A PHASE 1/2, RANDOMIZED, PLACEBO-CONTROLLED, OBSERVER-BLINDED TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MULTIVALENT GROUP B STREPTOCOCCUS VACCINE IN HEALTHY ADULTS 18 TO 49 YEARS OF AGE
Phase: PHASE2
Conditions: Group B Streptococcal Infections
Sponsor: Pfizer

Group B Streptococcus 6-Valent 
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A PHASE 1/2, RANDOMIZED, PLACEBO-CONTROLLED, OBSERVER-BLINDED 
TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND 
IMMUNOGENICITY OF A MULTIVALENT GROUP B STREPTOCOCCUS 
VACCINE IN HEALTHY ADULTS 18 TO 49 YEARS OF AGE
Investigational Product Number:
Investigational Product Name:
Group B Streptococcus 6-Valent 
 Vaccine (GBS6)
United States (US) Investigational New 
Drug (IND) Number:
17058
European Clinical Trials Database 
(EudraCT) Number:
Not applicable (N/A)
Protocol Number:
C1091001
Phase:
1/2
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Document History
Document
Version Date
Summary of Changes and Rationale
Protocol Amendment 3
29 August 
2017
Added language regarding an additional 
voluntary blood volume collection, at Visit 4
for a subset of subjects, to support assay 
development.  Changes were made to the 
following sections: Protocol Summary (study 
design), Schedule of Activities, Section 3, 
Section 6.7 and Section 7.3.
Clarified, in Section 4.2 exclusion criterion 14,
that “postvaccination” refers to the entire 
6-month study period.
Protocol Amendment 2
16 May 2017
Removed the contraception check at Visit 6 in
the Schedule of Activities and Section 6.9 to 
align with the 3 month duration of 
contraception use.
Revised exclusion criteria 3 to better clarify 
that chronic human immunodeficiency virus, 
hepatitis B and hepatitis C virus infections are
exclusionary.  
Removed the “for the duration of the study 
participation” language pertaining to method of 
contraception in exclusion criteria 4 and 
Section 4.4.1 to align with the 3 month duration 
of contraception use.

 
 
 
 
 
 
 
 
 
 
Clarified the unblinded site staff member’s 
role in using the IRT system to assign 
investigational product container numbers in 
Section 6.3 and Section 6.4.
Clarified in Section 7.7 that the sentinel 
stopping rules are 1 to 6, not 1 to 5. 
Removed the medical device language from 
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Document
Version Date
Summary of Changes and Rationale
Section 8.2.3 since this text is not applicable.
Protocol Amendment 1
08 March 2017 Added editorial changes throughout the 
document to improve clarity and to fix 
typographic errors.

 
 
 
Removed “New or worsening” from joint pain 
and muscle pain in Table 5 (Systemic Event 
Grading Scale) for internal alignment of 
wording throughout the protocol.

 
 
 
 
 
 

 
 
 
 
 
 

 
 
Modified wording in Section 7.5.2.3 to state 
that study staff must (vs may) contact subject to 
obtain additional information if a temperature 
of >102F is entered into an e-diary to make 
wording consistent with Section 6.10.
Added “The investigator determined it was not 
needed” to Section 6.10 to align with CRF 
approved template wording.
Rearranged the primary objective endpoints in 
chronological order according to collection
times in the study.

 
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Document
Version Date
Summary of Changes and Rationale
 

 
Modified immunogenicity blood draws at 
Visits 1 to 6 from 25 mL to 30 mL to facilitate 
sample collection at sites, eg, to accommodate 
the size of collection tubes.
Modified Section 6.11.1 to allow Visit 5 and 
Visit 6 to be performed via telephone contact 
for subjects staying in the study for safety 
follow-up procedures only.
Added vital sign collection to the screening 
visit.
Rearranged the stopping rules to keep the fever 
rules together.
Removed the medical device complaint 
reporting requirements section since this 
section is not applicable.
In Sections 5.8 and 7.7, revised unblinded
physician and statistician to unblinded sponsor 
personnel in the stopping rule assessment.
Original protocol
19 September
2016 
N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................9
APPENDICES .........................................................................................................................10
PROTOCOL SUMMARY.......................................................................................................11
SCHEDULE OF ACTIVITIES................................................................................................15
1. INTRODUCTION ...............................................................................................................17
1.1. Indication.................................................................................................................17
1.2. Background and Rationale ......................................................................................17
1.2.1. Disease Overview .......................................................................................17
1.2.2. GBS Disease in Infants and Pregnant Women ...........................................17
1.2.3. GBS Disease in Nonpregnant Adults .........................................................18
1.2.4. Rationale for Development of GBS6..........................................................19
1.2.4.1. Maternal Immunization as an Approach to Prevent 
Disease in Infants and Pregnant Women...........................................19
1.2.4.2. Maternal Antibody and Protection Against GBS Disease 
in Infants............................................................................................19
1.2.4.3. Clinical Experience With 
 
Vaccines and GBS 
 Vaccine ....................20
1.2.5. Group B Streptococcus 6-Valent 
 Vaccine .......20
1.2.6. Study Rationale...........................................................................................21
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................21
2.1. Primary Objective and Endpoints ...........................................................................21
2.1.1. Primary Objective.......................................................................................21
2.1.2. Primary Endpoints ......................................................................................21
2.2. Secondary Objective and Endpoint.........................................................................22
2.2.1. Secondary Objective...................................................................................22
2.2.2. Secondary Endpoint....................................................................................22
3. STUDY DESIGN.................................................................................................................22
3.1. Duration of Subject Participation............................................................................24
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3.2. Duration of Study....................................................................................................24
3.3. Number of Subjects.................................................................................................24
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................25
4.1. Inclusion Criteria.....................................................................................................25
4.2. Exclusion Criteria....................................................................................................26
4.3. Temporary Delay Criteria .......................................................................................28
4.3.1. Criteria for Temporarily Delaying Vaccine Administration ......................28
4.3.2. Criteria for Temporarily Delaying Blood Draw .........................................28
4.4. Lifestyle Requirements ...........................................................................................28
4.4.1. Contraception..............................................................................................28
4.5. Sponsor’s Qualified Medical Personnel..................................................................29
5. INVESTIGATIONAL PRODUCTS ...................................................................................29
5.1. Subject Compliance.................................................................................................30
5.2. Investigational Product Supplies.............................................................................30
5.2.1. Dosage Form(s) and Packaging..................................................................30
5.2.2. Preparation and Dispensing........................................................................31
5.3. Allocation to Investigational Product......................................................................31
5.4. Administration.........................................................................................................32
5.5. Investigational Product Storage ..............................................................................32
5.6. Investigational Product Accountability...................................................................33
5.6.1. Destruction of Investigational Product Supplies ........................................33
5.7. Blinding of the Site Personnel.................................................................................33
5.8. Blinding of the Sponsor...........................................................................................34
5.9. Breaking the Blind ..................................................................................................34
5.10. Concomitant Treatment(s).....................................................................................34
5.10.1. Prohibited Nonstudy Vaccines and Medications During the Study .........34
5.10.2. Permitted Nonstudy Vaccines and Medications During the Study ..........35
5.10.3. Recording Nonstudy Vaccinations and Concomitant Medications..........35
6. STUDY PROCEDURES .....................................................................................................35
6.1. Visit 0 – Screening for Sentinel-Cohort Subjects (Days -14 to -2 Prior to 
Vaccination) ..............................................................................................................35
6.2. Visit 0 – Rescreening Visit for Sentinel-Cohort Subjects (Days -14 to -2 
Prior to Vaccination), If Applicable ..........................................................................36
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6.3. Visit 1 – Vaccination (Day 1) for Sentinel-Cohort Subjects...................................37
6.4. Visit 1 – Vaccination (Day 1) for Expanded-Cohort Subjects................................38
6.5. Visit 2 – 1-Week Follow-up Visit (7-10 Days After Visit 1) for All Subjects .......40
6.6. Visit 3 – 2-Week Follow-up Visit (14-17 Days After Visit 1) for All Cohort 
Subjects......................................................................................................................41
6.7. Visit 4 – 1-Month Follow-up Visit (28-38 Days After Visit 1) for All Cohort 
Subjects......................................................................................................................41
6.8. Visit 5 – 3-Month Follow-up Visit (80-100 Days After Visit 1) for All 
Cohort Subjects .........................................................................................................42
6.9. Visit 6 – 6-Month Follow-up Visit (160-200 Days After Visit 1) for All 
Cohort Subjects .........................................................................................................42
6.10. Unscheduled Visits................................................................................................43
6.11. Subject Withdrawal...............................................................................................44
6.11.1. Withdrawal of Consent.............................................................................44
6.11.2. Lost to Follow-up .....................................................................................44
7. ASSESSMENTS..................................................................................................................45
7.1. Pregnancy Testing...................................................................................................45
7.2. Biological Samples..................................................................................................46
7.3. Immunogenicity ......................................................................................................46
7.4. GBS Microbiological Cultures................................................................................47
7.5. Safety Parameters....................................................................................................47
7.5.1. Subject Electronic Diary.............................................................................47
7.5.2. Grading Scale for Prompted Events ...........................................................48
7.5.2.1. Local Reactions.........................................................................48
7.5.2.2. Systemic Events ........................................................................49
7.5.2.3. Fever..........................................................................................50
7.5.3. Laboratory Tests .........................................................................................51
7.6. Use of Antipyretic/Pain Medication........................................................................51
7.7. Stopping Rules ........................................................................................................52
7.8. Other Safety Monitoring .........................................................................................53
7.8.1. Adverse Events...........................................................................................53
7.8.2. Immediate Adverse Events.........................................................................53
7.8.3. Medically Attended Adverse Events ..........................................................53
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7.8.4. Routine Medical Facility Visits and Elective Hospitalizations Not 
Associated With Adverse Events.....................................................................54
8. ADVERSE EVENT REPORTING......................................................................................54
8.1. Requirements...........................................................................................................54
8.1.1. Additional Details on Recording Adverse Events on the CRF...................55
8.1.2. Eliciting Adverse Event Information..........................................................55
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the 
Subject Withdrawal section)............................................................................55
8.1.4. Time Period for Collecting AE/SAE Information......................................56
8.1.4.1. Reporting SAEs to Pfizer Safety...............................................56
8.1.4.2. Recording Nonserious AEs and SAEs on the CRF...................56
8.1.5. Causality Assessment .................................................................................56
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ..................57
8.2. Definitions...............................................................................................................57
8.2.1. Adverse Events...........................................................................................57
8.2.2. Abnormal Test Findings .............................................................................58
8.2.3. Serious Adverse Events ..............................................................................58
8.2.4. Hospitalization............................................................................................59
8.3. Severity Assessment................................................................................................60
8.4. Special Situations ....................................................................................................60
8.4.1. Protocol-Specified Serious Adverse Events...............................................60
8.4.2. Potential Cases of Drug-Induced Liver Injury............................................60
8.4.3. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................62
8.4.3.1. Exposure During Pregnancy......................................................62
8.4.3.2. Exposure During Breastfeeding ................................................63
8.4.3.3. Occupational Exposure .............................................................63
8.4.4. Medication Errors .......................................................................................64
8.4.4.1. Medication Errors......................................................................64
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................65
9.1. Sample Size Determination.....................................................................................65
9.2. Immunogenicity Analysis .......................................................................................65
9.3. Safety Analysis........................................................................................................66
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9.4. Analysis Timing ......................................................................................................67
9.5. Data Monitoring Committee ...................................................................................67
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................67
11. DATA HANDLING AND RECORD KEEPING .............................................................68
11.1. Case Report Forms/Electronic Data Record .........................................................68
11.2. Record Retention...................................................................................................68
12. ETHICS..............................................................................................................................69
12.1. Institutional Review Board/Ethics Committee......................................................69
12.2. Ethical Conduct of the Study ................................................................................69
12.3. Subject Information and Consent..........................................................................69
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................70
13. DEFINITION OF END OF TRIAL...................................................................................70
13.1. End of Trial in All Participating Countries ...........................................................70
14. SPONSOR DISCONTINUATION CRITERIA ................................................................70
15. PUBLICATION OF STUDY RESULTS..........................................................................71
15.1. Communication of Results by Pfizer ....................................................................71
15.2. Publications by Investigators ................................................................................71
16. REFERENCES ..................................................................................................................73
LIST OF TABLES
Table 1.
Enrollment and Dose Escalation Design ..............................................................24
Table 2.
Planned Subjects: Total and Number in Each Group...........................................25
 
Table 4.
Local Reaction Grading Scale ..............................................................................49
Table 5.
Systemic Event Grading Scale..............................................................................50
Table 6.
Ranges for Fever...................................................................................................51
Table 7.
Laboratory Tests ...................................................................................................51
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APPENDICES
Appendix 1. Abbreviations......................................................................................................79
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PROTOCOL SUMMARY
Background and Rationale
Streptococcus agalactiae, also known as group B streptococcus (GBS), is an encapsulated, 
gram-positive coccus that is associated with lower intestinal and rectovaginal colonization.
There are 10 serotypes of GBS (Ia, Ib, II, III, IV, V, VI, VII, VIII, and IX) differentiated by 
the polysaccharide composition of their capsule. All GBS serotypes have been found to 
cause disease, but there is variability in their global prevalence and virulence. GBS disease 
is most frequently found in the very young—newborns and infants younger than 3 months of 
age—and the elderly, especially older adults with comorbid conditions. However, disease 
due to GBS has been reported in individuals of all ages, and pregnant women may be 
particularly susceptible to GBS disease as well.
Among young infants, GBS is a leading cause of invasive bacterial infection, a significant 
cause of infant morbidity and mortality globally, and the leading infectious cause of 
morbidity and mortality in infants in the United States.  Serious GBS disease, including 
sepsis, meningitis, and pneumonia, is associated with mortality rates of 6% to 14% in 
high-income countries and 10% to 60% in low- and middle-income countries (LMICs). Of 
infants surviving GBS meningitis, one study found mild to moderate neurologic sequelae in
25%, and 19% suffered severe sequelae, including cognitive delay, cerebral palsy, blindness, 
or hearing loss. In pregnant women, GBS may be associated with ascending infections 
ranging from relatively benign urinary tract infections to chorioamnionitis (which may result 
in stillbirth or preterm delivery) and puerperal sepsis (which may be fatal).  Serotypes Ia, Ib, 
II, III, and V are most frequently associated with GBS disease in infants. Serotype IV shows 
a trend of increased prevalence in certain regions. GBS disease in infants is often classified 
as early-onset disease (EOD), which occurs within the first week of life, and late-onset 
disease (LOD), which occurs between Days 7 and 90.
The reported burden of infant GBS disease varies globally, and is influenced by the intensity 
of the epidemiology surveillance for the organism, as well as by the frequency of healthcare 
interaction, leading to the potential for underreporting, and underuse of intrapartum antibiotic 
therapy (IAP) to prevent GBS disease. In regions, such as the United States, where there are 
significant efforts and resources allocated for universal GBS screening of pregnant women 
and use of IAP to prevent GBS disease, the number of cases of EOD decreased since the 
early 1990s when recommendations for prevention were introduced. The incidence of LOD 
has remained relatively unchanged through the introduction of IAP in the United States.  
Additionally, GBS disease in pregnant and postpartum women has not been reduced, as may 
be expected given the short course of administration during the intrapartum period only. In 
other countries where interventions are less widely used or a risk-based approach to IAP is 
used, such as in certain European countries, the trend in incidence rates may be unchanged or 
increasing slightly. Neither approach has eliminated GBS disease in infants. Even with 
potential underreporting, the highest rates of GBS disease are found in LMICs, where 
healthcare access and standards of prenatal care may vary, or the resources for significant 
preventive interventions are not available.
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Vaccination of pregnant women has been used globally in the prevention of neonatal tetanus 
and more recently for prevention of pertussis in young infants, and to protect women and 
their infants against influenza. Vaccination with tetanus toxoid, diphtheria toxoid, and 
acellular pertussis vaccine (Tdap) in pregnant women was introduced in the United States
and in the United Kingdom in response to a significant upsurge in pertussis cases in all age
groups. Maternal immunization against influenza was recommended by the US Advisory 
Committee on Immunization Practices (ACIP) because of the increased risks of influenza and 
related complications in pregnant women. Safety surveillance conducted to date has 
demonstrated no unusual patterns of pregnancy complications or fetal outcomes.
 
 
 
 
 
 
 
 
The Phase 1/2, randomized, placebo-controlled, observer-blinded study described here will 
be the first-in-human (FIH) evaluation of the investigational GBS6. 
 
 
 
 
 
  
 
 
Primary Objective and Endpoints
Primary Objective

To describe the safety and tolerability of various formulations of GBS6 at 3 dose levels in 
healthy adults 18 to 49 years of age.
Primary Endpoints

The proportion of sentinel-cohort subjects with clinical laboratory abnormalities 
following investigational product administration at the 1-week follow-up visit.
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
The proportion of subjects reporting prompted local reactions within 14 days following 
investigational product administration (redness, swelling, and pain at the injection site).

The proportion of subjects reporting prompted systemic events within 14 days following 
investigational product administration (fever, nausea/vomiting, diarrhea, headache, 
fatigue, muscle pain, and joint pain).

The proportion of subjects reporting adverse events (AEs) within 1 month following 
investigational product administration.

The proportion of subjects reporting medically attended adverse events (MAEs) and 
serious adverse events (SAEs) within 6 months following investigational product 
administration.
Study Design
This is a Phase 1/2, randomized, placebo-controlled, observer-blinded trial to evaluate the 
safety, tolerability, and immunogenicity of a multivalent GBS vaccine in healthy adults aged 
18 to 49 years.
Approximately 363 healthy adults aged 18 to 49 years of age will be randomized to receive a 
single dose of 1 of 3 dose levels of GBS6, formulated with or without AlPO4, or placebo 
(saline control).  This study will utilize a sentinel-cohort design 
 
 
 
 
 
 
Blood will be collected at screening and at the 1-week postvaccination follow-up visit in all 
subjects enrolled in each sentinel cohort for hematology and chemistry assessments. 
 
. For all 
subjects, blood will also be collected on the day of investigational product administration 
prior to study vaccination and 1 week, 2 weeks, 1 month, 3 months, and 6 months after 
vaccination for immunogenicity assessment. Local reactions and systemic events will be 
collected for 14 days after vaccination.  AEs will be assessed up to 1 month after vaccination. 
SAEs and MAEs will be assessed through 6 months after vaccination.  In addition, AEs 
occurring up to 48 hours after the Visit 5 and Visit 6 blood draws that are related to study 
procedures will be collected.
 
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Investigational Products
The investigational products are GBS6, composed of CPS of serotypes Ia, Ib, II, III, IV, and 
V, individually 
at dose levels of 5, 10, or 20 μg CPS/serotype/dose,
formulated with or without AlPO4, and placebo (saline control). Subjects will receive 1 dose 
of either GBS6, formulated with or without AlPO4, or placebo (saline control) at Visit 1 
administered intramuscularly by injecting 0.5 mL into the deltoid muscle, preferably of the 
nondominant arm.
Statistical Methods
This is a Phase 1/2 FIH study to assess the safety, tolerability, and immunogenicity of GBS6
administered with or without AlPO4, and the study sample sizes are not based on statistical 
considerations.
Descriptive summary statistics will be provided for immunogenicity and safety endpoints.
At the completion of the 1-month follow-up blood sampling and assays, an analysis of 
available immunogenicity and safety results will be conducted.  No multiplicity adjustments 
will be applied for these analyses.
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SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the Study Procedures, Section 6,
and Assessments, Section 7, sections of the protocol for detailed information on each procedure and assessment required for 
compliance with the protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities table, in order to 
conduct evaluations or assessments required to protect the well-being of the subject.
Visit Number
0
1
2
3
4
5
6
Visit Description 
Screening
Sentinel 
Cohorts Onlya
Vaccination
Sentinel 
Cohorts
Vaccination 
Expanded 
Cohorts
1-Week 
Follow-up 
Visit
2-Week 
Follow-up 
Visit
1-Month 
Follow-up 
Visit
3-Month 
Follow-up 
Visit
6-Month 
Follow-up Visit
Visit Window (Days)b
Day -14 to -2 
Prior to Day 1
Day 1
Day 1
7-10 Days 
After Visit 1
14-17 Days 
After Visit 1
28-38 Days 
After Visit 1
80-100 Days 
After Visit 1
160-200 Days 
After Visit 1
Informed consent
X
X
Demography
X
X
Medical history
X
X
Vital signs
X
X
X
Physical examination
X
X
Urine pregnancy test
X
X
Record nonstudy vaccine 
information
X
X
X
X
X
X
X
X
Record medication information
X
X
X
X
X
X
Review inclusion and exclusion 
criteria
X
X
Blood draw for hematology and 
chemistry assessmentsc
X
(~10 mL)
X
(~10 mL)
Prevaccination oral temperature
X
X
Review laboratory resultsd
X
X
Contraception checke
X
X
X
X
X
X
Review continued eligibility
X
X
X
X
X
X
Review temporary delay criteria
X
X
X
X
X
X
X
Assign single subject identifier 
X
X
Assign subject randomization and 
container number
X
X
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Visit Number
0
1
2
3
4
5
6
Visit Description 
Screening
Sentinel 
Cohorts Onlya
Vaccination
Sentinel 
Cohorts
Vaccination 
Expanded 
Cohorts
1-Week 
Follow-up 
Visit
2-Week 
Follow-up 
Visit
1-Month 
Follow-up 
Visit
3-Month 
Follow-up 
Visit
6-Month 
Follow-up Visit
Visit Window (Days)b
Day -14 to -2 
Prior to Day 1
Day 1
Day 1
7-10 Days 
After Visit 1
14-17 Days 
After Visit 1
28-38 Days 
After Visit 1
80-100 Days 
After Visit 1
160-200 Days 
After Visit 1
Blood draw for immunogenicity
assessmentc
X
(~30 mL)
X
(~30 mL)
X
(~30 mL)
X
(~30 mL)
X
(~30 mL or 
~50 mL)
X
(~30 mL)
X
(~30 mL)
Administer investigational product
X
X
Postvaccination observation (30 
minutes) and assessment of 
immediate adverse events
X
X
Dispense e-diary, thermometer, and 
measuring devicef
X
X
Review and/or collect e-diaryg
X
X
X
X
Record adverse events
X
X
X
X
X
X
Xi
Xi
Record medically attended adverse 
events and serious adverse events
X
X
X
X
X
X
X
X
Abbreviations: e-diary = electronic diary; GBS = group B streptococcus.
a.
If abnormal laboratory values (as defined in Screening, Section 6.1, and in Section 7.5.3) are reported at Visit 0 and the investigator believes the results to be erroneous, the 
abnormal laboratory parameters may be retested.  See Section 6.2 for further details.
b.
Day relative to start of study vaccination (Day 1).
c.
All blood volumes are approximate.  Blood draw for hematology and chemistry laboratory assessments will only be performed in subjects from the sentinel cohorts. At Visit 
4, an optional immunogenicity blood draw of approximately 50 mL will be collected from a subset of subjects who provide supplemental consent.
d.
Applies to sentinel-cohort subjects only.
e.
The contraception check is an opportunity to confirm that contraception is used consistently and correctly.
f.
Subjects will record reactogenicity events in an e-diary each evening for 14 days following vaccination. Remind subjects that study staff may contact them to obtain additional 
information on Grade 3 events entered into the e-diary.  Ask subjects to contact the investigator or site staff immediately if they are prompted by the e-diary from Day 1 to 
Day 14 following vaccination to determine if an unscheduled visit is required (see Section 6.10).
g.
Designated site staff will review e-diary data online following vaccination to evaluate subject compliance and as part of the ongoing safety review.
h.
i.
Only adverse events occurring up to 48 hours after each blood draw that are related to study procedures must be recorded in the case report form.
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1. INTRODUCTION
1.1. Indication
Group B streptococcus 6-valent 
 vaccine (GBS6) is being developed 
for:

Active immunization to prevent disease caused by group B streptococcus (GBS)
serotypes contained in the vaccine.
1.2. Background and Rationale
1.2.1. Disease Overview
Streptococcus agalactiae, also known as GBS, is an encapsulated, gram-positive coccus that 
is associated with lower intestinal and rectovaginal colonization.  There are 10 serotypes of 
GBS (Ia, Ib, II, III, IV, V, VI, VII, VIII, and IX) differentiated by the polysaccharide 
composition of their capsule.  All GBS serotypes have been found to cause disease, but there 
is variability in their global prevalence and virulence.1,2  GBS disease is most frequently 
found in the very young—newborns and infants younger than 3 months of age—and the 
elderly, especially older adults with comorbid conditions.3,4,5,6  However, disease due to GBS 
has been reported in individuals of all ages, and pregnant women may be particularly 
susceptible to GBS disease as well.7  Among infants, GBS may cause serious disease,
including sepsis, meningitis, and pneumonia; less common manifestations include skin and 
soft tissue, bone, and joint infections.8  In pregnant women, GBS may be associated with 
ascending infections ranging from relatively benign urinary tract infections to 
chorioamnionitis (which may result in stillbirth or preterm delivery) and puerperal sepsis 
(which may be fatal).9  Bacteremia without a focus, cellulitis, bone and joint infections, and 
urinary tract infections are common disease manifestation of GBS infection in older 
nonpregnant adults.5,10,11
1.2.2. GBS Disease in Infants and Pregnant Women
GBS is a leading cause of invasive bacterial infection in young infants and a significant cause 
of infant morbidity and mortality globally.4,12,13  The US Centers for Disease Control and 
Prevention (CDC) notes that it is a leading infectious cause of morbidity and mortality in 
infants in the United States.14  Serious GBS disease, including sepsis, meningitis, and 
pneumonia, is associated with mortality rates of 6% to 14% in high-income countries and 
10% to 60% in low- and middle-income countries (LMICs).13,15,16,17  Of infants surviving 
GBS meningitis, one study found mild to moderate neurologic sequelae in 25%, and 19% 
suffered severe sequelae, including cognitive delay, cerebral palsy, blindness, or hearing 
loss.18  Five serotypes (Ia, Ib, II, III, V) are most frequently associated with GBS disease in 
infants.  Another serotype (IV) shows a trend of increased prevalence in certain regions.4  
GBS disease in infants is often classified as early-onset disease (EOD), which occurs within 
the first week of life, and late-onset disease (LOD), which occurs between Days 7 and 90.6  
The most common clinical syndrome in EOD is sepsis/bacteremia without a focus, whereas 
LOD is more likely to be associated with a focus,3,6,15 with meningitis being more common in 
LOD (21%-59% of LOD cases).3,6,15  Additionally, serotype III appears to be a relatively 
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prominent cause of LOD (causing 51%-67% of LOD),3,6,15 whereas there appears to be 
greater diversity of serotypes causing EOD.
The reported burden of infant GBS disease varies globally, and is influenced by the intensity 
of the epidemiology surveillance for the organism, as well as by the frequency of healthcare 
interaction. This may therefore lead to the potential for underreporting, and underuse of 
intrapartum antibiotic therapy (IAP) to prevent GBS disease.4  In regions, such as the United 
States, where there are significant efforts and resources allocated for universal GBS 
screening of pregnant women and use of IAP to prevent GBS disease, it is notable that the 
number of cases of EOD decreased from a high of 1.7 cases/1000 live births since the early 
1990s when recommendations for prevention were introduced to 0.25 cases/1000 live births
in 2014.19,20  Despite declines in pediatric bacterial meningitis cases in the United States 
between 2003 and 2007, the incidence in children <2 months of age was unchanged. This 
reflects the persistence of GBS LOD, which is the primary cause of bacterial meningitis in 
that age group. 21 The incidence was 0.28 cases/1000 live births in 2014.20 Despite 
significant declines in the incidence of pediatric bacterial meningitis, the incidence among 
infants under 2 months of age, which is the group at greatest risk for bacterial meningitis, did 
not decrease.21 GBS disease in pregnant and postpartum women does not appear to have 
been reduced through the introduction of IAP in the United States,14 as may be expected 
given the short course of administration during the intrapartum period only.  In other 
countries, such as in certain European countries, where interventions are less widely used or 
a risk-based approach is used, the trend in incidence rates may be unchanged or increasing 
slightly.6,22 Neither approach has eliminated GBS disease in infants.  Furthermore, many 
countries around the world do not have the resources to implement IAP. Even with potential 
underreporting, the highest rates of GBS disease are found in LMICs,15 where healthcare 
access and standards of prenatal care may vary, or the resources for significant preventive 
interventions are not available.
1.2.3. GBS Disease in Nonpregnant Adults
Adults 65 years of age are at increased risk for GBS disease, as are adults of all ages with 
associated comorbid conditions such as diabetes mellitus, cancer, heart failure, and 
neurologic and urologic conditions.3,5,6,23,24  According to the CDC Active Bacterial Core 
surveillance (ABCs) system, the annual US incidence of invasive GBS in 2014 was 21.1
cases/100,000 in adults 65 to 74 years of age, 33.1/100,000 in adults 75 to 84 years of age, 
and 41.8/100,000 in adults 85 years of age.20 The distribution of serotypes causing the bulk 
of invasive disease in older adults overlaps with the serotypes causing GBS disease in 
infants.  Serotype V, however, is more prominent in adults than infants, and serotype IV is 
also emerging.5,6,24,25
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1.2.4. Rationale for Development of GBS6
1.2.4.1. Maternal Immunization as an Approach to Prevent Disease in Infants and 
Pregnant Women
Vaccination of pregnant women has been used globally in the prevention of neonatal tetanus 
and more recently for prevention of pertussis in young infants, and to protect women and 
their infants against influenza.26,27 Tetanus toxoid vaccine has been used to vaccinate 
pregnant women in parts of the world for many years as an effective tool to induce 
immunoglobulin G (IgG) antibodies that cross the placenta and after birth prevent neonatal
tetanus.27 There is also increasing experience on the safety, effectiveness, and acceptance of 
influenza vaccine and tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccine 
(Tdap) for use in pregnant women in various regions of the world to prevent disease in 
newborns and infants. Maternal immunization against influenza was recommended by the US 
Advisory Committee on Immunization Practices (ACIP) in 2004.28  In addition, in 2009, 
because of the increased risks of influenza and related complications in pregnant women, the 
ACIP recommended that pregnant women receive both the inactivated influenza A H1N1 
(2009) monovalent vaccine and the inactivated seasonal influenza vaccine during any stage 
of pregnancy.29  Safety surveillance conducted to date has demonstrated no unusual patterns 
of pregnancy complications or fetal outcomes.30 In the United States, Tdap vaccination was 
initially introduced for unvaccinated pregnant women, and further expanded to all 
pregnancies in 2012. The United Kingdom also introduced a Tdap vaccination program of 
pregnant women; both of these measures were taken in response to a significant upsurge in 
pertussis cases in all ages.  To date, these vaccines have demonstrated an acceptable safety 
profile with single and repeat dosing.31,32
1.2.4.2. Maternal Antibody and Protection Against GBS Disease in Infants
During the third trimester of pregnancy, only IgG antibodies are actively transported across 
the placenta.  This provides a means for protective antibody to be transferred from a mother 
to her newborn.33  The efficiency of antibody transfer depends on placental integrity, 
maternal total IgG, gestational age at delivery, and IgG subclass (IgG1 subclass is most 
efficiently transferred).27 Researchers measured antibody in sera collected at delivery from 
GBS-colonized mothers whose infants had developed EOD, and in GBS-colonized women 
whose infants had not developed EOD.  There was a correlation between low maternal 
antibody concentration to serotype III (as measured in an IgG assay) and infant susceptibility 
to EOD due to serotype III.34  Since the initial study, additional work was conducted 
demonstrating the correlation between serotype Ia–specific anti–capsular polysaccharide 
(CPS) antibody in the mother and protection of the baby against GBS EOD due to 
serotype Ia, and a directional effect with the serotype V antibody.35,36,37,38  This suggests that 
anti-CPS antibody protects against GBS disease, a mechanism similar to that exploited 
against other encapsulated organisms, and the antibody is transported across the placenta. 
These findings support the biological plausibility that increasing the levels of maternal 
anti-CPS IgG antibody by vaccination of pregnant women with serotype-specific 
antigens will increase the proportion of women with potentially 
protective levels of IgG and will result in placental transfer of protective antibody to a large 
number of infants.
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1.2.6. Study Rationale
This Phase 1/2, randomized, placebo-controlled, observer-blinded study will be the 
first-in-human (FIH) evaluation of the investigational GBS6.
 
 
 
 
 
 
 
 
 
 
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Primary Objective and Endpoints
2.1.1. Primary Objective

To describe the safety and tolerability of various formulations of GBS6 at 3 dose levels in 
healthy adults 18 to 49 years of age.
2.1.2. Primary Endpoints
The endpoints for the primary objective are listed below, in chronological order according to 
time of collection in the study:

The proportion of sentinel-cohort subjects with clinical laboratory abnormalities 
following investigational product administration at the 1-week follow-up visit.

The proportion of subjects reporting prompted local reactions within 14 days following 
investigational product administration (redness, swelling, and pain at the injection site).

The proportion of subjects reporting prompted systemic events within 14 days following 
investigational product administration (fever, nausea/vomiting, diarrhea, headache, 
fatigue, muscle pain, and joint pain).

The proportion of subjects reporting adverse events (AEs) within 1 month following 
investigational product administration.

The proportion of subjects reporting medically attended adverse events (MAEs) and 
serious adverse events (SAEs) within 6 months following investigational product 
administration.
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2.2. Secondary Objective and Endpoint
2.2.1. Secondary Objective

To describe the immunogenicity of various formulations of GBS6 at 3 dose levels for all 
vaccine serotypes.
2.2.2. Secondary Endpoint

GBS serotype-specific IgG geometric mean concentrations (GMCs) measured 1 month
after vaccination.
 
 
3. STUDY DESIGN
This is a Phase 1/2, randomized, placebo-controlled, observer-blinded trial to evaluate the 
safety, tolerability, and immunogenicity of 3 ascending dose levels of GBS6 formulated with 
or without AlPO4 administered in healthy adults aged 18 to 49 years.
Approximately 363 healthy adults aged 18 to 49 years of age will be randomized to receive a 
single dose of 1 of 3 dose levels of GBS6 formulated with or without AlPO4 or placebo 
(saline control).  This study will utilize a sentinel-cohort design 
 
 
 
 
 
 Safety data through 14 days for subjects enrolled in each sentinel cohort will be 
reviewed and if deemed acceptable, enrollment of the expanded cohort will proceed at that 
same dose level. Enrollment of subjects into the sentinel cohort at the next dose level will be 
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initiated in parallel and each site is only allowed to enroll subjects into 1 cohort at a time.
Enrollment will proceed this way in a staggered fashion throughout the study (see Table 1
below for a graphic description of the enrollment/escalation plan).
Blood will be collected at screening and at the 1-week postvaccination follow-up visit in all 
subjects enrolled in each sentinel cohort for hematology and chemistry assessments.
 
 
 For all subjects, 
blood will also be collected on the day of investigational product administration prior to 
study vaccination and 1 week, 2 weeks, 1 month, 3 months, and 6 months after vaccination 
for immunogenicity assessment. Local reactions and systemic events will be collected for 
14 days after vaccination. AEs will be assessed up to 1 month after vaccination. SAEs and 
MAEs will be assessed through 6 months after vaccination. In addition, AEs occurring up to 
48 hours after the Visit 5 and Visit 6 blood draws that are related to study procedures will be 
collected.
 
 
 
 
 
 
 
 
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Table 1.
Enrollment and Dose Escalation Design
Dose Escalation
Enrollment Strategy
Lowest Dose Cohort
GBS6: 5 ga/AlPO4
GBS6: 5 ga /no 
AlPO4
Placebo (saline 
control)
Enroll 
sentinel
cohortb
(n=40)
Review 
14-day 
safety data 
Complete enrollment of 
expanded cohortd
(n=81)
Middle Dose Cohort
GBS6: 10 ga/AlPO4
GBS6: 10 ga/no 
AlPO4
Placebo (saline 
control)
Enroll 
sentinel
cohort
(n=40)
Review 14-
day safety 
data 
Complete 
enrollment of 
expanded cohort
(n=81)
Highest Dose Cohort
GBS6: 20 ga/AlPO4
GBS6: 20 ga/no 
AlPO4
Placebo (saline 
control)
Enroll 
sentinel
cohort
(n=40)
Review 
14-day 
safety 
data 
Complete 
enrollment of 
expanded cohort
(n=81)
Abbreviations: AlPO4 = aluminum phosphate; CPS = capsular polysaccharide; 
.
3.1. Duration of Subject Participation
Each subject will participate in the study for approximately 6 months.
3.2. Duration of Study
The study duration will be approximately 14 months.
3.3. Number of Subjects
Approximately 363 subjects will be enrolled, 52 at each dose level/formulation and 51 in the 
placebo group.  An allocation target will not be set by sex; however, the intention is for sites
to enroll at least 50% women within each dose level group.  If there is a predominance of one 
sex enrolled, the sponsor may give direction to sites about sex-based enrollment.  Refer to
Table 2 for a detailed description of the number of subjects per group.  Subjects who 
withdraw or are withdrawn from the study after randomization will not be replaced, 
regardless of the reason for withdrawal.
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Table 2.
Planned Subjects: Total and Number in Each Group
Dose Level/Formulation Groups
Approximate Number of Subjects
TOTAL
Lowest 
Dose
GBS6 lowest dose (5 μgc) with AlPO4
52
GBS6 lowest dose (5 μgc) without AlPO4
52
Placebo (saline control)
17
TOTAL
121
Middle 
Dose
GBS6 middle dose (10 μgc) with AlPO4
52
GBS6 middle dose (10 μgc) without AlPO4
52
Placebo (saline control)
17
TOTAL
121
Highest 
Dose
GBS6 highest dose (20 μgc) with AlPO4
52
GBS6 highest dose (20 μgc) without AlPO4
52
Placebo (saline control)
17
TOTAL
121
Study 
TOTAL
363
Abbreviations: AlPO4 = aluminum phosphate; CPS = capsular polysaccharide.
4. SUBJECT ELIGIBILITY CRITERIA
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate.  All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular subject is suitable for this protocol.
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study.
4.1. Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Evidence of a personally signed and dated informed consent document (ICD) indicating 
that the subject has been informed of all pertinent aspects of the study.
2. Willing and able to comply with scheduled visits, investigational plan, laboratory tests,
and other study procedures, including completion of the electronic diary (e-diary) from 
Day 1 to Day 14 following administration of investigational product.
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3. Healthy adults (male and female) 18 to 49 years of age at enrollment who are determined 
by medical history, physical examination, and clinical judgment of the investigator to be 
eligible for inclusion in the study.
4. Expected to be available for the duration of the study and who can be contacted by 
telephone during study participation.
5. Negative urine pregnancy test at Visit 1 (prior to vaccination) for all female subjects who 
are of childbearing potential.
Female subjects of nonchildbearing potential must meet at least 1 of the following 
criteria:
a.
Achieved postmenopausal status, defined as follows: cessation of regular menses for 
at least 12 consecutive months with no alternative pathological or physiological 
cause; status may be confirmed with a serum follicle-stimulating hormone (FSH) 
level confirming the postmenopausal state;
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy; 
c.
Have medically confirmed ovarian failure.
All other female subjects (including female subjects with tubal ligations) are considered 
to be of childbearing potential.
4.2. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or subjects 
who are Pfizer employees, including their family members, directly involved in the 
conduct of the study.
2. Participation in other studies involving investigational drug(s) within 28 days prior to 
study entry (Visit 0 for subjects in sentinel cohorts, Visit 1 for subjects in expanded 
cohorts) and/or during study participation. Participation in purely observational studies is 
acceptable.
3. Other acute or chronic medical or psychiatric condition, including recent (within the past 
year) or active suicidal ideation or behavior, or laboratory abnormality that may increase 
the risk associated with study participation or investigational product administration or 
may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the subject inappropriate for entry into this study.  Chronic 
medical conditions include human immunodeficiency virus (HIV), chronic hepatitis B 
virus (HBV) infection (HBV surface antigen positive), and/or hepatitis C virus infection.
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4. Male subjects and female subjects of childbearing potential who are unwilling or unable
to use a highly effective method of contraception as outlined in this protocol for at least 
3 months after the last dose of investigational product.
5. For sentinel-cohort subjects only, laboratory test results at the screening visit outside of 
the normal reference range.  Refer to Section 6.1 for additional guidance if abnormal 
laboratory test results are reported.
6. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the investigational product or any 
diphtheria toxoid–containing or 
.
7. History of microbiologically proven invasive disease caused by group B streptococcus 
(S agalactiae).
8. Immunocompromised subjects with known or suspected immunodeficiency. 
9. Subjects who receive treatment with immunosuppressive therapy, including cytotoxic 
agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned 
receipt through the 6-month postvaccination blood draw.  If systemic corticosteroids have 
been administered short term (<14 days) for treatment of an acute illness, subjects should 
not be enrolled into the study until corticosteroid therapy has been discontinued for at 
least 30 days before investigational product administration. Inhaled/nebulized, 
intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
10. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality 
that may increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this 
study.
11. Bleeding diathesis or condition associated with prolonged bleeding that would in the 
opinion of the investigator contraindicate intramuscular injection.
 
14. Receipt or planned receipt of blood/plasma products or immunoglobulin, from 60 days 
before investigational product administration through the 6-month postvaccination blood
draw.
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4.3. Temporary Delay Criteria
The following conditions are temporary or self-limiting and a subject may be vaccinated 
and/or have blood drawn in the study once the condition(s) has/have resolved and no other 
exclusion criteria are met.  The prevaccination immunogenicity blood draw and vaccination 
should take place on the same day (Visit 1).
4.3.1. Criteria for Temporarily Delaying Vaccine Administration

Current febrile illness (body temperature 100.4F [38C]) or other acute illness within 
48 hours before investigational product administration.

Receipt of any inactivated vaccine within 14 days and any live vaccine within 28 days 
before investigational product administration.

Receipt of short-term (<14 days) systemic corticosteroids.  Investigational product 
administration should be delayed until systemic corticosteroid use has been discontinued 
for at least 30 days. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) 
corticosteroids are permitted.
4.3.2. Criteria for Temporarily Delaying Blood Draw
The following condition does not apply to the blood draw for hematology and chemistry 
assessments performed at the screening visit (and rescreening visits).

Receipt of antibiotic therapy within 72 hours before blood draw.
4.4. Lifestyle Requirements
4.4.1. Contraception
All male subjects and female subjects who are of childbearing potential and are sexually 
active with one or more members of the opposite sex must agree to use a highly effective 
method of contraception consistently and correctly for at least 3 months after the last dose of 
investigational product.  The investigator or his or her designee, in consultation with the 
subject, will confirm that the subject has selected an appropriate method of contraception for 
the individual subject from the permitted list of contraception methods (see below) and will 
confirm that the subject has been instructed in its consistent and correct use.  At time points 
indicated in the schedule of activities, the investigator or designee will inform the subject of 
the need to use highly effective contraception consistently and correctly and document the
conversation and the subject’s affirmation in the subject’s chart (subjects need to affirm their 
consistent and correct use of at least 1 of the selected methods of contraception).  In addition, 
the investigator or designee will instruct the subject to call immediately if the selected 
contraception method is discontinued or if pregnancy is known or suspected in the subject or 
the partner.
The following highly effective methods of contraception that are acceptable for use in this 
study include:
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1. Established use of hormonal methods of contraception associated with inhibition of 
ovulation (eg, oral, inserted, injected, implanted, transdermal) provided the subject or 
male subject’s female partner plans to remain on the same treatment throughout the entire 
study and has been using that hormonal contraceptive for an adequate period of time to 
ensure effectiveness (at least 1 month).  Please note: All female subjects using any form 
of hormonal contraception other than an implanted form must also agree to use an 
additional method of contraception such as condoms with spermicide.
2. Correctly placed copper-containing intrauterine device (IUD).
3. Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label).
4. For male subjects, condoms WITH a separate spermicide product (ie, foam, gel, film, 
cream, or suppository).
5. Male sterilization with absence of sperm in the postvasectomy ejaculate.
4.5. 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 supporting study documentation.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational product identifiers, subject study numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study. The contact number can also be used by investigator
staff if they are seeking advice on medical questions or problems; however, it should be used
only in the event that the established communication pathways between the investigator site 
and the study team are not available. It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study. The contact 
number is not intended for use by the subject directly, and if a subject calls that number, he 
or she will be directed back to the investigator site.
5. INVESTIGATIONAL PRODUCTS
For the purposes of this study, and per International Council for Harmonisation (ICH)
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33).
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For this study, the investigational product(s) are GBS6 (containing 5, 10, or 20 μg
CPS/serotype/dose, each formulated with or without AlPO4) and placebo (saline control).
Subjects will receive 1 dose of either GBS6, with or without AlPO4, or placebo (saline 
control) at Visit 1 administered intramuscularly by injecting 0.5 mL into the deltoid muscle, 
preferably of the nondominant arm. See Table 2 for more information on the investigational
product dose-level/formulation groups.
5.1. Subject Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
5.2. Investigational Product Supplies
GBS6 and placebo (saline control) will be provided by the sponsor to each study site.
Study vaccines will be packed and labeled as investigational product in accordance with 
current guidelines and applicable local and legal regulatory requirements.  The formulation 
of the investigational products is described below.
5.2.1. Dosage Form(s) and Packaging
GBS6 is composed of serotypes Ia, Ib, II, III, IV, and V CPS individually conjugated to the 
. 
 
There are 3 dose levels (5, 10, or 20 μg 
CPS/serotype/
each formulated either with 
AlPO4, 
, or without AlPO4.  See Table 3 for 
further details.
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5.2.2. Preparation and Dispensing
Investigational product preparation and dosing information will be provided in the 
investigational product (IP) manual.
GBS6 and placebo will be prepared by qualified unblinded site personnel according to the IP
manual.  The investigational product will be administered by qualified unblinded site 
personnel who keep the subjects blinded, 
 
The investigational product will be assigned using an interactive response technology (IRT)
drug management system at Visit 1.  The IRT system will assign subjects a unique container 
number from the system, which will be printed on the carton and the vial within the carton.  
Qualified unblinded personnel will dispense the assigned investigational product for 
preparation and administration.
 
5.3. Allocation to Investigational Product
Allocation of subjects to investigational product groups will be performed through the use of 
an IRT system (interactive Web-based response [IWR]). The unblinded dispensing 
personnel will be required to enter or select information including but not limited to the 
user’s identification (ID) and password, the protocol number, and the subject number. The 
unblinded dispenser will then be provided with a randomization number, investigational 
product assignment, and container number when investigational product is being supplied via 
the IRT system.  The IRT system will provide a confirmation report containing the subject 
number, randomization number, and container number assigned. The confirmation report 
must be retained by the unblinded dispenser in the unblinded site files.
The study-specific IRT quick reference guide will provide the contact information and 
further details on the use of the IRT system.
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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.
Preparation and administration of investigational products should be performed by an 
appropriately qualified, Good Clinical Practice (GCP)-trained, and vaccine-experienced 
member of the study staff (eg, physician, nurse, physician’s assistant, nurse practitioner, 
pharmacist, or medical assistant) as allowed by local, state, and institutional guidance.
Investigational product administration details will be recorded on the case report form (CRF).
Subjects will receive 1 dose of either GBS6, formulated with or without AlPO4, or placebo 
(saline control) at Visit 1 in accordance with the study’s schedule of activities.
GBS6 or placebo (saline control) should be administered intramuscularly by injecting 0.5 mL 
into the deltoid muscle, 
 
 
5.5. Investigational Product Storage
The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational products are stored in a secured area with controlled access under required 
storage conditions and in accordance with applicable regulatory requirements.
Investigational products should be stored in their original containers and in accordance with 
the labels.
Investigational product will be shipped at +2C to +8C to each study site after required 
regulatory and legal documents have been received by the sponsor.  Upon receipt at the study 
site, the investigational product should be immediately transferred to a +2C to +8C 
temperature-monitored refrigerator for storage.
The unblinded dispenser/administrator will ensure that all investigational products are stored 
in a secured area with controlled access under required storage conditions and in accordance 
with applicable regulatory requirements.
Any storage conditions stated in the SRSD (GBS6 IB) will be superseded by the storage 
conditions stated on the product label.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations 
(as applicable, including frozen, refrigerated, and/or room-temperature products).  This 
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should be captured from the time of investigational product receipt throughout the study.  
Even for continuous-monitoring systems, a log or site procedure that ensures active 
evaluation for excursions should be available.  The intent is to ensure that the minimum and 
maximum temperature is checked each business day to confirm that no excursion occurred 
since the last evaluation and to provide the site with the capability to store or view the 
minimum/maximum temperature for all nonworking days upon return to normal operations.  
The operation of the temperature-monitoring device and storage unit (for example, 
refrigerator), as applicable, should be regularly inspected to ensure they are maintained in 
working order.
Any excursions from the product label storage conditions should be reported to Pfizer upon 
discovery.  The site should actively pursue options for returning the product to the storage 
conditions described in the labeling, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer.
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides permission to use the investigational product.  It will not be considered a 
protocol deviation if Pfizer approves the use of the investigational product after the 
temperature excursion. Use of the investigational product prior to Pfizer approval will be 
considered a protocol deviation. Specific details regarding information the site should report 
for each excursion will be provided to the site in the IP manual.
5.6. Investigational Product Accountability
The unblinded dispenser/administrator at the investigator site must maintain adequate records 
documenting the receipt, use, loss, or other disposition of the investigational product 
supplies.  All investigational products will be accounted for using a drug accountability 
form/record.
5.6.1. Destruction of Investigational Product Supplies
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site).  If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
5.7. Blinding of the Site Personnel
 
  The study staff dispensing and administering the vaccine will be unblinded, but all 
other study personnel, including the principal investigator, and the subject, will be blinded. 
The principal investigator will assign the responsibility of unblinded dispenser and unblinded 
administrator to persons who will not participate in the evaluation of any study subject. More 
than 1 unblinded dispenser/administrator may be assigned. A member of the study site staff 
or clinic pharmacy should fulfill this role. Contact between the unblinded 
dispenser/administrator and study subjects should be kept to a minimum. The investigator, 
study coordinator, and any site staff other than the unblinded dispenser/administrator must 
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not be allowed to know the investigational product assigned to any study subject and must 
not be allowed to see the investigational product containers.
5.8. Blinding of the Sponsor
Sponsor study team members will remain blinded to vaccine assigned/received at the subject 
level, following the principles outlined in ICH E9 guideline on Statistical Principles for 
Clinical Trials, Section 2.3.1,56 until the analysis of all available safety and immunogenicity 
data 1 month after vaccination. In an event that unblinded results need to be submitted for 
regulatory communications prior to study team unblinding at the planned analysis, efforts 
will be made to ensure study team members involved in subject assessments are blinded.
Certain sponsor personnel not directly involved in the conduct of the study will review 
unblinded data as defined in an IRC charter per Pfizer standard operating procedures (SOPs). 
Unblinded sponsor personnel who are not part of the study team will be assigned to assess 
whether a stopping rule is triggered for ongoing safety review as well as to work with an
independent statistical team center for IRC review activities. Laboratory personnel 
performing the immunologic assays will remain blinded to vaccine assigned/received 
throughout the study.
5.9. Breaking the Blind
The study will be subject and investigator blinded.
At the initiation of the study, the investigator site will be instructed on the method for 
breaking the blind.  The method will be an electronic process.  Blinding codes should be 
broken only in exceptional circumstances when knowledge of the actual treatment code is 
absolutely essential for further management of the subject. Investigators are encouraged to 
discuss with a member of the study team if they believe that unblinding is necessary. When 
the blinding code is broken, the reason must be fully documented and entered on the CRF.
5.10. Concomitant Treatment(s)
5.10.1. Prohibited Nonstudy Vaccines and Medications During the Study

Investigational vaccines, drugs, or medical devices are prohibited during the course of the 
study.

Nonstudy 
 vaccines, blood/plasma products or 
immunoglobulins, and immunosuppressive therapy are prohibited during the course of 
the study.

Other nonstudy vaccines may not be given concomitantly with the investigational product 
or within 14 days after investigational product administration (except during an outbreak 
or pandemic situation).
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5.10.2. Permitted Nonstudy Vaccines and Medications During the Study

Licensed influenza vaccine may be given during the study starting 15 days after 
investigational product administration. If medically necessary (eg, pandemic), influenza 
vaccine may be given at any time.

Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted.

The use of antipyretics and other pain medication to treat symptoms associated with 
investigational product administration is permitted during subject participation in the 
study.

The use of prophylactic antipyretic medication, while permitted, is not recommended on 
the day prior to vaccination or the day of the investigational product administration.
5.10.3. Recording Nonstudy Vaccinations and Concomitant Medications
The name and date of administration for all nonstudy vaccinations received from the time of 
signing of the ICD to Visit 6 will be collected and recorded in the CRF.
Any medications taken from the signing of the ICD through Visit 4 will be recorded in the 
CRF.  Additionally, any medication taken to treat AEs (per Section 8.1.4) from the signing of 
the ICD through Visit 6 will be recorded in the CRF.
6. STUDY PROCEDURES
The schedule of procedures is summarized in the schedule of activities.  The day of 
vaccination is considered Day 1.
6.1. Visit 0 – Screening for Sentinel-Cohort Subjects (Days -14 to -2 Prior to 
Vaccination)
Subjects will be screened from 2 to 14 days prior to administration of the investigational 
product to confirm that they meet eligibility (all of the inclusion and none of the exclusion)
criteria for the study.
In the 14-day screening period, retesting of the clinical laboratory parameters will be allowed 
at the discretion of the investigator if abnormal test results are observed and if the 
investigator believes the results to be erroneous.  In this circumstance, subjects will return for 
a second screening visit within the 14-day screening period to reevaluate the abnormal 
laboratory parameters.
If the subject is found ineligible for the study on the basis of hematology and/or blood 
chemistry laboratory assessment and repeat testing is not warranted, the investigator may 
advise the subject of the results by telephone, and the subject will be withdrawn from further 
participation in the study.  All eligible subjects (without laboratory abnormalities) will 
proceed to Visit 1.
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The following procedures will be performed:

Obtain written informed consent before performing any study-specific procedures.

Assign single subject identifier using the IRT system.

Obtain and record the subject demography (including date of birth, sex, race, and 
ethnicity).

Obtain and record any medical history of clinical significance.

Perform physical examination evaluating any clinically significant abnormalities within 
the following body systems: general appearance; skin; head, eyes, ears, nose, and throat; 
heart; lungs; abdomen; musculoskeletal; extremities; neurological; and lymph nodes. 
Abnormal results must be recorded on source documents and the Physical Examination 
page of the CRF.

Measure vital signs, including weight, height, sitting blood pressure and pulse rate, 
respiratory rate, and temperature (oral).

Ensure and document that all of the inclusion criteria and none of the exclusion criteria 
are met, Section 4.

Obtain a blood sample (approximately 10 mL) for hematology and blood chemistry 
assessments.  Subjects with abnormal laboratory results (see below and Section 7.5.3) 
will not be eligible for randomization.  The following parameters will be assessed:

Hematology:  hemoglobin, hematocrit, red blood cell (RBC) count, white blood cell 
(WBC) count with differential, and platelets.

Blood chemistries:  alanine aminotransferase (ALT), aspartate aminotransferase 
(AST), alkaline phosphatase, total bilirubin, blood urea nitrogen (BUN), and 
creatinine.

Record nonstudy vaccinations and medications as described in Section 5.10.3.

Record AEs as described in Section 7.8 and Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRF.
6.2. Visit 0 – Rescreening Visit for Sentinel-Cohort Subjects (Days -14 to -2 Prior to 
Vaccination), If Applicable
If abnormal laboratory parameters are reported at Visit 0 and the investigator believes the 
results to be erroneous, a second screening visit may be conducted. The following 
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information will be collected and the following assessments will be made at a rescreening 
visit:

Ensure and document that all of the inclusion criteria and none of the exclusion criteria 
are met, Section 4.

Obtain a blood sample (approximately 10 mL) for analysis of hematology and blood 
chemistries, Section 7.5.3.  Retest only abnormal laboratory parameters from Visit 0.

Record nonstudy vaccinations and medications as described in Section 5.10.3.

Record AEs as described in Section 7.8 and Section 8.

Complete the source documents.

The investigator or an authorized designee completes the CRF.
If the subject is subsequently found ineligible for the study on the basis of hematology and/or 
blood chemistry laboratory assessment, the investigator may advise the subject of the results 
by telephone, and the subject will be withdrawn from further participation in the study. All 
eligible subjects will proceed to Visit 1.
6.3. Visit 1 – Vaccination (Day 1) for Sentinel-Cohort Subjects

Ensure that the subject continues to be eligible for the study, meets none of the subject 
withdrawal criteria as described in Section 6.11, and meets none of the temporary delay 
criteria as described in Section 4.3.

Review laboratory results.

Prior to vaccination, measure vital signs, including weight, height, sitting blood pressure 
and pulse rate, respiratory rate, and temperature (oral).

Prior to vaccination, perform a urine pregnancy test for female subjects of childbearing 
potential.

Prior to vaccination, collect a blood sample of approximately 30 mL for immunogenicity 
assessments. 

 

 
 

Verify understanding of and compliance with protocol requirements for contraception.
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
A blinded site staff member will use the IRT system to obtain the subject’s randomization
number. An unblinded site staff member will use the IRT system to assign the 
investigational product container number, prepare the investigational product, and deliver 
it to the investigational product administrator. Please refer to the IP manual for further 
instruction on this process.

The unblinded administrator administers a single 0.5-mL injection of investigational 
product into the deltoid muscle, preferably of the nondominant arm.

Blinded site staff must observe the subject for at least 30 minutes after investigational 
product administration for any acute reactions.  Record any acute reactions in the 
subject’s source documents and on the AE page of the CRF, and on an SAE form as 
applicable.

Issue a measuring device to measure local reactions and a digital thermometer for 
recording daily temperatures, and provide instructions on their use.

Issue the subject an e-diary and provide instructions on its completion.  Ask the subject to 
complete the e-diary from Day 1 to Day 14, with Day 1 being the day of vaccination.

Ask the subject to contact the site staff or investigator immediately if he or she is 
prompted by the e-diary from Day 1 to Day 14 following vaccination to determine if an 
unscheduled visit is required (eg, redness or swelling at the injection site measuring 
21 measuring device units [10.5 cm], etc).  Remind subjects that study staff may 
contact them to obtain additional information on Grade 3 events entered into the e-diary.

Ask the subject to contact the site staff or investigator if a medically attended event
(eg, emergency room) or hospitalization occurs.

Record nonstudy vaccinations and medications as described in Section 5.10.3.

Record AEs as described in Section 7.8 and Section 8.

Complete the subject’s source documents.

The investigator or an authorized designee completes the CRF and an unblinded site staff 
member updates the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate subject compliance and as part of the ongoing safety 
review.
6.4. Visit 1 – Vaccination (Day 1) for Expanded-Cohort Subjects

Obtain written informed consent before performing any study-specific procedures.

Assign single subject identifier using the IRT system.
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
Obtain and record the subject demography (including date of birth, sex, race, and 
ethnicity).

Obtain and record any medical history of clinical significance.

Perform physical examination evaluating any clinically significant abnormalities within
the following body systems: general appearance; skin; head, eyes, ears, nose, and throat; 
heart; lungs; abdomen; musculoskeletal; extremities; neurological; and lymph nodes. 
Abnormal results must be recorded on source documents and the Physical Examination 
page of the CRF.

Ensure and document that all of the inclusion criteria, none of the exclusion criteria, and 
none of the temporary delay criteria are met.

Prior to vaccination, measure vital signs, including weight, height, sitting blood pressure 
and pulse rate, respiratory rate, and temperature (oral).

Prior to vaccination, perform a urine pregnancy test for female subjects of childbearing 
potential.

Prior to vaccination, collect a blood sample of approximately 30 mL for immunogenicity 
assessments. 

 


Verify understanding of and compliance with protocol requirements for contraception.

A blinded site staff member will use the IRT system to obtain the subject’s randomization 
number. An unblinded site staff member will use the IRT system to assign the 
investigational product container number, prepare the investigational product, and deliver 
it to the investigational product administrator. Please refer to the IP manual for further 
instruction on this process.

The unblinded administrator administers a single 0.5-mL injection of investigational 
product into the deltoid muscle, preferably of the nondominant arm.

Blinded site staff must observe the subject for at least 30 minutes after investigational 
product administration for any acute reactions.  Record any acute reactions in the 
subject’s source documents and on the AE page of the CRF, and on an SAE form as 
applicable.
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
Issue a measuring device to measure local reactions and a digital thermometer for 
recording daily temperatures, and provide instructions on their use.

Issue the subject an e-diary and provide instructions on its completion.  Ask the subject to 
complete the e-diary from Day 1 to Day 14, with Day 1 being the day of vaccination.

Ask the subject to contact the site staff or investigator immediately if he or she is 
prompted by the e-diary from Day 1 to Day 14 following vaccination to determine if an 
unscheduled visit is required (eg, redness or swelling at the injection site measuring 
21 measuring device units [10.5 cm], etc).  Remind subjects that study staff may 
contact them to obtain additional information on Grade 3 events entered into the e-diary.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, emergency room) or hospitalization occurs.

Record nonstudy vaccinations and medications as described in Section 5.10.3.

Record AEs as described in Section 7.8 and Section 8.

Complete the subject’s source documents.

The investigator or an authorized designee completes the CRF and unblinded site staff 
member updates the investigational product accountability records.

The investigator or appropriately qualified designee reviews the e-diary data online 
following vaccination to evaluate subject compliance and as part of the ongoing safety 
review.
6.5. Visit 2 – 1-Week Follow-up Visit (7-10 Days After Visit 1) for All Subjects

Ensure that the subject continues to be eligible for the study, meets none of the subject 
withdrawal criteria as described in Section 6.11, and meets none of the blood draw 
temporary delay criteria as described in Section 4.3.

Verify understanding of and compliance with protocol requirements for contraception.

Collect a blood sample of approximately 30 mL for immunogenicity assessments.

For sentinel-cohort subjects only, obtain a blood sample (approximately 10 mL) for 
hematology and blood chemistry assessments.

Remind the subject to complete the e-diary from Day 1 to Day 14, with Day 1 being the 
day of vaccination.

Ask the subject to contact the site staff or investigator immediately if he or she is 
prompted by the e-diary from Day 1 to Day 14 following vaccination to determine if an 
unscheduled visit is required (eg, redness or swelling at the injection site measuring 
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21 measuring device units [10.5 cm], etc).  Remind subjects that study staff may 
contact them to obtain additional information on Grade 3 events entered into the e-diary.

Ask the subject to contact the site staff or investigator if a medically attended event 
(eg, emergency room) or hospitalization occurs.

The investigator or appropriately qualified designee reviews the e-diary data online to 
evaluate subject compliance and as part of the ongoing safety review.

Record nonstudy vaccinations and medications as described in Section 5.10.3.

Record AEs as described in Section 7.8 and Section 8.

Complete the subject’s source documents.

The investigator or an authorized designee completes the CRF.
6.6. Visit 3 – 2-Week Follow-up Visit (14-17 Days After Visit 1) for All Cohort Subjects

Ensure that the subject continues to be eligible for the study, meets none of the subject 
withdrawal criteria as described in Section 6.11, and meets none of the blood draw 
temporary delay criteria as described in Section 4.3.

Verify understanding of and compliance with protocol requirements for contraception.

Collect a blood sample of approximately 30 mL for immunogenicity assessments.

For sentinel-cohort subjects only, review laboratory results from the 1-week follow-up 
visit.

Review the subject’s e-diary data and collect the e-diary. Collect stop dates of any e-diary 
events ongoing on the last day that the e-diary was completed and record stop dates in the 
CRF.

Record nonstudy vaccinations and medications as described in Section 5.10.3.

Record AEs as described in Section 7.8 and Section 8.

Complete the subject’s source documents.

The investigator or an authorized designee completes the CRF.
6.7. Visit 4 – 1-Month Follow-up Visit (28-38 Days After Visit 1) for All Cohort Subjects

Ensure that the subject continues to be eligible for the study, meets none of the subject 
withdrawal criteria as described in Section 6.11, and meets none of the blood draw 
temporary delay criteria as described in Section 4.3.
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
Verify understanding of and compliance with protocol requirements for contraception.

Collect a blood sample of approximately 30 mL for immunogenicity assessments.
Alternatively, for subjects who have consented to participate in the subset, collect 
approximately 50 mL of blood.

Record nonstudy vaccinations and medications as described in Section 5.10.3.

Record AEs as described in Section 7.8 and Section 8.

Complete the subject’s source documents.

The investigator or an authorized designee completes the CRF.
6.8. Visit 5 – 3-Month Follow-up Visit (80-100 Days After Visit 1) for All Cohort 
Subjects

Ensure that the subject continues to be eligible for the study, meets none of the subject 
withdrawal criteria as described in Section 6.11, and meets none of the blood draw 
temporary delay criteria as described in Section 4.3.

Verify understanding of and compliance with protocol requirements for contraception.

Collect a blood sample of approximately 30 mL for immunogenicity assessments.

Record nonstudy vaccinations as described in Section 5.10.3.

Record AEs as described in Section 7.8 and Section 8.

Complete the subject’s source documents.

The investigator or an authorized designee completes the CRF.
6.9. Visit 6 – 6-Month Follow-up Visit (160-200 Days After Visit 1) for All Cohort 
Subjects

Ensure that the subject continues to be eligible for the study, meets none of the subject 
withdrawal criteria as described in Section 6.11, and meets none of the blood draw 
temporary delay criteria as described in Section 4.3.

Collect a blood sample of approximately 30 mL for immunogenicity assessments.

Record nonstudy vaccinations as described in Section 5.10.3.

Record AEs as described in Section 7.8 and Section 8.

Complete the subject’s source documents.
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
The investigator or an authorized designee completes the CRF.
6.10. Unscheduled Visits
If the subject reports redness or swelling at the injection site measuring 21 measuring 
device units (10.5 cm), fever 102.1F (39.0C), or severe injection site pain,
nausea/vomiting, diarrhea, headache, fatigue, muscle pain, or joint pain, a telephone contact 
must occur as soon as possible between the subject and the investigator or a medically 
qualified member of the study site staff to assess if an unscheduled visit is required. A site 
visit must be scheduled as soon as possible to assess the extent of the reaction unless:

The subject is unable to attend the unscheduled visit, or

The reaction is no longer present at the time of the telephone contact, or

The subject recorded an incorrect value in the e-diary (confirmation of an e-diary data 
entry error).

The investigator determined it was not needed.
This telephone contact will be recorded in the CRF and in the subject’s source 
documentation.
If the subject is unable to attend the unscheduled visit, any ongoing reactions must be 
assessed at the next scheduled visit (Visit 2, 3, and/or 4).
The reactions should be assessed by the investigator or a medically qualified member of the 
study staff such as a study physician or a study nurse, as applicable to the investigator’s local 
practice, who will:

Measure oral temperature.

Measure minimum and maximum diameters of redness (if present).

Measure minimum and maximum diameters of swelling (if present).

Assess any injection site pain that is present in accordance with the grading scale 
provided in Section 7.5.2.

Assess for lymphadenopathy associated with any present local reaction.

Assess any systemic events (nausea/vomiting, diarrhea, headache, fatigue, muscle pain, 
or joint pain) that are present in accordance with the grading scale provided in
Section 7.5.2.
The investigator or an authorized designee will complete the unscheduled visit page of the
CRF.
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Subjects will also be instructed to contact site staff if they experience any possible Grade 4 
prompted systemic event (ie, emergency room visit or hospitalization for headache, fatigue, 
muscle pain, joint pain, etc) within 14 days after vaccination.  Study staff may contact the 
subject to obtain additional information on Grade 3 events entered into the e-diary.  Lastly, 
subjects will be instructed to contact the site to report any significant illness, medical event,
or hospitalization that occurs during the study period.  The site should determine if an 
unscheduled visit to further evaluate the event is warranted in all such cases.
6.11. Subject Withdrawal
An investigator and/or sponsor can withdraw a subject from the study if deemed appropriate.  
In addition, if a subject fails to continue to meet the inclusion criteria, new information 
becomes available that would exclude the subject, or the subject develops a condition or 
situation that would meet exclusion criteria 
 
, the subject may be considered for withdrawal.
Reasons why a subject may discontinue or be withdrawn from the study include, but are not 
limited to, failure to meet entrance criteria (screening failure), AE, death, pregnancy, 
protocol violation, lost to follow-up, no longer willing to participate in the study, study 
terminated by sponsor, investigator declined further study participation, or any other reason.  
Subjects who have received the investigational product will not be replaced regardless of the 
reason for withdrawal.
6.11.1. Withdrawal of Consent
After investigational product administration at Visit 1, subjects who request to discontinue 
further study procedures (eg, blood draws) at upcoming visits, ie, Visits 2 to 6, will be asked 
to remain in the study for protocol-specified safety follow-up procedures. The only 
exception to this is when a subject specifically withdraws consent for any further contact 
with him or her. It is permissible that Visit 5 and Visit 6 be conducted via telephone contact
for subjects who are staying in the study for protocol-specified safety follow-up procedures
only.  Subjects should notify the investigator in writing of the decision to withdraw consent 
from future follow-up, whenever possible. The withdrawal of consent should be explained in 
detail in the medical records by the investigator, as to whether the withdrawal is only from 
further study procedures (eg, blood draws) and/or postvaccination study safety follow-up, 
and entered on the appropriate CRF page.
6.11.2. Lost to Follow-up
All reasonable efforts must be made to locate subjects to determine and report their ongoing
status. This includes follow-up with persons authorized by the subject as noted above. Lost 
to follow-up is defined by the inability to reach the subject after a minimum of 2 documented 
phone calls, faxes, or emails as well as lack of response by the subject to 1 registered mail 
letter. All attempts should be documented in the subject’s medical records. If it is 
determined that the subject has died, the site will use locally permissible methods to obtain 
the date and cause of death. If the investigator’s use of a third-party representative to assist 
in the follow-up portion of the study has been included in the subject’s informed consent, 
then the investigator may use a sponsor-retained third-party representative to assist site staff 
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with obtaining the subject’s contact information or other public vital status data necessary to 
complete the follow-up portion of the study. The site staff and representative will consult 
publicly available sources, such as public health registries and databases, in order to obtain 
updated contact information. If, after all attempts, the subject remains lost to follow-up, then 
the last-known-alive date as determined by the investigator should be reported and 
documented in the subject’s medical records.
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety (see also the 
Withdrawal From the Study Due to Adverse Events section, Section 8.1.3) or behavioral 
reasons, or the inability of the subject to comply with the protocol-required schedule of study 
visits or procedures at a given study site.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  All attempts to contact the subject and information received during contact attempts 
must be documented in the subject’s medical record.  In any circumstance, every effort 
should be made to document subject outcome, if possible.  The investigator should inquire 
about the reason for withdrawal, request that the subject return for a final visit, if applicable, 
and follow up with the subject regarding any unresolved AEs.
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test. In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the subject. When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible. The 
study team will be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
7.1. Pregnancy Testing
For female subjects of childbearing potential, a urine pregnancy test, with sensitivity of at 
least 25 mIU/mL, will be performed immediately before administration of investigational 
product.  A negative pregnancy test result is required before the subject may receive the 
investigational product. Pregnancy tests may also be repeated if requested by institutional 
review boards (IRBs)/ethics committees (ECs) or if required by local regulations. In the case 
of a positive confirmed pregnancy, the subject will be withdrawn from administration of 
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investigational product and from the study.  In the case of a positive confirmed pregnancy 
after administration of investigational product, the subject may remain in the study for blood 
sample collections and safety monitoring.
7.2. 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. 
Samples that remain after performing assays outlined in the protocol may be stored by Pfizer. 
Unless a time limitation is required by local regulations or ethical requirements, the samples 
will be stored for up to 15 years after the end of the study and then destroyed.  If allowed by 
the ICD, stored samples may be used for additional testing to better understand the immune 
responses to the vaccine(s) under study in this protocol, to inform the development of other 
products, and/or for vaccine-related assay work supporting vaccine programs.  No testing of 
the subject’s genetic material will be performed.
The subject may request that his or her samples, if still identifiable, be destroyed at any time; 
however, any data already collected from those samples will still be used for this research.  
The biological samples may be shared with other researchers as long as confidentiality is 
maintained and no testing of the subject’s genetic material is performed.
7.3. Immunogenicity
Blood samples (approximately 30 mL/visit) for immunogenicity assessments will be 
collected from all subjects prior to vaccination (Day 1) and at 1 week, 2 weeks, 1 month, 
3 months, and 6 months after vaccination.  Sample collection, processing, storage, and 
shipping information can be found in the 
.
The total volume of blood collected from each subject for immunogenicity will be 
approximately 180 mL (~30 mL/visit), or up to approximately 200 mL for those subjects 
who consent to a larger blood draw (~50 mL) at Visit 4.  Sera will be used for 
immunogenicity assessments and assay development purposes.
 
 
 
 
 
Immunogenicity assays will be performed at Pfizer Vaccine Research & Development 
Laboratory located at 401 North Middletown Road, Pearl River, NY 10965 and/or at a 
facility designated by Pfizer.
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7.5. Safety Parameters
Safety parameters will be assessed as described in the schedule of activities, Section 6, and 
below.
A medical history and physical examination will be performed on all subjects, to establish a 
baseline.  Significant medical history and observations from the physical examination will be 
documented in the CRF.
The safety parameters include e-diary reports of local reactions and systemic events that 
occur in the 14 days after investigational product administration. These prospectively 
collected occurrences of local reactions and systemic events are graded as described in
Section 7.5.2.
Acute reactions within the first 30 minutes after investigational product administration will 
be assessed and documented in the AE CRF.
In addition, AEs, MAEs, and SAEs are collected, recorded, and reported as defined in
Section 8.
7.5.1. Subject Electronic Diary
The subject will be asked to monitor and record local reactions, systemic events, fever, and 
antipyretics/pain medication used to treat symptoms, each evening for 14 days following 
vaccination (Day 1 through Day 14, where Day 1 is the day of vaccination) on a system that 
uses a personal digital assistant (PDA) or other technology.  This system, hereafter referred 
to as the subject’s 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.  
Data on local reactions, systemic events, and antipyretics/pain medication used to treat 
symptoms reported on the e-diary will be transferred electronically to the e-diary vendor, 
where they will be available for review by investigators, their qualified designees, and 
sponsor staff at all times via an internet-based portal.  At intervals agreed to by the vendor 
and Pfizer, these data will be transferred electronically to Pfizer for analysis and reporting.  
These data do not need to be reported by the investigator in the CRF.  However, if a subject 
withdraws because of prompted events reported in the e-diary, the event(s) should be 
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recorded on the AE page of the CRF, regardless of whether the investigator considers the 
event(s) to be clinically significant.
Investigators (or appropriately qualified designee) are required to review the e-diary data 
online to evaluate subject compliance and as part of the ongoing safety review (see Stopping 
Rules in Section 7.7).
The investigator or designee must contact the subject in order to obtain stop dates for any 
reactions 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 in the CRF by Visit 4.
7.5.2. Grading Scale for Prompted Events
The grading scales used in this study to assess AEs as described below are based on concepts 
outlined in the Food and Drug Administration (FDA) Center for Biologics Evaluation and 
Research (CBER) guidelines on toxicity grading scales for healthy adult volunteers enrolled 
in preventive vaccine clinical trials.57
7.5.2.1. Local Reactions
From Day 1 to Day 14, where Day 1 is the day of vaccination, subjects will be asked to 
assess redness, swelling, and pain at the injection site and to record the symptoms in the 
e-diary in the evening.  Redness and swelling will be measured and recorded in measuring 
device units (range: 1 to 21+), and then categorized during analysis as mild, moderate, or 
severe based on the grading scale in Table 4 below.  Measuring device units can be converted 
to centimeters according to the following scale: 1 measuring device unit = 0.5 cm.  Pain at 
the vaccine injection site will be assessed by the subject as mild, moderate, or severe 
according to the grading scale in Table 4 below.  A subject with a severe (Grade 3 or above) 
local reaction will be prompted to contact the investigator to perform an unscheduled visit 
and assess the reaction.
Only an investigator is able to classify a subject’s local reaction as Grade 4, after physical 
examination of the subject or documentation from another medically qualified source 
(eg, emergency room or hospital record), or, in the case of pain at the injection site only, 
telephone contact with the subject.  If a subject experiences a Grade 4 local reaction, the 
investigator must immediately notify the sponsor. Site staff will educate the subject regarding 
signs and symptoms that would prompt site contact. The procedure for notification of the 
sponsor is provided in the study documentation.
If a local reaction persists beyond the end of the e-diary period following vaccination, the 
subject will be requested to report that information and/or any new AEs that develop to the 
investigator.  The investigator will enter this additional information in the CRF.
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Table 4.
Local Reaction Grading Scale
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)a
Grade 4b
Pain at 
injection site
Does not interfere 
with activity
Repeated use of nonnarcotic 
pain reliever >24 hours 
or interferes with activity
Any use of narcotic pain 
reliever or prevents daily 
activityc
Emergency 
room visit or 
hospitalization
Erythema/
Redness
2.5 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm (11 to 
20 measuring device units)
>10 cm (21 measuring 
device units)
Necrosis or 
exfoliative 
dermatitis
Induration/
Swelling
2.5 cm to 5.0 cm 
(5 to 10 measuring 
device units)
>5.0 cm to 10.0 cm (11 to 
20 measuring device units)
>10 cm (21 measuring 
device units)
Necrosis
a.
Subjects experiencing Grade 3 local reactions are to be seen by the study site.
b.
Grade 4 assessment should be made by the investigator. Grade 4 will not be collected in the electronic diary
but will be recorded as an AE on the case report form.
c.
Prevents daily activity, ie, results in missed days of work or school or is otherwise incapacitating, or 
includes use of narcotics for analgesia.
7.5.2.2. Systemic Events
From Day 1 to Day 14, where Day 1 is the day of vaccination, subjects will be asked to 
assess nausea/vomiting, diarrhea, headache, fatigue, muscle pain, and joint pain and to record 
the symptoms in the e-diary in the evening.  The symptoms will be assessed by the subject as 
mild, moderate, or severe according to the grading scale in Table 5 below. Subjects will also 
be instructed to contact site staff if they experience any possible Grade 4 prompted systemic
event (ie, emergency room visit or hospitalization for nausea/vomiting, diarrhea, headache, 
fatigue, muscle pain, or joint pain) within 14 days after vaccination.  Study staff may also
contact the subject to obtain additional information on Grade 3 events entered into the 
e-diary.
Only an investigator is able to classify a subject’s systemic event as Grade 4, after physical 
examination of the subject or documentation from another medically qualified source 
(eg, emergency room or hospital record) or telephone contact with the subject.  If a subject 
experiences a Grade 4 systemic event, the investigator must immediately notify the sponsor. 
The procedure for notification of the sponsor is provided in the study documentation.
Further, if a systemic event persists beyond the end of the e-diary period following 
vaccination, the subject will be requested to report that information and/or any new AEs that 
develop to the investigator.  The investigator will enter this additional information in the 
CRF.
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Table 5.
Systemic Event Grading Scale
Mild 
(Grade 1)
Moderate 
(Grade 2)
Severe 
(Grade 3)a
Grade 4b
Nausea/Vomiting
No interference with 
activity or 1-2 times 
in 24 hours
Some interference 
with activity or >2 
times in 24 hours
Prevents daily 
activity; requires IV 
hydration
Emergency room 
visit or 
hospitalization for 
hypotensive shock
Diarrhea
2-3 loose stools in 
24 hours
4-5 loose stools in 
24 hours
6 loose stools in 
24 hours
Emergency room 
visit or 
hospitalization
Headache
No interference with 
activity
Repeated use of non-
narcotic pain reliever 
>24 hours or some 
interference with 
activity
Significant; any use 
of narcotic pain 
reliever or prevents 
daily activityc
Emergency room 
visit or 
hospitalization
Fatigue/Tiredness
No interference with 
activity
Some interference 
with activity
Significant; prevents 
daily activityc
Emergency room 
visit or 
hospitalization
Muscle pain
No interference with 
activity
Some interference 
with activity
Significant; prevents 
daily activityc
Emergency room 
visit or 
hospitalization
Joint pain
No interference with 
activity
Some interference 
with activity
Significant; prevents 
daily activityc
Emergency room 
visit or 
hospitalization
Abbreviation: IV = intravenous.
a.
Subjects experiencing Grade 3 systemic events are to be seen by the study site.
b.
Grade 4 assessment should be made by the investigator. Grade 4 will not be collected in the electronic diary 
but will be collected as an AE on the case report form.
c.
Prevents daily routine activity, ie, results in missed days of work or school or is otherwise incapacitating, or 
includes use of narcotics for analgesia.
7.5.2.3. Fever
In order to record information on fever, a digital thermometer will be given to the subject 
with instructions on how to measure oral temperature at home.  Temperature will be 
collected in the evening daily for 14 days following vaccination (Days 1 to 14, where Day 1 
is the day of vaccination) and at any time during the 14 days that fever is suspected.  Fever is 
defined as an oral temperature of 100.4°F (38.0°C).  The highest temperature for each day 
will be recorded in the e-diary.  In the event of a fever on Day 14, temperature will be 
collected daily until fever has resolved (1 day of temperature less than 100.4°F [38.0°C] in 
order to collect a stop date in the CRF).  A subject with a fever >104.0°F (>40.0°C) will be 
prompted to contact the investigator to assess the fever and perform an unscheduled visit as 
appropriate. Study staff must also contact the subject to obtain additional information if a 
temperature of >102F is entered into an e-diary. Temperature will be measured and recorded 
to 1 decimal place and then grouped into ranges for the analysis according to Table 6 below:
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Table 6.
Ranges for Fever
100.4°F to 101.1°F (38.0°C to 38.4°C)
101.2°F to 102.0°F (38.5°C to 38.9°C)
102.1°F to 104.0°F (39.0°C to 40.0°C)
>104.0°F (>40.0°C)
If a fever persists beyond the end of the e-diary period following vaccination, the subject will 
be requested to report that information and/or any new AEs that develop to the investigator.  
The investigator will enter this additional information in the CRF.
7.5.3. Laboratory Tests
For sentinel-cohort subjects, the safety laboratory tests in Table 7 will be performed at times 
defined in the schedule of activities and Section 6 of the protocol.
Table 7.
Laboratory Tests
Hematology
Chemistry
Hemoglobin
Hematocrit
RBC count
Platelet count
WBC count
Total neutrophils (Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN and creatinine
AST, ALT
Total bilirubin
Alkaline phosphatase
Abbreviations: Abs = absolute; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
BUN = blood urea nitrogen; RBC = red blood cell; WBC = white blood cell.
The FDA toxicity grading scale for healthy adult and adolescent volunteers enrolled in 
preventive vaccine clinical trials will be adapted for use in grading laboratory test 
abnormalities.
If abnormal laboratory parameters are reported at screening (Visit 0) or Visit 2 and the 
investigator believes the results to be erroneous, the abnormal laboratory parameters may be 
retested.
7.6. Use of Antipyretic/Pain Medication
From Day 1 to Day 14, where Day 1 is the day of vaccination, the subject will be asked to 
record the use of antipyretic and/or pain medication in the e-diary in the evening.
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7.8. Other Safety Monitoring
7.8.1. Adverse Events
AEs and SAEs reported outside of the e-diary are recorded and reported as described in
Section 8.
7.8.2. Immediate Adverse Events
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.
7.8.3. Medically Attended Adverse Events
MAEs will be assessed from screening for subjects enrolled in sentinel cohorts, from Visit 1 
for subjects enrolled in expanded cohorts, and up to Visit 6 (6-month follow-up visit) after 
vaccination with the investigational product.
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An MAE is defined as a nonserious AE that results in an evaluation at a medical facility.
7.8.4. Routine Medical Facility Visits and Elective Hospitalizations Not Associated With 
Adverse Events
Routine visits to medical facilities and elective hospitalizations not associated with an AE 
(ie, healthcare visits for preventive care, or for routine physical examinations) will not be 
collected.
8. ADVERSE EVENT REPORTING
8.1. Requirements
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report Form 
to Pfizer Safety.  These requirements are delineated for 3 types of events: (1) SAEs; 
(2) nonserious AEs; and (3) exposure to the investigational product under study during 
pregnancy or breastfeeding, and occupational exposure.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 24 
Hours of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the investigational 
product under study during 
pregnancy or breastfeeding, and 
occupational exposure
All (regardless of whether associated 
with an AE), except occupational 
exposure
Exposure during pregnancy, 
exposure via breastfeeding, 
occupational exposure (regardless of 
whether associated with an AE)
Abbreviation: CT = clinical trial.
All observed or volunteered events regardless of investigational product group or suspected 
causal relationship to the investigational product(s) will be reported as described in the 
following paragraphs.
Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information.  This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
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(see the Serious Adverse Events section, Section 8.2.3, below).  In addition, the investigator 
may be requested by Pfizer Safety to obtain specific follow-up information in an expedited 
fashion.  This information is more detailed than that recorded on the CRF.  In general, this 
will include a description of the event in sufficient detail to allow for a complete medical 
assessment of the case and independent determination of possible causality.  Any information 
relevant to the event, such as concomitant medications and illnesses, must be provided.  In 
the case of a subject death, a summary of available autopsy findings must be submitted as 
soon as possible to Pfizer Safety.  Any pertinent additional information must be reported on 
the CT SAE Report Form; additional source documents (eg, medical records, CRF, 
laboratory data) are to be sent to Pfizer Safety ONLY upon request.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
The investigator must contact the Pfizer study physician directly as soon as possible after 
becoming aware of a severe AE occurring within 14 days in the sentinel and expanded 
cohorts or SAE occurring within 30 days after vaccination.  Additional information regarding 
such events and the reporting requirements can be found in the 
8.1.1. Additional Details on Recording Adverse Events on the CRF
All events detailed in the table above will be recorded on the AE page(s) of the CRF.  It 
should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE Report 
Form for reporting of SAE information.
8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study subject.  In addition, each study subject will be questioned about the 
occurrence of AEs in a nonleading manner.
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the Subject 
Withdrawal section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF.
When a subject withdraws from the study because of an SAE, the SAE must be recorded on 
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section, Section 8.1, above.
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8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and MAEs/SAEs (“active collection 
period”) for each subject begins from the time the subject provides informed consent, which 
is obtained before the subject’s participation in the study (ie, before undergoing any 
study-related procedure and/or receiving investigational product), through and including the 
screening visit, and from Visit 1 to Visit 4.  Between Visit 4 and Visit 6, only MAEs and 
SAEs will be reported.  In addition, AEs occurring up to 48 hours after the Visit 5 and Visit 6 
blood draws that are related to study procedures must be reported.
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 investigational 
product are to be reported to the sponsor.
For subjects who are screen failures, the active collection period ends when screen failure 
status is determined.
8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.
SAEs occurring in a subject after the active collection period has ended are reported to Pfizer 
Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
8.1.4.2. Recording Nonserious AEs and SAEs on the CRF
During the active collection period, both nonserious AEs and SAEs are recorded on the CRF.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.1.5. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
nonserious); the investigator must record the causal relationship on the CRF, and report such 
an assessment in accordance with the SAE reporting requirements, if applicable.  An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the investigational product caused or contributed to an AE; generally the facts 
(evidence) or arguments to suggest a causal relationship should be provided.  If the 
investigator does not know whether or not the investigational product caused the event, then 
the event will be handled as “related to investigational product” for reporting purposes, as 
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defined by the sponsor.  If the investigator’s causality assessment is “unknown but not 
related” to investigational product, this should be clearly documented on study records.
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
8.2. Definitions
8.2.1. Adverse Events
An AE is any untoward medical occurrence in a study subject administered a product or 
medical device; the event need not necessarily have a causal relationship with the treatment 
or usage.  Examples of AEs include, but are not limited to: 

Abnormal test findings;

Clinically significant signs and symptoms;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.
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8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or

Test result leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
recording as an AE.
8.2.3. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Or that is considered to be:

An important medical event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
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8.2.4. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE.  Examples include:

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of a persistent pretreatment laboratory abnormality);

Social admission (eg, subject has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE.  For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE.
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8.3. Severity Assessment
GRADE If required on the AE page of the CRF, the investigator will use the adjectives 
MILD, MODERATE, or SEVERE to describe the maximum intensity of the AE.
For purposes of consistency, these intensity grades are defined as follows:
1
MILD
Does not interfere with subject’s usual function.
2
MODERATE
Interferes to some extent with subject’s usual function.
3
SEVERE
Interferes significantly with subject’s usual function.
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the subject’s usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections, and will be handled as SAEs in 
the safety database.
8.4.2. Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some subjects, transaminase elevations are a harbinger of a more 
serious potential outcome.  These subjects fail to adapt and therefore are “susceptible” to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury 
(DILI).  Subjects who experience a transaminase elevation above 3 times the upper limit of 
normal (× ULN) should be monitored more frequently to determine if they are an “adaptor” 
or are “susceptible.”
Liver function tests (LFTs) are not required as a routine safety monitoring procedure in 
subjects enrolled in expanded cohorts in this study.  However, should an investigator deem it 
necessary to assess LFTs because a subject presents with clinical signs/symptoms, such LFT 
results should be managed and followed as described below.
In the majority of DILI cases, elevations in AST and/or ALT precede total bilirubin (Tbili) 
elevations (>2 × ULN) by several days or weeks.  The increase in Tbili typically occurs 
while AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and Tbili values will be 
elevated within the same laboratory sample).  In rare instances, by the time Tbili elevations 
are detected, AST/ALT values might have decreased.  This occurrence is still regarded as a 
potential DILI.  Therefore, abnormal elevations in either AST OR ALT in addition to Tbili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
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criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the subject’s 
individual baseline values and underlying conditions.  Subjects who present with the 
following laboratory abnormalities should be evaluated further as potential DILI (Hy’s law) 
cases to definitively determine the etiology of the abnormal laboratory values:

Subjects with AST/ALT and Tbili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a Tbili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available;

For subjects with baseline AST OR ALT OR Tbili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:
o
Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).
o
Preexisting values of Tbili above the normal range: Tbili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and Tbili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.
The subject should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and Tbili, laboratory tests should 
include albumin, creatine kinase (CK), direct and indirect bilirubin, gamma-glutamyl 
transferase (GGT), prothrombin time (PT)/international normalized ratio (INR), total bile 
acids, alkaline phosphatase, and acetaminophen drug and/or protein adduct levels.  
Consideration should also be given to drawing a separate tube of clotted blood and an 
anticoagulated tube of blood for further testing, as needed, for further contemporaneous 
analyses at the time of the recognized initial abnormalities to determine etiology.  A detailed 
history, including relevant information, such as review of ethanol, acetaminophen (either by 
itself or as a coformulated product in prescription or over-the-counter medications), 
recreational drug, supplement (herbal) use and consumption, family history, sexual history, 
travel history, history of contact with a jaundiced person, surgery, blood transfusion, history 
of liver or allergic disease, and potential occupational exposure to chemicals, should be 
collected.  Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging 
(eg, biliary tract) may be warranted.
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All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
Tbili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
8.4.3. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and 
Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.4.3.1. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an EDP occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).

A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy.
If a subject or subject’s partner becomes or is found to be pregnant during the subject’s 
treatment with the investigational product, the investigator must report this information to 
Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, regardless of 
whether an SAE has occurred.  In addition, the investigator must submit information 
regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a subject 
reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or 
spillage) to Pfizer Safety using the EDP supplemental form.  This must be done irrespective 
of whether an AE has occurred and within 24 hours of awareness of the exposure.  The 
information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural 
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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 to Pfizer Safety as SAEs 
follows:

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product.
Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the subject with the Pregnant Partner Release of Information Form 
to deliver to his partner.  The investigator must document in the source documents that the 
subject was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.3.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.4.3.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a subject enrolled in the study, the 
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information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
8.4.4. Medication Errors
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report Form to 
Pfizer Safety Within 24 Hours of Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Abbreviations: CRF = case report form; CT = clinical trial.
8.4.4.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong subject, or at the wrong time, or at the wrong dosage strength.
Medication errors include:

Medication errors involving subject exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject.
Other examples include, but are not limited to:

The administration of expired investigational product;

The administration of an incorrect investigational product;

The administration of an incorrect dosage;

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.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF.
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Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
9. DATA ANALYSIS/STATISTICAL METHODS
Methodology for summary and statistical analyses of the data collected in this study is 
outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
All analyses for both immunogenicity and safety data will be of descriptive nature.
9.2. Immunogenicity Analysis
For the immunogenicity analyses, 2 analysis populations will be defined: evaluable 
immunogenicity and modified intent-to-treat (mITT) populations.  To be included in the
evaluable immunogenicity population, in general the subject must have been eligible for the 
study, have received GBS6 or placebo as randomized, have had blood drawn within the 
specified time frames, have at least 1 valid and determinate assay result for the proposed 
analysis, and have no other major protocol violations.  The evaluable immunogenicity 
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population will be considered the primary population.  To be included in the mITT 
population, a subject must have at least 1 valid and determinate assay result related to the 
proposed analysis.
The immunogenicity data will be summarized according to the vaccine as received for the 
evaluable immunogenicity population and as randomized for the mITT population.
Immunogenicity endpoints are secondary or 
 in the study as listed in Section 2.2
and Section 2.3.  Descriptive summary statistics will be provided for all immunogenicity 
endpoints.  No formal comparison between dose groups will be made.
Descriptive evaluations include serotype-specific IgG GMCs and 
GBS serotype-specific IgG concentrations will be logarithmically transformed for analysis. 
For each serotype, GMCs will be calculated at all blood draw visits. Two (2)-sided 95% 
confidence intervals (CIs) for the GMCs will be constructed by back transformation of the 
CIs for the mean of the logarithmically transformed assay results computed using Student’s
t distribution.
 
 
 
Detailed analyses of all the immunogenicity endpoints including graphical displays will be 
described in the SAP.
9.3. Safety Analysis
All subjects receiving a dose of GBS vaccine or placebo will be included in the safety 
population. For the safety analyses, subjects will be analyzed according to the investigational 
product received.
The safety endpoints as listed in Section 2.1 are primary in the study and their analyses are 
based on the safety population.
The safety analyses are descriptive evaluations of local reactions, systemic events, AEs, 
MAEs, SAEs, and laboratory abnormalities.  AEs will be categorized according to the 
Medical Dictionary for Regulatory Activities (MedDRA).
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Descriptive summary statistics (eg, counts and percentages) will be provided for AEs, e-diary 
events collected, and laboratory abnormalities, with 2-sided 95% exact CIs as appropriate.
9.4. Analysis Timing
At the completion of the 1-month follow-up blood sampling and assays, an analysis of 
available immunogenicity and safety results will be conducted.  Analysis results with the 
safety data cutoff at 1 month after vaccination will be reviewed by the E-DMC.  
Additionally, the IRC will review safety data summaries prior to the enrollment of the 
expanded cohort at the same dose level as well as the initiation of each dose escalation as 
planned.  Data may also be summarized at other time points for regulatory purposes.  No 
multiplicity adjustments will be applied for these assessments.
After the completion of the 6-month follow-up visit, a clinical study report (CSR) including 
all safety and immunogenicity data gathered from before to within the 6 months following 
investigational product will be issued.
9.5. Data Monitoring Committee
This study will use an IRC and an E-DMC.
 
 
 
 
 
 
 
 
 
10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and GCPs are being followed.  The monitors may review source documents to 
confirm that the data recorded on CRFs are accurate.  The investigator and institution will 
allow Pfizer monitors/auditors or its agents and appropriate regulatory authorities direct 
access to source documents to perform this verification.  This verification may also occur 
after study completion.
During study conduct and/or after study completion, the investigator site may be subject to 
review by the IRB/EC, and/or to quality assurance audits performed by Pfizer, or companies 
working with or on behalf of Pfizer, and/or to inspection by appropriate regulatory 
authorities.
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The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the investigator site for the inspection and will allow Pfizer or its 
agent, whenever feasible, to be present during the inspection.  The investigator site and 
investigator will promptly resolve any discrepancies that are identified between the study 
data and the subject’s medical records.  The investigator will promptly provide copies of the 
inspection findings to Pfizer or its agent.  Before response submission to the regulatory 
authorities, the investigator will provide Pfizer or its agents with an opportunity to review 
and comment on responses to any such findings.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true. Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry.
In most cases, the source documents are the hospital or the physician subject chart.  In these 
cases, data collected on the CRFs must match the data in those charts.
In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.
11.2. Record Retention
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, CRFs and hospital records), all original signed 
ICDs, copies of all CRFs, safety reporting forms, source documents, and detailed records of 
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treatment disposition, and adequate documentation of relevant correspondence (eg, letters, 
meeting minutes, and telephone call reports).  The records should be retained by the 
investigator according to the ICH guidelines, according to local regulations, or as specified in 
the clinical study agreement (CSA), whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or an independent third party arranged by Pfizer.
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.
The investigator must obtain Pfizer’s written permission before disposing of any records, 
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board/Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, ICDs, and other relevant documents, eg, recruitment advertisements, if 
applicable, from the IRB/EC.  All correspondence with the IRB/EC should be retained in the 
investigator file.  Copies of IRB/EC approvals should be forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements, and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
Helsinki.
12.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where
required by law.
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by Pfizer in order to de-identify study subjects. The investigator
site will maintain a confidential list of subjects who participated in the study, linking each 
subject’s numerical code to his or her actual identity.  In case of data transfer, Pfizer will 
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maintain high standards of confidentiality and protection of subjects’ personal data consistent 
with applicable privacy laws.
The ICDs and any subject recruitment materials must be in compliance with ICH GCP, local 
regulatory requirements, and legal requirements, including applicable privacy laws.
The ICDs used during the informed consent process and any subject recruitment materials 
must be reviewed and approved by Pfizer, approved by the IRB/EC before use, and available 
for inspection.
The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study and possible risks associated with participation.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed. The investigator 
will retain the original of each subject’s signed consent document.
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in All Participating Countries
End of trial in all participating countries is defined as last subject last visit (LSLV).
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of GBS6
at any time.
If a study is prematurely terminated, Pfizer will promptly notify the investigator.  After 
notification, the investigator must contact all participating subjects and the hospital pharmacy 
(if applicable) in a timely manner.  As directed by Pfizer, all study materials must be 
collected and all CRFs completed to the greatest extent possible.
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15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  US 
Basic Results are submitted for posting within 1 year of the primary completion date (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final subject was examined or received an intervention for 
the purposes of final collection of data for the primary outcome, whether the clinical study 
concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product.  However, 
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
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publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed. If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI will reference that primary publication. However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at 
all participating sites, the investigator is free to publish separately, subject to the other 
requirements of this section.
For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II – “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues.
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16. REFERENCES
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11
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years: a nationwide surveillance study.  Lancet Infect Dis. 
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pertussis vaccine (Tdap) in pregnant women--Advisory Committee on 
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38
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Heyderman RS, Madhi SA, French N, et al. Group B streptococcus 
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randomised phase 2, open-label, multicentre trial. Lancet Infect Dis. 
2016;16(5):546-555.
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response to routine infant vaccination [abstract ESPID-0274]. European 
Society for Paediatric Infectious Diseases; 2014; Dublin, Ireland.
53
Leroux-Roels G, Maes C, Willekens J, et al. Identification of 
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Industry, September 2007.
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Appendix 1. Abbreviations
This following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
ABCs
Active Bacterial Core surveillance
ACIP
Advisory Committee on Immunization Practices (United States)
AE
adverse event
AlPO4
aluminum phosphate
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BUN
blood urea nitrogen
CBER
Center for Biologics Evaluation and Research
CDC
Centers for Disease Control and Prevention
CI
confidence interval
CK
creatine kinase
CPS
capsular polysaccharide
CRF
case report form
CSA
clinical study agreement
CSR
clinical study report
CT
clinical trial
DILI
drug-induced liver injury
EC
ethics committee
e-diary
electronic diary
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
EOD
early-onset disease
EU
European Union
FDA
Food and Drug Administration (United States)
FIH
first-in-human
FSH
follicle-stimulating hormone
GBS
group B streptococcus
GBS6
group B streptococcus 6-valent 
 vaccine
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMC
geometric mean concentration
HBV
hepatitis B virus
HIV
human immunodeficiency virus
IAP
intrapartum antibiotic therapy
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
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Abbreviation
Term
ID
identification
IgG
immunoglobulin G
IND
investigational new drug application
INR
international normalized ratio
IP
investigational product
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
IUD
intrauterine device
IWR
interactive Web-based response
LFT
liver function test
LMIC
low- and middle-income country
LOD
late-onset disease
LSLV
last subject last visit 
MAE
medically attended adverse event
MedDRA
Medical Dictionary for Regulatory Activities 
mITT
modified intent-to-treat
N/A
not applicable
NaCl
sodium chloride
 
PCD
primary completion date
PDA
personal digital assistant
PI
principal investigator
PT
prothrombin time
SAE
serious adverse event
SAP
statistical analysis plan
SOP
standard operating procedure
SRSD
single reference safety document
Tbili
total bilirubin
Tdap
tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccine
ULN
upper limit of normal
UK
United Kingdom
US
United States
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