaccination for persons aged 11 or 12 years, persons entering high school, and first-year 
college students living in residence halls. This recommendation was expanded in 2007 to 
include routine vaccination with MCV4 for all adolescents in the United States. In 2010, 
following recognition of waning immunity after a single dose of MCV4, the ACIP revised 
their recommendation to provide for routine vaccination of adolescents, preferably at age 11 
or 12 years, with a booster dose at age 16 years.7
In the United States in 2011, the incidence of meningococcal disease was 0.06 and 0.15 per 
100,000 population for 11- to 17-year-olds and 18- to 22-year-olds, respectively, higher than 
that seen for the general population.8 Incidence rates of MnB disease during recent outbreaks 
at college campuses in the United States have, however, been as high as 134 per 100,000 
among undergraduates at Princeton University during a 2013/2014 outbreak and 21.1 per 
100,000 among 17- to 22-year-olds at the University of California Santa Barbara during a 
2013 outbreak.9,10

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 25
Vaccine candidates aimed at producing antibodies to the capsular polysaccharide of 
serogroup B N meningitidis are unlikely to be useful, because they are poorly immunogenic 
given the chemical similarity between the serogroup B capsular polysaccharide and 
molecules found on human neuronal cells.11 Vaccines produced from outer membrane 
vesicles (OMVs) prepared from MnB strains have been shown to have clinical efficacy 
against homologous strains but not against heterologous strains.12,13 A recombinant, 
multicomponent MnB vaccine (Bexsero) is licensed in the European Union (EU), Canada, 
Australia, and Chile, and recommendations for use are still under consideration in various 
countries.  Trumenba® (bivalent rLP2086), developed by Pfizer, has recently (October 2014) 
been approved in the United States for use in individuals 10 through 25 years of age for 
active immunization to prevent IMD caused by MnB. The US Centers for Disease Control 
and Prevention’s Advisory Committee on Immunization Practices (ACIP) has assigned a 
Category B recommendation for administration of MnB vaccines for adolescents and young 
adults aged 16 to 23 years, with particular focus on the 16- to 18-year age group. A 
Category A recommendation was assigned for MnB vaccination of certain groups of persons 
at increased risk for serogroup B meningococcal disease, including for persons aged 10 
years during outbreaks of serogroup B meningococcal disease.14 Broad implementation of a 
safe and immunogenic vaccine against diverse MnB strains is expected to provide substantial 
improvement in prevention of this uncommon but severe bacterial infection and a reduction 
in the burden of disease.
1.2.2. Bivalent Recombinant Lipoprotein 2086 Vaccine
Trumenba is a subcapsular protein vaccine based on major surface components that are 
antigenically invariant and expressed in most disease-associated meningococci.15 Trumenba 
utilizes a conserved, surface-exposed lipoprotein, lipoprotein 2086 (LP2086), as a vaccine 
target.16 In the meningococcus, LP2086 is a virulence factor that binds human factor H. The 
LP2086 gene is present in 100% of MnB strains in Pfizer’s strain collection of more than 
1800 strains isolated from patients with invasive disease in the United States and Europe. 
The lipoproteins segregate into 2 antigenically and immunologically distinct subfamilies, A 
and B. Subfamily B proteins are expressed in approximately 70% of isolates, and 
subfamily A proteins are expressed in approximately 30% of isolates. rLP2086 has been 
expressed in E coli and formulated in a bivalent vaccine composed of 1 subfamily A strain 
and 1 subfamily B strain of rLP2086. The recombinant proteins have been characterized 
biochemically and have elicited bactericidal antibodies effective against subfamily A and B 
strains in nonclinical studies.17
1.2.3. Functional Antibody Assay as a Surrogate of Efficacy
MnB clearance from the bloodstream is primarily by complement-mediated bacteriolysis, 
and an effective complement system is critical for resistance against infections caused by 
MnB. Individuals with complement deficiencies have an increased risk of developing MnB 
disease.18,19 The in vivo complement-mediated bacteriolysis of MnB is mimicked by the in 
vitro serum bactericidal assay using human complement (hSBA), a functional serological 
assay shown to be the correlate of protection against IMD20 and recognized as the surrogate 
marker of vaccine efficacy.21,22,23

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 29
Studies B1971010 and B1971011 demonstrated an acceptable safety profile when bivalent 
rLP2086 was administered alone or in combination with Repevax and Gardasil, respectively.
The immunogenicity data from completed Phase 2 clinical studies using the final formulation 
provide evidence of a robust immune response in adolescent and adult populations. In 
particular, 3 Phase 2 clinical studies conducted in adolescents (B1971010, B1971011, and 
B1971012) demonstrated that a substantial proportion of subjects exhibited potentially 
protective responses after 2 vaccine doses, as assessed by hSBA with test strains that 
expressed fHBP antigens heterologous to those of vaccine antigens. Further, the proportions 
of subjects with hSBA responses increased following a third dose of bivalent rLP2086.
These 3 studies formed the basis of approval in the United States via an accelerated 
regulatory pathway.
Complete information for this compound may be found in the single reference safety 
document (SRSD), which for this study is the IB. The SRSDs for the concomitant vaccines 
are specified in the primary studies’ protocols.
1.2.5. Study Rationale
The purpose of Stage 1 of the study is to assess the longevity of immune responses following 
receipt of a vaccination course of 2 or 3 doses of bivalent rLP2086.
This study was initiated in September 2012 to assess the longevity of immune responses in 
adolescents (aged 10 to <19 years at the time of entry into a primary study) following 
receipt of a vaccination regimen of 2 or 3 doses of bivalent rLP2086 in a primary study (a 
previously conducted Pfizer study using the final formulation of bivalent rLP2086). This 
study was amended in January 2015 to add a booster dose of bivalent rLP2086 at 
approximately 4 years following the final dose of the 2- or 3-dose primary bivalent rLP2086 
vaccination series.  The study was, therefore, divided into Stage 1 (4-year persistence of 
immune responses following receipt of a primary vaccination series) and the booster stage 
(follow-up through 12 months after booster vaccination). 
The study is now amended to further evaluate safety and immune responses up to 26 months 
following a single booster dose of bivalent rLP2086. The 26-month postbooster follow-up is 
being conducted for a subset of booster stage subjects who previously received bivalent 
rLP2086 in a primary series of either a 0-, 2-, and 6-month or a 0- and 6-month schedule.
The rationale for focusing on this subset of subjects is based on the fact that the 0-, 2-, and 
6-month and the 0- and 6-month schedules are the dosing schedules approved by the FDA.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 32
2.2.2. Primary Safety Endpoints (Booster Stage)

Percentages of subjects reporting local reactions via the electronic diary (e-diary) by type 
(pain at the injection site, redness, and swelling) and by severity after a booster 
vaccination of bivalent rLP2086. 

Percentages of subjects reporting systemic events via the e-diary by type (fever, 
vomiting, diarrhea, headache, fatigue, chills, muscle pain other than muscle pain at the 
injection site, and joint pain) and by severity after a booster vaccination of bivalent 
rLP2086. 

Percentage of subjects reporting the use of antipyretic medication via the e-diary after a 
booster vaccination of bivalent rLP2086.

Percentages of subjects with at least 1 AE occurring during the following time periods:

From Visit 7 to Visit 8

Percentages of subjects with at least 1 SAE during the following periods: 

From Visit 7 to Visit 8

From Visit 8 to Visit 9

From Visit 7 to Visit 9

Percentages of subjects with at least 1 NDCMC occurring during the following time 
periods:

From the 6-month safety telephone call in the primary study to Visit 6 (Stage 1)

From Visit 7 to Visit 8

From Visit 8 to Visit 10

From Visit 7 to Visit 10

From Visit 8 to Visit 11 (only subjects proceeding to Visit 11)

From Visit 7 to Visit 11 (only subjects proceeding to Visit 11)

Percentages of subjects with at least 1 medically attended event occurring during the 
following time periods:

From Visit 7 to Visit 8

From Visit 8 to Visit 9

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 35
Table 5.
Study Design Overview
STAGE 1
BOOSTER STAGE
Visit 
purpose
Blood 
draw
Blood
draw
Blood 
draw
Blood 
draw
Blood 
draw
Blood 
draw
Booster 
vaccination
Blood 
draw
6-Month 
telephon
e contact
Blood 
draw
Blood 
draw
Visit number
1
2
3
4
5
6
7
8
9
10
11
Approximate 
month 
6
12
18
24
36
48
48
1 Month 
after 
booster
6 Months 
after 
booster
12 
Months 
after 
booster
26 
Months 
after 
booster
Vaccination
Bivalent 
rLP2086
Blood draw
20 
mL
20 
mL
20 
mL
20 
mL
20 
mL
20 
mL
20 mL
20 mL
20 mL
3.2. Approximate Duration of Subject Participation
The duration of subject participation will be approximately 3.5 years for Stage 1 of the study,
an additional 1 year for those subjects who enroll in the booster stage for Visits 7 to 10 and 
an additional approximately 1 year for subjects participating in Visit 11. The total duration 
for subjects participating in both Stage 1 and the booster stage will be approximately 
5.5 years.
3.3. Approximate Duration of the Study
Study duration will be approximately 6 years.
3.4. Approximate Number of Subjects
It is anticipated that up to approximately 800 subjects will participate in this study.
The booster stage of the study (Visits 7 to 11) is optional for eligible subjects at selected 
sites, so the number may be less than 800 for Visits 7 to 10. It is estimated that up to 200 of 
these subjects will continue to Visit 11.
4. SUBJECT SELECTION
This study can fulfill its objectives only if appropriate subjects are enrolled. The following 
eligibility criteria are designed to select subjects for whom protocol treatment is considered 
appropriate. All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether this protocol is suitable for a particular subject. 
For the purposes of subject selection into Stage 1, the original planned schedule is as follows:

If the subject’s vaccine assignment is known at the time of subject enrollment in 
Study B1971033, the bivalent rLP2086 administration schedule detailed in the initially 
implemented version of the primary study protocol, 15 days for the third dose of 
bivalent rLP2086, applies.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 36

If the subject’s vaccine assignment is blinded at the time of enrollment in 
Study B1971033, the investigational product administration schedule detailed in the 
initially implemented version of the primary study protocol, 15 days for the third 
injection, applies.
Subjects should preferably start the study with Visit 1 but may enter at Visit 2 where 
circumstances necessitate a measure of flexibility.
Subjects wishing to participate in the booster stage of the study must have completed Stage 1.
Only subjects who received bivalent rLP2086 in a primary study on either a 0-, 2-, and 
6-month or a 0- and 6-month schedule will be eligible to continue to Visit 11.
4.1. Inclusion Criteria
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before the subject is included in the study. 
The inclusion criteria listed for Stage 1 are required for enrollment into Stage 1 of the study. 
The criteria listed for the booster stage are required, in addition to Stage 1 inclusion criteria, 
in order to be eligible to continue into the booster stage of the study.
4.1.1. Stage 1
1. Evidence of a personally signed and dated informed consent document (ICD) indicating 
that the subject (or a legal representative) has been informed of all pertinent aspects of
the study.
2. Subjects who are willing and able to comply with scheduled visits, laboratory tests, and 
other study procedures.
3. Subjects who completed a primary study and received all the scheduled injections within 
the originally planned schedule, either with bivalent rLP2086 (either 2 or 3 doses) or with 
investigational product in cases where subject vaccine assignment is blinded at the time 
of consent for Study B1971033.
4. Subjects who completed the blood draw following the last vaccination and subjects who 
completed the 6-month follow-up telephone call in the primary study. 
4.1.2. Booster Stage
4.1.2.1. Booster Stage Visits 7 to 10
1. Evidence of a personally signed and dated ICD indicating that the subject or subject’s 
parent(s)/legal guardian has been informed of all pertinent aspects for Visits 7 to 10 of 
the booster stage of the study.
2. Subject continues to meet all Stage 1 inclusion and none of the Stage 1 exclusion criteria.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 37
3. Subject is confirmed as having received bivalent rLP2086 in the primary vaccination 
study.
4. Subject has completed B1971033 Stage 1 and completed the Visit 6 blood draw.
5. Subject is available for the entire period of the booster stage and the subject or subject’s 
parent(s)/legal guardian 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 and at risk for pregnancy must agree 
to use a highly effective method of contraception through Visit 10 of the booster stage. 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. Refer to Section 4.5 for 
further information.
8. Negative urine pregnancy test for all female subjects on the day of the booster dose.
4.1.2.2. Booster Stage Visit 11
1. For subject participating in Visit 11, evidence of a personally signed and dated ICD 
indicating that the subject or subject’s parent(s)/legal guardian has been informed of all 
pertinent aspects of Visit 11.
2. Subject continues to meet all Stage 1 inclusion and none of the Stage 1 exclusion criteria.
3. Subject must have received 2 or 3 doses of bivalent rLP2086 in the primary study on a 
0-, 2-, and 6-month or a 0- and 6-month schedule.
4. Subject must have completed booster vaccination at Visit 7.
4.2. Exclusion Criteria
The exclusion criteria listed for Stage 1 must not be met for enrollment in Stage 1 of the 
study. In order to be eligible for enrollment into the booster stage of the study, the exclusion 
criteria listed for the booster stage must not be met, in addition to not meeting any of the 
exclusion criteria for Stage 1.
Criteria are listed for Stage 1 and the booster stage of the study:
4.2.1. Stage 1
1. Subjects who are investigational 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 directly involved in the conduct of the 
study.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 38
2. With the exception of the primary study of bivalent rLP2086, participation in other 
studies within the 1-month (30-day) period before study Visit 1 and/or during study 
participation. Participation in purely observational studies is permitted. 
3. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that 
may increase the risk associated with study participation 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.
4. History of culture-proven disease caused by N meningitidis or Neisseria gonorrhoeae.
5. Bleeding diathesis or condition associated with prolonged bleeding time that would 
contraindicate blood draw.
6. Receipt of any blood products, including gamma globulin, in the period from 6 months 
before any study visit.
7. Vaccination with any licensed or experimental meningococcal serogroup B vaccine since 
being enrolled in the primary Pfizer-sponsored MnB study (other than study vaccines 
permitted in the primary study).
8. Subjects who were not compliant with primary study eligibility criteria while enrolled in 
the primary study.
4.2.2. Booster Stage
1. Subjects who are scheduled to receive 1 or more doses of a human papillomavirus (HPV) 
vaccine as part of a 3-dose series during the 28 days after the booster vaccination.
2. A previous anaphylactic reaction to any vaccine or vaccine-related component.
3. Subjects receiving any allergen immunotherapy with a nonlicensed product or receiving 
allergen immunotherapy with a licensed product and are not on stable maintenance doses.
4. Bleeding diathesis or condition associated with prolonged bleeding time that would 
contraindicate intramuscular injection.
5. 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.
6. Significant neurological disorder or history of seizure (excluding simple febrile seizure).
7. Current chronic use of systemic antibiotics.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 39
8. Current participation in another investigational study.  Participation in purely 
observational studies is acceptable.
9. Received any investigational vaccines, drugs, or devices within 28 days before 
administration of the booster vaccination.
10. Any neuroinflammatory or autoimmune condition, including, but not limited to, 
transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.
11. Pregnant female subjects, breastfeeding female subjects, male subjects with partners who 
are currently pregnant, or male and female subjects of childbearing potential who are 
unwilling or unable to use a highly effective method of contraception as outlined in this 
protocol through Visit 10 of the study.
4.3. Criteria for Temporarily Delaying Vaccine Administration during the Booster 
Stage
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:

Current febrile illness (temperature 38.0°C [100.4°F]) or other acute illness within 
48 hours before study vaccine administration.

Subject has received a nonlive vaccine (or intramuscular/sublingual allergen 
immunotherapy) within the previous 14 days or live vaccine within the previous 28 days.

Subject has received a vaccine containing all or any individual antigens included in
MCV4, tetanus, diphtheria, and acellular pertussis (Tdap), or HPV vaccines within the 
previous 28 days. See Section 5.8.

Subject is less than 5 days into a course of systemic antibiotic therapy.

Subject has received systemic (oral, intravenous, or intramuscular) corticosteroid therapy 
within the previous 28 days.
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:

Subject has received a dose of systemic antibiotics less than 5 days before blood 
collection.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 40
4.5. Lifestyle Guidelines
The following guidelines are relevant only to subjects who participate in the booster stage.
All male and female subjects who, in the opinion of the investigator, are biologically capable 
of having children and are sexually active must agree to use a highly effective method of 
contraception consistently and correctly through Visit 10 of the study (Month 12 after
booster vaccination). Visit 11 (26 months after booster vaccination) is being added to the 
booster stage of this protocol amendment after subjects have completed Visit 10. Therefore, 
the contraception requirements do not apply to Visit 11. 
The investigator or his/her designee, in consultation with the subject, will select the most 
appropriate method of contraception for the individual subject from the permitted list of 
contraception methods (see below), and instruct the subject in its consistent and correct use. 
Subjects need to affirm that they meet at least one of the selected methods of contraception. 
The investigator or his/her designee, at each study visit, will discuss with the subject the need 
to use highly effective contraception consistently and correctly according to the schedule of 
activities and document such conversation in the subject’s chart. In addition, the investigator 
will instruct the subject to call immediately if the selected birth control method is 
discontinued or if pregnancy is known or suspected. 
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:

Established use of oral, injected, or implanted hormonal methods of contraception is
allowed provided the subject 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.

Correctly placed copper-containing intrauterine device (IUD).

Male condom or female condom used WITH a spermicide (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.

Male sterilization with absence of sperm in the postvasectomy ejaculate.

Bilateral tubal ligation or bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label).
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.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 41
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 compound identifiers, subject study number, 
contact information for the investigational site, and contact details for a help desk in the 
event that the investigational 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.  The help desk number can also be used by 
investigational staff if they are seeking advice on medical questions or problems; however, it 
should only be used in the event that the established communication pathways between the 
investigational site and the study team are not available.  It is therefore intended to augment, 
but not replace, the established communication pathways between the investigational site and 
study team for advice on medical questions or problems that may arise during the study.  The 
help desk 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 investigational site.
5. INVESTIGATIONAL PRODUCT
Subjects participating in the booster stage will receive 1 dose of bivalent rLP2086 at Visit 7.
Standard vaccination practices should 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.
Investigational product administration details (ie, date of administration, kit number, volume, 
route, and site of administration) will be recorded on the case report form (CRF). 
Investigational product accountability will be documented as per Section 5.6.
In the event of a product quality complaint, which is defined as a report regarding a physical, 
chemical, microbiologic, or other alleged defect of a Pfizer Vaccine Research investigational 
product, the investigator or designee will telephone the responsible person at Pfizer as 
detailed in the SRM and follow the instructions therein.
5.1. Allocation to Investigational Product
At enrollment into Stage 1 of the study, the site personnel registered the subjects into the 
study via the use of an interactive voice response system (IVRS) or interactive Web-based 
response system (IWRS). The purpose was to allocate a subject number and track subject
visits. 
At enrollment in the booster stage, allocation of open-label vaccine kits to subjects will 
proceed through the use of an IVRS, an IWRS, or an equivalent system that is accessible 
24 hours a day, 365 days a year. The kit number should be obtained from the IVRS prior to 
vaccination. The site personnel (study coordinator or specified designee) will be required to 
enter or select information that will include the user identification and password, the project 
and protocol number, the investigator site number, the fax number, the subject number, and 
the date of birth of the subject. The site personnel will then be provided with a subject 
number and kit number. 

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 43
5.4. 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.
Investigational product administration details (ie, date of administration, volume, route, and 
site of administration) will be recorded on the CRF.  Investigational product accountability 
will be documented as per Section 5.6.
Bivalent rLP2086 booster vaccination will be administered intramuscularly at approximately 
48 months (Visit 7) following the last dose of bivalent rLP2086 received in the primary study 
by injecting 0.5 mL into the deltoid muscle. 
5.5. Investigational Product Storage
All vaccines will be shipped at +2C to +8C to each study site upon request.  Upon receipt 
at the study site, the vaccines should be immediately transferred to a +2C to +8C 
temperature-monitored refrigerator for storage. For storage, the preferred orientation of the 
vaccine is horizontal.
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 study.  Even for 
continuous-monitoring systems, a log or site procedure that ensures active daily evaluation 
for excursions should be available.  The operation of the temperature-monitoring device and 
storage unit (for example, refrigerator), as applicable, should be regularly inspected to ensure 
it is maintained in working order.
The refrigerator must be locked and secure and have limited access. It is the responsibility of 
the investigator(s) (or designee) to record daily refrigerator temperature readings (working 
days only), to maintain a daily temperature log for the refrigerator, and to alert the sponsor of 
any deviations. Investigational product must be stored as indicated.
Once an excursion is identified, the investigational product must be quarantined and not used 
until the sponsor provides documentation of permission to use the investigational product.  
Specific details regarding information the site should report for each excursion will be 
provided to the site. 
Any excursions from the product-label storage conditions should be reported upon discovery. 
The site should actively pursue options for returning the product to storage conditions as 
described in the labeling, as soon as possible. Deviations from storage requirements, 
including any actions taken, must be documented and reported to the sponsor.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 44
In case of temperature deviations, the investigational products cannot be used and should be 
quarantined until the sponsor provides documentation of permission to use the investigational 
products. Guidance on temperature monitoring and procedures for the review of temperature 
deviations will be provided in the SRM.
Storage conditions stated in the bivalent rLP2086 IB will be superseded by the storage 
conditions stated in the labeling.
Investigators and site staff are required to check refrigerator temperatures daily and ensure 
that thermometers are working correctly as required for proper storage of investigational 
products.  Any temperature excursions must be reported immediately.
5.6. Investigational Product Accountability
The investigator’s site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the vaccine supplies. Investigational product accountability applies to 
such products when they are required by the protocol and supplied (shipped) by the sponsor.
Unused investigational product must 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 are 
discarded at the point of use. Investigational product return must be documented on the 
accountability log.
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site).
5.7. Concomitant Treatment(s)
Throughout the study, nonstudy vaccinations occurring from the final blood draw in the 
primary study until Visit 11 will be recorded in the CRF.
In the booster stage, any allergen immunotherapy occurring from Visit 7 until Visit 11 will 
also be recorded in the CRF.
In the booster stage, 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 Visit 7 through Visit 11 will be recorded in the 
CRF.
5.8. Prohibited During the Study

Receipt of any blood products, including gamma globulin, in the period from 6 months 
before any study visit.

Vaccines containing all or any individual antigens included in MCV4, Tdap, and HPV 
vaccines are not permitted 28 days before or after study vaccination. 

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 45

Other nonlive or live nonstudy vaccines are not permitted within 14 and 28 days, 
respectively, before or after study vaccination.

Intramuscular/sublingual allergen immunotherapy is not permitted within 14 days before 
or after study vaccination.

Systemic (oral, intravenous, or intramuscular) corticosteroid therapy within 28 days 
before or after study vaccination.
5.9. 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 
vaccines) as specified above.

Nonstudy vaccines (other than vaccines containing all or any individual antigens included 
in MCV4, Tdap, and HPV vaccines) that are part of recommended immunization 
schedules are allowed any time during the study but should not be administered within 
14 days (for nonlive vaccines) and 28 days (for live vaccines) of study vaccine 
administration.

Antipyretics and other pain medications to treat symptoms associated with investigational 
product are permitted.

Antipyretics and other pain medications to prevent symptoms associated with 
investigational product are not encouraged.

Local anesthetic may be applied before blood draw.

Topical antibiotics are permitted.

Topical and inhaled corticosteroids are permitted.
5.10. Prior Treatment
5.10.1. Prohibited Prior Treatments
The following are prohibited:

Receipt of any blood products, including gamma globulin, in the period from 6 months 
before any study visit.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 46
6. STUDY PROCEDURES 
If the subject’s primary study vaccine assignment is known at the time of consent for 
Study B1971033, the visits in Study B1971033 should be scheduled relative to the last dose 
of bivalent rLP2086 in the primary study. If the subject’s primary study vaccine assignment 
is blinded at the time of consent for Study B1971033, the visits in Study B1971033 should be 
scheduled relative to the last injection of investigational product in the primary study.
Subjects should preferably start the study with Visit 1 but may enter at Visit 2 where 
circumstances necessitate a measure of flexibility.
6.1. Informed Consent Process
All parties will ensure protection of subject personal data and will not include subject names 
on any sponsor forms, reports, or publications, or in any other disclosures, except where 
required by law. For further information, please refer to the Subject Information and Consent
section (Section 13.3).
6.2. Stage 1
6.2.1. Study Visit 1 – Serology Follow-up (6 Months [150-240 Days] After the Last Dose 
of Bivalent rLP2086 in the Primary Study, or After the Last Injection of Investigational 
Product in the Primary Study if Vaccine Assignment Is Blinded)
Before any study procedure takes place, a signed and dated ICD has to be collected for this 
study.  The following information will be collected and the following assessments will be 
made at Visit 1:

Collect vital sign measurements, including blood pressure, pulse rate, and temperature 
(oral).

Confirm that the subject meets the inclusion criteria and none of the exclusion criteria.

Draw a blood sample of approximately 20 mL as described in the SRM and the schedule 
of activities (Table 1).

Record AEs as described in Section 8 and the AE reporting schedule (Table 3).

Record NDCMCs identified from the 6-month telephone call in the primary study.

Record RRIs and nonserious AEs occurring during the 48-hour period after the blood 
draw.

Record any nonstudy vaccination received since the final blood draw in the primary 
study.

Complete the source documents.

Complete the CRF.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 47
6.2.2. Study Visit 2 – Serology Follow-up (12 Months [330-390 Days] After the Last 
Dose of Bivalent rLP2086 in the Primary Study, or After the Last Injection of 
Investigational Product in the Primary Study if Vaccine Assignment Is Blinded)
The following information will be collected and the following assessments will be made at 
Visit 2:

If the subject has been enrolled at Visit 2, obtain written informed consent before 
performing study-specific procedures.

Collect vital sign measurements, including blood pressure, pulse rate, and temperature 
(oral).

Ensure the subject continues to be eligible for the study.

Draw a blood sample of approximately 20 mL as described in the SRM and the schedule 
of activities (Table 1).

Record AEs as described in Section 8 and the AE reporting schedule (Table 3).

Inquire whether the subject had any NDCMCs since the last visit.

Record RRIs and nonserious AEs occurring during the 48-hour period after the blood 
draw.

Record any nonstudy vaccination received since the previous visit or since the final blood 
draw in the primary study for subjects enrolled at Visit 2.

Complete the source documents.

Complete the CRF.
6.2.3. Study Visit 3 – Serology Follow-up (18 Months [510-570 Days] After the Last 
Dose of Bivalent rLP2086 in the Primary Study, or After the Last Injection of 
Investigational Product in the Primary Study if Vaccine Assignment Is Blinded)
The following information will be collected and the following assessments will be made at 
Visit 3:

Collect vital sign measurements, including blood pressure, pulse rate, and temperature 
(oral).

Ensure the subject continues to be eligible for the study.

Draw a blood sample of approximately 20 mL as described in the SRM and the schedule 
of activities (Table 1).

Record AEs as described in Section 8 and the AE reporting schedule (Table 3).

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 48

Inquire whether the subject had any NDCMCs since the last visit.

Record RRIs and nonserious AEs occurring during the 48-hour period after the blood 
draw.

Record any nonstudy vaccination received since the previous visit.

Complete the source documents.

Complete the CRF.
6.2.4. Study Visit 4 – Serology Follow-up (24 Months [676-764 Days] After the Last 
Dose of Bivalent rLP2086 in the Primary Study, or After the Last Injection of 
Investigational Product in the Primary Study if Vaccine Assignment Is Blinded)
The following information will be collected and the following assessments will be made at 
Visit 4:

Collect vital sign measurements, including blood pressure, pulse rate, and temperature 
(oral).

Ensure the subject continues to be eligible for the study.

Draw a blood sample of approximately 20 mL as described in the SRM and the schedule 
of activities (Table 1).

Record AEs as described in Section 8 and the AE reporting schedule (Table 3).

Inquire whether the subject had any NDCMCs since the last visit.

Record RRIs and nonserious AEs occurring during the 48-hour period after the blood 
draw.

Record any nonstudy vaccination received since the previous visit.

Complete the source documents.

Complete the CRF.
6.2.5. Study Visit 5 – Serology Follow-up (36 Months [1036-1124 Days] After the Last 
Dose of Bivalent rLP2086 in the Primary Study, or After the Last Injection of 
Investigational Product in the Primary Study if Vaccine Assignment Is Blinded)
The following information will be collected and the following assessments will be made at 
Visit 5:

Collect vital sign measurements, including blood pressure, pulse rate, and temperature 
(oral).

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 49

Ensure the subject continues to be eligible for the study.

Draw a blood sample of approximately 20 mL as described in the SRM and the schedule 
of activities (Table 1).

Record AEs as described in Section 8 and the AE reporting schedule (Table 3).

Inquire whether the subject had any NDCMCs since the last visit.

Record RRIs and nonserious AEs occurring during the 48-hour period after the blood 
draw.

Record any nonstudy vaccination received since the previous visit.

Complete the source documents.

Complete the CRF.
6.2.6. Study Visit 6 – Serology Follow-up (48 Months [1396-1484 Days] After the Last 
Dose of Bivalent rLP2086 in the Primary Study, or After the Last Injection of 
Investigational Product in the Primary Study if Vaccine Assignment Is Blinded)
The following information will be collected and the following assessments will be made at 
Visit 6:

Collect vital sign measurements, including blood pressure, pulse rate, and temperature 
(oral).

Ensure the subject continues to be eligible for the study.

Draw a blood sample of approximately 20 mL as described in the SRM and the schedule 
of activities (Table 1).

Record AEs as described in Section 8 and the AE reporting schedule (Table 3).

Inquire whether the subject had any NDCMCs since the last visit.

Record RRIs and nonserious AEs occurring during the 48-hour period after the blood 
draw.

Record any nonstudy vaccination since the previous visit.

Complete the source documents.

Complete the CRF.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 50
6.3. Booster Stage
6.3.1. Visit 7, Booster Vaccination of Bivalent rLP2086 (48 Months [1396-1484 Days] 
After the Last Dose of Bivalent rLP2086 in the Primary Study, and within 42 Days 
After Visit 6)
Visit 6 procedures must precede Visit 7 procedures, even if conducted on the same day.
For subjects who are not completing Visit 6 on the same day as Visit 7:

Collection of vital sign measurements and recording of nonstudy vaccinations should be 
repeated on the day of Visit 7 as indicated below and in the schedule of activities.

Visit 7 procedures should be conducted within 42 days after Visit 6.
In the case of temporary delay of vaccination, the procedures and assessments will be 
reperformed or reconfirmed on the day of vaccination. 

Obtain written informed consent, specific for participation in Visits 7 to 10 of the booster 
stage, before performing the booster stage-specific procedures. The date of informed 
consent will be recorded in the CRF.

Complete the study visit/AE checklist to:

Inquire whether the subject had any NDCMCs 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.

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 the presence of chronic conditions and/or medical history of significance, 
including relevant surgical procedures and cardiac medical history.

Perform a 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.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 51

On the day of vaccination, perform a urine pregnancy test on all female subjects. A 
negative pregnancy test result is required before the subject may receive the 
investigational product.

On the day of vaccination, collect vital sign measurements, before administration of 
vaccine, including blood pressure, pulse rate, and temperature (oral).

On the day of vaccination, record nonstudy vaccinations and allergen immunotherapy as 
described in Section 5.7.

Ensure that all of the inclusion criteria for Stage 1 and the booster stage, none of the 
exclusion criteria for Stage 1 and the booster stage, and none of the temporary delay 
criteria are met.

If a subject is eligible for the booster stage of the study, allocate a vaccine kit to the 
subject using an IVRS, IWRS, or equivalent system.

Administer a single 0.5-mL intramuscular injection of bivalent rLP2086 into the upper 
deltoid muscle. The time of 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 (see 
Section 7.2).

Record AEs as described in the Safety section (Section 7.2), the Adverse Event Reporting 
section (Section 8), and the AE reporting schedule (Table 3). The 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 Section 5.7.

Issue an e-diary to the subject or the subject’s parent(s)/legal guardian and provide 
instruction on its completion. 

Ask the subject to complete the e-diary from Day 1 to Day 7 after vaccination.

Issue a caliper, measuring tape/ruler, and digital thermometer and provide instructions on 
their use. 

Instruct the subject or subject’s parent(s)/legal guardian to use the caliper to measure 
the maximum diameter of redness and swelling at the injection site each day for the 
7 days after study vaccination and record in the e-diary as described in Section 7.4.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 52

Instruct the subject or subject’s parent(s)/legal guardian to contact the investigator 
immediately if the subject experiences a severe redness or swelling (>20 caliper units) 
at the injection site, a fever 39C (102.1F), or a severe headache within 7 days after 
vaccination, as an unscheduled visit should be arranged (Section 6.4).

If the reaction exceeds the maximum size the caliper is able to measure (>21 caliper 
units, Section 7.5.1), the subject or subject’s parent(s)/legal guardian 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. 

Instruct the subject or subject’s parent(s)/legal guardian 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.

Instruct the subject or subject’s parent(s)/legal guardian 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 subject or subject’s parent(s)/legal guardian 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 subject or 
subject’s parent(s)/legal guardian in order to obtain stop dates for any local reactions, 
systemic events, or use of antipyretic medication that was 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.
6.3.2. Visit 8 (28 to 42 Days after Visit 7), Postvaccination Blood Draw 1

Ensure that the subject continues to be eligible for the study and meets none of the 
withdrawal criteria (Section 4) and none of the temporary delay of blood draw criteria 
(Section 4.4).

Collect vital sign measurements, including blood pressure, pulse rate, and temperature 
(oral).

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.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 53

Complete the study visit/AE checklist to:

Inquire whether the subject had any NDCMCs since the last visit as described in 
Section 8 and the AE reporting schedule (Table 3).

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. Refer to the SRM for additional details.

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 Safety section (Section 7.2), the Adverse Event Reporting 
section (Section 8), and the AE reporting schedule (Table 3).

Review AEs that were ongoing since the previous visit and record their end dates or 
confirm that they are still continuing. 

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.7).

Record nonstudy vaccinations and allergen immunotherapy as described in the 
Concomitant Treatment(s) section (Section 5.7).

Collect a blood sample (approximately 20 mL).

Provide the subject with a memory aid. Instruct the subject to use the memory aid 
between Visits 8 and 10 to remind him or her to review with study site personnel any 
significant illnesses, hospitalizations, NDCMCs, or visits to a medical facility. Please 
refer to the SRM for additional details. 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 (168 to 196 Days after Visit 7), Safety Telephone Contact
Telephone contact should occur approximately 6 months after the booster vaccination; this 
contact should be attempted for all subjects who have received booster vaccination, including 
subjects who withdraw from the booster stage prior to Visit 9, unless they have withdrawn 
consent.

Ensure that the subject continues to be eligible for the study and meets none of the 
withdrawal criteria (Section 4) and none of the temporary delay of blood draw criteria 
(Section 4.4).

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 54

Complete the study visit/telephone contact checklist to:

Inquire whether the subject had any NDCMCs since the last visit as described in 
Section 8 and the AE reporting schedule (Table 3).

Inquire about SAEs, NDCMCs, and AEs that resulted in evaluation at a medical 
facility since the last visit. Please refer to the SRM for additional details.

Inquire about neuroinflammatory and autoimmune conditions, such as transverse 
myelitis, uveitis, optic neuritis, and multiple sclerosis.  Please refer to the SRM for 
additional details.

Review AEs that were ongoing since the previous visit and record their end dates or 
confirm that they are still continuing.

Report any SAEs to the sponsor as defined in Section 8.7.

Record AEs as described in the Safety section (Section 7.2) the Adverse Event Reporting 
section (Section 8), and the AE reporting schedule (Table 3).

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.7).

Record nonstudy vaccinations and allergen immunotherapy as described in the 
Concomitant Treatment(s) section (Section 5.7).

Complete the source documents.

Complete the CRFs.
6.3.4. Visit 10 (12 Months [330-390 Days] after Visit 7), Postvaccination Blood Draw 2

Ensure that the subject continues to be eligible for the study (Section 4) and meets none 
of the temporary delay of blood draw criteria (Section 4.4).

Collect vital sign measurements, including blood pressure, pulse rate, and temperature 
(oral).

Record AEs as described in the Safety section (Section 7.2), the Adverse Event Reporting 
section (Section 8), and the AE reporting schedule (Table 3).

Record NDCMCs as described in the Safety section (Section 7.2), the Adverse Event
Reporting section (Section 8), and the AE reporting schedule (Table 3).

Review AEs that were ongoing since the previous visit and record their end dates or 
confirm that they are still continuing. 

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 55

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.7).

Record nonstudy vaccinations and allergen immunotherapy as described in the 
concomitant treatment section (Section 5.7).

Collect a blood sample (approximately 20 mL).

Complete the source documents.

Complete the CRFs.

Remind the subject or subject’s parent(s)/legal guardian to report any AEs or RRIs within 
48 hours following Visit 10.
6.3.5. Visit 11 (26 Months [750-810 Days] after Visit 7), Postvaccination Blood Draw 3

Obtain written informed consent specific for participation in Visit 11 of the booster stage 
before performing any Visit 11 procedures. The informed consent specific to Visit 11 
may be obtained at Visit 11 or any earlier visit.  The date of informed consent will be 
recorded in the CRF.

Ensure that subjects participating in Visit 11 have met Visit 11 eligibility criteria
(Section 4) and meet none of the temporary delay of blood draw criteria (Section 4.4).

Collect vital sign measurements, including blood pressure, pulse rate, and temperature 
(oral).

Record AEs as described in the Safety section (Section 7.2), the Adverse Event Reporting 
section (Section 8), and the AE reporting schedule (Table 3).

Record NDCMCs as described in the Safety section (Section 7.2), the Adverse Event
Reporting section (Section 8), and the AE reporting schedule (Table 3).

Review AEs that were ongoing since the previous visit and record their end dates or 
confirm that they are still continuing. 

Report any SAEs to the sponsor as defined in Section 8.7.

Complete the study visit/telephone contact checklist.

Record concomitant medications used to treat AEs as described in the Concomitant 
Treatment(s) section (Section 5.7).

Record nonstudy vaccinations and allergen immunotherapy as described in the 
Concomitant Treatment(s) section (Section 5.7).

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 56

Collect a blood sample (approximately 20 mL).

Complete the source documents.

Complete the CRFs.

Remind the subject or subject’s parent(s)/legal guardian to report any AEs or RRIs within 
48 hours following Visit 11. 
6.4. Unscheduled Visits
If the subject or parent(s)/legal guardian reports a severe redness or swelling at the injection 
site (>20 caliper units), a temperature 39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 subject contact will be documented in the CRF.
If the reaction exceeds the maximum size the caliper is able to measure (>21 caliper units), 
ensure the 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 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 in 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. 
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), subject request, 
investigator request, death, discontinuation of the study by the sponsor, protocol violation, 
and being lost to follow-up.  Subjects will not be replaced.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 57
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.  When possible, the investigator will perform the procedures indicated for the next 
visit.  If the subject has received the booster vaccination, but withdraws prior to Visit 9, 
provide the subject with a memory aid and complete the activities detailed for Visit 9. 
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 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 the subject to return for a final visit, if applicable, 
and follow-up with the subject regarding any unresolved AEs.
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 fashion.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 58
7.1. Immunogenicity
To facilitate immunogenicity analyses, subjects will have approximately 20 mL of blood 
collected at Visits 1 through 6, 8, 10, and 11. Sample collection, storage, and shipping 
information can be found in the SRM.
All serum samples should be frozen in an upright position in a laboratory-grade manual-
defrost freezer that does not cycle and forms ice that must be removed (a non–frost-free 
freezer) and that maintains a temperature of -20C or lower within the limits specified by the 
manufacturer.
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.
7.1.1. Bivalent rLP2086 Serum Bactericidal Assay - Primary Test Strains
For assessment of the immune response to bivalent rLP2086, functional antibodies will be 
analyzed in hSBAs with MnB strains. The hSBA measures antibodies in human sera that 
initiate complement-dependent killing of the target meningococcal strain. Four (4) primary 
test strains,
 (A22), 
 (A56), 
 (B24), and 
 (B44), will be 
used in the hSBAs for determination of the immunogenicity endpoints in sera obtained from 
all subjects at all study visits. The MnB hSBAs are validated before any testing is 
performed.
Sera obtained 1 month following the last vaccination with bivalent rLP2086 in the primary 
study will be reassayed concurrently with sera obtained during B1971033 study visits. 
Sera in subjects who did not receive bivalent rLP2086 in study B1971015 (Group 2) will also 
be assayed in amendment 3.
Pfizer plans to complete all MnB hSBA testing at its Pearl River Laboratories.
7.1.2. Bivalent rLP2086 Serum Bactericidal Assay - Secondary Test Strains
Ten (10) secondary test strains may be used to perform hSBA testing in sera obtained from 
subjects.
Sera obtained from subjects 1 month following the last vaccination with bivalent rLP2086 in 
the primary study and prior to booster vaccination with bivalent rLP2086 (Visit 6), as well as 
1 month, 12 months, and 26 months after the booster vaccination (Visits 8, 10, and 11), may 
be used for hSBA testing on the 10 secondary test strains.
hSBA tests are qualified for the 10 secondary test strains.
CCI
CCI
CCI
CCI

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 59
7.2. Safety
Any subject who receives 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 the schedule of activities (Table 1 and Table 2):

Physical examination, including measurement of vital signs.

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 review of NDCMCs as well as a physical 
examination will be performed on all subjects at Visit 7 to establish a baseline. 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 in 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 
prospectively collected reactogenicity events are considered solicited AEs and include the 
following:

Local reactions at the site of investigational product administration (redness, swelling, 
and pain at the injection site).

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 on the CRF. If a subject does not complete the diary for 7 days, end 
dates of local reactions, systemic events, and antipyretic medication that were ongoing on the 
last day the e-diary was completed by the subject will be collected on the CRF.
Immediate AEs, defined as AEs occurring within the first 30 minutes after investigational 
product administration, will be assessed and documented in the AE CRF. The time of onset 
will be recorded for any AEs that occur on the same day as investigational product 
administration.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 60
Medically attended events and NDCMCs will be also assessed throughout the study and 
documented on the appropriate AE CRF. A medically attended event is defined as a 
nonserious AE that results in an evaluation at a medical facility. An NDCMC 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), NDCMCs, and visits to other medical facilities will be 
assessed at study visits as specified in the AE reporting schedule (Table 3) 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, completed at each scheduled 
study visit/telephone contact, and included in the source documentation. Please refer to the 
SRM for details.
Subjects will be given a memory aid at Visit 8. The memory aid will be used to remind 
subjects to review with study site personnel any significant illnesses, hospitalizations, 
NDCMCs, or visits to a medical facility. Subjects may use the memory aid as needed during 
the safety telephone call at Visit 9 to prompt recall of events. This 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 the study visit or telephone call will be included in the 
source documents and entered into the CRF.
In addition, AEs and SAEs will be collected as defined in AE reporting schedule (Table 3). 
For the purposes of this study, these are referred to as unsolicited AEs and will be recorded 
and reported as described in Section 8.
7.3. Pregnancy Testing
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 the booster dose. 
A negative pregnancy test result is required before the subject may receive investigational 
product.
Pregnancy tests may also be repeated as per request of institutional review boards 
(IRBs)/ethics committees (ECs) or if required by local regulations.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 61
7.4. Electronic Diary
The subject or subject’s parent(s)/legal guardian will be issued an e-diary, 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 
vaccination. Grading scales for local reactions and systemic events are based on US Food 
and Drug Administration (FDA) Guidance for Industry, Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.25 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. End dates of 
local reactions, systemic events, and use of antipyretic medication (associated with vaccine 
administration) that were ongoing on the last day the e-diary was completed will be collected 
on the CRF. The investigator or designee must contact the parent(s)/legal guardian in order 
to obtain stop dates for any e-diary events (such as local reactions and systemic events, 
including fever) ongoing on the last day that the e-diary was completed.
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.
7.5. Local Reactions
Local reactions (redness, swelling, and pain at injection site) at the site of the study vaccine 
injection will be recorded daily for 7 days (Day 1 to Day 7) after booster vaccination.
7.5.1. Injection Site 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 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 subject or subject’s parent(s)/legal guardian 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 subject or subject’s 
parent(s)/legal guardian 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.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 62
Table 6.
Grading of Redness and Swelling
None
0 to 2.0 cm (0 to 4 caliper units)
Mild
2.5 to 5.0 cm (5 to 10 caliper units)
Moderate
5.5 to 10.0 cm (11 to 20 caliper units)
Severe
>10.0 cm (>20 caliper units)
7.5.2. Injection Site Pain
The subject or, where relevant, the parent(s)/legal guardian will be asked to assess whether 
pain is present at the injection site for the first 7 days following vaccination (Day 1 to Day 7).  
If the subject experiences injection site pain, the pain will be graded using the following 
scale:
Table 7.
Grading of Pain
Mild
Does not interfere with activity
Moderate
Interferes with activity
Severe
Prevents daily activity
The assessment will then be recorded in the e-diary.
7.6. Systemic Events
7.6.1. Temperature
A digital thermometer will be given to the subject or, where relevant, parent(s)/legal guardian 
with instructions on how to measure the child’s temperature at home. Temperature will be 
collected at bedtime daily for 7 days (Day 1 to Day 7) after 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 presented for the 
following ranges:
Table 8.
Temperature Categories
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)

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 63
7.6.2. Use of Antipyretic Medication
The use of antipyretic medication will be recorded in the e-diary daily during the active 
safety observation period (Day 1 to Day 7) immediately following the booster vaccination of 
bivalent rLP2086. The use of antipyretics to prevent fever or pain is not encouraged.
7.6.3. Other Systemic Events
The e-diary will be used to record the presence of other systemic events, including vomiting, 
diarrhea, chills, headache, fatigue, 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 following 
scales:
Table 9.
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
Joint pain
Does not interfere with 
activity
Some interference
with activity
Prevents daily routine 
activity
Abbreviation: IV=intravenous.
7.7. Risks and Benefits
Potential risks associated with participation in Stage 1 of this study are limited to those 
associated with drawing blood (bruising, mild bleeding, momentary discomfort, fainting, 
and, rarely, infection), as well as any potential long-term side effects (later-emerging events) 
that may be related to bivalent rLP2086, administered previously in the primary studies. 
Refer to the most recent version of the bivalent rLP2086 IB for a summary of the known 
risks and potential benefits of the vaccine to human subjects after primary and booster 
vaccinations.
There may be pain and/or bruising with blood collections or with vaccine injection.
Any newly identified risks to the subjects must be reported promptly by the sponsor to the 
investigators.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 64
8. ADVERSE EVENT REPORTING
8.1. Adverse Events
All observed or volunteered AEs regardless of vaccine group or suspected causal relationship 
to the investigational product(s) will be reported as described in the following sections.
For all AEs, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as an SAE 
requiring immediate notification to Pfizer or its designated representative. For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of the 
AE. The investigator is required to assess causality. 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.
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.
8.2. Reporting Period
For SAEs, the active reporting period to Pfizer or its designated representative begins from 
the time that the subject provides informed consent for the booster stage, which is obtained 
prior to the subject’s participation in the booster stage of the study, ie, prior to undergoing 
any booster stage study-related procedure and/or receiving investigational product, through 
and including Visit 9, which is to occur 6 months after administration of the investigational 
product. SAEs occurring to a subject after the active reporting period has ended should be 
reported to the sponsor 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 the 
study vaccine are to be reported to the sponsor.
NDCMCs identified from the time of the 6-month telephone call in the primary study
through Visit 11 must be recorded in the CRF. 
Particular care should be taken at all visits during the booster stage to note and report any 
neuroinflammatory and autoimmune conditions, such as transverse myelitis, uveitis, optic 
neuritis, and multiple sclerosis. The investigator is required to assess whether the AE may be 
related to the subject’s participation in the study.
At all visits, stop dates for any reported AEs that were ongoing at the previous visit will be 
recorded in the CRF.  The investigator must instruct the subject or, where relevant, 
parent(s)/legal guardian on the need to report AEs and SAEs during this time period.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 65
SAEs with an onset during Stage 1 (ie, prior to the booster stage) will be reported under the 
primary study protocol (ie, the protocol the subject was enrolled in PRIOR to being enrolled 
in B1971033).  SAEs with an onset during the booster stage will be reported under Study 
B1971033. 
8.2.1. Stage 1
In addition to items noted in Section 8.2, in Stage 1, investigators are reminded of the 
obligation to report SAEs occurring during Stage 1 of B1971033 that an investigator may 
become aware of by reporting the event back to the primary study by following the SAE 
reporting procedures as specified in the protocol for the primary study. At a minimum, all 
SAEs that the investigator believes have at least a reasonable possibility of being related to 
study vaccine are to be reported to the sponsor. AEs, including SAEs and suspected 
unexpected serious adverse reactions (SUSARs), reported to the primary study from which 
the subjects proceeded into this follow-on study (B971033, Stage 1) will be reported to 
regulatory authorities in accordance with applicable local regulations.
At Visits 1-6 (Stage 1), the site will inquire about any RRIs (Section 8.6) and nonserious AEs 
occurring during the 48-hour period after blood draw. These events must be recorded in the 
CRF and the events must be followed. 
8.2.2. Booster Stage
In addition to the reporting requirements noted in Section 8.2, in the booster stage, all 
nonserious AEs occurring from the time the subject provides informed consent for the 
booster stage to Visit 8, and then from Visit 8 until 48 hours after the Visit 8 blood draw and 
from Visit 10 and Visit 11 until 48 hours after each blood draw, will be reported and 
recorded.
SAEs and nonserious AEs resulting in evaluation at a medical facility (medically attended 
events) are reportable from Visits 7 through 9.
Any RRIs within 48 hours following Visits 10 and 11 will also be reported.
8.3. Definition of an Adverse Event
An AE is any untoward medical occurrence in a clinical investigation 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 symptoms and signs;

Changes in physical examination findings;

Hypersensitivity;

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 66

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, they may include the signs or symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.
8.4. Medication Errors
Medication errors may result, in this study, from the administration or consumption of the 
wrong vaccine, by the wrong subject, at the wrong time, or at the wrong dosage strength. 
Such medication errors occurring to a study participant are to be captured on the medication 
error CRF, which is a specific version of the AE page, and on the SAE form when 
appropriate. In the event of medication dosing error, the sponsor should be notified 
immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including, but not limited to:

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;

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 67

The administration of investigational product that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the 
investigational product under question is acceptable for use.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is captured on the medication error version of the AE page 
and, if applicable, any associated AE(s) are captured on an AE CRF page.
8.5. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows: 

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, 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 
reporting as an AE.
8.6. Research-Related Injury
Should a subject in the first 48 hours following blood draw, in the investigator’s opinion, 
suffer a medically important RRI caused by his or her participation in the study, Pfizer or its 
representative must be informed immediately.
A medically important RRI 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;

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 

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 68
outcomes listed in the definition above, the important medical event should be reported as an 
RRI.
An investigator may be requested by Pfizer 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 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 or its 
designated representative.
8.7. Serious Adverse Events
An SAE 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);

Results in congenital anomaly/birth defect.
Lack of efficacy in an approved indication should be reported as an SAE.
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 section on 
Medical Device Complaint Reporting Requirements).  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.  

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 69
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.
8.7.1. Protocol-Specified Serious Adverse Events 
There are no protocol-specified SAEs in this study.  All SAEs will be reported by the 
investigator as described in previous sections, and will be handled as SAEs in the safety 
database (see section on Serious Adverse Event Reporting Requirements).
8.7.2. Potential Cases of Drug-Induced Liver Injury 
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in this 
study.  However, should an investigator deem it necessary to run LFTs because of clinical 
sign/symptom presentation in a subject, such LFT results should be handled and followed up 
as described below.
Abnormal values in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 
levels concurrent with abnormal elevations in total bilirubin level that meet the criteria 
outlined below in the absence of other causes of liver injury are considered potential cases of 
drug-induced liver injury (potential Hy’s law cases) and should always be considered 
important medical events.
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the subject’s individual baseline values and underlying conditions. Subjects who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values:

Subjects with AST or ALT and total bilirubin baseline values within the normal range 
who subsequently present with AST or ALT values 3 times the upper limit of 
normal (X ULN) concurrent with a total bilirubin value 2 X ULN with no evidence 
of hemolysis and an alkaline phosphatase value 2 X ULN or not available;

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 70

For subjects with preexisting ALT OR AST OR total bilirubin values above the 
ULN, the following threshold values should be used in the definition mentioned 
above:

For subjects with preexisting AST or ALT baseline values above the normal 
range: AST or ALT values 2 times the baseline values and 3 X ULN, or 
8 X ULN (whichever is smaller).
Concurrent with:

For subjects with preexisting values of total bilirubin above the normal range: 
Total bilirubin level increased from baseline by an amount of at least 1 X ULN or
if the value reaches ≥3 X ULN (whichever is smaller).
The subject should return to the investigational 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, laboratory tests should include 
albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl 
transferase, prothrombin time (PT)/international normalized ratio (INR), and alkaline 
phosphatase. A detailed history, including relevant information, such as review of ethanol, 
acetaminophen, recreational drug and supplement consumption, family history, occupational 
exposure, sexual history, travel history, history of contact with a jaundiced person, surgery, 
blood transfusion, history of liver or allergic disease, and work exposure, should be collected. 
Further testing for acute hepatitis A, B, or C infection and liver imaging (eg, biliary tract) 
may be warranted. All cases confirmed on repeat testing as meeting the laboratory criteria 
defined above, with no other cause for LFT abnormalities identified at the time, should be 
considered potential Hy’s law cases irrespective of availability of all the results of the 
investigations performed to determine etiology of the abnormal LFTs. Such potential Hy’s 
law cases should be reported as SAEs.
8.8. 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 should be assessed for medical 
importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 71

Respite care (eg, caregiver relief);

Skilled nursing facilities;

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 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 AEs.  However, the medical condition for which the procedure was performed 
should be reported if it meets the definition of an AE.  For example, an acute appendicitis 
that begins during the AE reporting period should be reported as the AE, and the resulting 
appendectomy should be recorded as treatment of the AE.
8.9. Severity Assessment
Table 10.
Severity Assessment Grade
GRADE 
If required on the AE CRFs, 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.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 72
Table 10.
Severity Assessment Grade
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.
8.10. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
nonserious); the investigator must record the causal relationship in the CRF, as appropriate, 
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 (see the section on Reporting Requirements).  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, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable.
8.11. Exposure during Pregnancy
For both unapproved/unlicensed products and marketed products, an EDP occurs if:
1. 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; 
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).
2. 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. 

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 73
If a study subject or study subject’s partner becomes or is found to be pregnant during the 
study subject’s treatment with the investigational product, the investigator must submit this 
information to the Pfizer drug safety unit on a Serious Adverse Event (SAE) Report Form 
and Exposure during Pregnancy (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) 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 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).
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 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 investigator. 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 study 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.
8.12. 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.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 74
An occupational exposure is reported to the drug safety unit within 24 hours of the 
investigator’s awareness, using the SAE Report Form, regardless of whether there is an 
associated AE/SAE. Since the information does not pertain to a subject enrolled in the study, 
the information is not reported on a CRF; however, a copy of the completed SAE Report 
Form is maintained in the investigator site file.
8.13. Withdrawal Due to Adverse Events (See also the Section on Subject Withdrawal)
Withdrawal due to AE should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on the appropriate AE CRF 
page.
When a subject withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below.
8.14. Eliciting Adverse Event Information
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject/parent/legally acceptable representative.  In addition, each study 
subject/parent/legally acceptable representative will be questioned about AEs.
8.15. Reporting Requirements
Each AE is to be assessed to determine if it meets the criteria for SAEs.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.
8.15.1. Serious Adverse Event Reporting Requirements
If an SAE occurs, Pfizer is to be notified within 24 hours of investigator awareness of the 
event.
In particular, if the SAE is fatal or life-threatening, notification to Pfizer must be made 
immediately, irrespective of the extent of available AE information. This time frame also 
applies to additional new information (follow-up) on previously forwarded SAE reports as 
well as to the initial and follow-up reporting of EDP, exposure via breastfeeding, and 
occupational exposure cases.
For subjects enrolled in the booster stage, 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. These 
procedures do not replace any of the standard SAE reporting requirements as described 
above. Additional information can be found in the SRM.
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study subject initially seeks treatment elsewhere), the
investigator is to report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 75
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the time frames for reporting specified above.  In addition, an investigator 
may be requested by Pfizer to obtain specific additional follow-up information in an 
expedited fashion.  This information collected for SAEs is more detailed than that captured 
on the AE CRF.  In general, this will include a description of the AE 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
medications, 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. 
8.15.2. Nonserious Adverse Event Reporting Requirements
All AEs will be reported on the AE page of the CRF.  It should be noted that the form for 
collection of SAE information is not the same as the AE CRF.  Where the same data are 
collected, the forms must be completed in a consistent manner.  For example, the same AE 
term should be used on both forms.  AEs should be reported using concise medical 
terminology on the CRFs as well as on the form for collection of SAE information.
The investigator must 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 as described in Section 8. Additional information can be found in the SRM.
8.15.3. Medical Device Complaint Reporting Requirements
All medical device complaints regardless of whether the medical device complaint is 
associated with an AE will be collected 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 have led 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.
8.15.4. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including SUSARs, will be carried out in accordance with applicable local 
regulations.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 76
9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this study 
will be documented in a statistical analysis plan (SAP), which will be finalized before the 
start of any analyses and will be maintained by the sponsor.  This document may modify the 
plans outlined in the protocol; however, any major modifications of the primary endpoint 
definition and/or its analysis will be reflected both in the amended protocol and in the SAP.  
The SAP amendment will follow the protocol amendment.
9.1. Sample Size Determination
Study sample size is not based on statistical considerations. In recognition of the variability 
introduced with the inclusion of subject populations from various studies (such as population 
age, number of doses received, and concomitant vaccine usage), the study aims to enroll up 
to 800 subjects to allow for sufficient numbers when describing findings with regard to 
particular variables.
9.2. Immunogenicity Analysis
This is a descriptive study; no hypothesis testing will be performed. Therefore, an estimation 
approach will be utilized for immunogenicity.
The immunogenicity descriptive summaries will be presented for the overall population as 
well as by subgroup (eg, dose schedule, age group, administration of concomitant vaccine, 
region). A mixed model with repeated measures adjusted with covariates (dose schedule, age 
group, region, etc) will also be used to estimate the GMTs at different time points (including 
time points from the primary studies).
The empirical reverse cumulative distribution curves (RCDCs) of hSBA titer will be 
presented graphically for each of the 4 primary strains at each sampling time point.
hSBA assays using the 4 primary test strains will be conducted using sera obtained at Visits 1 
to 6 from all subjects entered into stage 1, including subjects who did not receive bivalent 
rLP2086 in the primary study (B1971015 Group 2). Serum samples collected at Visits 8, 10,
and 11 during the booster stage will also be analyzed by hSBA against the 4 primary test 
strains.
9.2.1. Analysis of Primary Endpoint
The proportion of subjects in each group achieving hSBA titer LLOQ at each blood 
sampling time point will be computed for each of the 4 primary test strains along with 
2-sided exact 95% confidence intervals (CIs).26

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 78
For each of the primary studies, there will be a descriptive comparison between the subjects 
enrolled in Study B1971033 and the remaining subjects, to assess representativeness. This 
comparison will include demographic characteristics as well as immune responses 1 month 
after the final dose of bivalent rLP2086 or injected saline, such as the percentage of subjects 
with titers LLOQ and GMTs to the 4 primary strains.
9.5. Safety Analysis
The safety population will be used for all safety analyses. For Stage 1 time points, the safety 
population will include all subjects who have at least 1 blood draw in the study. For the 
booster stage, the safety population will include all subjects who have received the booster 
vaccination and for whom safety information is available. Missing safety data will not be 
replaced or imputed. For summaries that include Visit 11 or after Visit 10, the subset of 
subjects of the safety booster population who participated in Visit 11 will be used.
The proportion of subjects reporting local reactions at the investigational product 
administration site and systemic events and use of antipyretic medication within the 7-day 
period after the booster vaccination will be descriptively summarized.  Severities of local 
reactions and systemic events reported after vaccination will also be descriptively 
summarized.  Two (2)-sided exact 95% CIs will be presented with the proportions.
All of the AEs and RRIs will be categorized according to the Medical Dictionary for 
Regulatory Activities (MedDRA) and will be summarized. A medically attended event is 
defined as a nonserious AE that results in an evaluation at a medical facility. An NDCMC is 
defined as a disease or medical condition not previously identified that is expected to be 
persistent or otherwise long-lasting in its effects. All summaries will show the number and 
percentage of subjects experiencing at least 1 event and the number of events. Two (2)-sided 
exact 95% CIs will also be presented for the percentages.
9.6. Analysis Timing
Because of the timing of enrollment into the primary studies, subjects will reach the booster 
stage of Study B1971033 over an extended period. An interim analysis will be conducted 
after Visit 8 (1 month after the booster vaccination) immunogenicity data for all subjects who 
participated in the B1971012 primary study are available. There may also be an interim 
analysis when the B1971012 subjects have Visit 10 (12 months after the booster vaccination)
immunogenicity data available.
The information will be used for internal decision making on further development of the 
vaccine, and will not modify the current study. Since the study is descriptive, there will be 
no type I error impact for these interim analyses.
The final analysis will be conducted once Visit 11 (26 months after the booster vaccination) 
immunogenicity data for all enrolled subjects are available.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 79
9.7. Data Monitoring Committee
This study will use an external data monitoring committee (EDMC). The independent 
statistical center (ISC) will provide the safety reports to the EDMC. 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.  
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.
10. QUALITY CONTROL AND QUALITY ASSURANCE
During study conduct, Pfizer or its agent will conduct periodic monitoring visits 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.
The study 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.
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. BIOLOGICAL SAMPLES
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.
Any remaining sera will be stored, and may be used for additional assays to assess immune 
response to vaccines given as part of this protocol or for assay development. The sera will 
not be used for any unrelated research and no genetic testing will be performed. The samples 
will be stored for up to 15 years after the end of the study and then destroyed. The subject or, 
where relevant, the subject’s parent(s)/legal guardian may request that his or her samples, if 
still identifiable, be destroyed at any time; however, any data already collected from that 
sample will still be used for this research. The serum samples will remain the property of the 
sponsor and may be shared with other researchers as long as confidentiality is maintained.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 80
12. DATA HANDLING AND RECORD KEEPING
12.1. 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's or the physician's subject chart.  In 
these cases, data collected on the CRFs must match the data in those charts.
In some cases, the CRF, or part of the CRF, may also serve as source documents.  In these 
cases, a document should be available at the investigator’s site as well as at Pfizer and clearly 
identify those data that will be recorded in the CRF, and for which the CRF will stand as the 
source document.
12.2. Record Retention
To enable evaluations and/or 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 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 International Council for Harmonisation (ICH), 
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.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 81
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
13. ETHICS
13.1. Institutional Review Board (IRB)/Ethics Committee (EC)
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.
13.2. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences [CIOMS] 2002), Guidelines for GCP (ICH 1996), and the Declaration of Helsinki 
(World Medical Association 1996 and 2008).
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on GCP, and applicable local regulatory requirements and laws.
13.3. 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 a numerical code consisting 
of a numbering system provided by Pfizer in order to de-identify study subjects. The study 
site will maintain a confidential list of subjects who participated in the study linking their 
numerical code to the subject’s actual identity. In case of data transfer, Pfizer will maintain 
high standards of confidentiality and protection of subject personal data consistent with 
applicable privacy laws.
The informed consent/assent documents 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 must be 
reviewed by the sponsor, approved by the IRB/EC before use, and available for inspection.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 82
In addition, a study-specific assent form will be provided to the subjects, as required by local 
regulations, who have not yet reached the legal age of majority.  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."
The investigator must ensure that each study subject, or his or her legally acceptable 
representative, or 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 legally acceptable representative/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, as permitted by the IRB/EC and consistent with local regulatory and 
legal requirements, then 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/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.
If the study includes minor subjects who reach the age of majority during the study, as 
recognized under local law, they must be reconsented 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 the subject's legally acceptable representative, 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.
13.4. Subject Recruitment
Subject recruitment efforts are not required for this study because, as of protocol 
amendment 3, all subjects have been enrolled.
13.5. 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 
competent 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.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 83
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.
14. DEFINITION OF END OF TRIAL
14.1. 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.
14.2. End of Trial in All Other Participating Countries
End of trial in all other participating countries is defined as the end of the clinical phase of 
the study, which will be 48 hours after the last study visit (Visit 11) for the last subject 
(LSLV). At this time, sites will be closed out, the IRB/EC will be informed, and no further 
CIOMS reports will be sent.
15. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, drug safety problems, or at the discretion of Pfizer.  In 
addition, Pfizer retains the right to discontinue development of bivalent rLP2086 at any time.
If a study is prematurely terminated or discontinued, 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.
16. PUBLICATION OF STUDY RESULTS
16.1. 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.
www.clinicaltrials.gov

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 84
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 for 
studies in adult populations or within 6 months of the primary completion date for studies in 
pediatric populations.
Primary completion date 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 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 primary completion date for studies in adult populations or within 6 months of the 
primary completion date 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.
16.2. Publications by Investigators
Pfizer has no objection to publication by an investigator of any information collected or 
generated by the investigator, whether or not the results are favorable to the investigational 
vaccine. 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 before it is submitted or otherwise disclosed.
The investigator will provide manuscripts, abstracts, or the full text of any other intended 
disclosure (poster presentation, invited speaker or guest lecturer presentation, etc) to Pfizer at 
least 30 days before they are 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 (other than the study results themselves) before disclosure.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 85
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all centers.  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.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 86
17. REFERENCES
1
EU-IBIS Network. Invasive Neisseria meningitidis in Europe 2006. 
London, UK: Health Protection Agency; 2006. Available:
http://www.euibis.org/documents/2006_meningo.pdf. 16 Nov 2009.
2
Centers for Disease Control and Prevention. Active Bacterial Core 
Surveillance (ABCs) Report, Emerging Infections Program Network, 
Neisseria meningitidis, 2007. Atlanta, GA: CDC; 2008. Available: 
http://www.cdc.gov/abcs/survreports/mening07.htm. 16 Nov 2009.
3
Harrison LH, Trotter CL, Ramsay ME. Global epidemiology of 
meningococcal disease. Vaccine 2009;27(Suppl 2):B51-B63. 
doi:10.1016/j.vaccine.2009.04.063.
4
MacLennan J, Kafatos G, Neal K, et al. Social behavior and 
meningococcal carriage in British teenagers. Emerg Infect Dis 
2006;12(6):950-7.
5
Plotkin S, Orenstein W, Offit P. Epidemiologic risk factors for acquiring 
disease. In: Vaccines, 5th ed. Amsterdam: Elsevier; 2008: p. 400-1.
6
Maiden MCJ, Ibarz-Pavón AB, Urwin R, et al. Impact of meningococcal 
serogroup C conjugate vaccine on carriage and herd immunity. J Infect 
Dis 2008;197(5):737-43.
7
Updated Recommendations for Use of Meningococcal Conjugate 
Vaccines --- Advisory Committee on Immunization Practices (ACIP), 
2010. Available: 
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6003a3.html. 06 Jan 
2015.
8
Centers for Disease Control and Prevention. Active Bacterial Core 
Surveillance (ABCs) Report, Emerging Infections Program Network, 
Neisseria meningitidis, 2011. Atlanta, GA: CDC; 2012. Available: 
http://www.cdc.gov/abcs/reports-findings/survreports/mening11.html. 14 
Dec 2014.
9
Addressing the challenges of serogroup B meningococcal disease 
outbreaks on campuses: a report by the National Foundation for 
Infectious Diseases. May 2014. Available: 
http://www.nfid.org/publications/reports/meningococcal-b-outbreaks.pdf. 
14 Dec 2014.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 87
10
Wendling P. Campus meningitis outbreaks tamed but can our approach 
last? February 2014. Available: 
http://www.clinicalneurologynews.com/index.php?id=9843&cHash=071
010&tx_ttnews[tt_news]=239545. 14 Dec 2014.
11
Finne J, Leinonen M, Makela PH. Antigenic similarities between brain 
components and bacteria causing meningitis. Implications for vaccine 
development and pathogenesis. Lancet 1983;2(8346):355-7.
12
Holst JD, Martin D, Arnold R, et al. Properties and clinical performance 
of vaccines containing outer membrane vesicles from Neisseria 
meningitidis. Vaccine 2009;27(Suppl 2):B3-B12.
13
Martin SL, Borrow R, van der Ley P, et al. Effect of sequence variation 
in meningococcal PorA outer membrane protein on the effectiveness of a 
hexavalent PorA outer membrane vesicle vaccine. Vaccine 
2000;18:2476-81
14
Centers for Disease Control and Prevention. Use of serogroup B 
meningococcal vaccines in adolescents and young adults: 
recommendations of the Advisory Committee on Immunization Practices, 
2015. MMWR Morb Mortal Wkly Rep 2015;64(41):1171-6.
15
Caugant DA, Maiden MC. Meningococcal carriage and disease –
population biology and evolution. Vaccine 2009;27(Suppl 2):B64-B70. 
doi:10.1016/j.vaccine.2009.04.061.
16
Fletcher LD, Bernfield L, Barniak V, et al. Vaccine potential of the 
Neisseria meningitidis 2086 lipoprotein. Infect Immun 2004;72(4):2088-
100.
17
Anderson A, Jansen K, Eiden J. New frontiers in meningococcal 
vaccines. Exp Rev Vaccines 2011;10(5):617-34.
18
Mathew S, Overturf GD. Complement and properidin deficiencies in 
meningococcal disease. Pediatr Infect Dis J 2006;25(3):255-6.
19
Schneider MC, Exley RM, Chan H, et al. Functional significance of 
factor H binding to Neisseria meningitidis. J Immunol 
2006;176(12):7556-78.
20
Borrow R, Balmer P, Miller E. Meningococcal surrogates of protection –
serum bactericidal antibody activity. Vaccine 2005;23(17-18):2222-7.

PF-05212366 (Bivalent rLP2086)
B1971033
Final Protocol Amendment 4, 20-March-2017
Page 88
21
Miller E, Salisbury D, Ramsay M. Planning, registration, and 
implementation of an immunisation campaign against meningococcal 
serogroup C disease in the UK: a success story. Vaccine 2002;20:S58-
S67.
22
Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the 
meningococcus. I. The role of humoral antibodies. J Exp Med 
1969;129:1307-26.
23
Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the 
meningococcus. II. Development of natural immunity. J Exp Med 
1969;129:1327-48.
24
Murphy E, Andrew L, Lee KL, et al. Sequence diversity of the factor H 
binding vaccine candidate in epidemiologically relevant strains of 
serogroup B Neisseria meningitidis. J Infect Dis 2009;200(3):379-89.
25
US Department of Health and Human Services, Food and Drug 
Administration, Center for Biologics Evaluation and Research. Guidance 
for Industry, Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials. September 
2007. Available: http://www.fda.gov/cber/gdlns/toxvac.pdf. 14 Dec 2014.
26
Clopper CJ, Pearson ES. The use of confidence or fiducial limits 
illustrated in the case of the binomial. Biometrika 1934;26:404-13.