A PHASE 3, RANDOMIZED, PARTIALLY DOUBLE-BLIND TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY TODDLERS 12 THROUGH 23 MONTHS OF AGE WITH 2 PRIOR INFANT DOSES OF PREVENAR 13
Phase: PHASE3
Conditions: Pneumococcal Disease
Sponsor: Pfizer

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
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A PHASE 3, RANDOMIZED, PARTIALLY DOUBLE-BLIND TRIAL TO 
EVALUATE THE SAFETY AND IMMUNOGENICITY OF 20-VALENT 
PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY TODDLERS 12 
THROUGH 23 MONTHS OF AGE WITH 2 PRIOR INFANT DOSES OF 
PREVENAR 13 
 
 
Study Intervention Number: 
PF-06482077 
Study Intervention Name: 
20-valent pneumococcal conjugate vaccine 
(20vPnC) 
US IND Number: 
EudraCT Number: 
CCI  
CCI 
 
ClinicalTrials.gov ID: 
TBD 
Protocol Number: 
B7471027 
Phase: 
3 
Brief Title: Safety and Immunogenicity of 20vPnC in Toddlers With 2 Prior Doses of 
Prevenar 13 
 
 
 
 
 
 
 
 
 
 
 
 
PFIZER CONFIDENTIAL 
This document and accompanying materials contain confidential information belonging to Pfizer. Except 
as otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) 
or use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified. 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
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Document History 
 
Document 
Version Date 
Original protocol 
10 December 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PFIZER CONFIDENTIAL 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
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TABLE OF CONTENTS 
LIST OF TABLES .....................................................................................................................8 
1. PROTOCOL SUMMARY .....................................................................................................9 
1.1. Synopsis .....................................................................................................................9 
1.2. Schema.....................................................................................................................12 
1.3. Schedule of Activities ..............................................................................................13 
1.3.1. Schedule of Activities: 2-Dose 20vPnC Group ..........................................13 
1.3.2. Schedule of Activities: 1-Dose 20vPnC Group and 13vPnC (Control) 
Group ...............................................................................................................15 
2. INTRODUCTION ................................................................................................................17 
2.1. Study Rationale ........................................................................................................20 
2.2. Background ..............................................................................................................21 
2.2.1. Clinical Overview .......................................................................................21 
2.3. Benefit/Risk Assessment .........................................................................................22 
2.3.1. Risk Assessment .........................................................................................23 
2.3.2. Overall Benefit/Risk Conclusion ................................................................24 
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS ............................................................24 
4. STUDY DESIGN .................................................................................................................25 
4.1. Overall Design .........................................................................................................25 
4.1.1. Approximate Duration of Participation for Each Participant ......................27 
4.1.2. Approximate Number of Participants..........................................................27 
4.2. Scientific Rationale for Study Design .....................................................................27 
4.3. Justification for Dose ...............................................................................................27 
4.4. End of Study Definition ...........................................................................................28 
5. STUDY POPULATION ......................................................................................................28 
5.1. Inclusion Criteria .....................................................................................................28 
5.2. Exclusion Criteria ....................................................................................................29 
5.3. Lifestyle Considerations ..........................................................................................30 
5.4. Screen Failures .........................................................................................................30 
5.5. Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention ...........................30 
PFIZER CONFIDENTIAL 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
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5.5.1. Criteria for Temporarily Delaying Vaccine Administration........................31 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ..................................31 
6.1. Study Intervention(s) Administered .........................................................................31 
6.1.1. Administration .............................................................................................32 
6.1.2. Medical Devices ..........................................................................................32 
6.2. Preparation, Handling, Storage, and Accountability................................................32 
6.2.1. Preparation and Dispensing .........................................................................34 
6.3. Measures to Minimize Bias: Randomization and Blinding .....................................34 
6.3.1. Allocation to Study Intervention .................................................................34 
6.3.2. Breaking the Blind ......................................................................................34 
6.3.3. Blinding of the Sponsor ..............................................................................35 
6.4. Study Intervention Compliance ...............................................................................35 
6.5. Dose Modification ...................................................................................................35 
6.6. Continued Access to Study Intervention After the End of the Study ......................35 
6.7. Treatment of Overdose ............................................................................................35 
6.8. Concomitant Therapy ..............................................................................................36 
6.8.1. Prohibited Concomitant Vaccines and Treatments .....................................36 
6.8.2. Permitted Concomitant Vaccines and Treatments ......................................36 
6.8.3. Recording Prior and Concomitant Vaccines and Treatments .....................37 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................................37 
7.1. Discontinuation of Study Intervention .....................................................................37 
7.2. Participant Discontinuation/Withdrawal From the Study .......................................38 
7.2.1. Withdrawal of Consent ...............................................................................38 
7.3. Lost to Follow-Up ...................................................................................................39 
8. STUDY ASSESSMENTS AND PROCEDURES ...............................................................39 
8.1. Efficacy and/or Immunogenicity Assessments ........................................................40 
8.1.1. Immunogenicity Assessments .....................................................................40 
8.1.2. Biological Samples .....................................................................................41 
8.2. Safety Assessments ..................................................................................................41 
8.2.1. Physical Examinations ................................................................................42 
PFIZER CONFIDENTIAL 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
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8.2.2. Participant Electronic Diary ........................................................................ 42 
8.2.3. Grading Scale for Prompted Events ............................................................ 42 
8.2.3.1. Local Reactions ......................................................................... 43 
8.2.3.2. Systemic Event Symptoms and Fever ....................................... 44 
8.2.4. Clinical Safety Laboratory Assessments ..................................................... 46 
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................. 46 
8.3.1. Time Period and Frequency for Collecting AE and SAE Information ....... 47 
8.3.1.1. Reporting SAEs to Pfizer Safety ............................................... 47 
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF ................... 47 
8.3.2. Method of Detecting AEs and SAEs ........................................................... 48 
8.3.3. Follow-Up of AEs and SAEs ...................................................................... 48 
8.3.4. Regulatory Reporting Requirements for SAEs ........................................... 48 
8.3.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure ..................................................... 49 
8.3.5.1. Exposure During Pregnancy ...................................................... 49 
8.3.5.2. Exposure During Breastfeeding ................................................. 50 
8.3.5.3. Occupational Exposure .............................................................. 51 
8.3.6. Cardiovascular and Death Events ................................................................ 51 
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs .............................................................................. 51 
8.3.8. Adverse Events of Special Interest ............................................................. 51 
8.3.8.1. Lack of Efficacy ........................................................................ 51 
8.3.9. Medical Device Deficiencies ...................................................................... 51 
8.3.9.1. Time Period for Detecting Medical Device Deficiencies .......... 52 
8.3.9.2. Follow-Up of Medical Device Deficiencies .............................. 52 
8.3.9.3. Prompt Reporting of Device Deficiencies to the Sponsor ......... 52 
8.3.9.4. Regulatory Reporting Requirements for Device 
Deficiencies........................................................................................ 53 
8.3.10. Medication Errors ...................................................................................... 53 
8.4. Pharmacokinetics ..................................................................................................... 54 
8.5. Genetics ................................................................................................................... 54 
8.5.1. Specified Genetics ....................................................................................... 54 
PFIZER CONFIDENTIAL 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
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8.6. Biomarkers ............................................................................................................... 54 
8.7. Immunogenicity Assessments ................................................................................. 54 
8.8. Health Economics .................................................................................................... 54 
8.9. Study Procedures ..................................................................................................... 54 
8.9.1. 2-Dose 20vPnC Group ................................................................................ 55 
8.9.1.1. Visit 1 (Dose 1 Visit: Day 1) ..................................................... 55 
8.9.1.2. Visit 2 (Dose 2 Visit: 56 to 70 Days After Dose 1) ................... 56 
8.9.1.3. Visit 3 (Follow-Up Visit: 28 to 42 Days After Dose 2) ............ 58 
8.9.2. 1-Dose 20vPnC Group and 13vPnC (Control) Group ................................ 58 
8.9.2.1. Visit 1 (Dose 1 Visit: Day 1) ..................................................... 58 
8.9.2.2. Visit 2 (Follow-Up Visit: 28 to 42 Days After Dose 1) ............ 60 
8.9.3. Unscheduled Visits ..................................................................................... 61 
9. STATISTICAL CONSIDERATIONS ................................................................................. 62 
9.1. Statistical Hypotheses .............................................................................................. 62 
9.1.1. Estimands .................................................................................................... 62 
9.2. Analysis Sets ............................................................................................................ 63 
9.3. Statistical Analyses .................................................................................................. 63 
9.3.1. General Considerations ............................................................................... 64 
9.3.2. Analysis for Binary Data ............................................................................. 64 
9.3.3. Analysis for Continuous Data ..................................................................... 65 
9.3.3.1. Geometric Mean ........................................................................ 65 
CCI 
 
CCI 
 
9.3.4. Primary Endpoint(s)/Estimand(s) Analysis ................................................ 65 
9.3.5. Secondary Endpoint(s)/Estimand(s) Analysis ............................................ 66 
CCI 
 
9.4. Interim Analyses ...................................................................................................... 67 
9.5. Sample Size Determination ..................................................................................... 67 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................... 69 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ................ 69 
PFIZER CONFIDENTIAL 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
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10.1.1. Regulatory and Ethical Considerations .....................................................69 
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP .........................................................................70 
10.1.2. Financial Disclosure ..................................................................................70 
10.1.3. Informed Consent Process ........................................................................70 
10.1.4. Data Protection ..........................................................................................71 
10.1.5. Committees Structure ................................................................................71 
CCI 
 
10.1.6. Dissemination of Clinical Study Data .......................................................72 
10.1.7. Data Quality Assurance .............................................................................73 
10.1.8. Source Documents ....................................................................................74 
10.1.9. Study and Site Start and Closure ...............................................................75 
10.1.10. Publication Policy ...................................................................................76 
10.1.11. Sponsor’s Qualified Medical Personnel ..................................................76 
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting ......................................................................78 
10.2.1. Definition of AE ........................................................................................78 
10.2.2. Definition of an SAE .................................................................................79 
10.2.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period ............................................................................81 
10.2.4. Reporting of SAEs ....................................................................................84 
10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-Up Assessments 
Potential Cases of Drug-Induced Liver Injury ..........................................................86 
10.4. Appendix 4: AEs, ADEs, SAEs, SADEs, USADEs, and Device 
Deficiencies: Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting in Medical Device Studies ..............................................88 
10.4.1. Definition of AE and ADE ........................................................................88 
10.4.2. Definition of SAE, SADE, and USADE ...................................................88 
10.4.3. Definition of Device Deficiency ...............................................................89 
10.4.4. Recording/Reporting and Follow-Up of Medical Device 
Deficiencies ......................................................................................................89 
10.4.5. Reporting of SAEs ....................................................................................91 
10.4.6. Reporting of SADEs .................................................................................91 
PFIZER CONFIDENTIAL 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
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10.5. Appendix 5: Alternative Measures During Public Emergencies .......................... 92 
10.5.1. Telehealth Visits ........................................................................................ 92 
10.5.2. Study Intervention ..................................................................................... 92 
10.6. Appendix 6: Abbreviations .................................................................................... 93 
11. REFERENCES ................................................................................................................... 96 
 
LIST OF TABLES 
Table 1. 
Grading Scales for Local Reactions ..........................................................43 
Table 2. 
Grading Scales for Systemic Event Symptoms .........................................45 
Table 3. 
Ranges for Fever ......................................................................................46 
Table 4. 
Precision of Percentage of Participants With Predefined IgG 
Concentrations ...........................................................................................67 
Table 5. 
Probability of Observing an Event Given a Specified Incidence 
Rate and Assuming 120 Participants per Group .......................................68 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PFIZER CONFIDENTIAL 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
Page 9 
 
 
1. PROTOCOL SUMMARY 
1.1. Synopsis 
Pfizer is developing a new 20-valent pneumococcal conjugate vaccine (20vPnC) to expand 
protection against pneumococcal disease beyond that covered by current pneumococcal 
vaccines in toddlers. 20vPnC has the same composition as 13vPnC (Prevenar 13®), but 
contains an additional 7 polysaccharide conjugates targeting serotypes responsible for a 
substantial burden of remaining pneumococcal disease. 20vPnC uses the same platform and 
contains the same excipients as 13vPnC. Phase 2 safety and immunogenicity data in infants 
support further development of 20vPnC in the pediatric population. 
This Phase 3, multicenter, randomized, partially double-blind study will be conducted at 
investigator sites in Europe. The purpose of this study is to describe the safety and 
immunogenicity of 1 or 2 doses of 20vPnC administered to European toddlers ≥12 to 
<24 months of age who have received 2 doses of 13vPnC in infancy (prior to 12 months of 
age and >56 days prior to vaccination in this study). A single dose of 13vPnC will serve as 
the control vaccine. 
Approximately 360 toddlers ≥12 to <24 months of age at the time of consent, who previously 
received 2 infant doses of 13vPnC (prior to 12 months of age), will be enrolled and 
randomized in a 1:1:1 ratio to receive either 1 or 2 doses of 20vPnC or 1 dose of 13vPnC 
(control). The vaccine in toddlers randomized to receive 1 dose will be double-blind, as 
20vPnC and 13vPnC have the same appearance and a single dose will be administered at 
Visit 1 of the study. For participants randomized to receive 2 doses of 20vPnC, the 
parents/legal guardians and site staff will know the randomization assignment for these 
participants, as the participant will need to return for a second vaccination visit and will 
receive 20vPnC at both Visit 1 and Visit 2. 
Blood will be drawn from all participants for immunogenicity assessments before 
administration of study intervention and 1 month after the vaccination (last vaccination in the 
group receiving 2 doses) in each group. 
Local reactions (redness, swelling, and pain at the injection site), systemic events (fever, 
decreased appetite, drowsiness/increased sleep, and irritability), and use of antipyretic/pain 
medication will be prompted for and collected by the participant’s parent(s)/legal guardian(s) 
in an e-diary, device or application, from Day 1 through Day 7 after each vaccination (where 
Day 1 is the day of vaccination). 
AEs and SAEs will be collected from the time the participant’s parent(s)/legal guardian(s) 
provides informed consent through 1 month after the dose (last dose in the group receiving 
2 doses) of 20vPnC or 13vPnC. 
 
 
 
 
 
 
PFIZER CONFIDENTIAL 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
Page 10 
 
 
Objectives, Endpoints, and Estimands 
 
Objectives 
Endpoints 
Estimands 
Primary Safety Objective 
Primary Safety Endpoints 
Primary Safety Estimands 
• 
To describe the safety 
profile of 20vPnC 
• 
Prompted local reactions 
(redness, swelling, and pain at 
the injection site) 
• 
Prompted systemic events 
(fever, decreased appetite, 
drowsiness/increased sleep, and 
irritability) 
• 
AEs 
• 
SAEs 
In participants receiving at least 
1 dose of study intervention with 
safety follow-up after the assigned 
vaccination: 
• 
The percentage of participants 
reporting prompted local 
reactions within 7 days after the 
last assigned vaccination in each 
group 
• 
The percentage of participants 
reporting prompted systemic 
events within 7 days after the 
last assigned vaccination in 
each group 
• 
The percentage of participants 
reporting AEs within 1 month 
after the last assigned 
vaccination in each group 
• 
The percentage of participants 
reporting SAEs within 1 month 
after the last assigned 
vaccination in each group 
Primary Immunogenicity 
Objective 
Primary Immunogenicity 
Endpoint 
Primary Immunogenicity 
Estimand 
• 
To describe the immune 
responses to the additional 
7 serotypes after 1 or 2 
doses of 20vPnC 
• 
Pneumococcal serotype-specific 
IgG concentration 
In participants complying with the 
key protocol criteria (evaluable 
participants) in each group: 
• 
Percentages of participants with 
predefined serotype-specific 
IgG concentrations for the 7 
additional serotypes 1 month 
after the last assigned 
vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
PFIZER CONFIDENTIAL 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
Page 11 
 
 
 
Objectives 
Endpoints 
Estimands 
Secondary Immunogenicity 
Objective 
Secondary Immunogenicity 
Endpoints 
Secondary Immunogenicity 
Estimands 
• 
To further describe the 
immune response of 
20vPnC after 1 or 2 doses 
• 
Pneumococcal serotype-specific 
IgG concentration 
• 
Pneumococcal serotype-specific 
OPA titers 
In evaluable participants in each 
group: 
• 
IgG GMCs for the vaccine 
serotypes 1 month after the last 
assigned vaccination 
• 
Percentages of participants with 
predefined IgG concentrations 
for the 13 matched serotypes 
1 month after the last assigned 
vaccination 
• 
OPA GMTs for the vaccine 
serotypes 1 month after the last 
vaccination 
 
Number of Participants 
Approximately 360 (120 in each vaccination group) toddlers will be enrolled to reach a target 
of 315 evaluable participants (105 in each vaccination group). 
The 360 toddlers who have been previously vaccinated with 2 doses of 13vPnC prior to 
12 months of age will be enrolled in 3 vaccination groups: 
• 2-Dose 20vPnC group: Approximately 120 participants will receive 2 doses of 20vPnC. 
• 1-Dose 20vPnC group: Approximately 120 participants will receive 1 dose of 20vPnC. 
• 13vPnC control group: Approximately 120 participants will receive 1 dose of 13vPnC. 
Duration of Participation for Each Participant 
Each participant will participate in the study for approximately 1 or 3 months, if randomized 
to receive 1 dose or 2 doses, respectively. 
CCI 
 
 
 
 
 
 
 
 
 
 
 
PFIZER CONFIDENTIAL 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
Page 12 
 
 
Statistical Methods 
The primary safety objective will be evaluated by descriptive summary statistics for local 
reactions and systemic events after the last assigned vaccine, and AEs, including SAEs, for 
1 month after the last assigned vaccine in each group. 
The primary immunogenicity objective will be evaluated by descriptive summary statistics 
on the proportion of participants with predefined serotype-specific IgG concentrations for the 
7 additional serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) 1 month after the last assigned 
vaccination. Additionally, the percentages of participants with predefined serotype-specific 
IgG concentrations for the 13 matched serotypes, serotype-specific IgG GMCs, OPA 
 
the specified time points for each vaccine group to provide further characterization of the 
immune response. 
1.2. Schema 
Not applicable. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PFIZER CONFIDENTIAL 
GMTs, CCI 
will be provided for 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
Page 13 
 
 
 
1.3. Schedule of Activities 
1.3.1. Schedule of Activities: 2-Dose 20vPnC Group 
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section (Section 8) 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 in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
 
Visit Number 
1 
2 
3 
Visit Description 
Dose 1 Visit 
Dose 2 Visit 
Follow-Up After Dose 2 
Visit Window (Days) 
Day 1 
56 to 70 Days 
After Visit 1 
28 to 42 Days 
After Visit 2 
Obtain informed consent 
X 
Assign participant number via IRT 
X 
Record demography 
X 
Perform clinical assessment, including medical historya 
X 
Record 13vPnC history 
X 
Record nonstudy vaccinations 
X 
X 
X 
Record concomitant medications to treat SAEs only 
X 
X 
X 
Obtain prevaccination temperature (measured as 
appropriate for age) 
X 
X 
Review inclusion and exclusion criteria 
X 
Review continued eligibility 
X 
X 
Review temporary delay criteria 
X 
X 
Assign randomization number and study intervention 
container number via the IRT 
X 
Obtain blood sample (~5 mL) 
Xb 
X 
Administer 20vPnC into the left thigh or left arm (as 
appropriate for the age and size of the child) 
X 
X 
If applicable, administer and record routine pediatric 
vaccinationsc 
X 
X 
 
PFIZER CONFIDENTIAL 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
Page 14 
 
 
 
Visit Number 
1 
2 
3 
Visit Description 
Dose 1 Visit 
Dose 2 Visit 
Follow-Up After Dose 2 
Visit Window (Days) 
Day 1 
56 to 70 Days 
After Visit 1 
28 to 42 Days 
After Visit 2 
Observe and record acute reactions for 30 minutes after 
study intervention administration 
X 
X 
Provide parent(s)/legal guardian(s) with participant 
contact card 
X 
Provide parent(s)/legal guardian(s) with an e-diary (or 
assist with application download to a personal device), 
thermometer, and measuring device and instruct to collect 
prompted local reactions, systemic events, and 
antipyretic/pain medication until 7 days after each 
20vPnC vaccinationd 
X 
X 
Review and/or collect e-diary (as applicable)e 
X 
X 
Record and report AEs and SAEs 
X 
X 
Abbreviation: IRT = interactive response technology. 
a. 
If deemed necessary as part of the clinical assessment, the physical examination may include assessments of the general appearance, skin, head, 
lymph nodes, cardiovascular, respiratory, gastrointestinal, and neurological systems. 
b. Blood sample will be collected before vaccination. 
c. 
Administer permitted routine pediatric vaccinations (as applicable) after the study vaccination into a limb other than the site of the 20vPnC injection. 
Prohibited and permitted vaccines are described in Section 6.8.1 and Section 6.8.2, respectively. 
d. The participant’s parent(s)/legal guardian(s) will be instructed to contact the study staff if the participant experiences severe redness or swelling 
>14 caliper units, severe pain at the 20vPnC injection site, a fever >40.0°C, or an emergency room visit or hospitalization. 
e. 
Designated site staff will review e-diary data online at frequent intervals (daily is optimal) for the 7 days following each dose of 20vPnC to evaluate 
participant compliance and as part of the ongoing safety review. 
 
 
 
 
 
 
 
 
 
 
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PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
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 Final Protocol, 10 December 2021 
 
Page 15 
 
 
 
1.3.2. Schedule of Activities: 1-Dose 20vPnC Group and 13vPnC (Control) Group 
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section (Section 8) 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 in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
 
Visit Number 
1 
2 
Visit Description 
Dose 1 Visit 
Follow-Up After Dose 1 
Visit Window (Days) 
Day 1 
28-42 Days After Dose 1 
Obtain informed consent 
X 
Assign participant number via IRT 
X 
Record demography 
X 
Perform clinical assessment, including medical historya 
X 
Record 13vPnC history 
X 
Record nonstudy vaccinations 
X 
X 
Record concomitant medications to treat SAEs only 
X 
X 
Obtain prevaccination temperature (measured as appropriate for age) 
X 
Review inclusion and exclusion criteria 
X 
Review continued eligibility 
X 
Review temporary delay criteria 
X 
Assign randomization number and study intervention container 
number via the IRT 
X 
Obtain blood sample (~5 mL) 
Xb 
X 
Administer 13vPnC or 20vPnC into the left thigh or left arm (as 
appropriate for the age and size of the child) 
X 
If applicable, administer and record routine pediatric vaccinationsc 
X 
Observe and record acute reactions for 30 minutes after study 
intervention administration 
X 
Provide parent(s)/legal guardian(s) with participant contact card 
X 
 
 
PFIZER CONFIDENTIAL 

PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
Page 16 
 
 
 
Visit Number 
1 
2 
Visit Description 
Dose 1 Visit 
Follow-Up After Dose 1 
Visit Window (Days) 
Day 1 
28-42 Days After Dose 1 
Provide parent(s)/legal guardian(s) with an e-diary (or assist with 
application download to a personal device), thermometer, and 
measuring device and instruct to collect prompted local reactions, 
systemic events, and antipyretic/pain medication until 7 days after 
20vPnC or 13vPnC vaccinationd 
X 
Review and/or collect e-diarye 
X 
Record and report AEs and SAEs 
X -------------------------------------------------------------------------- X 
Abbreviation: IRT = interactive response technology. 
a. 
If deemed necessary as part of the clinical assessment, the physical examination may include assessments of the general appearance, skin, head, lymph 
nodes, cardiovascular, respiratory, gastrointestinal, and neurological systems. 
b. Blood sample will be collected before vaccination. 
c. 
Administer permitted routine pediatric vaccinations (as applicable) after the study vaccination into a limb other than the site of the 20vPnC or 13vPnC 
injection. Prohibited and permitted vaccines are described in Section 6.8.1 and Section 6.8.2, respectively. 
d. The participant’s parent(s)/legal guardian(s) will be instructed to contact the study staff if the participant experiences severe redness or swelling 
>14 caliper units, severe pain at the 20vPnC or 13vPnC injection site, a fever >40.0°C, or an emergency room visit or hospitalization. 
e. 
Designated site staff will review e-diary data online at frequent intervals (daily is optimal) for the 7 days following 20vPnC or 13vPnC vaccination to 
evaluate participant compliance and as part of the ongoing safety review. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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2. INTRODUCTION 
Pneumococcal Disease 
Streptococcus pneumoniae are gram-positive encapsulated cocci that are a leading cause of 
bacteremia, bacterial meningitis, pneumonia, and AOM and continue to be a major global 
public health concern.1,2,3 Serious pneumococcal disease may occur at any age; however, 
children <5 years and adults ≥65 years of age are at particularly increased risk.4 Individuals 
with certain comorbidities and immunocompromising conditions are also at risk, especially 
persons with chronic heart, lung, liver, and renal disease, as well as those who are 
functionally asplenic. The global burden of pneumococcal disease has been substantially 
impacted by pneumococcal conjugate vaccines. Between 2010 and 2019, an estimated 
175 million cases of pneumococcal disease and 625,000 deaths worldwide have been 
prevented by 13vPnC in children <5 years of age according to global modeling studies.5 
S pneumoniae caused an estimated 14.5 million cases of serious disease and 826,000 deaths 
annually in children <5 years of age prior to introduction of pneumococcal conjugate 
vaccines.2 It has been estimated that in 2015, several years following introduction of 
pneumococcal conjugate vaccines into the national infant immunization programs of more 
than 100 countries, the global disease burden had declined, but S pneumoniae still accounted 
for 2.6 million cases of severe pneumococcal disease, 332,000 deaths in children <5 years of 
age, and 11% of deaths in children between the ages of 1 and 5 years.6 
The overall IPD burden was estimated in 2013 to have decreased approximately 90% in the 
population <5 years of age in the US since the introduction of pneumococcal conjugate 
vaccines; however, there was a slight increase in the proportions of IPD cases associated with 
hospitalization (63% to 71%), and the IPD case fatality rate was also slightly but statistically 
significantly increased (2% to 3%) in that age group.7 However, disease due to serotypes not 
covered by those vaccines remains and causes significant morbidity and mortality. 
Remaining pneumococcal disease due to 20vPnC serotypes was estimated for 13 countries to 
be between 46% and 77% in a recent analysis, corresponding to approximately 1.23 million 
cases, 160 deaths, and $214 million in direct medical costs annually across the 13 included 
countries.8 
National IPD surveillance data in England and Wales for the epidemiological year 
2016-2017, approximately 10 years after the introduction of 7vPnC in the national infant 
immunization program and 6 years after the introduction of 13vPnC, showed that the overall 
incidence of IPD was 9.87 per 100,000 population, with an incidence of 13.90 per 100,000 
population <2 years of age.9 The data for England and Wales are consistent with the patterns 
observed in data from the EU for 2017, which showed an overall IPD incidence of 6.2 cases 
per 100,000 population, with an incidence of 14.5 per 100,000 infants under 1 year of age.10 
Pediatric surveillance studies conducted between 2007 and 2013 in 8 US children’s hospitals, 
and between 1997 and 2010 in a referral center in Utah, found case fatality rates of 10% and 
13% with pneumococcal meningitis, respectively. These studies also found that between 52% 
and 63% of children surviving pneumococcal meningitis experience neurologic sequelae.11,12 
More recent pediatric surveillance conducted between 2014 and 2017 in 8 US children’s 
 
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hospitals following 13vPnC introduction in 2010 showed that 76.1% of residual IPD was 
caused by non-13vPnC serotype isolates. Serotypes 10A, 12F, 15B/15C, 22F, and 33F 
accounted for 36% of isolates causing IPD. 
The most common clinical presentations of IPD due to non-13vPnC serotypes included 
bacteremia (49.6%), meningitis (19.1%), and pneumonia (18.8%).13 These data demonstrate 
the continued need for expanded serotype coverage. 
Surveillance studies conducted in 2010-2012 by the CDC found that S pneumoniae remains 
among the most common pathogens identified in CAP requiring hospitalization in the US in 
both children and adults.14,15 It was the most common bacterial cause in children <2 years of 
age, even in the setting of a 43% reduction in CAP hospitalizations over the previous decade 
between 1997-1999 and 2007-2009, due to the introduction to 7vPnC.14,16 
Surveillance reported in 2017 by the ECDC showed that among cases of IPD for which the 
clinical presentation was known across all age groups, septicemia was reported in 35%, 
bacteremic pneumonia in 42%, meningitis in 19%, meningitis and septicemia in 1%, and 
other clinical syndromes in 3% of cases. The most common clinical presentations in children 
<5 years of age were septicemia and bacteremic pneumonia equally (1-4 years of age) and 
meningitis (<1 year of age).10 Data from nationwide surveillance networks in France for the 
year 2012 showed the rate of IPD among children <2 years of age to be 17.2 per 100,000 
population, with the incidence of pneumococcal meningitis among children <2 years of age 
to be 4.5 per 100,000 population. Of note, meningitis comprised 26.4%, 7.8%, and 19.6% of 
all cases of IPD in children <2 years of age, 2 through 4 years of age, and 5 through 15 years 
of age, respectively.17 The relatively high rates of meningitis among these pediatric 
populations are of particular concern not only because of the severity of the acute disease, 
but also because of the neurological sequelae that are frequently associated with meningitis. 
These data suggest that S pneumoniae remains an important cause of serious disease in the 
US and worldwide. 
S pneumoniae is one of the common bacterial causes of AOM.18,19 While AOM is generally 
not considered a serious disease, it does carry the risk of more serious complications. These 
complications can range from the development of chronic or recurrent otitis media 
necessitating surgical intervention (tympanostomy tube placement), and hearing loss with 
potential developmental and language delays, to invasive extension leading to mastoiditis and 
meningitis.20 
Although the introduction of pneumococcal conjugate vaccines into the US and other 
national infant immunization programs worldwide has brought about substantial reductions 
in the various manifestations of pneumococcal disease in pediatric (infants and children) 
populations, a substantial burden of pneumococcal disease remains. Serotypes not included 
in existing vaccines continue to contribute significantly to the morbidity and mortality caused 
by pneumococcal disease. 
 
 
 
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Vaccines to Prevent Pneumococcal Disease 
Pneumococcal Polysaccharide Vaccines 
The polysaccharide capsule has been identified as an important virulence factor for this 
pathogen. While more than 95 pneumococcal serotypes, differentiated by their capsular 
polysaccharide composition, have been identified, serious disease is generally caused by a 
smaller subset of serotypes.21,22 Anticapsular antibodies directed against the specific 
serotype bind to the capsule and promote complement-mediated opsonophagocytic killing 
and clearance of the organism.23 Pneumococcal disease can be prevented with 
polysaccharide-based vaccines that induce antibody responses with functional 
(opsonophagocytic) activity and target the capsular serotypes responsible for disease.24 
Vaccines containing free polysaccharides have been licensed since the 1970s. One such 
vaccine, PPSV23, has been licensed in the US since 1983.25,26 PPSV23 contains capsular 
polysaccharides for 23 serotypes (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 
17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F). Pneumococcal vaccines containing free 
polysaccharides such as PPSV23 elicit a T-cell–independent immune response. 
Unconjugated polysaccharide vaccines do not induce robust responses in certain populations 
(eg, immunocompromised persons, and children <2 years of age), nor do they generate 
immunologic memory, so that their protective effect wanes over 2 to 5 years.4,26,27,28 
Moreover, their ability to prevent nonbacteremic pneumonia, CAP, and AOM is limited or 
lacking.24,28,29,30,31 In addition, polysaccharide vaccines do not reduce VT nasopharyngeal 
carriage, which is important for herd immunity.31 PPSV23 is not recommended for children 
<2 years of age and only recommended in children >2 years of age who are at high risk for 
IPD to provide some degree of protection from disease caused by serotypes not covered by 
existing pneumococcal conjugate vaccines.24 
Pneumococcal Polysaccharide Conjugate Vaccines 
Pneumococcal conjugate vaccines contain polysaccharides that are covalently linked 
(conjugated) to an immunogenic protein. This modification results in T-cell–dependent 
immune responses, which have been shown to be protective in young children, older adults, 
and populations with high-risk conditions.27,32 7vPnC was the first pneumococcal conjugate 
vaccine to be licensed (2000) and was indicated for prevention of pneumococcal disease in 
infants and young children on the basis of efficacy studies. 7vPnC contained capsular 
polysaccharide conjugates for 7 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), 
each covalently linked to CRM197, a nontoxic variant of diphtheria toxin. These 7 serotypes 
were responsible for approximately 80% to 90% of IPD in children <5 years of age in the US 
and approximately 60% to 80% of IPD in the same age group in Europe at that time 
(1998-2000).33,34,35,36,37 These serotypes also accounted for a high proportion of 
antibiotic-resistant strains.38 7vPnC demonstrated efficacy against VT IPD, pneumonia, and 
AOM in large randomized, controlled efficacy studies in infants.39,40 
 
 
 
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The 7vPnC components contained in a related pneumococcal conjugate vaccine also were 
demonstrated to be efficacious against clinically/radiographically defined pneumonia.41,42,43,44 
Following introduction of 7vPnC, reduction of nasopharyngeal carriage and transmission has 
resulted in indirect herd effects, with a 92% reduction of 7vPnC VT IPD in older adults 
≥65 years of age.45 
13vPnC was developed to expand serotype coverage and was licensed in the US in 2010. In 
the EU, 13vPnC was initially indicated for use in infants from 6 weeks to 5 years of age, but 
the indication was later expanded to include children and adolescents up to 17 years of age. 
13vPnC includes the same S pneumoniae serotypes as 7vPnC and an additional 
6 polysaccharide conjugates for serotypes 1, 3, 5, 6A, 7F, and 19A.32,36,46 The vaccine was 
licensed for use in infants and young children based on comparisons of serotype-specific 
serum IgG antibody concentrations to the serotypes in 7vPnC, with supportive data to 
demonstrate the functional activity of the immune responses. 13vPnC was later licensed in 
adults based on demonstration of efficacy against CAP due to serotypes contained in 13vPnC 
in adults 65 years of age and older.47 13vPnC has replaced 7vPnC and is licensed in the US 
and many other countries, with national recommendations for use in children and older 
adults.48,49,50,51 It has also been prequalified by the WHO for use in national infant 
immunization programs in lower- and middle-income countries.52,53 Surveillance data from 
several countries following introduction of 13vPnC into the routine infant immunization 
program have demonstrated vaccine effectiveness against 13vPnC VT IPD in the vaccinated 
population.54,55,56 
Development of 20vPnC 
20vPnC is modeled after 7vPnC and 13vPnC, and contains polysaccharides of capsular 
serotypes of S pneumoniae, each covalently linked to CRM197. The amount of 
polysaccharide (2.2 µg/dose) selected for each new serotype (8, 10A, 11A, 12F, 15B, 22F, 
and 33F) contained in 20vPnC mirrors the approach taken for the addition of the 6 new 
serotypes when developing 13vPnC. 20vPnC contains the same components as 13vPnC, 
including the 13 polysaccharide conjugates, excipients (polysorbate 80, succinate buffer, 
sodium chloride), and aluminum phosphate, in addition to the 7 new polysaccharide 
conjugates. Additional epidemiology data of the 7 serotypes and the preclinical program are 
described in the 20vPnC IB. The vaccine is being developed for use in the pediatric 
population and is licensed for adults in the US. 
2.1. Study Rationale 
The purpose of the study is to assess safety and immunogenicity data with 1 or 2 doses of 
20vPnC in toddlers ≥12 to <24 months of age who have received 2 doses of 13vPnC in 
infancy (prior to 12 months of age), CCI 
 
 
 
 
 
 
 
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2.2. Background 
20vPnC is being developed to further expand protection against the global burden of vaccine- 
preventable pneumococcal disease in children over that of 13vPnC. 20vPnC was licensed for 
adults in the US in June 2021, and as of October 2021 is under review by the CHMP in 
Europe. 20vPnC contains the serotypes present in 13vPnC and 7 additional serotypes 
(8, 10A, 11A, 12F, 15B, 22F, and 33F) individually conjugated to CRM197. As noted above, 
20vPnC uses the same platform and contains the same excipients as 7vPnC and 13vPnC. 
These 7 additional serotypes were selected based on their relative prevalence as a cause of 
IPD, their generalized geographic distribution, and other factors that would support inclusion, 
such as the presence of antibiotic resistance (11A, 15B), association with outbreaks (8, 12F), 
and greater disease severity, eg, meningitis, mortality (10A, 11A, 
22F).57,58,59,60,61,62,63,64,65,66,67,68 These 7 serotypes have a long-standing association with 
serious pneumococcal disease and are responsible for a substantial burden of remaining 
pneumococcal disease. 
The incidence of IPD due to these 7 serotypes in children <5 years of age has remained 
relatively stable or slightly increased over the past several years, and these serotypes cause a 
significant amount of IPD in children.69,70,71,72,73,74,75 These 7 serotypes contribute 
significantly to the burden of IPD in the US and elsewhere. It is estimated that between 2015 
and 2016, these 7 serotypes accounted for 34% to 39% of IPD in children in the US.76 In the 
EU, according to the ECDC annual IPD epidemiological report, in 2017, approximately 75% 
of cases in children <5 years of age were caused by a serotype not in 13vPnC, increasing 
from 63% in 2013. Five of the 10 most common serotypes included serotypes 8, 10A, 11A, 
12F, and 22F, with serotypes 8, 10A, 12F, and 24F being among the most common in 
children in this age group.10 
2.2.1. Clinical Overview 
Safety and immunogenicity data from Phase 1, Phase 2, and Phase 3 studies in more than 
5000 adults receiving 20vPnC have shown that 20vPnC has a safety and immunogenicity 
profile similar to 13vPnC. 
Additionally, a Phase 2 study (B7471003) of 20vPnC in healthy infants was performed. In 
the study, 460 US infants ≥42 to ≤98 days of age were randomized to receive either blinded 
20vPnC or 13vPnC at 2, 4, 6, and 12 months of age. 
20vPnC was well tolerated in the study, with a safety profile similar to that of the 13vPnC 
group in the study and consistent with other pneumococcal conjugate vaccines. Immune 
responses (either IgG GMCs or percentages of participants meeting a predefined IgG 
concentration) after 3 and 4 doses of 20vPnC were similar to those in the 13vPnC group. 
These data supported Phase 3 studies in infants, toddlers, children, and adolescents. The 
ongoing Phase 3 pediatric studies are described in the 20vPnC IB. 
 
 
 
 
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2.3. Benefit/Risk Assessment 
13vPnC is a licensed vaccine and the most common AEs noted in children <5 years of age 
after vaccination are primarily related to local reactions (injection site pain or tenderness, 
redness, and swelling) and systemic events (fever, irritability, decreased appetite, and 
increased sleep). 20vPnC contains the same components and excipients as 13vPnC, along 
with the polysaccharide conjugates for the 7 additional pneumococcal serotypes. Thus, the 
AE profile of 20vPnC is expected to be similar to 13vPnC, but AEs may be different with 
20vPnC. 
In a randomized, active-controlled, double-blind study with a 2-arm parallel design 
(B7471003), 20vPnC was administered to 460 infants ≥42 to ≤98 days of age naïve to 
pneumococcal vaccine. The vaccine was well tolerated and the AE profile was consistent 
with events commonly seen in this age group and similar to those seen in the 13vPnC group. 
The most common AEs after 20vPnC administration were local reactions (pain, redness, and 
swelling at the injection site) and systemic events (fever, irritability, drowsiness/increased 
sleep, and decreased appetite). 
As with any vaccine, an allergic reaction can occur. The allergic reaction can vary from a 
skin rash to swelling of the face or lips, wheezing, and/or shortness of breath. A severe 
allergic reaction (anaphylactic shock, collapse, or shock-like state [hypotonic-hyporesponsive 
episode]) may also occur. There may also be additional risks related to the vaccines 
administered in the study that are not known at this time. 
Safety assessments described in the protocol and ongoing review of safety data by the 
investigator and sponsor study team will serve to monitor and mitigate these risks. 
13vPnC is approved for the prevention of pneumococcal disease due to the serotypes in the 
vaccine. 20vPnC was licensed for adults in the US in June 2021 for the prevention of 
pneumococcal pneumonia and IPD, and as of October 2021 is under review by the CHMP in 
Europe. Both vaccines may provide a clinical benefit to those receiving it. 
In the B7471003 study, 20vPnC induced immune responses to the pneumococcal serotypes 
in the vaccine. This suggests that protection against pneumococcal disease will be similar to 
13vPnC. If 20vPnC is successful in Phase 3 studies, and approved in the pediatric 
population, it is anticipated to provide a public health benefit by reducing the burden of 
pneumococcal disease (invasive and noninvasive) due to vaccine serotypes. 
Pfizer considers that the available information from Study B7471003 with 20vPnC, the 
available safety profile of similar pneumococcal conjugate vaccines (ie, 7vPnC and 13vPnC), 
and the limited risks from study procedures support a favorable benefit-risk profile for 
20vPnC and this study. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of 20vPnC may be found in the IB, which is the SRSD for this study. The 
SRSD for the 13vPnC control is the EU SmPC. 
 
PFIZER CONFIDENTIAL 

 
PF-06482077 (20-valent Pneumococcal Conjugate Vaccine [20vPnC]) 
Protocol B7471027 
 Final Protocol, 10 December 2021 
 
 
2.3.1. Risk Assessment 
 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention(s): 20vPnC and 13vPnC 
Local reactions to the vaccine (injection site pain 
or tenderness, redness, and swelling) and systemic 
events (fever, irritability, decreased appetite, and 
increased sleep) may occur. 
13vPnC is a licensed vaccine and used in infants 
and children for immunization globally. 20vPnC 
contains the same components and excipients as 
13vPnC, but also contains the polysaccharide 
conjugates for the 7 additional pneumococcal 
serotypes. Thus, the AE profile of 20vPnC is 
expected to be similar to that of 13vPnC. 
The study employs the use of a reactogenicity 
e-diary, which allows the investigator to monitor 
local reactions and systemic events in real time 
through an electronic portal. Severe reactions will 
require an unscheduled telephone call, and visit if 
required, to be conducted per protocol. 
All study participants will be observed for at least 
30 minutes after vaccination. 
Study Procedures 
Participants will be required to attend healthcare 
facilities during the global SARS-CoV-2 
pandemic. 
Without appropriate social distancing and PPE, 
there is a potential for increased exposure to 
SARS-CoV-2. 
Pfizer will work with sites to ensure appropriate 
COVID-19 prevention strategies. 
Venipuncture will be performed during the study. 
There is the risk of bleeding, bruising, hematoma 
formation, and infection at the venipuncture site. 
Only appropriately qualified personnel will 
perform blood draws. 
The volume and frequency of blood sample 
collection required during the study has been 
minimized as much as possible. 
 
 
 
 
 
 
 
 
 
 
 
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2.3.2. Overall Benefit/Risk Conclusion 
Taking into account the measures to minimize risk to study participants, the potential risks 
identified in association with 20vPnC, and 13vPnC (licensed for infants and children 
globally), are justified by the anticipated benefits that may be afforded to healthy toddler 
participants. 
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS 
 
Objectives 
Endpoints 
Estimands 
Primary Safety Objective 
Primary Safety Endpoints 
Primary Safety Estimands 
• To describe the safety profile 
of 20vPnC 
• 
Prompted local reactions 
(redness, swelling, and pain 
at the injection site) 
• 
Prompted systemic events 
(fever, decreased appetite, 
drowsiness/increased sleep, 
and irritability) 
• 
AEs 
• 
SAEs 
In participants receiving at least 1 dose 
of study intervention with safety 
follow-up after the assigned 
vaccination: 
• 
The percentage of participants 
reporting prompted local reactions 
within 7 days after the last 
assigned vaccination in each group 
• 
The percentage of participants 
reporting prompted systemic 
events within 7 days after the last 
assigned vaccination in each group 
The percentage of participants 
reporting AEs within 1 month after 
the last assigned vaccination in 
each group 
• 
The percentage of participants 
reporting SAEs within 1 month 
after the last assigned vaccination 
in each group 
Primary Immunogenicity 
Objective 
Primary Immunogenicity 
Endpoint 
Primary Immunogenicity Estimand 
• 
To describe the immune 
responses to the additional 7 
serotypes after 1 or 2 doses 
of 20vPnC 
Pneumococcal serotype-specific 
IgG concentration 
In participants complying with the key 
protocol criteria (evaluable 
participants) in each group: 
• 
Percentages of participants with 
predefined serotype-specific IgG 
concentrations for the 7 additional 
serotypes 1 month after the last 
assigned vaccination 
 
 
 
 
 
 
 
 
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Objectives 
Endpoints 
Estimands 
Secondary Immunogenicity 
Objective 
Secondary Immunogenicity 
Endpoints 
Secondary Immunogenicity 
Estimands 
• To further describe the 
immune response of 20vPnC 
after 1 or 2 doses 
• 
Pneumococcal serotype- 
specific IgG concentration 
• 
Pneumococcal serotype- 
specific OPA titers 
In evaluable participants in each group: 
• 
IgG GMCs for the vaccine 
serotypes 1 month after the last 
assigned vaccination 
• 
Percentages of participants with 
predefined IgG concentrations for 
the 13 matched serotypes 1 month 
after the last assigned vaccination 
• OPA GMTs for the vaccine 
serotypes 1 month after the last 
assigned vaccination 
CCI 
 
 
 
 
4. STUDY DESIGN 
4.1. Overall Design 
This Phase 3, multicenter, randomized, partially double-blind study will be conducted at 
investigator sites in Europe. The purpose of this study is to provide safety and 
immunogenicity data with 20vPnC in European toddlers ≥12 to <24 months of age who have 
received 2 doses of 13vPnC in infancy (prior to 12 months of age) and who will receive 1 or 
2 doses of 20vPnC during the study. 13vPnC will serve as the control. 
 
 
 
 
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Approximately 360 toddlers ≥12 to <24 months of age at the time of consent, who previously 
received 2 infant doses of 13vPnC (prior to 12 months of age), will be enrolled and 
randomized in a 1:1:1 ratio to receive either 1 or 2 doses of 20vPnC, or 1 dose of 13vPnC 
(control). The vaccine in toddlers randomized to receive 1 dose will be double-blind, as 
20vPnC and 13vPnC have the same appearance and a single dose will be administered at 
Visit 1 of the study. For participants randomized to 2 doses of 20vPnC, the parents/legal 
guardians and site staff will know that these participants will need to return for a second 
vaccination visit and that they will receive 20vPnC at both Visit 1 and Visit 2. The last 
assigned vaccinations will be the single vaccination at Visit 1 in the groups randomized to 
receive 1 dose of 20vPnC or 13vPnC (control) and the second vaccination given at Visit 2 in 
the group randomized to receive 2 doses. 
On Day 1 (Visit 1) of the study, participants will be assessed for eligibility and information 
will be collected, including medical history and 13vPnC history. 
Participants will receive 20vPnC or 13vPnC. Participants will be observed for 30 minutes 
after vaccination, and any reactions occurring during that time will be recorded as AEs. The 
participant’s parent(s)/legal guardian(s) will be provided with an e-diary or e-diary 
application, thermometer, and measuring device and instructed to collect prompted local 
reactions (redness, swelling, and pain at the injection site) and systemic events (fever, 
decreased appetite, drowsiness/increased sleep, and irritability) occurring within 7 days after 
each vaccination. The use of antipyretic/pain medications will also be prompted for and 
collected daily in the e-diary for 7 days after vaccination. The participant’s parent(s)/legal 
guardian(s) will be instructed to contact the study staff if the participant experiences redness 
or swelling >14 caliper units, severe pain at the 20vPnC or 13vPnC injection site, or fever 
>40.0°C or has an emergency room visit or hospitalization. 
Blood will be drawn from all participants for immunogenicity assessments before 
administration of study intervention and 1 month after the vaccination (last vaccination in the 
group receiving 2 doses) in each vaccine group. 
Participants in the 2-dose 20vPnC group will return 56 to 70 days after Visit 1 for Visit 2. 
Participants will be assessed for continued eligibility and information will be collected from 
the participant’s parent(s)/legal guardian(s) on AEs, including nonserious AEs and SAEs, 
and e-diary follow-up (as needed). Concomitant medications used to treat SAEs will be 
recorded, as will information on nonstudy vaccinations given since the last visit. No blood 
will be drawn before Dose 2. Dose 2 of 20vPnC (0.5 mL) will be administered and 
participants observed for 30 minutes after vaccination. The remainder of the visit and 
instructions to the parents/legal guardians will be done as in Visit 1. 
Participants in the 1-dose 20vPnC group and 13vPnC (control) group will return 28 to 
42 days after Visit 1 (Visit 2) and participants in the 2-dose 20vPnC group will return 28 to 
42 days after Visit 2 (Visit 3) for their follow-up visits. Information will be collected from 
the participant’s parent(s)/legal guardian on AEs, SAEs, and e-diary follow-up (as needed), 
as described above for Visit 2 for the 2-dose 20vPnC group. Participants will have blood 
 
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drawn for immunogenicity assessment. Other licensed nonstudy vaccines may be 
administered after the blood draw at this visit. 
In the case of extreme circumstances, such as natural disasters or a pandemic, visits for 
follow-up or procedures may need to be conducted through other means (eg, telephone calls). 
4.1.1. Approximate Duration of Participation for Each Participant 
Each participant will participate in the study for approximately 1 to 3 months, depending on 
randomization. 
4.1.2. Approximate Number of Participants 
Approximately 360 (120 in each vaccination group) participants will be enrolled to reach a 
target of 315 evaluable participants (105 in each vaccination group). 
The 360 participants who have been previously vaccinated with 2 doses of 13vPnC prior to 
12 months of age will be enrolled in 3 vaccination groups: 
• 2-Dose 20vPnC group: Approximately 120 participants will receive 2 doses of 20vPnC. 
• 1-Dose 20vPnC group: Approximately 120 participants will receive 1 dose of 20vPnC. 
• 13vPnC (control) group: Approximately 120 participants will receive 1 dose of 
13vPnC. 
4.2. Scientific Rationale for Study Design 
This Phase 3, multicenter, randomized, partially double-blind study will be conducted at 
investigator sites in Europe. CCI 
 The purpose of this study 
is to describe the safety and immunogenicity of 1 or 2 vaccinations administered to toddlers 
≥12 to <24 months of age who received 2 doses of 13vPnC in infancy (prior to 12 months of 
age and >56 days prior to vaccination in this study). A single dose of 13vPnC will serve as 
the control vaccine. 
4.3. Justification for Dose 
20vPnC is modeled after 7vPnC and 13vPnC, and contains capsular polysaccharides from 
pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 
19F, 22F, 23F, and 33F individually conjugated to CRM197. The vaccine is formulated to 
contain 2.2 µg of each saccharide, except for 4.4 µg of 6B, per 0.5-mL dose. This study uses 
a schedule of 1 dose or 2 doses of pneumococcal conjugate vaccine administered in toddlers 
≥12 to <24 months of age. These schedules have been used with 13vPnC (in unvaccinated 
children [2-dose schedule] in this age group, and children who have begun their series with 
2 prior infant doses of 7vPnC [1-dose schedule]), and are included in the 13vPnC SmPC. 
 
 
 
 
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4.4. End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the study. 
5. STUDY POPULATION 
This study can fulfill its objectives only if appropriate participants are enrolled. The 
following eligibility criteria are designed to select participants 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 participant is suitable for this 
protocol. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1. Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age and Sex: 
1. Male or female toddlers ≥12 to <24 months of age at the time of consent. 
Informed Consent: 
2. Participants whose parent(s)/legal guardian(s) is capable of giving signed informed 
consent as described in Appendix 1, which includes compliance with the requirements 
and restrictions listed in the ICD and in this protocol. 
Type of Participant and Disease Characteristics: 
3. Participant has received exactly 2 infant doses of 13vPnC prior to 12 months of age 
confirmed by written documentation. The last dose of 13vPnC must have been 
administered >56 days before enrollment into the study. 
4. Participants whose parent(s)/legal guardian(s) are willing and able to comply with all 
scheduled visits, investigational plan, and other study procedures. 
5. Healthy toddlers determined by clinical assessment, including medical history and 
clinical judgment, to be eligible for the study. 
6. Expected to be available for the duration of the study and whose parents(s)/legal 
guardian(s) can be contacted by telephone during study participation. 
 
 
 
 
 
 
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5.2. Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions: 
1. History of severe adverse reaction associated with a vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of 13vPnC, 20vPnC, or any diphtheria 
toxoid–containing vaccine. 
2. Significant neurological disorder or history of seizure (excluding febrile seizure) or 
significant stable or evolving disorders such as cerebral palsy, encephalopathy, 
hydrocephalus, or other significant disorders. 
3. Major known congenital malformation or serious chronic disorder. 
4. History of microbiologically proven invasive disease caused by S pneumoniae. 
5. Known or suspected immunodeficiency or other conditions associated with 
immunosuppression, including, but not limited to, immunoglobulin class/subclass 
deficiencies, DiGeorge syndrome, generalized malignancy, HIV infection, leukemia, 
lymphoma, or organ or bone marrow transplant. 
6. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection. 
7. Congenital, functional, or surgical asplenia. 
8. Other medical condition or laboratory abnormality that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for the 
study. 
Prior/Concomitant Therapy: 
9. Previous vaccination with any investigational pneumococcal vaccine, or planned receipt 
through study participation. 
10. Currently receives treatment with immunosuppressive therapy, including cytotoxic agents 
or systemic corticosteroids, or planned receipt through the last blood draw. If systemic 
corticosteroids have been administered short term (<14 days) for treatment of an acute 
illness, participants should not be enrolled into the study until corticosteroid therapy has 
been discontinued for at least 28 days before study intervention administration. 
Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted. 
 
 
 
 
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11. Receipt of blood/plasma products or immunoglobulins (including hepatitis B 
immunoglobulin) or planned receipt through the last planned blood draw in the study. 
Prior/Concurrent Clinical Study Experience: 
12. Participation in other studies involving investigational drug(s), investigational vaccines, 
or investigational devices within 28 days prior to study entry and/or during study 
participation. An exception to this is an investigational vaccine authorized by the 
national regulatory agency for use in infants or toddlers to prevent pandemic disease. 
Participation in purely observational studies is acceptable. 
Other Exclusions: 
13. Children or grandchildren who are direct descendants of investigator site staff members 
or Pfizer employees who are directly involved in the conduct of the study. 
Diagnostic Assessments: 
Not applicable. 
5.3. Lifestyle Considerations 
No restrictions are required. 
5.4. Screen Failures 
Screen failures are defined as participants whose parent(s)/legal guardian(s) have consented 
for them to participate in the clinical study but are not subsequently randomly assigned to 
study intervention. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants to meet the CONSORT publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, and any AEs and SAEs 
recorded from signing the informed consent until the time of determination of screen failures. 
Individuals who do not meet the criteria for participation in this study (screen failure) may 
not be rescreened. 
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Administration of 
Study Intervention 
The following conditions are temporary or self-limiting and a participant may be vaccinated 
in the study once the condition(s) has/have resolved and no other exclusion criteria are met. 
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5.5.1. Criteria for Temporarily Delaying Vaccine Administration 
• Current febrile illness (eg, rectal temperature ≥38.0°C or other acute illness within 48 
hours before study intervention administration. 
• Receipt of any inactivated or otherwise nonlive vaccine within 14 days or any live 
vaccine within 28 days before study intervention administration, with the exceptions of: 
1) influenza vaccine, which may be given at any time during the influenza season if the 
participant is of the appropriate age to receive it; and 2) permitted concomitant vaccines 
on the same day as study intervention (Section 6.8.1 and Section 6.8.2). 
• Receipt of short-term (<14 days) systemic corticosteroids. Study intervention 
administration should be delayed until systemic corticosteroid use has been discontinued 
for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin, eyes, 
or ears) corticosteroids are permitted. 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol. 
6.1. Study Intervention(s) Administered 
20vPnC is a sterile liquid suspension formulation containing saccharides from pneumococcal 
serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, 
and 33F individually conjugated to CRM197. The vaccine is formulated to contain 2.2 µg of 
each saccharide, except for 4.4 µg of 6B, per 0.5-mL dose. The vaccine contains 5 mM 
succinate buffer, 150 mM sodium chloride, 0.02% polysorbate 80, and 125 µg aluminum as 
aluminum phosphate, per 0.5-mL dose. 
13vPnC is a sterile liquid suspension formulation containing saccharides from pneumococcal 
serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F individually conjugated to 
CRM197. The vaccine is formulated to contain 2.2 µg of each saccharide, except for 4.4 µg 
of 6B, per 0.5-mL dose. The vaccine contains 295 μg succinate buffer, 0.85% sodium 
chloride, 100 μg polysorbate 80, and 125 µg aluminum as aluminum phosphate, per 0.5-mL 
dose. 
 
20vPnC and 13vPnC are both white suspensions and have a matching appearance, and will 
be supplied as prefilled syringes. 
 
 
 
 
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All vaccines listed in this section will be provided by Pfizer as prefilled syringes. Each 
syringe will be packaged in a carton with a label and a tamper-evident seal, and will be 
labeled as required per country requirement (refer to the IP manual). 
6.1.1. Administration 
Participants will receive either 1 or 2 doses of 20vPnC or 1 dose of 13vPnC in accordance 
with the study’s SoA. 
20vPnC and 13vPnC should be administered intramuscularly by injecting 0.5 mL into the 
anterolateral thigh muscle of the left leg or left arm (as appropriate for the age and size of the 
toddler) by a designated site staff member. All nonstudy vaccinations should be 
administered into a limb other than the site of the 20vPnC or 13vPnC injection. The location 
of the injection of each vaccine administered (study intervention and other vaccinations) will 
be recorded on the CRF. 
Standard vaccination practices must be observed and vaccine must not be injected into blood 
vessels. Appropriate medication and other supportive measures for management of an acute 
hypersensitivity reaction should be available in accordance with local guidelines for standard 
immunization practices. 
Administration of study interventions should be performed by an appropriately qualified, 
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. 
Study intervention administration details will be recorded on the CRF. 
6.1.2. Medical Devices 
In this study, medical devices being deployed are the 20vPnC and 13vPnC prefilled syringes. 
Instructions for medical device use are provided in the IP manual. 
Medical device incidents, including those resulting from malfunctions of the device, must be 
detected, documented, and reported by the study personnel throughout the study. Please refer 
to Section 8.3.9 for details. 
6.2. Preparation, Handling, Storage, and Accountability 
1. 
 
 
 
 
 
 
 
 
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2. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study interventions received and any discrepancies are 
reported and resolved before use of the study intervention. 
 
 
 
 
 
 
 
 
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Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP manual. 
 
6.2.1. Preparation and Dispensing 
See the IP manual for instructions on how to prepare the study intervention for 
administration. Study intervention should be prepared and dispensed by an appropriately 
qualified and experienced member of the study staff (eg, physician, nurse, physician’s 
assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as allowed by 
local, state, and institutional guidance. 
6.3. Measures to Minimize Bias: Randomization and Blinding 
6.3.1. Allocation to Study Intervention 
Allocation of participants to vaccine groups will proceed through the use of an IRT system 
(IWR). The site personnel (study coordinator or specified designee) will be required to enter 
or select information including but not limited to the user’s ID and password, the protocol 
number, and the participant number. 
The site personnel will then be provided with a vaccine assignment, randomization number, 
and DU or container number when study intervention is being supplied via the IRT system. 
The IRT system will provide a confirmation report containing the participant number, 
randomization number, and DU or container number assigned. The confirmation report must 
be stored in the site’s files. 
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system. 
6.3.2. Breaking the Blind 
Toddlers randomized to receive 1 dose of 20vPnC or 13vPnC (control) at Visit 1 will be 
participants in the double-blind portion of the study, as the vaccines have the same 
appearance. For toddlers randomized to 2 doses of 20vPnC, the parent(s)/legal guardian(s) 
and site staff will know that these toddlers will receive 20vPnC at both Visit 1 and Visit 2. 
 
 
 
 
 
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At the initiation of the study, the investigator site will be instructed on the method for 
breaking the blind for an individual participant. 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 participant. 
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 recorded in 
the source documentation and entered on the CRF. 
6.3.3. Blinding of the Sponsor 
Sponsor personnel directly involved in evaluating participant data will be blinded to vaccine 
assignment of both 1-dose groups (1-dose 20vPnC and 1-dose 13vPnC groups) until the final 
analysis of the study, following the principles outlined in the ICH E9 guideline on Statistical 
Principles for Clinical Trials.77 A data blinding plan will be created to describe the blinding 
requirements and unblinding events. Laboratory personnel performing the immunologic 
assays will be blinded to vaccine assignment of all 3 groups until all assays have been 
completed and assay results finalized. 
6.4. Study Intervention Compliance 
All doses of study intervention will be administered by the appropriately designated study 
staff at the investigator site. 
6.5. Dose Modification 
Not applicable. 
6.6. Continued Access to Study Intervention After the End of the Study 
No intervention will be provided to study participants at the end of their study participation. 
6.7. Treatment of Overdose 
For this study, more than 1 dose of study intervention within a 24-hour time period will be 
considered an overdose. 
Pfizer does not recommend specific treatment for an overdose. 
In the event of an overdose, the investigator should: 
1. Contact the medical monitor within 24 hours. 
2. Closely monitor the participant for any AEs/SAEs. 
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF. 
4. Overdose is reportable to Pfizer Safety only when associated with an SAE. 
 
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Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant. 
6.8. Concomitant Therapy 
6.8.1. Prohibited Concomitant Vaccines and Treatments 
• Receipt of any investigational vaccines, drugs, or medical devices is prohibited during 
study participation. See the one exception to this in Section 6.8.2 below. 
• Receipt of nonstudy pneumococcal vaccine is prohibited during study participation. 
• Topical anesthetic at the site of vaccination is prohibited. 
• Receipt of blood/plasma products, immunoglobulins, and/or immunosuppressive therapy 
(including a ≥14-day course of systemic corticosteroids) is prohibited through Visit 3 for 
participants in the 2-dose 20vPnC group and through Visit 2 for participants in the 1-dose 
20vPnC group and 13vPnC (control) group. 
6.8.2. Permitted Concomitant Vaccines and Treatments 
• Licensed inactivated influenza vaccine may be given at any time during the study per 
national recommendations. If administered concomitantly, these vaccines must be 
injected into a limb other than the site of the 20vPnC or 13vPnC injection. 
• Investigational vaccines authorized by the national regulatory agency for use in infants or 
toddlers to prevent pandemic disease. 
• Receipt of meningococcal conjugate vaccines is permitted only after the last blood 
sample is collected in each vaccination group. 
• Receipt of other licensed nonstudy vaccines (except pneumococcal and meningococcal 
vaccines described above) is permitted. However, if feasible, it is recommended that 
licensed nonstudy vaccines be administered at least 14 days (for nonlive vaccines) or at 
least 28 days (for live vaccines) before or after 20vPnC or 13vPnC administration. 
Measles, mumps, and rubella and varicella vaccines can be administered concomitantly 
into a limb other than the site of the 20vPnC or 13vPnC injection. 
• The use of prophylactic antipyretic/pain medication, while permitted, is not 
recommended on the day of study intervention administration (before or after 
vaccination). If symptoms develop, the use of antipyretic/pain medication is allowed. 
• Topical anesthetic at the site of blood draw is permitted. 
 
 
 
 
 
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• Inhaled/nebulized, topical (skin, eyes, or ears), or localized injections of corticosteroids 
(eg, intra-articular or intrabursal administration) are permitted during participant 
participation in the study. 
• Prescription and nonprescription medications, vitamins, minerals, and herbal remedies 
are permitted during the study. 
6.8.3. Recording Prior and Concomitant Vaccines and Treatments 
The name and date of administration of the 2 infant doses of 13vPnC given prior to 
12 months of age will be collected and recorded in the CRF. The name(s) and date(s) of 
administration are to be obtained from sources, such as medical records or vaccination cards. 
The name and date of administration for all nonstudy vaccinations received should be 
collected from the time of signing of the ICD to the last study visit and will be recorded in 
the CRF. 
Medications taken to treat SAEs from the signing of the ICD to the final visit will be 
recorded on the CRF. 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1. Discontinuation of Study Intervention 
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention include the following: AEs, participant’s 
parent(s)’/legal guardian(s)’ request, investigator request, and protocol deviation (including 
no longer meeting all the inclusion criteria, or meeting 1 or more exclusion criteria). 
Note that discontinuation of study intervention does not represent withdrawal from the study. 
If study intervention is permanently discontinued, and the participant’s parent(s)/legal 
guardian(s) consents, the participant will remain in the study and AEs and SAEs will be 
collected for 1 month after the last (most recent) study vaccination. See the SoAs 
(Section 1.3.1 and Section 1.3.2) for data to be collected at the time of discontinuation of 
study intervention and follow-up for any further evaluations that need to be completed. 
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, postvaccination study follow-up, 
and/or future collection of additional information. 
 
 
 
 
 
 
 
 
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7.2. Participant Discontinuation/Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her parent(s)’/legal guardian(s)’ 
request. Reasons for discontinuation from the study include the following: 
• Refused further study procedures; 
• Lost to follow-up; 
• Death; 
• Study terminated by sponsor; 
• At the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
The participant will be permanently discontinued from the study intervention and the study at 
that time. 
If a participant’s parent(s)/legal guardian withdraws the participant from the study, the 
parent(s)/legal guardian(s) may request destruction of any remaining samples taken and not 
tested, and the investigator must document any such requests in the site study records and 
notify the sponsor accordingly. 
If the participant’s parent(s)/legal guardian withdraws the participant from the study and also 
withdraws consent (see Section 7.2.1 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. 
7.2.1. Withdrawal of Consent 
A participant whose parent(s)/legal guardian(s) request to discontinue receipt of study 
intervention will remain in the study and must continue to be followed for protocol-specified 
follow-up procedures. The only exception to this is when a participant’s parent(s)/legal 
guardian(s) specifically withdraws consent for any further contact with him or her or persons 
previously authorized by the participant’s parent(s)/legal guardian(s) to provide this 
information. A participant’s parent(s)/legal guardian(s) 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 receipt of study intervention 
or also from study procedures and/or postvaccination study follow-up, and entered on the 
appropriate CRF page. In the event that vital status (whether the participant is alive or dead) 
is being measured, publicly available information should be used to determine vital status 
only as appropriately directed in accordance with local law. 
 
 
 
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7.3. Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and the participant’s parent(s)/legal guardian(s) is unable to be contacted by 
the study site. 
The following actions must be taken if a participant fails to attend a required study visit: 
• The site must attempt to contact the participant’s parent(s)/legal guardian(s) and 
reschedule the missed visit as soon as possible, counsel the participant’s 
parent(s)/legal guardian(s) on the importance of maintaining the assigned visit 
schedule, and ascertain whether the participant’s parent(s)/legal guardian(s) wishes to 
and/or should continue in the study; 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant’s parent(s)/legal guardian(s) 
(where possible, 3 telephone calls and, if necessary, a certified letter to the 
participant’s last known mailing address or local equivalent methods). These contact 
attempts should be documented in the participant’s medical record; 
• Should the participant’s parent(s)/legal guardian(s) continue to be unreachable, the 
participant will be considered to have withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES 
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
The date of birth will be collected to critically evaluate the immune response and safety 
profile by age. 
Study procedures and their timing are summarized in the SoAs (Section 1.3.1 and 
Section 1.3.2). Protocol waivers or exemptions are not allowed. 
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention. 
Adherence to the study design requirements, including those specified in the SoAs, is 
essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
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Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible. The study team must 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. 
The total blood sampling volume for individual participants in this study is approximately 
10 mL. 
8.1. Efficacy and/or Immunogenicity Assessments 
8.1.1. Immunogenicity Assessments 
Blood samples (approximately 5 mL per sample) will be collected from all participants prior 
to vaccination at Visit 1 for all groups, at Visit 2 for the 1-dose 20vPnC group and 13vPnC 
(control) group, and at Visit 3 for the 2-dose 20vPnC group. These are the immunogenicity 
time points. 
Pneumococcal Responses 
IgG responses to the 20 pneumococcal serotypes contained in 20vPnC 
IgG concentrations for the serotypes present in 20vPnC (1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 
11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F) will be determined on all sera 
collected prior to vaccination at Visit 1 for all groups, at Visit 2 for the 1-dose 20vPnC group 
and 13vPnC (control) group, and at Visit 3 for the 2-dose 20vPnC group. The 
serotype-specific IgG concentrations will be measured by Pfizer’s Luminex-based assay 
platform. 
OPA responses to the 20 pneumococcal serotypes contained in 20vPnC 
OPA titers for serotypes present in 20vPnC (1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 
15B, 18C, 19A, 19F, 22F, 23F, and 33F) will be determined in randomly selected subsets of 
sera collected prior to vaccination at Visit 1 for all groups, at Visit 2 for the 1-dose 20vPnC 
group and 13vPnC (control) group, and at Visit 3 for the 2-dose 20vPnC group. 
 
 
 
 
 
 
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8.1.2. 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 participant’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 
 
The participant’s parent(s)/legal guardian(s) may request the participant’s samples, if still 
identifiable, be destroyed at any time; however, any data already collected from those 
samples will still be used for this research. The biological samples may be shared with other 
researchers as long as confidentiality is maintained and no testing of the participant’s genetic 
material is performed. 
8.2. Safety Assessments 
Planned time points for all safety assessments are provided in the SoAs (see Section 1.3.1 
and Section 1.3.2). Unscheduled clinical laboratory measurements may be obtained at any 
time during the study to assess any perceived safety issues. 
A clinical assessment, including medical history and measurement of temperature, will be 
performed on all participants prior to vaccination to determine participant eligibility and to 
establish a clinical baseline. Significant medical history and significant findings from any 
physical examination (if performed) will be recorded as medical history on the CRF. 
Temperature measurement prior to vaccination will be documented and recorded on the CRF. 
The participant will be observed for 30 minutes after each study vaccination and any 
reactions occurring during that time will be recorded as AEs. 
Prompted local reactions (redness, swelling, and pain at the injection site), systemic events 
(fever, drowsiness/increased sleep, decreased appetite, and irritability), and use of pain/fever 
medication will be prompted for and collected by the participant’s parent(s)/legal guardian(s) 
daily for 7 days after each study vaccination (where Day 1 is the day of vaccination) in an e- 
diary. These prompted e-diary events are graded as described in Section 8.2.3. AEs and SAEs 
will be collected as defined in Section 8.3. 
 
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AEs and SAEs will be recorded and reported from the time the participant’s parent(s)/legal 
guardian(s) provides informed consent through 1 month after the last vaccination. 
Causality and severity of AEs and SAEs will be assessed for all participants. 
8.2.1. Physical Examinations 
A targeted physical examination will not be conducted routinely, but only based on the 
clinical assessment at enrollment, or if needed to further assess the participant during the 
study. Physical examination findings collected during the study will be considered source 
data and will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 2) must be reported according to the processes in 
Sections 8.3.1 to 8.3.3. 
8.2.2. Participant Electronic Diary 
The participant’s parent(s)/legal guardian(s) will be asked to monitor and record local 
reactions, specific systemic events, and antipyretic/pain medication taken for 7 days, each 
evening, following each vaccination using an e-diary (in a provisioned device or application 
on a personal device). This allows recording of these assessments only within a fixed time 
window, thus providing the accurate representation of the participant’s experience. Data on 
local reactions, specific systemic events, and antipyretic/pain medication reported in 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. 
The daily e-diary data will not be captured in the CRF. However, if a participant withdraws 
because of prompted events reported in the e-diary, the event(s) should be recorded on the 
AE page of the CRF, regardless of whether the investigator considers the event(s) to be 
clinically significant. 
The investigator or designee must obtain stop dates for any local reactions or specific 
systemic events ongoing on the last day that the e-diary was completed. The stop dates 
should be entered in the CRF. 
Designated site staff will review the e-diary data online at frequent intervals (daily is 
optimal) for the 7 days following each dose of 20vPnC or 13vPnC to evaluate participant 
compliance and reported events as part of the ongoing safety review. 
8.2.3. Grading Scale for Prompted Events 
The grading scales used in this study to assess prompted events as described below are based 
on concepts outlined in the FDA CBER guidelines on toxicity grading scales for adults and 
adolescent volunteers enrolled in preventive vaccine clinical trials, but have been adapted for 
applicability to healthy infants. 
 
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8.2.3.1. Local Reactions 
For the first 7 days following each study vaccination (Day 1 through Day 7, where Day 1 is 
the day of vaccination), the participant’s parent(s)/legal guardian(s) will be asked to assess 
redness, swelling, and pain at the 20vPnC or 13vPnC 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 (caliper) units (range: 1 to >14; an entry in the e-diary of 15 
will denote >14), and then categorized during analysis as mild, moderate, or severe based on 
the grading scale in Table 1. 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 participant’s parent(s)/legal guardian(s) as mild, 
moderate, or severe according to the grading scale in Table 1. The participant’s 
parent(s)/legal guardian(s) will be prompted to contact the investigator if the participant 
experiences a severe (Grade 3) or above local reaction to assess the reaction and perform an 
unscheduled assessment or visit as appropriate. 
Only an investigator is able to classify a participant’s local reaction as Grade 4, after physical 
examination of the participant or documentation from another medically qualified source 
(eg, emergency room or hospital record). If a participant experiences a Grade 4 local 
reaction, the investigator must immediately notify the sponsor. Site staff will educate the 
participant’s parent(s)/legal guardian(s) regarding signs and symptoms that would prompt 
site contact. 
The procedure for notification of the sponsor is provided in the SRM or equivalent. 
 
Table 1. 
Grading Scales for Local Reactions 
 
Local Reaction 
GRADE 1 
Mild 
GRADE 2 
Moderate 
GRADE 3a 
Severe 
GRADE 4b 
Redness 
1 to 4 caliper units 
(or measuring 
device units) 
= 
>0 to 2.0 cm 
5 to 14 caliper 
units 
(or measuring 
device units) 
= 
>2.0 to 7.0 cm 
>14 caliper units 
(or measuring 
device units) 
= 
>7 cm 
Necrosis or exfoliative dermatitis 
Swelling 
1 to 4 caliper units 
(or measuring 
device units) 
= 
>0 to 2.0 cm 
5 to 14 caliper 
units 
(or measuring 
device units) 
= 
>2.0 to 7.0 cm 
>14 caliper units 
(or measuring 
device units) 
= 
>7 cm 
Necrosis 
 
 
 
 
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Table 1.  Grading Scales for Local Reactions 
 
Local Reaction 
GRADE 1 
Mild 
GRADE 2 
Moderate 
GRADE 3a 
Severe 
GRADE 4b 
Pain at injection site 
(tenderness) 
Hurts if gently 
touched 
(eg, whimpers, 
winces, protests, or 
withdraws) 
Hurts if gently 
touched, with 
crying 
Causes limitation 
of limb movement 
Emergency room visit or 
hospitalization for severe pain 
(tenderness) at injection site 
Abbreviation: CRF = case report form. 
a. 
Parents/legal guardians of the participants experiencing local reactions >14 caliper units (>7.0 cm) are to be 
contacted by the study site. An unscheduled visit may be required. 
b. Grade 4 assessment should be made by the investigator. Grade 4 will not be collected in the e-diary but will be 
collected as an AE on the CRF. The severity of the local reaction should be graded using the AE grading scale 
in Section 8.3. 
Note: If the size of the redness and/or swelling falls between 2 measuring device units, the higher measuring device 
unit number will be recorded in the e-diary. 
 
 
8.2.3.2. Systemic Event Symptoms and Fever 
8.2.3.2.1. Systemic Event Symptoms 
For the first 7 days following each vaccination (Day 1 through Day 7, where Day 1 is the day 
of vaccination), the participant’s parent(s)/legal guardian(s) will be asked to assess decreased 
appetite, drowsiness/increased sleep, and irritability and to record the symptoms in the 
e-diary (in a provisioned device or application on a personal device) in the evening. The 
symptoms will be assessed by the participant’s parent(s)/legal guardian(s) as mild, moderate, 
or severe according to the grading scale in Table 2. The participant’s parent(s)/legal 
guardian(s) will also be instructed to contact site staff if the participant experiences any 
possible Grade 4 prompted systemic event (ie, emergency room visit or hospitalization for 
severe decreased appetite, severe drowsiness/increased sleep, or severe irritability) within 
7 days after vaccination. Study staff may also contact the participant’s parent(s)/legal 
guardian(s) to obtain additional information on Grade 3 events entered into the e-diary. 
Only an investigator is able to classify a participant’s systemic event as Grade 4, after 
physical examination of the participant or documentation from another medically qualified 
source (eg, emergency room or hospital record) or telephone contact with the participant’s 
parent(s)/legal guardian(s). If a participant experiences a Grade 4 systemic event, the 
investigator must immediately notify the sponsor. 
The procedure for notification of the sponsor is provided in the SRM or equivalent. 
 
 
 
 
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Table 2. 
Grading Scales for Systemic Event Symptoms 
 
Systemic Event 
GRADE 1 
Mild 
GRADE 2 
Moderate 
GRADE 3 
Severe 
GRADE 4a 
Decreased appetite 
(loss of appetite) 
Decreased interest in 
eating 
Decreased oral 
intake 
Refusal to feed 
Emergency room visit 
or hospitalization for 
severe decreased 
appetite 
(loss of appetite) 
Drowsiness 
(increased sleep) 
Increased or 
prolonged sleeping 
bouts 
Slightly subdued 
interfering with 
daily activity 
Disabling, not 
interested in 
usual daily 
activity 
Emergency room visit 
or hospitalization for 
severe drowsiness 
(increased sleep) 
Irritability 
(fussiness) 
(synonymous with 
restless sleep; 
decreased sleep) 
Easily consolable 
Requiring 
increased 
attention 
Inconsolable; 
crying cannot 
be comforted 
Emergency room visit 
or hospitalization for 
severe irritability 
(fussiness) 
Abbreviation: CRF = case report form. 
a. 
Grade 4 assessment should be made by the investigator. Grade 4 will not be collected in the e-diary but 
will be collected as an AE on the CRF. The severity of the systemic event should be graded using the AE 
severity grading scale in Section 8.3. 
 
 
8.2.3.2.2. Fever 
In order to record information on fever, a digital thermometer will be given to the 
participant’s parent(s)/legal guardian(s) with instructions on how to measure temperature at 
home. Temperature will be collected in the evening, daily, for 7 days following vaccination 
(Days 1 through 7, where Day 1 is the day of vaccination) and at any time during the 7 days 
that fever is suspected. Fever is defined as an axillary temperature of ≥38.0°C. The highest 
temperature for each day will be recorded in the e-diary. In the event of a fever on the last 
day of diary collection, temperature will be collected daily until fever has resolved (1 day of 
temperature less than 38.0°C in order to collect a stop date in the CRF). A participant’s 
parent(s)/legal guardian(s) will be prompted to contact the investigator if the participant 
experiences a fever >40.0°C within the 7 days following vaccination to assess the fever and 
perform an unscheduled assessment, as applicable (see Section 8.9.3). Study staff may also 
contact the participant’s parent(s)/legal guardian(s) to obtain additional information if a 
temperature of >38.9°C is entered into an e-diary. Temperature will be measured and 
recorded to 1 decimal place and then grouped into ranges for the analysis; see Table 3. 
 
 
 
 
 
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Table 3. 
Ranges for Fever 
 
≥38.0°C to 38.4°C 
>38.4°C to 38.9°C 
>38.9°C to 40.0°C 
>40.0°C 
Note: Fever is defined as temperature ≥38.0°C. 
 
 
8.2.3.2.3. Use of Antipyretic/Pain Medication 
The participant’s parent(s)/legal guardian(s) will be asked to record the use of 
antipyretic/pain medication (yes/no) in the e-diary (in a provisioned device or application on 
a personal device) in the evening, daily, for 7 days after each dose of study intervention. The 
use of prophylactic antipyretic/pain medication, while permitted, is not recommended on the 
day of study intervention administration (before or after vaccination). If symptoms develop, 
the use of antipyretic/pain medication is allowed. 
8.2.4. Clinical Safety Laboratory Assessments 
Clinical safety laboratory assessments will not be collected in this study. 
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting 
The definitions of an AE and an SAE can be found in Appendix 2. 
The definitions of device-related safety events (ADEs and SADEs) can be found in 
Appendix 4. Device deficiencies are covered in Section 8.3.9. 
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally 
authorized representative), or they may arise from clinical findings of the investigator or 
other healthcare providers (clinical signs, test results, etc). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
During the active collection period as described in Section 8.3.1, each participant’s 
parent/legal guardian/legally authorized representative will be questioned about the 
occurrence of AEs in a nonleading manner. 
 
 
 
 
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In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion. 
8.3.1. Time Period and Frequency for Collecting AE and SAE Information 
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant’s parent(s)/legal guardian(s) 
provides informed consent, which is obtained before the participant’s participation in the 
study (ie, before undergoing any study-related procedure and/or receiving study 
intervention), through the final visit. At the final visit the participant’s parent(s)/legal 
guardian(s) will be asked to report any AEs and SAEs, including hospitalizations, that have 
occurred since the last visit. 
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. 
For participants who are screen failures, the active collection period ends when screen failure 
status is determined. 
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn. 
If a participant permanently discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the Vaccine SAE Reporting Form. 
Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any 
SAE, including a death, at any time after a participant has completed the study, and he/she 
considers the event to be reasonably related to the study intervention, the investigator must 
promptly report the SAE to Pfizer using the Vaccine SAE Reporting Form. 
8.3.1.1. Reporting SAEs to Pfizer Safety 
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the Vaccine SAE Reporting Form immediately 
upon awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 2. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available. 
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF 
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF. 
 
 
 
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The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant. 
8.3.2. Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant’s parent(s)/legal guardian(s) is the preferred 
method to inquire about AE occurrences. 
8.3.3. Follow-Up of AEs and SAEs 
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3). 
In general, follow-up information 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 participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 2. 
8.3.4. Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRB/EC, and investigators. 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary. 
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements. 
 
 
 
 
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8.3.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure 
Environmental exposure occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include exposure during pregnancy, exposure during 
breastfeeding, and occupational exposure. 
Any such exposure to the study intervention under study is reportable to Pfizer Safety within 
24 hours of investigator awareness. 
8.3.5.1. Exposure During Pregnancy 
An EDP occurs if: 
• A female is found to be pregnant while being exposed or having been exposed to study 
intervention due to environmental exposure. Below are examples of environmental EDP: 
• A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion, inhalation, or skin 
contact. 
• A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion, inhalation, or skin contact then exposes his female 
partner prior to or around the time of conception. 
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 
• If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the Vaccine SAE Reporting Form and EDP 
Supplemental Form. Since the exposure information does not pertain to the participant 
enrolled in the study, the information is not recorded on a CRF; however, a copy of the 
completed Vaccine SAE Reporting Form is maintained in the investigator site file. 
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
 
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preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported). 
Abnormal pregnancy outcomes are considered SAEs. 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 including 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 study intervention. 
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 participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner. 
8.3.5.2. Exposure During Breastfeeding 
An exposure during breastfeeding occurs if: 
A female is found to be breastfeeding while being exposed or having been exposed to study 
intervention (ie, environmental exposure). An example of environmental exposure during 
breastfeeding is a female family member or healthcare provider who reports that she is 
breastfeeding after having been exposed to the study intervention by ingestion, inhalation, or 
skin contact. 
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred. The 
information must be reported using the Vaccine SAE Reporting Form. When exposure 
during breastfeeding occurs in the setting of environmental exposure, the exposure 
information does not pertain to the participant enrolled in the study, so the information is not 
recorded on a CRF. However, a copy of the completed Vaccine SAE Reporting Form is 
maintained in the investigator site file. 
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 
 
 
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authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding. 
8.3.5.3. Occupational Exposure 
The investigator must report any instance of occupational exposure to Pfizer Safety within 
24 hours of the investigator’s awareness using the Vaccine SAE Reporting Form, regardless 
of whether there is an associated SAE. Since the information about the occupational 
exposure does not pertain to a participant enrolled in the study, the information is not 
recorded on a CRF; however, a copy of the completed Vaccine SAE Reporting Form must be 
maintained in the investigator site file. 
8.3.6. Cardiovascular and Death Events 
Not applicable. 
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Not applicable. 
8.3.8. Adverse Events of Special Interest 
Not applicable. 
8.3.8.1. Lack of Efficacy 
The investigator must report signs, symptoms, and/or clinical sequelae resulting from lack of 
efficacy. Lack of efficacy or failure of expected pharmacological action is reportable to 
Pfizer Safety only if associated with an SAE. 
The investigator must report signs, symptoms, and/or clinical sequelae resulting from lack of 
efficacy. Lack of efficacy or failure of expected pharmacological action in an approved 
indication constitutes an SAE and should be reported to Pfizer Safety. 
8.3.9. Medical Device Deficiencies 
Medical devices being provided for use in this study as the study interventions are supplied 
in prefilled syringes. In order to fulfill regulatory reporting obligations worldwide, the 
investigator is responsible for the detection and documentation of events meeting the 
definitions of device deficiency that occur during the study with such devices. 
The definition of a medical device deficiency can be found in Section 10.4.3. 
Note: AEs and/or SAEs that are associated with a medical device deficiency will follow the 
same processes as other AEs or SAEs, as outlined in Sections 8.3.1 through 8.3.4 and 
Appendix 2 of the protocol. 
 
 
 
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8.3.9.1. Time Period for Detecting Medical Device Deficiencies 
Medical device deficiencies that result in an incident will be detected, documented, and 
reported during all periods of the study in which the medical device is used. 
Importantly, reportable device deficiencies are not limited to problems with the device itself 
but also include incorrect or improper use of the device and even intentional misuse, etc. 
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such deficiency is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor. 
The method of documenting medical device deficiencies is provided in Section 10.4.4. 
8.3.9.2. Follow-Up of Medical Device Deficiencies 
Follow-up applies to all participants, including those who discontinue study intervention. 
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency. 
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the investigator. 
8.3.9.3. Prompt Reporting of Device Deficiencies to the Sponsor 
When a device deficiency occurs: 
1. The investigator notifies the sponsor by telephone or email within 1 business day of 
determining that the incident meets the protocol definition of a medical device 
deficiency. 
2. The device deficiency must be recorded on the Medical Device Complaint form. 
3. If an AE (either serious or nonserious) associated with the device deficiency occurs, 
then the AE must be entered into the AE section of the CRF. 
4. If an SAE associated with the device deficiency is brought to the attention of the 
investigator, the investigator must immediately notify Pfizer Safety of the SAE 
(see Section 8.3.1.1). All relevant details related to the role of the device in the event 
must be included in the Vaccine SAE Reporting Form as outlined in Section 8.3.1.1 
and Section 8.3.1.2. 
The sponsor will be the contact for the receipt of device deficiency information. 
 
 
 
 
 
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8.3.9.4. Regulatory Reporting Requirements for Device Deficiencies 
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies. 
The investigator or responsible person according to local requirements (eg, the head of the 
medical institution) will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC. 
8.3.10. Medication Errors 
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength. 
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors. 
 
Safety Event 
Recorded on the CRF 
Reported on the Vaccine SAE 
Reporting 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 
 
Medication errors include: 
• Medication errors involving participant exposure to the study intervention; 
• Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant. 
Other examples include, but are not limited to: 
• The administration of expired study intervention; 
• The administration of an incorrect study intervention; 
• The administration of an incorrect dosage; 
• The administration of study intervention that has undergone temperature excursion 
from the specified storage range, unless it is determined by the sponsor that the study 
intervention under question is acceptable for use. 
 
 
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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 within 24 hours. 
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 the AE page of the 
CRF. 
Medication errors should be reported to Pfizer Safety within 24 hours on a Vaccine SAE 
Reporting Form only when associated with an SAE. 
8.4. Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.5. Genetics 
8.5.1. Specified Genetics 
Genetics (specified analyses) are not evaluated in this study. 
8.6. Biomarkers 
Biomarkers are not evaluated in this study. 
8.7. Immunogenicity Assessments 
Immunogenicity assessments as described in Section 8.1. 
8.8. Health Economics 
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study. 
8.9. Study Procedures 
The study procedures are summarized in the SoAs (see Section 1.3.1 and Section 1.3.2. The 
day of Vaccination 1 is considered to be Day 1. 
Unless specified in the sections below, the order of key procedures within a given visit may 
have some flexibility. 
 
 
 
 
 
 
 
 
 
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8.9.1. 2-Dose 20vPnC Group 
8.9.1.1. Visit 1 (Dose 1 Visit: Day 1) 
Prior to vaccination: 
• Obtain a personally signed and dated ICD indicating that the participant’s parent(s)/legal 
guardian(s) has been informed of all pertinent aspects of the study before performing any 
study-specific procedures. 
• Assign a participant number via the IRT. 
• Obtain and record the participant’s demographic information (including date of birth, sex, 
race, and ethnicity). The complete date of birth (ie, DD-MMM-YYYY) will be collected 
as permitted per local regulations to critically evaluate the immune response and safety 
profile by age. 
• Perform a clinical assessment including medical history; record any findings on the 
medical history CRF. If deemed necessary as part of the clinical assessment, the physical 
examination may include assessments of the general appearance, skin, head, lymph 
nodes, cardiovascular, respiratory, gastrointestinal, and neurological systems. 
• Record receipt of 2 infant doses of 13vPnC (prior to 12 months of age), including dates 
given. 
• Measure and record the participant’s temperature as appropriate for the age of the toddler, 
according to routine local practice (°C). 
• Ensure that all inclusion criteria, none of the exclusion criteria, and none of the temporary 
delay criteria are met. 
• Assign a randomization number and study intervention container number via the IRT. 
This must be the last step before proceeding. A site staff member will prepare the study 
intervention according to the IP manual. 
After randomization: 
• Collect a blood sample of approximately 5 mL for immunogenicity. 
• Administer a single 0.5-mL injection of 20vPnC into the left anterolateral thigh or left 
arm (as appropriate for the age and size of the child). 
• If applicable, administer routine pediatric vaccinations into a limb other than the site of 
the 20vPnC injection and capture all details of the concomitant vaccine given on the same 
day as study intervention administration, including the name, date of administration, and 
site of administration, on the CRF. 
 
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• Site staff will observe the participant for 30 minutes after vaccination for any reactions. 
Record any AEs on the CRF and on an SAE form as applicable. Record concomitant 
medications used to treat SAEs. 
• Issue the participant’s parent(s)/legal guardian(s) a measuring device (caliper) to measure 
20vPnC injection site reactions and a digital thermometer and provide instructions on 
their use. 
• Issue the participant’s parent(s)/legal guardian(s) an e-diary (device or application). 
Provide instructions on use and completion of the e-diary. Ask the participant’s 
parent(s)/legal guardian(s) to complete the e-diary from Day 1 through Day 7, with Day 1 
being the day of vaccination. 
• Ask the participant’s parent(s)/legal guardian(s) to contact the investigator site staff or 
investigator as soon as possible during the 7-day postvaccination period if the participant 
has a fever >40.0°C, redness and/or swelling at the 20vPnC or 13vPnC injection site 
measuring >14 measuring device units (>7 cm), or severe 20vPnC injection site pain 
(causes limitation of limb movement) to determine if the event requires further 
assessment by the investigator. 
• Ask the participant’s parent(s)/legal guardian(s) to contact the investigator or investigator 
site staff as soon as possible if any significant illness or medical event (eg, emergency 
room visit or hospitalization) occurs. 
• Provide the parent(s)/legal guardian(s) with the participant contact card containing the 
study and investigator information (see Section 10.1.11). 
• Inform the participant’s parent(s)/legal guardian(s) that the use of prophylactic 
antipyretic/pain medication, while permitted, is not recommended on the day of 20vPnC 
administration (before or after vaccination). If symptoms develop, the use of 
antipyretic/pain medication is allowed. 
• The investigator or appropriately qualified designee reviews the e-diary data online at 
frequent intervals for the 7 days following vaccination to evaluate participant compliance 
and as part of the ongoing safety review. 
8.9.1.2. Visit 2 (Dose 2 Visit: 56 to 70 Days After Dose 1) 
• Ensure and document that the participant continues to be eligible for the study 
(see Section 7.2 for participant discontinuation/withdrawal) and none of the temporary 
delay criteria are met (Section 5.5.1). 
• Record nonstudy vaccinations administered since Visit 1, as described in Section 6.8. 
 
 
 
 
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• Review the participant’s e-diary data with the participant’s parent(s)/legal guardian(s); 
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. 
• Determine whether any AEs (includes nonserious AEs and SAEs) have occurred since 
the previous visit and follow up on any previously reported events to determine the 
outcome (ie, record stop dates or confirm if they are still continuing) and record as 
described in Section 10.2, and record concomitant medications used to treat SAEs. 
• Measure and record the participant’s temperature as appropriate for the age of the toddler, 
according to routine local practice (°C). 
• Administer a single 0.5-mL injection of 20vPnC into the left anterolateral thigh or left 
arm (as appropriate for the age and size of the child). 
• If applicable, administer routine pediatric vaccinations into a limb other than the site of 
the 20vPnC injection and capture all details of the concomitant vaccine given on the same 
day as study intervention administration, including the name, date of administration, and 
site of administration, on the CRF. 
After vaccination: 
• Site staff will observe the participant for 30 minutes after vaccination for any reactions. 
Record any AEs on the CRF and on an SAE form as applicable. Record concomitant 
medications used to treat SAEs. 
• Confirm that the e-diary is working and review instructions if necessary. Remind the 
participant’s parent(s)/legal guardian(s) to complete the e-diary from Day 1 through 
Day 7, with Day 1 being the day of vaccination. Provide a thermometer or measuring 
device if needed. 
• Ask the participant’s parent(s)/legal guardian(s) to contact the investigator site staff or 
investigator as soon as possible during the 7-day postvaccination period if the participant 
has a fever >40.0°C, redness and/or swelling at the 20vPnC injection site measuring 
>14 measuring device units (>7 cm), or severe 20vPnC injection site pain (causes 
limitation of limb movement), to determine if the event requires further assessment by the 
investigator. 
• Remind the participant’s parent(s)/legal guardian(s) to contact the investigator or 
investigator site staff as soon as possible if any significant illness or medical event 
(eg, emergency room visit or hospitalization) occurs during the study period. 
• Confirm whether the parent(s)/legal guardian(s) still possesses the participant contact 
card. Provide a participant contact card if needed. 
 
 
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• Remind the participant’s parent(s)/legal guardian(s) that the use of prophylactic 
antipyretic/pain medication, while permitted, is not recommended on the day of 20vPnC 
administration. If symptoms develop, the use of antipyretic/pain medication is allowed. 
• The investigator or appropriately qualified designee reviews the e-diary data online at 
frequent intervals for the 7 days following vaccination to evaluate participant compliance 
and as part of the ongoing safety review. 
8.9.1.3. Visit 3 (Follow-Up Visit: 28 to 42 Days After Dose 2) 
• Ensure and document that the participant continues to be eligible for the study (see 
Section 7.2 for participant discontinuation/withdrawal). 
• Record nonstudy vaccinations administered since Visit 2, as described in Section 6.8. 
• Review the participant’s e-diary data with the participant’s parent(s)/legal guardian(s); 
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. 
• Collect any sponsor-provisioned e-diary. 
• Determine whether any AEs and SAEs have occurred since the previous visit and follow 
up on any previously reported events to determine the outcome (ie, record stop dates or 
confirm if they are still continuing) and record as described in Section 10.2, and record 
concomitant medications used to treat SAEs. 
• Collect a blood sample of approximately 5 mL for immunogenicity (a topical anesthetic 
is permitted). 
• The investigator or an authorized designee completes the CRF. 
8.9.2. 1-Dose 20vPnC Group and 13vPnC (Control) Group 
8.9.2.1. Visit 1 (Dose 1 Visit: Day 1) 
Prior to vaccination: 
• Obtain a personally signed and dated ICD indicating that the participant’s parent(s)/legal 
guardian(s) has been informed of all pertinent aspects of the study before performing any 
study-specific procedures. 
• Assign a participant number via the IRT. 
 
 
 
 
 
 
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• Obtain and record the participant’s demographic information (including date of birth, sex, 
race, and ethnicity). The complete date of birth (ie, DD-MMM-YYYY) will be collected 
as permitted per local regulations to critically evaluate the immune response and safety 
profile by age. 
• Perform a clinical assessment including medical history; record any findings on the 
medical history CRF. If deemed necessary as part of the clinical assessment, the physical 
examination may include assessments of the general appearance, skin, head, lymph 
nodes, cardiovascular, respiratory, gastrointestinal, and neurological systems. 
• Record receipt of 2 infant doses of 13vPnC (prior to 12 months of age), including dates 
given. 
• Measure and record the participant’s temperature as appropriate for the age of the toddler, 
according to routine local practice (°C). 
• Ensure that all inclusion criteria, none of the exclusion criteria, and none of the temporary 
delay criteria are met. 
• Assign a randomization number and study intervention container number via the IRT. 
This must be the last step before proceeding. A site staff member will prepare the study 
intervention according to the IP manual. 
After randomization: 
• Collect a blood sample of approximately 5 mL for immunogenicity. 
• Administer a single 0.5-mL injection of 20vPnC or 13vPnC into the left anterolateral 
thigh or left arm (as appropriate for the age and size of the child). 
• If applicable, administer routine pediatric vaccinations into a limb other than the site of 
the 20vPnC injection and capture all details of the concomitant vaccine given on the same 
day as study intervention administration, including the name, date of administration, and 
site of administration, on the CRF. 
• Site staff will observe the participant for 30 minutes after vaccination for any reactions. 
Record any AEs on the CRF and on an SAE form as applicable. Record concomitant 
medications used to treat SAEs. 
• Issue the participant’s parent(s)/legal guardian(s) a measuring device (caliper) to measure 
20vPnC or 13vPnC (control) injection site reactions and a digital thermometer to measure 
temperature, and provide instructions on their use. 
 
 
 
 
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• Issue the participant’s parent(s)/legal guardian(s) an e-diary (device or application). 
Provide instructions on use and completion of the e-diary. Ask the participant’s 
parent(s)/legal guardian(s) to complete the e-diary from Day 1 through Day 7, with Day 1 
being the day of vaccination. 
• Ask the participant’s parent(s)/legal guardian(s) to contact the investigator site staff or 
investigator as soon as possible during the 7-day postvaccination period if the participant 
has a fever >40.0°C, redness and/or swelling at the 20vPnC or 13vPnC injection site 
measuring >14 measuring device units (>7 cm), or severe 20vPnC or 13vPnC injection 
site pain (causes limitation of limb movement) to determine if the event requires further 
assessment by the investigator. 
• Ask the participant’s parent(s)/legal guardian(s) to contact the investigator or investigator 
site staff as soon as possible if any significant illness or medical event (eg, emergency 
room visit or hospitalization) occurs. 
• Provide the parent(s)/legal guardian(s) with the participant contact card containing the 
study and investigator information (see Section 10.1.11). 
• Inform the participant’s parent(s)/legal guardian(s) that the use of prophylactic 
antipyretic/pain medication, while permitted, is not recommended on the day of 20vPnC 
or 13vPnC administration. If symptoms develop, the use of antipyretic/pain medication 
is allowed. 
• Record AEs and SAEs during the visit as described in Section 8.3 and record 
concomitant medications as described in Section 6.8.3. 
• The investigator or an authorized designee completes the CRF and updates the study 
intervention accountability records. 
• The investigator or appropriately qualified designee reviews the e-diary data online at 
frequent intervals for the 7 days following vaccination to evaluate participant compliance 
and as part of the ongoing safety review. 
8.9.2.2. Visit 2 (Follow-Up Visit: 28 to 42 Days After Dose 1) 
• Ensure and document that the participant continues to be eligible for the study 
(see Section 7.2 for participant discontinuation/withdrawal). 
• Record nonstudy vaccinations administered since Visit 1, as described in Section 6.8. 
• Review the participant’s e-diary data with the participant’s parent(s)/legal guardian(s); 
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. 
 
 
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• Collect any sponsor-provisioned e-diary. 
• Determine whether any AEs and SAEs have occurred since the previous visit and follow 
up on any previously reported events to determine the outcome (ie, record stop dates or 
confirm if they are still continuing) and record as described in Section 10.2, and record 
concomitant medications used to treat SAEs. 
• Collect a blood sample of approximately 5 mL for immunogenicity (a topical anesthetic 
is permitted). 
• The investigator or an authorized designee completes the CRF. 
8.9.3. Unscheduled Visits 
If the participant’s parent(s)/legal guardian(s) reports redness or swelling at the injection site 
measuring >14 measuring device units (>7 cm), severe injection site pain, or a fever >40.0°C 
during the 7-day postvaccination period, a telephone contact must occur as soon as possible 
between the investigator or medically qualified designee and the participant’s parent(s)/legal 
guardian(s) to assess if an unscheduled investigator site visit is required. Note that for a 
fever >40.0°C, the participant’s parent(s)/legal guardian(s) should be instructed not to delay 
seeking medical care, as appropriate, while arranging for an unscheduled visit if applicable. 
A visit should be scheduled as soon as possible to assess the extent of the injection site 
reaction, unless any of the following is true: 
• The participant’s parent(s)/legal guardian(s) is unable to bring the participant to the 
unscheduled visit. 
• The reaction is no longer present at the time of the telephone contact. 
• The participant’s parent(s)/legal guardian(s) recorded an incorrect value in the e-diary 
(confirmation of an e-diary data entry error). 
• The PI or authorized designee determined it was not needed. 
This telephone contact will be recorded in the participant’s source documentation and the 
CRF. 
If the participant’s parent(s)/legal guardian(s) is unable to bring the participant to an 
unscheduled visit, or the PI or authorized designee determined it was not needed, any 
ongoing reactions must be assessed at the next study visit. 
During the unscheduled visit, 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: 
 
 
 
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• Measure temperature (°C) as appropriate for the age of the toddler, according to local 
practice. 
• Measure minimum and maximum diameters of redness (if present). 
• Measure minimum and maximum diameters of swelling (if present). 
• Assess injection site pain (if present) in accordance with the grades provided in 
Section 8.2.3.1. 
• Assess for other findings associated with the reaction and record on the AE page of the 
CRF, if appropriate. 
The investigator or an authorized designee will complete the unscheduled visit assessment 
page of the CRF. 
The participant’s parent(s)/legal guardian(s) will also be instructed to contact investigator site 
staff if the participant experiences any emergency room visit or hospitalization for decreased 
appetite, drowsiness/increased sleep, irritability, or local reaction within 7 days of 
vaccination. 
The participant’s parent(s)/legal guardian(s) will also be instructed to contact the investigator 
site to report any significant illness, medical event, or hospitalization that occurs during the 
study period. The investigator site should determine if an unscheduled visit to further 
evaluate the event is warranted in all such cases. 
Additionally, study staff may contact the participant’s parent(s)/legal guardian(s) to obtain 
additional information on Grade 3 events entered into the e-diary. 
9. STATISTICAL CONSIDERATIONS 
Methodology for summary and statistical analysis of the data collected in this study is 
outlined here and further detailed in a 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. 
9.1. Statistical Hypotheses 
9.1.1. Estimands 
The primary objectives of the study are to describe the safety profile and immune response to 
1 or 2 doses of 20vPnC in healthy toddlers (≥12 to <24 months of age) who received 2 infant 
doses of Prevenar 13. Estimands to address the study objectives are provided in Section 3. 
For estimands to evaluate the immunogenicity objectives, these estimands estimate the 
immune response in the hypothetical setting where participants follow the study schedule and 
protocol requirements. Immunogenicity results that are below the LLOQ will be set to 
0.5 × LLOQ in the analysis. 
 
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In the safety evaluation, missing e-diary data will not be imputed. Missing AE dates and 
missing AE severity will be imputed according to Pfizer safety rules. No other missing 
information will be imputed in the safety analysis. 
Immunogenicity and safety results will be provided by descriptive summary statistics for 
each vaccine group. There is no formal hypothesis test for any safety or immunogenicity 
result. 
9.2. Analysis Sets 
For purposes of analysis, the following analysis sets are defined: 
 
Participant Analysis Set 
Description 
Enrolled 
"Enrolled" means all participants who sign the ICD. 
Randomized 
All participants who are assigned a randomization number in 
the IWR system. 
Evaluable immunogenicity 
All eligible randomized participants who receive the vaccine 
to which they are randomly assigned at each dose, have at 
least 1 valid immunogenicity result collected within an 
appropriate window at 1 month after the last assigned 
vaccination, and have no other major protocol deviations as 
determined by the clinician monitor. 
Participants will be grouped according to the vaccine as 
randomized in the analysis based on the evaluable 
immunogenicity population. 
CCI 
Safety 
All participants who receive at least 1 dose of the study 
intervention and have safety data reported after any dose. 
Participants will be grouped according to the vaccine as 
administered in the analysis based on the safety population. 
 
9.3. Statistical Analyses 
The SAP will be developed and finalized before database lock and will describe the 
participant populations to be included in the analyses and procedures for accounting for 
missing, unused, and spurious data. This section is a summary of the planned statistical 
analyses of the primary, secondary, and CCI 
 endpoints. 
 
 
 
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9.3.1. General Considerations 
For all the immunogenicity endpoints, the analysis will be primarily based on the evaluable 
 
9.3.2. Analysis for Binary Data 
Descriptive statistics for categorical variables (eg, proportions) are the percentage (%), the 
numerator (n) and the denominator (N) used in the percentage calculation, and the 2-sided 
95% CIs where applicable. 
The exact 95% CI for binary endpoints for each group will be computed using the 
F distribution (Clopper-Pearson). 
Three-Tier Approach for AE Summary 
A 3-tier approach will be used to summarize AEs. Under this approach, AEs are classified 
into 1 of 3 tiers: 
1. Tier 1 events are prespecified events of clinical importance and are identified in a list in 
the product’s safety review plan. There is no Tier 1 event identified for 20vPnC at this 
stage. 
2. Tier 2 events are those that are not Tier 1 but are considered “relatively common”; 
a MedDRA preferred term is defined as a Tier 2 event if there are at least 4 participants in 
at least 1 vaccine group reporting the event. 
3. Tier 3 events are those that are neither Tier 1 nor Tier 2 events. 
For both Tier 1 (if any identified later) and Tier 2 events, the 95% CIs for the difference in 
percentage of participants reporting the events between each of the 20vPnC groups and the 
13vPnC group will be calculated using the Miettinen and Nurminen method. 
In addition, for Tier 1 events (if any identified later), the asymptotic p-values will also be 
presented for the difference in percentage of participants reporting the events between each 
of the 20vPnC groups and the 13vPnC group, based on the same test statistic and under the 
assumption that the test statistic is asymptotically normally distributed. 
Descriptive summary statistics will be provided for Tier 3 events for each vaccine group. 
 
 
 
 
 
 
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9.3.3. Analysis for Continuous Data 
Unless otherwise stated, descriptive statistics for continuous variables are n, mean, median, 
standard deviation, minimum, and maximum. 
9.3.3.1. Geometric Mean 
The geometric mean for each vaccine group will be calculated as the mean of the 
logarithmically transformed assay results and then exponentiating the mean. The 2-sided 
95% CI will be obtained by exponentiating the limits of the CI for the mean of the 
logarithmically transformed assay results based on Student’s t distribution. 
 
 
 
 
 
9.3.4. Primary Endpoint(s)/Estimand(s) Analysis 
 
Objective 
Estimands 
Statistical Analysis Methods 
Safety 
• 
Proportions of participants with 
local reactions (redness, swelling, 
and pain at the injection site) 
within 7 days after the last assigned 
vaccination from each group 
• 
Proportions of participants with 
systemic events (fever, decreased 
appetite, irritability, and 
drowsiness/increased sleep) within 
7 days after the last assigned 
vaccination from each group 
• 
Descriptive summary statistics for 
participants with each local 
reaction/systemic event within 7 days 
after each dose by maximum severity 
and cumulatively across severity levels 
• 
• 
AEs from vaccination to 1 month 
after the last assigned vaccination 
in each group 
• 
Three-tier approach 
• 
• 
SAEs from vaccination to 1 month 
after the last assigned vaccination 
in each group 
• 
Descriptive summary statistics 
 
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Objective 
Estimands 
Statistical Analysis Methods 
Immunogenicity 
• 
Percentage of participants with IgG 
concentrations to the 7 additional 
serotypes with a predefined levela 
1 month after the last assigned 
vaccination in each group 
• 
Descriptive summary statistics 
• 
a. 
The predefined level is 0.35 µg/mL for all 7 additional serotypes. 
 
9.3.5. Secondary Endpoint(s)/Estimand(s) Analysis 
 
Objective 
Estimands 
Statistical Analysis Methods 
Immunogenicity 
• 
GMC of IgG concentrations to 
each of the 20 vaccine serotypes 
1 month after the last assigned 
vaccination in each group 
• 
GMC and 2-sided 95% CI 
• 
Percentage of participants with IgG 
concentrations to the 13vPnC 
serotypes with a predefined levela 
1 month after the last assigned 
vaccination in each group. 
• 
Descriptive summary statistics 
• 
• 
GMT of OPA titers to each of the 
20 vaccine serotypes 1 month after 
the last assigned vaccination in 
each group 
• 
GMT and 2-sided 95% CI 
a. 
The predefined level is 0.35 µg/mL for all 13vPnC serotypes except serotypes 5, 6B, and 19A, which 
have predefined levels of 0.23, 0.10, and 0.12, respectively. 
 
 
 
 
 
 
 
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9.4. Interim Analyses 
No formal interim analysis will be conducted for this study. 
9.5. Sample Size Determination 
A total of approximately 360 participants will be randomized for approximately 
315 evaluable participants, with an estimate of 105 evaluable participants per vaccine group. 
The sample size of the study is determined primarily based on considerations of 
accumulating adequate data to evaluate the safety and immunogenicity of 1 or 2 doses of 
20vPnC in healthy toddlers with 2 prior infant doses of 13vPnC. 
Table 4 displays the lower 2-sided 95% confidence limit of the percentage of participants 
with predefined IgG concentrations for the primary immunogenicity endpoint. Assumed true 
proportions ranging from 80% to 100% are displayed in order to help quantify the expected 
precision assuming 105 evaluable participants in each vaccine group. 
 
Table 4. 
Precision of Percentage of Participants With Predefined IgG 
Concentrations 
 
Assumed True Proportion 
(%) 
Lower 95% Confidence Limit of Proportion (%), 105 Evaluable 
Participants per Group 
80 
71 
85 
78 
90 
83 
95 
89 
100 
97 
Abbreviation: IgG = immunoglobulin G. 
Note: Lower confidence limits of 2-sided 95% CI are calculated using the Clopper and Pearson method, 
assuming the observed number of participants with predefined IgG concentrations is 105 × true proportion. 
 
 
 
 
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The primary safety objective includes the endpoints for AEs reported within 1 month after 
the last assigned vaccination in each group. With 120 participants in each vaccine group, the 
probability of observing at least 1 AE in each is greater than 90%, assuming a true rate of at 
least 2% (Table 5). 
 
Table 5. 
Probability of Observing an Event Given a Specified Incidence Rate and 
Assuming 120 Participants per Group 
 
Sample Size 
True Rate of AEs 
Probability of Observing at Least 1 AE 
120 
1.0% 
70.1% 
120 
2.0% 
91.1% 
120 
5.0% 
99.8% 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1. Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines; 
• Applicable ICH GCP guidelines; 
• Applicable laws and regulations, including applicable privacy laws. 
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents (eg, 
advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC by 
the investigator, and reviewed and approved by the IRB/EC before the study is initiated. 
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants. 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC; 
• Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures; 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 
536/2014 for clinical studies (if applicable), European Medical Device Regulation 
2017/745 for clinical device research (if applicable), and all other applicable local 
regulations. 
 
 
 
 
 
 
 
 
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10.1.1.1. 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 study 
intervention, 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 participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of. 
10.1.2. Financial Disclosure 
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study. 
10.1.3. Informed Consent Process 
The investigator or his/her representative will explain the nature of the study, including the 
risks and benefits, to the participant’s parent(s)/legal guardian(s) and answer all questions 
regarding the study. The participant’s legally authorized representative should be given 
sufficient time and opportunity to ask questions and to decide whether or not to participate in 
the trial. 
Participants’ parent(s)/legal guardian(s) must be informed that their participation is voluntary. 
Participants’ parent(s)/legal guardian(s) will be required to sign a statement of informed 
consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, privacy 
and data protection requirements, where applicable, and the IRB/EC or study center. 
The investigator must ensure that each study participant’s parent(s)/legal guardian(s) is fully 
informed about the nature and objectives of the study, the sharing of data related to the study, 
and possible risks associated with participation, including the risks associated with the 
processing of the participant’s personal data. 
The participant’s parent(s)/legal guardian(s) must be informed that the participant’s personal 
study-related data will be used by the sponsor in accordance with local data protection law. 
The level of disclosure must also be explained to the participant’s parent(s)/legal guardian(s). 
The participant’s parent(s)/legal guardian(s) must be informed that the participant’s medical 
records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/EC members, and by inspectors 
from regulatory authorities. 
 
 
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The investigator further must ensure that each study participant’s parent(s)/legal guardian(s) 
is fully informed about his or her right to access and correct the participant’s personal data 
and to withdraw consent for the processing of the participant’s personal data. 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD. 
The participant’s parent(s)/legal guardian(s) must be reconsented to the most current version 
of the ICD(s) during their participation in the study. 
A copy of the ICD(s) must be provided to the participant’s parent(s)/legal guardian(s). 
10.1.4. Data Protection 
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data. 
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law. 
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record ID. In case of 
data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws. 
10.1.5. Committees Structure 
10.1.5.1. Data Monitoring Committee 
This study will use a DMC. The DMC is independent of the study team and includes only 
external members. The DMC charter describes the role of the DMC in more detail. 
The DMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter. The recommendations made by the DMC will be forwarded 
to the appropriate authorized Pfizer personnel for review and final decision. Pfizer will 
 
 
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communicate such decisions, which may include summaries of aggregate analyses of safety 
data to regulatory authorities, investigators, as appropriate. 
10.1.6. Dissemination of Clinical Study Data 
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs. 
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 results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law. 
EudraCT 
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements. 
www.pfizer.com 
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are 
posted to www.clinicaltrials.gov. 
Documents within marketing authorization packages/submissions 
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website. Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods. Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data. Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015. 
 
 
 
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Data sharing 
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make data from these trials available 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted. 
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes. 
10.1.7. Data Quality Assurance 
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document. 
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties. 
QTLs are predefined parameters that are monitored during the study. Important deviations 
from the QTLs and any remedial actions taken will be summarized in the clinical study 
report. 
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. This 
verification may also occur after study completion. 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. 
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or on-site monitoring), are provided in the data management plan and 
monitoring plan maintained and utilized by the sponsor or designee. 
 
 
 
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The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data. 
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained. 
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems. 
The investigator(s) will notify the sponsor or its agents immediately of any regulatory retain 
notification in relation to the study. Furthermore, the investigator will cooperate with the 
sponsor or its agents to prepare the investigator site for the inspection and will allow the 
sponsor 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 participant's medical records. The investigator will promptly provide 
copies of the inspection findings to the sponsor or its agent. Before response submission to 
the regulatory authorities, the investigator will provide the sponsor or its agents with an 
opportunity to review and comment on responses to any such findings. 
10.1.8. Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site. 
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available. 
Definition of what constitutes source data and its origin can be found in the clinical 
monitoring plan, which is maintained by the sponsor. 
Description of the use of the computerized system is documented in the Data Management 
Plan, which is maintained by the sponsor. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
 
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being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP guidelines, and all applicable regulatory requirements. 
10.1.9. Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date. 
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time upon notification to the CRO if 
requested to do so by the responsible IRB/EC or if such termination is required to protect the 
health of study participants. 
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to: 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or the ICH GCP 
guidelines; 
• Inadequate recruitment of participants by the investigator; 
• Discontinuation of further study intervention development. 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights. 
 
 
 
 
 
 
 
 
 
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10.1.10. Publication Policy 
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 18 months after the end of the 
study (or study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications, 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to 
provide comments, and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results. 
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors. 
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites. In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by mutual 
agreement. 
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply. 
10.1.11. 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/study portal or other electronic system. 
To facilitate access to appropriately qualified medical personnel for study-related medical 
questions or problems, participants are provided with an Emergency Contact Card (ECC) at 
the time of informed consent. The ECC contains, at a minimum, (a) protocol and study 
intervention identifiers, (b) participant’s study identification number, (c) site emergency 
phone number active 24 hours/day, 7 days per week, and (d) Pfizer Call Center number. 
The ECC is intended to augment, not replace, the established communication pathways 
between the investigator, site staff, and study team. The ECC is to be used by healthcare 
professionals not involved in the research study only, as a means of reaching the investigator 
 
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or site staff related to the care of a participant. The Pfizer Call Center number should only be 
used when the investigator and site staff cannot be reached. The Pfizer Call Center number is 
not intended for use by the participant directly; if a participant calls that number directly, he 
or she will be directed back to the investigator site. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting 
10.2.1. Definition of AE 
 
AE Definition 
• An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention. 
• Note: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention. 
 
 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator. Any abnormal laboratory test 
results that meet any of the conditions below must be recorded as an AE: 
• Is associated with accompanying symptoms. 
• Requires additional diagnostic testing or medical/surgical intervention. 
• 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. 
• Exacerbation of a chronic or intermittent preexisting condition, including either an 
increase in frequency and/or intensity of the condition. 
• New condition detected or diagnosed after study intervention administration, even 
though it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE or SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae. 
 
 
 
 
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Events NOT Meeting the AE Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 
 
10.2.2. Definition of an SAE 
 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one 
or more of the criteria listed below: 
a.  Results in death 
b. Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe. 
c.  Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious. 
 
 
 
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Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle), that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e.  Is a congenital anomaly/birth defect 
f. Is a suspected transmission via a Pfizer product of an infectious agent, pathogenic 
or non-pathogenic, is considered serious. 
The event may be suspected from clinical symptoms or laboratory findings indicating 
an infection in a participant exposed to a Pfizer product. The terms “suspected 
transmission” and “transmission” are considered synonymous. These cases are 
considered unexpected and handled as serious expedited cases by pharmacovigilance 
personnel. Such cases are also considered for reporting as product defects, if 
appropriate. 
g. Other situations: 
• Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations, such as significant 
medical events that may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious. 
• Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse. 
 
 
 
 
 
 
 
 
 
 
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10.2.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active 
Collection Period 
 
AE and SAE Recording/Reporting 
The table below summarizes the requirements for recording AEs on the CRF and for 
reporting SAEs on the Vaccine SAE Reporting Form to Pfizer Safety throughout the active 
collection period. These requirements are delineated for 3 types of events: (1) SAEs; (2) 
nonserious AEs; and (3) exposure to the study intervention under study during pregnancy 
or breastfeeding, and occupational exposure. 
It should be noted that the Vaccine SAE Reporting 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 Vaccine SAE 
Reporting Form for reporting of SAE information. 
Safety Event 
Recorded on the CRF 
Reported on the Vaccine 
SAE Reporting Form to 
Pfizer Safety Within 
24 Hours of Awareness 
SAE 
All 
All 
Nonserious AE 
All 
None 
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding. 
All AEs or SAEs associated with 
exposure during pregnancy or 
breastfeeding. 
Note: Instances of EDP or EDB 
not associated with an AE or SAE 
are not captured in the CRF. 
All instances of EDP are 
reported (whether or not 
there is an associated SAE).* 
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE).** 
Environmental or 
occupational exposure to 
the product under study 
to a non-participant (not 
involving EDP or EDB). 
None. Exposure to a study non- 
participant is not collected on the 
CRF. 
The exposure (whether or 
not there is an associated AE 
or SAE) must be 
reported.*** 
* 
EDP (with or without an associated AE or SAE): any pregnancy information is reported to Pfizer 
Safety using the Vaccine SAE Reporting Form and EDP Supplemental Form; if the EDP is associated 
with an SAE, then the SAE is reported to Pfizer Safety using the Vaccine SAE Reporting Form. 
** EDB is reported to Pfizer Safety using the Vaccine SAE Reporting Form, which would also include 
details of any SAE that might be associated with the EDB. 
*** Environmental or occupational exposure: AEs or SAEs associated with occupational exposure are 
reported to Pfizer Safety using the Vaccine SAE Reporting Form. 
 
 
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• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event. 
• The investigator will then record all relevant AE/SAE information in the CRF. 
• It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the Vaccine SAE 
Reporting Form/AE or SAE CRF page. 
• There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety. 
• The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
GRADE 
If required on the AE page of the CRF, the investigator will use the 
adjectives MILD, MODERATE, SEVERE, or LIFE-THREATENING 
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 participant's usual 
function. 
2 
MODERATE 
Interferes to some extent with participant's 
usual function. 
3 
SEVERE 
Interferes significantly with participant's 
usual function. 
4 
LIFE-THREATENING 
Life-threatening consequences; urgent 
intervention indicated. 
 
 
 
 
 
 
 
 
 
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Assessment of Causality 
• The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. The investigator will use clinical judgment 
to determine the relationship. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated. 
• The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE or SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the sponsor. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
• If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for reporting 
purposes, as defined by the sponsor. 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 Vaccine SAE Reporting Form and in 
accordance with the SAE reporting requirements. 
 
 
 
 
 
 
 
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Follow-Up of AEs and SAEs 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations, as medically indicated or as requested by the 
sponsor, to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers. 
• If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology. 
• New or updated information will be recorded in the originally submitted 
documents. 
• The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information. 
 
10.2.4. Reporting of SAEs 
 
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool 
• The primary mechanism for reporting an SAE to Pfizer Safety will be the 
electronic data collection tool. 
• If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as the data 
become available. 
• After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form 
(see next section) or to Pfizer Safety by telephone. 
 
 
 
 
 
 
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SAE Reporting to Pfizer Safety via Vaccine SAE Reporting Form 
• Facsimile transmission of the Vaccine SAE Reporting Form is the preferred 
method to transmit this information to Pfizer Safety. 
• In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the Vaccine SAE Reporting Form sent by overnight mail 
or courier service. 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Vaccine SAE Reporting Form pages within the designated 
reporting time frames. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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10.3. Appendix 3: Liver Safety: Suggested Actions and Follow-Up Assessments 
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 participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.” 
LFTs are not required as a routine safety monitoring procedure in this study. However, 
should an investigator deem it necessary to assess LFTs because a participant 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 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 
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 
participant’s individual baseline values and underlying conditions. Participants 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: 
• Participants 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 participants 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: 
• 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). 
 
 
 
 
 
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• 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 participant 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 for suspected Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, total bile acids, and alkaline phosphatase. 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/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or 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, liver imaging (eg, biliary tract), and collection of serum 
samples for acetaminophen/paracetamol drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities. 
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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10.4. Appendix 4: AEs, ADEs, SAEs, SADEs, USADEs, and Device Deficiencies: 
Definitions and Procedures for Recording, Evaluating, Follow-Up, and Reporting in 
Medical Device Studies 
Definitions of a Medical Device Deficiency 
The definitions and procedures detailed in this appendix are in accordance with ISO 14155 
and the European MDR 2017/745 for clinical device research (if applicable). 
Both the investigator and the sponsor will comply with all local reporting requirements for 
medical devices. 
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.2 for the list of sponsor 
medical devices). 
10.4.1. Definition of AE and ADE 
 
AE and ADE Definition 
• An AE is defined in Appendix 2 (Section 10.2.1). 
• An ADE is defined as an AE related to the use of an investigational medical device. 
This definition includes any AEs resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device as well as any event resulting 
from use error or from intentional misuse of the investigational medical device. 
 
10.4.2. Definition of SAE, SADE, and USADE 
 
SAE Definition 
• An SAE is defined in Appendix 2 (Section 10.2.3). 
SADE Definition 
• An SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE. 
• Any device deficiency that might have led to an SAE if appropriate action had not 
been taken, intervention had not occurred, or circumstances had been less fortunate. 
 
 
 
 
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USADE Definition 
• A USADE is a serious adverse device effect that by its nature, incidence, severity, 
or outcome has not been identified in the current version of the risk analysis 
management file. 
 
10.4.3. Definition of Device Deficiency 
 
Device Deficiency Definition 
• A device deficiency is an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety, or performance. Device deficiencies 
include malfunctions, use errors, and inadequate information supplied by the 
manufacturer. 
 
10.4.4. Recording/Reporting and Follow-Up of Medical Device Deficiencies 
 
Device Deficiency Recording 
• When a device deficiency occurs, it is the responsibility of the investigator to 
review all documentation (eg, hospital progress notes, laboratory reports, and 
diagnostic reports) related to the event. 
• The investigator will then record all relevant device deficiency information in the 
participant’s medical records, in accordance with the investigator’s normal clinical 
practice and will also capture the required information on the Medical Device 
Complaint form. 
• It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of following the reporting process described 
in the Medical Device Complaint form. 
• There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety. 
• If the investigator determines that the medical device deficiency may have injured 
the participant (ie, the medical device deficiency is associated with an AE or SAE), 
then the investigator will attempt to establish a diagnosis of the event based on 
signs, symptoms, and/or other clinical information. Whenever possible, the 
diagnosis will be documented in the participant’s medical record and recorded as 
the AE or SAE rather than the individual signs/symptoms. Requirements for 
 
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recording and reporting an AE or SAE are provided in Appendix 2 
(Section 10.4.1). 
• For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident. 
• A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency. This includes any amendment to the device design to prevent 
recurrence. 
 
 
Assessment of Causality Occurring in Conjunction With a Medical Device Deficiency 
• If an AE or SAE has occurred in conjunction with a medical device deficiency, the 
investigator must assess the relationship between each occurrence of the AE or 
SAE and the medical device deficiency. The investigator will use clinical 
judgment to determine the relationship. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment. 
• For each device deficiency, the investigator must document in the medical notes 
that he/she has reviewed the device deficiency and has provided an assessment of 
causality. 
• There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to the sponsor. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
 
 
 
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Follow-Up of Medical Device Deficiency 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations, as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the device deficiency as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers. 
• New or updated information regarding the nature of the device deficiency will be 
recorded in the originally completed Medical Device Complaint form. 
• New or updated information regarding any SAE that was potentially associated 
with the medical device deficiency will be submitted to Pfizer Safety on the 
Vaccine SAE Reporting Form within 24 hours of receipt of the information, 
according to the requirements provided in Appendix 2. 
 
10.4.5. Reporting of SAEs 
Reporting of an SAE to Pfizer Safety must be performed according to the processes 
described in Appendix 2 (Section 10.2.4). 
10.4.6. Reporting of SADEs 
 
SADE Reporting to Pfizer Safety 
Note: There are additional reporting obligations for medical device deficiencies that are 
potentially related to SAEs (ie, an SADE) that must fulfill the legal responsibility to notify 
appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies. 
• Any device deficiency that is associated with an SAE must be reported to the 
sponsor within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency. 
• The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE. These shall be reported to the 
regulatory authorities and IRBs/ECs as required by national regulations. 
 
 
 
 
 
 
 
 
 
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10.5. Appendix 5: Alternative Measures During Public Emergencies 
The alternative study measures described in this section are to be followed during public 
emergencies, including the COVID-19 pandemic. This appendix applies for the duration of 
the COVID-19 pandemic and will become effective for other public emergencies only upon 
written notification from Pfizer. 
Use of these alternative study measures is expected to cease upon the return of business as 
usual (including the lifting of any quarantines and travel bans/advisories). 
10.5.1. Telehealth Visits 
In the event that in-clinic study visits cannot be conducted, every effort should be made to 
follow up on the safety of study participants at scheduled visits per the SoA or unscheduled 
visits. Telehealth visits may be used to continue to assess participant safety and collect data 
points. Telehealth includes the exchange of healthcare information and services via 
telecommunication technologies (eg, audio, video, video-conferencing software) remotely, 
allowing the participant and the investigator to communicate on aspects of clinical care, 
including medical advice, reminders, education, and safety monitoring. The following 
assessments must be performed during a telehealth visit. 
• Review and record any AEs and SAEs since the last contact. Refer to Section 8.3. 
• Review and record any new or changes in concomitant medications to treat SAEs since 
the last contact. 
Study participants’ parent(s)/legal guardian(s) must be reminded to promptly notify site staff 
about any change in their health status. 
10.5.2. Study Intervention 
If the safety of a trial participant is at risk because they cannot complete required evaluations 
or adhere to critical mitigation steps, then discontinuing that participant from study 
intervention must be considered. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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10.6. Appendix 6: Abbreviations 
The following is a list of abbreviations that may be used in the protocol. 
 
Abbreviation 
Term 
7vPnC 
7-valent pneumococcal conjugate vaccine 
13vPnC 
13-valent pneumococcal conjugate vaccine 
20vPnC 
20-valent pneumococcal conjugate vaccine 
ADE 
adverse device effect 
AE 
adverse event 
ALT 
alanine aminotransferase 
AOM 
acute otitis media 
AST 
aspartate aminotransferase 
CAP 
community-acquired pneumonia 
CBER 
Center for Biologics Evaluation and Research (US) 
CDC 
Centers for Disease Control and Prevention (US) 
CFR 
Code of Federal Regulations 
CHMP 
Committee for Medicinal Products for Human Use 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
creatine kinase 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
CRM197 
cross-reactive material 197 
CRO 
contract research organization 
CSR 
clinical study report 
DILI 
drug-induced liver injury 
DMC 
data monitoring committee 
DU 
dispensable unit 
EC 
ethics committee 
ECC 
emergency contact card 
ECDC 
European Centre for Disease Prevention and Control 
ECG 
electrocardiogram 
EDB 
exposure during breastfeeding 
eCRF 
electronic case report form 
e-diary 
electronic diary 
CCI 
EDP 
exposure during pregnancy 
EMA 
European Medicines Agency 
EU 
European Union 
EudraCT 
European Clinical Trials Database 
FDA 
Food and Drug Administration (US) 
 
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Abbreviation 
Term 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
CCI 
GMR 
geometric mean ratio 
GMT 
geometric mean titer 
HIV 
human immunodeficiency virus 
IB 
investigator’s brochure 
ICD 
informed consent document 
ICH 
International Council for Harmonisation 
ID 
identification 
IgG 
immunoglobulin G 
IND 
investigational new drug application 
INR 
international normalized ratio 
IPAL 
Investigational Product Accountability Log 
IPD 
invasive pneumococcal disease 
IP manual 
investigational product manual 
IRB 
institutional review board 
IRT 
interactive response technology 
ISO 
International Organization for Standardization 
IWR 
interactive Web-based response 
LFT 
liver function test 
LLOQ 
lower limit of quantitation 
MDR 
medical device regulation 
MedDRA 
Medical Dictionary for Regulatory Activities 
OPA 
opsonophagocytic activity 
PI 
principal investigator 
CCI 
PPE 
personal protective equipment 
PPSV23 
23-valent pneumococcal polysaccharide vaccine 
PT 
prothrombin time 
QTL 
quality tolerance limit 
CCI 
SADE 
serious adverse device effect 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SmPC 
summary of product characteristics 
SoA 
schedule of activities 
SOP 
standard operating procedure 
SRM 
study reference manual 
SRSD 
single reference safety document 
 
 
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Abbreviation 
Term 
SUSAR 
suspected unexpected serious adverse reaction 
TBili 
total bilirubin 
ULN 
upper limit of normal 
US 
United States 
USADE 
unanticipated serious adverse device effect 
VT 
vaccine-type 
WHO 
World Health Organization 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Pilishvili T, Lexau C, Farley MM, et al. Sustained reductions in invasive pneumococcal 
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PFIZER CONFIDENTIAL 

 
 
Document Approval Record 
 
 
B7471027 Clinical Protocol, 10Dec2021 
 
A PHASE 3, RANDOMIZED, PARTIAL DOUBLE-BLIND TRIAL TO EV 
ALUATE THE SAFETY AND IMMUNOGENICITY OF 20-VALENT PN 
EUMOCOCCAL CONJUGATE VACCINE IN HEALTHY TODDLERS 1 
2 to 23 MONTHS OF AGE WITH TWO PRIOR INFANT DOSES OF P 
REVENAR 13 
 
 
PPD 
 
PPD 
 
13-Dec-2021 23 58 41 
Final Approval 
 
15-Dec-2021 00 03 19 
Final Approval 
Signed By: 
Date(GMT) 
Signing Capacity 
Document Name: 
Document Title: