Safety and Immunogenicity of a Pneumococcal Conjugate Vaccine in Healthy Adults Aged 50 to 84 Years
Phase: PHASE2
Conditions: Pneumococcal Immunization
Sponsor: Sanofi

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Title Page 
Protocol Title: 
Safety and Immunogenicity of a Pneumococcal Conjugate Vaccine in Healthy Adults Aged 50 to 
84 Years 
Study Code: PSK00009 
Protocol Version Number: 3.0 
Amendment Number: 1 
Compound: 21-valent pneumococcal conjugate vaccine, SP0202 
Study Phase: II 
Short Title: 
Study of a Pneumococcal Conjugate Vaccine in Adults Aged 50 to 84 Years. 
Sponsor Name and Legal Registered Address: 
Sanofi Pasteur Inc. 
Discovery Drive, Swiftwater, PA 18370-0187, US 
Manufacturer: 
SK Bioscience CO., Ltd. 
310 Pangyo-ro, Bundang-gu, Seongnami-si, Gyeonggi-do, 13494, South Korea 
Regulatory Agency Identifier Number(s): 
BB-IND: 018207 
Approval Date: 30 November 2020 
Medical Monitor Name and Contact Information are provided in the Operating Guidelines. 
The study centers, the Investigators at each center, and the Coordinating Investigators are listed in 
a separate document. 
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Document History 
 
Previous 
Version 
Date 
Comments 
1.0 
26 May 2020 
Version submitted and approved by IRB / IEC. 
Updated in response to comments provided by the Health 
Authorities (CBER) prior to study initiation. 
2.0 
24 August 2020 
First version used in the study at the time of FVFS 
IRB: Institutional Review Board; IEC: Independent Ethics Committee 
Overall Rationale for the Amendment: 
The study has been amended to add a Data Monitoring Committee (DMC) review. An unblinded 
review will be performed by the DMC when at least 150 participants have been vaccinated and 
have safety data up to 30 days after injection available. The results from this DMC review will be 
supportive to the Sponsor decision-making process as regards to the SP0202 clinical development 
plan. 
 
 
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Table of Contents 
List of Tables .................................................................................................................................... 7 
List of Figures .................................................................................................................................. 8 
1 
Protocol Summary ............................................................................................................. 9 
1.1 
Synopsis ............................................................................................................................ 9 
1.2 
Schema ............................................................................................................................ 11 
1.3 
Schedule of Activities (SoA) .......................................................................................... 12 
2 
Introduction ..................................................................................................................... 14 
2.1 
Study Rationale ............................................................................................................... 14 
2.2 
Background ..................................................................................................................... 15 
2.3 
Benefit/Risk Assessment ................................................................................................ 16 
2.3.1 
Risks from Study Participation ..................................................................................... 17 
2.3.2 
Benefits from Study Participation ................................................................................ 18 
2.3.3 
COVID-19 risk assessment .......................................................................................... 18 
2.3.4 
Overall Benefit-Risk Conclusion .................................................................................. 18 
3 
Objectives and Endpoints ............................................................................................... 19 
4 
Study Design .................................................................................................................... 20 
4.1 
Overall Design ................................................................................................................ 20 
4.2 
Scientific Rationale for Study Design ............................................................................. 20 
4.3 
Justification for Dose ...................................................................................................... 21 
4.4 
End of Study Definition .................................................................................................. 21 
5 
Study Population ............................................................................................................. 22 
5.1 
Inclusion Criteria ............................................................................................................ 22 
5.2 
Exclusion Criteria ........................................................................................................... 22 
5.3 
Lifestyle Considerations ................................................................................................. 24 
5.4 
Screen Failures ................................................................................................................ 24 
6 
Study Intervention ........................................................................................................... 24 
6.1 
Study Intervention(s) Administered ................................................................................ 24 
6.2 
Preparation/Handling/Storage/Accountability ................................................................ 26 
6.3 
Measures to Minimize Bias: Randomization and Blinding ............................................ 27 
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6.3.1 
Randomization and Allocation Procedures .................................................................. 27 
6.3.2 
Blinding and Code-breaking Procedures ...................................................................... 27 
6.4 
Study Intervention Compliance ...................................................................................... 29 
6.5 
Concomitant Therapy ...................................................................................................... 29 
6.5.1 
Rescue Medicine ........................................................................................................... 30 
6.6 
Dose Modification .......................................................................................................... 30 
7 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal .......................................................................................... 31 
7.1 
Discontinuation of Study Intervention ............................................................................ 31 
7.1.1 
Temporary contraindications ........................................................................................ 31 
7.2 
Participant Discontinuation/Withdrawal from the Study ................................................ 31 
7.3 
Lost to Follow-up ............................................................................................................ 32 
8 
Study Assessments and Procedures ............................................................................... 32 
8.1 
Efficacy and Immunogenicity Assessments ................................................................... 33 
8.1.1 
Efficacy Assessments ................................................................................................... 33 
8.1.2 
Immunogenicity Assessments ...................................................................................... 33 
8.2 
Safety Assessments ......................................................................................................... 34 
8.2.1 
Medical History ............................................................................................................ 34 
8.2.2 
Physical Examinations .................................................................................................. 34 
8.2.3 
Vital Signs .................................................................................................................... 34 
8.2.4 
Clinical Safety Laboratory Assessments ...................................................................... 34 
8.3 
Adverse Events and Serious Adverse Events ................................................................. 35 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information ......................... 35 
8.3.2 
Method of Detecting AEs and SAEs ............................................................................ 36 
8.3.3 
Follow-up of AEs and SAEs ........................................................................................ 36 
8.3.4 
Regulatory Reporting Requirements for SAEs ............................................................ 37 
8.3.5 
Pregnancy ..................................................................................................................... 37 
8.3.6 
Adverse Events of Special Interest ............................................................................... 37 
8.4 
Treatment of Overdose ................................................................................................... 38 
8.5 
Pharmacokinetics ............................................................................................................ 38 
8.6 
Pharmacodynamics ......................................................................................................... 38 
8.7 
Genetics ........................................................................................................................... 38 
8.8 
Biomarkers ...................................................................................................................... 38 
8.9 
Immunogenicity Assessments ......................................................................................... 38 
8.10 
Medical Resource Utilization and Health Economics .................................................... 38 
9 
Statistical Considerations ............................................................................................... 38 
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9.1 
Statistical Hypotheses ..................................................................................................... 38 
9.2 
Sample Size Determination ............................................................................................. 39 
9.3 
Populations for Analyses ................................................................................................ 39 
9.4 
Statistical Analyses ......................................................................................................... 40 
9.4.1 
General Considerations ................................................................................................. 40 
9.4.2 
Safety Analyses ............................................................................................................ 41 
9.4.3 
Immunogenicity Analyses ............................................................................................ 41 
9.4.4 
Other Analyses ............................................................................................................. 42 
9.5 
Interim Analyses ............................................................................................................. 42 
9.6 
Data Monitoring Committee (DMC) .............................................................................. 42 
10 
Supporting Documentation and Operational Considerations .................................... 43 
10.1 
Appendix: Regulatory, Ethical, and Study Oversight Considerations ............................ 43 
10.1.1 
Regulatory and Ethical Considerations ........................................................................ 43 
10.1.2 
Financial Disclosure ..................................................................................................... 44 
10.1.3 
Informed Consent Process ............................................................................................ 44 
10.1.4 
Data Protection and Future Use of Stored Samples ..................................................... 45 
10.1.5 
Committees Structure ................................................................................................... 46 
10.1.6 
Dissemination of Clinical Study Data .......................................................................... 46 
10.1.7 
Data Quality Assurance ................................................................................................ 46 
10.1.8 
Source Documents ........................................................................................................ 47 
10.1.9 
Study and Site Start and Closure .................................................................................. 47 
10.1.10 
Publication Policy ......................................................................................................... 48 
10.2 
Appendix: Clinical Laboratory Tests .............................................................................. 48 
10.3 
Appendix: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ............................................................................ 48 
10.3.1 
Definition of AE ........................................................................................................... 49 
10.3.2 
Definition of SAE ......................................................................................................... 51 
10.3.3 
Recording and Follow-Up of AE and/or SAE .............................................................. 52 
10.3.4 
Reporting of SAEs ........................................................................................................ 54 
10.3.5 
Assessment of Intensity ................................................................................................ 55 
10.3.5.1 
Tables for Clinical Abnormalities .............................................................................. 55 
10.3.5.1.1 
Solicited AR Intensity Grading Scale ...................................................................... 55 
10.3.5.1.2 
Unsolicited AE Intensity Grading Scale .................................................................. 61 
10.4 
Appendix: Collection of Pregnancy Information ............................................................ 61 
10.5 
Appendix: Risk-based Approach .................................................................................... 63 
10.6 
Appendix: Abbreviations ................................................................................................ 64 
10.7 
Appendix: Protocol Amendment History ....................................................................... 66 
11 
References ........................................................................................................................ 67 
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12 
Sponsor Signature Page .................................................................................................. 69 
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List of Tables 
Table 1.1: Schedule of activities ................................................................................................... 12 
Table 2.1: Specificities of the 4 formulations evaluated in Phase I study PSK00007 .................. 14 
Table 2.2: Potential risks of clinical significance and risk management ...................................... 17 
Table 3.1: Objectives and endpoints ............................................................................................. 19 
Table 4.1: Overall design .............................................................................................................. 20 
Table 6.1: Identity of study intervention(s) ................................................................................... 25 
Table 10.1: Solicited injection site reactions: terminology, definitions, and intensity scales ....... 56 
Table 10.2: Solicited systemic reactions: terminology, definitions, and intensity scales ............. 58 
 
 
 
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List of Figures 
Figure 1.1: Graphical study design ................................................................................................ 11 
 
 
 
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1 
Protocol Summary 
1.1 
Synopsis 
Protocol Title: 
Safety and Immunogenicity of a Pneumococcal Conjugate Vaccine in Healthy Adults Aged 50 to 
84 Years 
Short Title: 
Study of a Pneumococcal Conjugate Vaccine in Adults Aged 50 to 84 Years 
Rationale: 
The SP0202 investigational vaccine is intended to provide protection against diseases caused by 
the Streptococcus pneumoniae serotypes included in the vaccine, in population from infants to 
elderly. There are two types of pneumococcal vaccines available in the United States: Prevnar 13 
(a 13-valent conjugated vaccine) and Pneumovax 23 (a 23-valent unconjugated vaccine). Both 
vaccines are recommended in the US population aged 65 years or above (1). SP0202 
investigational vaccine contains 21 serotypes that are conjugated to carrier protein. PSK00009 is a 
Phase II study that will evaluate the immunogenicity and safety of 3 SP0202 formulations that 
differ by the antigen content for a few serotypes, administered as a single dose to healthy adults 
aged 50 to 84 years. Two groups will serve as control and receive a single dose of either 
Prevnar 13 or Pneumovax 23. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Immunogenicity 
To assess the immune response of the 
3 SP0202 formulations, Prevnar 13, 
and Pneumovax 23 30 days after the 
administration of the single dose 
vaccination 
• 
Serotype specific OPA titers for all pneumococcal 
serotypes included in the SP0202 formulations, as 
determined by multiplex opsonophagocytic assay 
(MOPA), at baseline (D01) and 30 days after 
vaccination (D31) 
• 
Serotype specific OPA titers ratio (post/pre-injection) 
for all pneumococcal serotypes included in the SP0202 
formulations as determined by MOPA 
• 
Serotype-specific IgG concentrations for all 
pneumococcal serotypes included in the SP0202 
formulations as measured by electro-chemiluminescence 
assay (ECL), at baseline (D01) and 30 days after 
vaccination (D31) 
• 
Serotype-specific IgG concentration ratios 
(post/pre-vaccination) for all pneumococcal serotypes 
included in the SP0202 formulations as measured by 
ECL 
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Safety 
To assess the safety profile of the 3 
SP0202 formulations, Prevnar 13, and 
Pneumovax 23 
• 
Presence of any unsolicited systemic AEs reported in 
the 30 minutes after injection of a SP0202 formulation, 
Prevnar 13, or Pneumovax 23 
• 
Presence of solicited (ie, pre-listed in the participant’s 
DC and in the case report form (CRF)) injection site 
reactions occurring up to 7 days after the day of 
injection (D08) of a SP0202 formulation, Prevnar 13, 
or Pneumovax 23 
• 
Presence of solicited (ie, pre-listed in the participant’s 
DC and in the CRF) systemic reactions occurring up to 
7 days after the day of injection (D08) of a SP0202 
formulation, Prevnar 13, or Pneumovax 23 
• 
Presence of unsolicited (spontaneously reported) AEs 
up to 30 days after the day of injection (D31) of a 
SP0202 formulation, Prevnar 13, or Pneumovax 23 
• 
Presence of SAEs and AESIs, throughout the study 
period (up to 6-month follow-up) 
 
Overall Design 
Type of design 
Parallel, multicenter (approximately 8 sites) 
Phase 
II 
Control method 
Active -controlled 
(controls = Prevnar 13 and Pneumovax 23) 
Study population 
Healthy adults aged 50 to 84 years 
Countries 
United States of America 
Level and method of blinding 
Modified double-blind (observer-blind) 
Study intervention assignment method 
Randomization with stratification by sites and age 
group (ie 50-64 years and 65 to 84 years) 
Review group 
Safety Management Team (SMT) and Data 
Monitoring Committee 
 
Disclosure Statement: 
This is a parallel group prevention study with 5 groups that is Participant, Investigator and 
Outcomes Assessor blinded. 
Number of Participants: 
A total of 750 participants, approximatively 150 in each group (approximately 375 participants 
aged 50 to 64 years and 375 participants aged 65 to 84 years) are expected to be randomized. 
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Group 
Number of 
Participants 
Formulation Name 
Group 1 
150 
SP0202-IIb 
Group 2 
150 
SP0202-VI 
Group 3 
150 
SP0202-VII 
Group 4 
150 
Prevnar 13® 
Group 5 
150 
Pneumovax 23® 
 
Intervention Groups and Duration: 
Eligible participants will be randomized in a 1:1:1:1:1 ratio to receive a single intramuscular (IM) 
injection of either 1 of the 3 SP0202 formulations or Prevnar 13 or Pneumovax 23 at Day (D)01. 
The duration of each participant’s participation will be approximately 6 months. 
Data Monitoring Committee: Yes 
1.2 
Schema 
The graphical design of PSK00009 study is presented in Figure 1.1. 
Figure 1.1: Graphical study design 
 
BL: Blood sample 
VAC: vaccination 
TC: telephone call 
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1.3 
Schedule of Activities (SoA) 
Visits procedures are detailed in the Operating Guidelines. 
Table 1.1: Schedule of activities 
Phase II Study, 2 Visits, 1 Phone Call, 1 Vaccination, 2 Blood Samples, Approximately 6 
Months Duration Per Participant 
Visit/Contact 
Collection of 
information in the 
CRF 
Visit 1 
Visit 2* 
Phone call 
6-month safety 
follow-up 
Study timelines (days) 
 
D01 
D31 
D181 
Time windows (days) 
 
NA 
[+14 D] 
+14 
Visit procedures: 
 
 
 
 
Informed consent 
X 
X 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
Collection of demographic data† 
X 
X 
 
 
Urine pregnancy test (if applicable)‡ 
 
X 
 
 
Collection of Medical history 
X 
Significant  
Medical History 
X 
 
 
Physical examination (including body 
temperature)§ 
 
X 
X 
 
Randomization/allocation of 
participant number 
X 
X 
 
 
Blood sampling (BL), 20 mL 
X 
BL0001 
Pre-vac 
BL0002 
 
Vaccination (vac) 
X 
X 
 
 
Immediate surveillance (30 min) 
X 
X 
 
 
Diary card provided** 
 
X 
 
 
Collection of solicited injection site 
and systemic reactions 
X 
D01 – D08 
 
 
Collection of unsolicited adverse 
events (AEs) 
X 
To be reported at any 
time from D01 to D31 
 
Diary card reviewed and collected 
 
 
X†† 
 
Memory aid provided 
 
 
X 
 
Telephone call 
 
 
 
X 
Memory aid reviewed 
 
 
 
X‡‡ 
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Collection of concomitant 
medications 
X 
Reportable 
concomitant 
medication 
X 
X 
 
Collection of serious and non-serious 
adverse events of special interest 
(AESIs) 
X 
To be reported at any time during the 
study 
Collection of serious adverse events 
(SAEs) 
X 
To be reported at any time during the 
study 
Collection of pregnancies 
X 
To be reported at any time during the 
study 
End of Active Phase participation 
record 
X 
 
X 
 
*  The investigator or an authorized designee will interview the participant to collect the information recorded in the DC and will 
attempt to clarify anything that is incomplete or unclear. 
†  To comply with US FDA expectations, Sponsors are to enroll participants who reflect the demographics for clinically relevant 
populations with regard to age, gender, race and ethnicity as described in 
https://www.fda.gov/downloads/regulatoryinformations/guidances/ucml126396.pdf. 
‡  In female participants of childbearing potential (ie, not post-menopausal for at least 1 year, or surgically sterile). 
§  Physical examination based on medical history will be performed at Visit 1. Targeted physical examination may also be 
performed at Visit 2, as necessary. 
**  Participants will use this diary card to record information about solicited reactions from D01 to D08, as well as unsolicited 
AEs, SAEs, and AESIs until Visit 2. 
††  Staff will collect the diary card at Visit 2, and review any solicited reactions ongoing at Visit 2, Unsolicited AEs, concomitant 
medication, SAEs and AESIs. 
‡‡  During this call the staff will review the memory aid with the participant and determine whether the participant experienced 
any SAE or AESI not yet reported. 
CRF: case report form 
 
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2 
Introduction 
2.1 
Study Rationale 
The SP0202 investigational vaccine is intended to provide protection against disease caused by 
the Streptococcus pneumoniae serotypes included in the vaccine, in population, from infants to 
elderly. Compared to the licensed vaccines Prevnar 13 and Pneumovax 23, SP0202 investigational 
vaccine contains 21 serotypes:13 serotypes common to those of Prevnar 13 (1, 3, 4, 5, 6A, 6B, 7F, 
9V, 14, 18C, 19A, 19F and 23F) and 8 additional serotypes ( 8, 9N, 10, 11A, 12F, 15B, 22F, 33F); 
the later are common to Pneumovax 23. These 21 serotypes are conjugated to 2 different protein 
carriers, either tetanus toxoid (TTxd) or cross-reacting material 197, a non-toxic mutant of 
diphtheria toxin (CRM197). These two protein carriers included in the PCV21 formulation have 
proven safety records. The long-term benefit of unconjugated vaccines in elderly population was 
recently discussed as their protection-induced is weak and short lived because of the absence of B-
cell memory production following immunization (2) (3). Therefore, the conjugation technology 
using a carrier protein to polysaccharides has been used to increase immunogenicity in elderly 
population. Protein carrier specific T-cells provide the signal needed for maturation of the B-cell 
response and generation of B-cell memory, and production of high affinity antibodies.  
Four formulations of SP0202 investigational vaccine (with different content of serotypes and 
different serotypes conjugated to either TTxd or CRM197) were evaluated in Phase I study 
PSK000007. They differed by the number of serotypes conjugated to TTxd (2 or 4) and by the 
dosage of some serotype specific polysaccharides compared to existing PCV13. (Table 2.2). 
Table 2.1: Specificities of the 4 formulations evaluated in Phase I study PSK00007 
Formulation name 
Formulation specificities 
SP0202-I 
SP0202-II 
SP0202-III 
SP0202-IV 
Based on PSK00007 safety and immunogenicity results, 3 formulations designed to optimize 
SP0202 immunogenicity and secure the identification of a lead formulation for Phase III have 
been developed (see Table 6.1 for their composition). All 3 formulations will include 4 serotypes 
conjugated to TTxd (serotypes 1, 5, 15B and 22F). It is to be noted that the TTxd content will be 
decreased compared to SP0202-II formulation tested in the Phase I study following changes in the 
manufacturing process of serotypes 15B and 22F (increased polysaccharide / tetanus toxoid ratio, 
expected to improve immune response). 
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With regards to the antigen content per serotypes: 
• Formulation IIb will include 
 µg for all serotypes but 6B (
 µg) 
• Formulation VI will differentiate from IIb with serotypes 3, 19A and 19F at 
 µg  
• Formulation VII will differentiate from IIb with serotypes 3, 4, 9V, 19A and 19F at 
 µg  
The SP0202 investigational vaccine is designed for immunization of infants/toddlers and elderly 
against pneumococcal disease. Phase II study PSK00008 including toddlers aged 12-15 months, 
and infants aged 42 to 89 days will be conducted in parallel with the current Phase II study 
PSK00009 including healthy adults aged 50 to 84 years. 
2.2 
Background 
S. pneumoniae (or pneumococcus) is a Gram-positive diplococcus, encapsulated with a diverse 
range of polysaccharides. Based on the differences in the polysaccharide capsule, 98 different 
serotypes of S. pneumoniae have been described (4) (5) (6). The most common disease-causing 
serotypes observed throughout the world are generally similar. However, there may be large 
variations in the relative serotype prevalence in these regions, particularly between developed and 
developing countries (7). 
The microorganism, through the asymptomatic colonization of the nasopharynx, is a major cause 
of several infections, including pneumonia, meningitis, bacteremia, sinus and otitis media (6). 
Infections characterized by the isolation of S. pneumoniae from a normal sterile site, such as 
blood, cerebrospinal fluid, or synovial fluid, identified as occurrences of invasive pneumococcal 
disease (IPD). 
In order to offer protection against S. pneumoniae infections, vaccines against serotype specific 
capsular polysaccharides have been developed. The first pneumococcal polysaccharide vaccines 
(PPSV) were brought to the market in 1947 and offered protection against serious infections 
caused by 6 serotypes of S. pneumoniae. In 1977, the first 14-valent vaccine was licensed and in 
1983 the vaccine coverage was expanded to 23 S. pneumoniae serotypes (8). In the following 
years, 23-valent PPSVs were shown to reduce the risk of IPD in adults (9), although protection 
against pneumococcal pneumonia has not yet been convincingly demonstrated (10) (11). In 
addition, PPSVs have shown a poor immunogenicity in children aged less than 2 years (ie, the 
most vulnerable age group to pneumococcal infections), an inability to generate immune memory 
at any age, and no effect on pneumococcal carriage (12) (13) (14). 
As a way to offer a stronger and longer-lasting protection to populations in which PPSVs are the 
least immunogenic (ie, children under 2 years, adults over 65 years, and immunocompromised 
persons), second generation pneumococcal vaccines have been developed by conjugating 
S. pneumoniae capsular polysaccharides with carrier proteins to induce both humoral and cellular 
immune response (12). Pneumococcal conjugate vaccines (PCVs) have been shown to be effective 
in preventing pneumococcal pneumonia, IPD, and otitis in children (15) (16) (17) (18) (19) (20). 
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Ever since the introduction of a 7-valent PCV in 2000a, the overall number of IPD cases, 
especially the number of cases due to serotypes covered by the vaccine, has been declining (13) 
(14). Strengthening this trend, the introduction of a 10-valent PCV (2009)b and a 13-valent PCV 
(2010)c has confirmed the indirect benefit generated by reduction both in carriage of vaccine 
serotypes (ie, herd immunity in unvaccinated population) and in antimicrobial resistance (13) (21) 
(22). PCVs have had an important impact on public health in developed countries, as well as 
worldwide; since global roll out (9). 
However, it is now acknowledged that serotypes covered by marketed PCVs tend to be replaced 
as pathogens by other circulating serotypes (21) (23) (24). Less fit or emergent serotypes simply 
take advantage of an ecological niche left vacant (25). One of most notable examples is serotype 
19A which emerged as a predominant serotype in several countries with no PCV7 vaccination 
programs (7). 
Currently, few strategies aiming to mitigate this phenomenon of serotype replacement are being 
developed. One possible solution would be to design a vaccine that combines 2 classes of 
complementary antigens, one to prevent colonization (ie, pneumococcal polysaccharides) and 
another to limit virulence transition (ie, protein antigens that selectively target pneumococci 
virulence transition) (26). The proof of concept of such an approach has not been demonstrated to 
date. Another possible solution is to introduce a PCV that includes a higher number of serotypes 
to cover the emerging ones and hence to protect against a higher number of pneumococcal strains 
causing invasive disease. 
Sanofi Pasteur has decided to move forwards with the latter approach, a next generation of PCV 
comprising 21 serotypes (PCV21). Such a vaccine candidate has the potential to address important 
medical and public health needs by providing broader coverage for the leading serotypes 
associated with pneumococcal diseases. 
2.3 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks, reasonably expected 
adverse events, the potential risks, and uncertainties of SP0202 may be found in the Investigator’s 
Brochure (IB). 
                                                 
a Prevnar®. Pneumococcal 7-valent Conjugate vaccine (Diphtheria CRM197 Protein), Pfizer Inc. 
b Synflorix®. Pneumococcal conjugate vaccine (Non-typeable Haemophilus influenzae [NTHi] protein D, diphtheria 
or tetanus toxoid conjugates) absorbed, GlaxoSmithKline Biological S.A. 
c Prevnar 13®. Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 protein), Pfizer Inc. 
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2.3.1 
Risks from Study Participation 
The potential risks of clinical significance and risk management are summarized in Table 2.2 
Table 2.2: Potential risks of clinical significance and risk management 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale 
for Risk 
Risk Management 
Investigated Vaccine: SP0202 
• 
Anaphylaxis 
• 
Guillain-Barré Syndrome 
• 
Arthus-type hypersensitivity 
• 
Gastrointestinal disorders 
(vomiting) 
• 
Headache 
• 
Myalgia, arthralgia 
Refer to IB Section 6 for more 
information regarding potential 
risks 
All vaccines have the potential to 
cause allergic reactions or 
anaphylaxis in individuals who 
may be sensitized to components 
of the vaccine. 
Refer to the IB Section 5 and 
Section 6 for more information 
regarding the data from previous 
experience with the investigated 
vaccine. 
Exclusion criteria 8 and 9 for 
those at increased risk. 
Observation period after 
vaccination for early detection 
and treatment. 
Comparator: Prevnar 13 
Refer to the package insert for 
more information regarding 
potential risks. 
Identified and potential risks 
observed in clinical trials and/or 
post-marketing surveillance. 
Exclusion/inclusion criteria take 
in account contraindications, 
warnings and precautions as 
defined in product label. 
Comparator: Pneumovax 23 
Refer to the package insert for 
more information regarding 
potential risks. 
Identified and potential risks 
observed in clinical trials and/or 
post-marketing surveillance. 
Exclusion/inclusion criteria take 
in account contraindications, 
warnings and precautions as 
defined in product label. 
Study Procedures 
Vasovagal reactions (syncope), 
or psychogenic reactions to 
needle (vaccine injection or 
blood sampling). 
Anxiety-related reactions can 
occur following, or even before, 
any vaccination as a psychogenic 
response to the needle injection 
or blood draw, and may be 
accompanied by several 
neurological signs such as 
transient visual disturbance, 
paresthesia or seizure-like 
activity. 
Observation period after 
vaccination for early detection 
and treatment. 
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2.3.2 
Benefits from Study Participation 
Four formulations of SP0202 investigational vaccine were evaluated in Phase I clinical study 
(PSK00007) that was carried out in healthy adults aged 19 to 49 years old in the US.
 
 
 Based on PSK00007 results, 3 formulations have been 
selected for further evaluation in the target population. These 3 formulations will be evaluated in 
this Phase II study. It is expected that adults aged 50 to 84 years who will be vaccinated with 
SP0202 will develop an immune response against the 21 serotypes, although there is no guarantee. 
Participants who will receive Prevnar 13 will likely be protected against pneumococcal disease 
due to 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). 
Participants who will receive Pneumovax 23 will likely be protected against pneumococcal 
disease due to 23 serotypes (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 
19A, 19F, 20, 22F, 23F, and 33F). 
As with any vaccines, SP0202 formulations and Prevnar 13, and Pneumovax 23, vaccines 
administered during the study may not protect 100% of individuals against the disease they are 
designed to prevent. 
2.3.3 
COVID-19 risk assessment 
SP0202 is a pneumococcal vaccine. It would not cause immune suppression. Therefore, the risk 
that a participant in this study will contract Covid-19 disease solely due to the administration of 
the study vaccine will be similar to the risk that a person not participating in this study will 
contract Covid-19. However, the risk of exposure to infected people cannot be completely 
excluded as the participants may need to expose to public area (eg, commute to the site and at the 
site). 
2.3.4 
Overall Benefit-Risk Conclusion 
Considering the measures taken to minimize risk to participants enrolled in this study, the 
potential risks that may result from study participation are balanced by the anticipated benefits 
that may be afforded to participants. 
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3 
Objectives and Endpoints 
Table 3.1: Objectives and endpoints 
Objectives 
Endpoints 
Immunogenicity 
To assess the immune response of the 3 
SP0202 formulations, Prevnar 13, and 
Pneumovax 23, 30 days after the 
administration of the single dose 
vaccination 
• Serotype-specific OPA titers for all pneumococcal 
serotypes included in the SP0202 formulations, as 
determined by multiplex opsonophagocytic assay 
(MOPA), at baseline (D01) and 30 days after 
vaccination (D31) 
• Serotype-specific OPA titers ratio (post/pre-injection) 
for all pneumococcal serotypes included in the SP0202 
formulations as determined by MOPA 
• Serotype-specific IgG concentrations for all 
pneumococcal serotypes included in the SP0202 
formulations as measured by 
electro-chemiluminescence assay (ECL), at baseline 
(D01) and 30 days after vaccination (D31) 
• Serotype-specific IgG concentration ratios 
(post/pre-injection) for all pneumococcal serotypes 
included in the SP0202 formulations as measured by 
ECL 
Safety 
To assess the safety profile of the 3 
SP0202 formulations, Prevnar 13, and 
Pneumovax 23 
• Presence of any unsolicited systemic AEs reported in 
the 30 minutes after injection of a SP0202 
formulation, Prevnar 13, or Pneumovax 23 
• Presence of solicited (ie, pre-listed in the participant’s 
DC and in the CRF) injection site reactions occurring 
up to 7 days after the day of injection (D08) of a 
SP0202 formulation, Prevnar 13, or Pneumovax 23 
• Presence of solicited (ie, pre-listed in the participant’s 
DC and in the CRF) systemic reactions occurring up to 
7 days after the day of injection (D08) of a SP0202 
formulation, Prevnar 13, or Pneumovax 23 
• Presence of unsolicited (spontaneously reported) AEs 
up to 30 days after the day of injection (D31) of a 
SP0202 formulation, Prevnar 13, or Pneumovax 23 
• Presence of SAEs and AESIs, throughout the study 
period (up to 6-month follow-up) 
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4 
Study Design 
4.1 
Overall Design 
The design of the study is summarized in Table 4.1. 
Table 4.1: Overall design 
Type of design 
Parallel, multicenter 
Phase 
II 
Control method 
Active-controlled 
(controls = Prevnar 13 and Pneumovax 23) 
Study population 
Healthy adults aged 50 to 84 years 
Level and method of blinding 
Modified double-blind (observer-blind) 
Study intervention assignment method 
Randomization with stratification by sites and by age 
group 
Number of participants 
750 participants, approximately 150 in each group 
(approximately 375 aged 50 to 64 years and 375 aged 65 
to 84 years) 
Intervention groups 
In each site and age group, randomization in a 1:1:1:1:1 
ratio to receive a single injection of either 1 of the 3 
formulations of SP0202, Prevnar 13, or Pneumovax 23 
Total duration of study participation 
Approximately 6 months 
Countries 
United States of America 
Use of an Independent Data Monitoring 
Committee, Dose Escalation Committee, or 
similar review group 
Yes 
4.2 
Scientific Rationale for Study Design 
PSK00009 is a Phase II study that will evaluate the immunogenicity and safety of 3 SP0202 
formulations administered as a single dose to healthy adults aged 50 to 84 years naïve to prior 
pneumococcal vaccine administration. Two groups will serve as controls and receive a single dose 
of either Prevnar 13 or Pneumovax 23.  
In the US, pneumococcal vaccination with Prevnar 13 (a 13-valent conjugated vaccine) or 
Pneumovax 23 (a 23-valent unconjugated vaccine) is recommended by ACIP as follows (27): 
• Pneumovax 23: for all immunocompetent adults ≥ 65 years old (yo), for people 19 to 64 yo 
with certain conditions and for adults 19 to 64 yo who smoke cigarettes. 
• Prevnar 13: in adults with certain medical conditions, for immunocompetent adults ≥ 65 yo 
who have not previously received Prevnar 13 based on shared clinical decision-making. 
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In this study, Prevnar 13 will serve as a reference vaccine for safety assessment and for 
immunogenicity of the 13 common serotypes with SP0202. Pneumovax 23 will provide a 
reference for the immune response to the 8 additional serotypes in SP0202 formulations. 
Given the acceptable safety data generated in PSK00007 study (Phase I study), no early safety 
data review is planned for this study. The safety will be continuously monitored by the Sponsor. 
The safety data collected will be entered into the CRF and summarized by the Sponsor. Blinded 
reviews will be performed by the Sponsor during the Safety Management Team (SMT) meetings. 
An unblinded review by a Data Monitoring Committee (DMC) will also be conducted to assess 
the safety data, including AESIs, SAEs and safety profile of each SP0202 formulation when at 
least 150 participants have been vaccinated and have safety data up to D31 (30 days after 
injection) available. The DMC will also review the unblinded safety data collected on all 
participants up to D31. 
Due to differences in the appearance of SP0202, Prevnar 13, and Pneumovax 23 products, the 
study will have an observer-blinded design (double-blind across SP0202 formulations) to limit 
any bias in the assessment of safety. The designated vaccine preparer(s)/administrator(s) will be 
unblinded given the different aspect of the products, but neither the participant nor the investigator 
nor the study staff in charge of vaccination will know which vaccine will be administered. The 
unblinded designated vaccine preparer(s)/administrator(s) will not be involved in any of the 
blinded study assessments (eg, immunogenicity, safety). The Investigators (or delegate) in charge 
of safety assessment, the study staff who collect the safety data, and the laboratory personnel who 
analyze the blood samples will not know which product was administered. 
Note: at this stage and based on currently available information, this is not known whether prior 
history of exposure to SARS-CoV-2 (2019-nCoV) would impact the immune response to 
pneumococcal vaccines. 2019-nCoV serology screening prior to vaccination is not included. 
However, serum samples could be tested to determine participants’ sero-status regarding 2019-
nCOV at the time of the study if deemed necessary according to the available scientific 
knowledge. This assessment may be done during immunogenicity assessment or at any time. 
4.3 
Justification for Dose 
The vaccination schedule of a single dose for pneumococcal vaccine in elderly population is per 
standard procedure recommended by CDC (1). 
The antigen content for each serotypes is similar to Prevnar 13, except for serotypes 3, 19A and 
19F in formulation SP0202 VI and serotypes 3, 4, 9V, 19A, and 19F in formulation VII. 
4.4 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed the last phone call 
planned in the SoA. 
The end of the study is defined as the date of the last visit of the last participant in the study. 
However, for periodic safety reports, the study is considered completed when the clinical study 
report is finalized. 
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5 
Study Population 
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 for the study only if all of the following criteria are met: 
I01: 
Aged 50 to 84 years on the day of inclusiona. 
I02: 
Informed consent has been signed and dated. 
I03: 
Able to attend all scheduled visits and to comply with all trial procedures. 
5.2 
Exclusion Criteria 
Participants are not eligible for the study if any of the following criteria are met: 
E01: 
Participant is pregnant, or lactating, or of childbearing potential and not using an 
effective method of contraception or abstinence from at least 4 weeks prior to 
vaccination until at least 4 weeks after vaccination. To be considered of non-
childbearing potential, a female must be post-menopausal for at least 1 year, or 
surgically sterile. 
E02: 
Participation at the time of the study enrollment (or in the 4 weeks preceding the trial 
vaccination) or planned participation during the present trial period in another clinical 
trial investigating a vaccine, drug, medical device or medical procedure 
E03: 
Receipt of any vaccine in the 4 weeks preceding the trial vaccination or planned 
receipt of any vaccine from enrollment through the last blood sampling Visit, except 
for influenza vaccination, which may be received at least 2 weeks before study 
vaccine. This exception includes monovalent pandemic influenza vaccines and 
multivalent influenza vaccines. 
E04: 
Previous vaccination against S. pneumoniae with either a pneumococcal conjugated 
vaccine (PCV) or a pneumococcal polysaccharide vaccine (PPSV). 
E05: 
Receipt of immune globulins, blood or blood-derived products in the past 3 months. 
E06: 
Known or suspected congenital or acquired immunodeficiency, or receipt of 
immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, 
within the preceding 6 months; or long-term systemic corticosteroid therapy 
(prednisone or equivalent for more than 2 consecutive weeks within the past 3 
months). 
                                                 
a “50 to 84 years” means from the day of the 50th birthday to the day before the 85th birthday 
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E07: 
History of S. pneumoniae infection or disease, confirmed either serologically, or 
microbiologically. 
E08: 
History of Guillain-Barré syndrome occurring within 6 weeks after a prior dose of a 
TTxd-containing vaccine. 
E09: 
Experienced an Arthus-type hypersensitivity reaction following a prior dose of a 
TTxd-containing vaccine < 10 years ago. 
E10: 
Known systemic hypersensitivity to any of the vaccine components, or history of a 
life-threatening reaction to the vaccines used in the trial or to a vaccine containing any 
of the same substancesa. 
E11: 
Verbal report of thrombocytopenia contraindicating IM vaccination in the 
Investigator’s opinion 
E12: 
Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, 
contraindicating IM vaccination in the Investigator’s opinion. 
E13: 
At risk of invasive pneumococcal disease (eg, participant with functional or anatomic 
asplenia, participants with severe asthma, participants travelling to countries with high 
endemicity). 
E14: 
Deprived of freedom by an administrative or court order, or in an emergency setting, 
or hospitalized involuntarily. 
E15: 
Current alcohol abuse or drug addiction. 
E16: 
Chronic illness that, in the opinion of the Investigator, is at a stage where it might 
interfere with trial conduct or completionb. 
E17: 
Any condition that in the opinion of the Investigator could interfere with the 
evaluation of the vaccine (eg, under investigation or monitoring for possible 
coronavirus disease 2019 [COVID-19]) 
E18: 
Moderate or severe acute illness/infection (according to investigator judgment) on the 
day of vaccination or febrile illness (temperature ≥ 100.4°F). A prospective participant 
should not be included in the study until the condition has resolved or until 3 days 
after the febrile event has subsided. 
E19: 
Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood 
draw. 
                                                 
a The component of the SP0202 formulations are listed in Section 6.1 and in the Investigator’s Brochure. The 
components of Prevnar 13 and Pneumovax 23 are listed in Section 6.1 and in their prescribing information. 
b Participants with pre-existing stable chronic condition, determined based on medical history and clinical judgement 
of the investigator are eligible. 
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E20: 
Identified as an Investigator or employee of the Investigator or study center with direct 
involvement in the proposed study, or identified as an immediate family member (ie, 
parent, spouse, natural or adopted child) of the Investigator or employee with direct 
involvement in the proposed study. 
If the participant has a primary physician who is not the Investigator, the site should contact this 
physician with the participant’s consent to inform him / her of the participant’s participation in the 
study. In addition, the site should ask this primary physician to verify exclusion criteria relating to 
previous therapies, such as receipt of blood products or previous vaccines. 
5.3 
Lifestyle Considerations 
No other restrictions than the ones listed in the exclusion criteria or in the contraindications for 
subsequent vaccinations are required. 
5.4 
Screen Failures 
Screen failures are defined as participants who are contacted by the sites and agree to participate 
in the clinical study but are not subsequently randomly assigned to study intervention because 
they do not meet the criteria for participation in the study (eg, inclusion and/or exclusion criteria). 
Screening information is recorded in the source documents. 
Individuals who do not meet the criteria for participation in this study (screen failure) cannot be 
rescreened. 
6 
Study Intervention 
Study intervention is defined as any investigational intervention(s), marketed product(s), placebo, 
or medical device(s) intended to be administered to a study participant according to the study 
protocol. 
Note: routine vaccine administered outside of study protocol are not considered as study 
interventions. 
6.1 
Study Intervention(s) Administered 
Study interventions are described in Table 6.1. 
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Table 6.1: Identity of study intervention(s) 
Group Name 
Group 1 
SP0202-IIb 
Group 2 
SP0202-VI 
Group 3 
SP0202-VII 
Group 4 
Prevnar 13 
Group 5 
Pneumovax 23 
Intervention 
Name 
Pneumococca
l Conjugate
Vaccine
Pneumococcal 
Conjugate 
Vaccine 
Pneumococcal 
Conjugate 
Vaccine 
Pneumococcal 
13-valent
Conjugate
Vaccine
Pneumococcal 
Vaccine 
Polyvalent 
Use 
Experimental 
Experimental 
Experimental 
Active 
comparator 
Active 
comparator 
IMP and NIMP 
IMP 
IMP 
IMP 
IMP 
IMP 
Type 
Vaccine 
Vaccine 
Vaccine 
Vaccine 
Vaccine 
Dose 
Formulation 
Suspension 
for injection 
in a pre-filled 
syringe 
Suspension for 
injection in a 
pre-filled 
syringe 
Suspension for 
injection in a 
pre-filled 
syringe 
Suspension for 
injection in a 
pre-filled 
syringe  
Solution for 
injection in a 
pre-filled 
syringe 
Unit Dose 
Strength(s) 
 µg of 
polysaccharid
e from 
S. pneumonia
e serotypes 3,
4, 6A, 7F, 8,
9N, 9V, 10A,
11A, 12F, 14,
18C, 19A,
19F, 23F,
33F, and 
µg of
polysaccharid
e for serotype
6B;
individually
conjugated to
CRM197
protein
 µg of
polysaccharid
e from
pneumococca
l serotypes 1,
5, 15B and
22F
individually
conjugated to
TTxd carrier
protein
 µg of 
polysaccharide 
from 
S. pneumoniae
serotypes 4,
6A, 7F, 8, 9N,
9V, 10A, 11A,
12F, 14, 18C,
23F, 33F, and
 µg of
polysaccharide
for serotypes
3, 6B, 19A,
and 19F;
individually
conjugated to
CRM197
protein
 µg of
polysaccharide
from
pneumococcal
serotypes 1, 5,
15B, and 22F
individually
conjugated to
TTxd carrier
protein
 µg of 
polysaccharide 
from 
S. pneumoniae
serotypes 6A,
7F, 8, 9N,
10A, 11A,
12F, 14, 18C,
23F, 33F, and
 µg of
polysaccharide
for serotypes
3, 4, 6B, 9V,
19A, and 19F;
individually
conjugated to
CRM197
protein
 µg of
polysaccharide
from
pneumococcal
serotypes 1, 5,
15B, and 22F;
individually
conjugated to
TTxd Carrier
protein
2.2 µg of 
polysaccharide 
from 
S. pneumoniae
serotypes 1, 3,
4, 5, 6A, 7F,
9V, 14, 18C,
19A, 19F, 23F
and 4.4 µg of
polysaccharide
for serotype
6B;
individually
conjugated to
CRM197
protein
25 µg of 
polysaccharide 
from 
S. pneumoniae
serotypes 1, 2,
3, 4, 5, 6B, 7F,
8, 9N, 9V,
10A, 11A, 12F,
14, 15B, 17F,
18C, 19A, 19F,
20, 22F, 23F
and 33F
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Excipients / 
Diluent 
Succinic acid, 
NaCl, 
Polysorbate 80
, aluminum 
(0.125 mg) 
and water for 
injection 
NaCl, Phenol 
and water for 
injection 
Dosage Level 
0.5 mL per dose 
Number of doses 
/ Dosing Interval 
1 dose 
Route of 
Administration 
IM injection 
Site of 
Administration 
Deltoid muscle in the upper arm 
Injection Site 
Side 
On the arm opposite to blood sample 
Sourcing 
Provided by the Sponsor 
Packaging and 
Labeling 
Each study intervention will be provided in an individual box. All will be labeled as 
required per country requirement. 
Current/Former 
Name(s) or 
Alias(es) 
Not 
applicable 
Not applicable 
Not applicable 
Prevnar 13® 
Pneumovax®2
3 
Batch Number 
TBD 
TBD 
TBD 
TBD 
TBD 
IMP: Investigational Medicinal Product; NIMP: Non-Investigational Medicinal Product; CRM197: Cross-Reacting 
material 197; TBD: To be determined 
6.2 
Preparation/Handling/Storage/Accountability 
Detailed guidance and information are provided in the Operating Guidelines. 
1) The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention. 
2) Only participants enrolled in the study may receive study intervention and only authorized 
site staff may supply or administer study intervention. All study intervention must be stored 
in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized site staff. 
3) The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (ie, 
receipt, reconciliation, and final disposition records). 
4) Further guidance and information for the final disposition of unused study interventions are 
provided in the Operating Guidelines. 
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5) Prior to administration, all study products must be inspected visually for cracks, broken seals, 
correct label content, and extraneous particulate matter and / or discoloration, whenever 
solution or container permit. If one of these conditions exists, the vaccine must not be 
administered, a replacement dose is to be used, and the event is to be reported to the Sponsor. 
6) Since some study intervention are a suspension containing an adjuvant, it has to be shaken 
vigorously prior use to obtain a homogenous suspension. Do not use the study intervention if 
it cannot be resuspended. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1 
Randomization and Allocation Procedures 
This study will be a randomized, modified double-blind study for 5 vaccine groups. 
On the day of enrollment, participant who meet the inclusion/exclusion criteria and sign the 
informed consent form (ICF) will be randomly assigned to Groups 1 through 5 in a 1:1:1:1:1 ratio, 
stratified according to sites and age group such that each group will have approximately 150 
participants (around 75 participants aged 50 to 64 years and around 75 participants aged 65 to 84 
years). 
The unblinded vaccinator or delegate will connect to the IRT, enter the identification and security 
information, and confirm a minimal amount of data in response to IRT prompts. The IRT will 
then provide the group assignment and have the site staff confirm it. The full detailed procedures 
for group allocation are described in the Operating Guidelines. If the participant is not eligible to 
participate in the study, then the information will only be recorded on the participant recruitment 
log. 
Participant numbers that are assigned by the IRT will consist of a 12-digit string (a 3-digit country 
identifier, a 4-digit study center identifier, and a 5-digit participant identifier). The first digit of the 
participant identifier will be “1” for participants aged 50 to 64 years and “2” for participants aged 
65 to 84 years. For example, Participant 840000210005 is the fifth participant aged 50 to 64 years 
enrolled in Center Number 2 in the US (840 being the US code country). 
Participant numbers should not be reassigned for any reason. The randomization codes will be 
kept securely in the IRT and an internal system. 
6.3.2 
Blinding and Code-breaking Procedures 
The study will be performed in a modified double-blind fashion: 
• The unblinded qualified trial staff member, independent of the immunogenicity and safety 
evaluations and other trial evaluations will administer the study intervention. 
• The Investigators (or delegates) in charge of safety assessment, the trial staff who collect the 
safety data, and the laboratory personnel who analyze the blood samples will be blinded and 
not know which product was administered. 
• 
The participant will not know which product was administered. 
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• Only the study staff who prepare and administer the vaccine and are not involved with the 
safety evaluation will know which vaccine is administered 
The Investigator responsible for safety assessment will not attend the vaccination session but will 
be available in case of emergency (anaphylactic shock). 
Treatment numbers will be used to identify each vaccine syringe for the purpose of 
randomization, vaccination and the recording of the study intervention administered. Treatment 
numbers will be randomly assigned to study interventions syringes. The IRT vendor will be 
responsible for assigning the treatment group identification and treatment number to be received 
by the enrolled participant. The participant, the Investigator, and the study staff members who 
collect the safety data and laboratory personnel who analyze the blood samples will all be blinded 
to the group assignment. The individual responsible for preparing / administering study 
intervention will not be authorized to collect any safety / serology data. 
The code may be broken in the event of an AE only when the identification of the vaccine 
received could influence the treatment of the participant. Code-breaking should be limited to the 
participant(s) experiencing the AE. 
The blind can be broken by the Investigator or a delegate through the IRT system, as explained in 
the code-breaking procedures described in the Operating Guidelines. Once the emergency has 
been addressed by the site, the Investigator or a delegate must notify the Sanofi Pasteur 
Responsible Medical Officer (RMO) if a participant’s code was broken. All contact attempts with 
the Sponsor prior to unblinding are to be documented in the source documents, and the code-
breaking case report form (CRF) is to be completed. 
The Independent Ethics Committees (IEC) / Institutional Review Boards (IRB) must be notified 
of the code-breaking, in accordance with local regulations. All documentation pertaining to the 
event must be retained in the site’s study records and in the Sanofi Pasteur files. Any intentional 
or unintentional code-breaking must be reported, documented, and explained, and the name of the 
person who requested it must be provided to the Sponsor. 
A request for the code to be broken may also be made: 
• by the Global Pharmacovigilance (GPV) Department through an internal system for 
reporting to Health Authorities in the case of an unexpected SAE considered causally 
related as described in International Council for Harmonization (ICH) E2A. In this case, 
the code will be broken only for the participant(s) in question. The information resulting 
from code-breaking (ie, the participant’s vaccine or group assignment) will not be 
communicated to either the Investigator or the immediate team working on the study, 
except for the GPV representative. 
A first statistical analysis of the safety and immunogenicity data obtained up to 30 days after 
vaccination (V02) will be conducted once data are available and an interim database lock has been 
conducted. The blind of participants will be broken for the analysis, but the randomization list will 
not be provided to Investigators until completion of the 6-month safety follow-up and will be kept 
internally. A final analysis will be conducted once the 6-month safety data has been collected and 
the final database lock has occurred. If the V01-V02 immunogenicity data release is planned at 
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the time or after the 6-month follow-up data availability, only one final database lock and one 
analysis including all data may be conducted. 
The DMC will conduct an unblinded review of the safety data when at least 150 participants have 
been vaccinated and have safety data up to D31 (30 days after injection) available. The DMC will 
also conduct another unblinded review of the safety data collected on all participants up to D31. 
An unblinded external independent statistician will share the unblinded safety data with the DMC 
members. The information will not be communicated to either the Investigator or the Sponsor 
study team before the end of the trial and database lock. 
If during the internal SMT/DMC review a further in-depth review of the data and partial or full 
unblinding is required by the Sponsor, it will be done by an independent statistician and 
communicated to the Sponsor. 
The code-breaking procedures are described in the Operating Guidelines and in the DMC charter. 
6.4 
Study Intervention Compliance 
The following measures will ensure that the study intervention is administered as planned (see 
Table 6.1), and that any noncompliance is documented so that it can be accounted for in the data 
analyses: 
• All vaccinations will be administered by qualified and trained study personnel 
• The person in charge of study intervention management at the site will maintain 
accountability records of study intervention delivery to the study site, study intervention 
inventory at the site, dose given to each participant, and unused or wasted doses 
6.5 
Concomitant Therapy 
At the time of enrollment, ongoing medications and other therapies (eg, blood products) should be 
recorded in the source documenta as well as new medications prescribed for new medical 
conditions / AEs during study participation. 
Documentation in the CRF of ongoing concomitant medication(s) will be limited to specific 
categories of medication(s) of interest beginning on the day of first vaccination. This may include 
medications of interest that were started prior to the day of vaccination. 
Reportable medications will be collected in the CRF from the day of vaccination (D01) to the end 
of the solicited and unsolicited follow-up period (D31 + 14 days). 
Reportable medications include medications that impact or may impact the consistency of the safety 
information collected after any vaccination and/or the immune response to vaccination. Three standard 
categories of reportable medications are defined: 
                                                 
a Participant will be required to document in the DC all medications received. 
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• Category 1: medications impacting or that may have an impact on the evaluation of the 
safety (eg, antipyretics, analgesics, and non-steroidal anti-inflammatory drugs [NSAIDs], 
systemic steroids/corticosteroids [therapy duration for less than 2 consecutive weeks]) 
• Category 2: medications impacting or that may have an impact on the immune response 
(eg, other vaccines [including influenza vaccine in the 2 weeks [14 days] preceding or 
following any IM vaccination], blood products, antibiotic classes taken within 3 day [72 
hours] prior to blood draw that may interfere with bioassays used by the Global Clinical 
Immunology [GCI] department or other testing laboratories, immune-suppressors, 
immune-modulators with immunosuppressive properties, anti-proliferative drugs such as 
DNA synthesis inhibitors, immune globulins in the 3 months preceding vaccination) 
• Category 3: medications impacting or that may have an impact on both the safety and the 
immune response (eg, long-term systemic corticosteroids therapy [prednisone or 
equivalent for more than 2 consecutive weeks]) 
The information reported in the CRF for each reported medication will be limited to: 
• Trade name for a medication composed of several molecules OR international nonproprietary 
name (INN) for a medication composed of one single molecule 
• Origin of prescription: prophylaxis Yes/No. Medication(s) prescribed for AE prophylaxisa will 
be recorded in the Action Taken of the AE collection tables. 
• Medication category (1, 2, or 3) 
• Start and stop dates 
Dosage and administration route, homeopathic medication, topical steroids (inhaled, otic, 
ophthalmic, nasal etc.) treatments will not be recorded. Topical analgesics should not be applied at 
the site of vaccination; however, if they are applied inadvertently to the vaccination site, they should 
be recorded as a Category 1 medication in this specific instance. 
Medications given in response to an AE will be captured in the “Action Taken” section of the AE 
CRF only. No details will be recorded in the concomitant medication CRF unless the medication(s) 
received belongs to one of the pre-listed categories. Medications will not be coded. 
6.5.1 
Rescue Medicine 
Appropriate medical equipment and emergency medications, including epinephrine (1:1000), 
must be available on site in the event of an anaphylactic, vasovagal, or other immediate allergic 
reaction. 
6.6 
Dose Modification 
Not applicable. 
                                                 
a Medication(s) prescribed for preventing AE occurrence (eg, paracetamol to reduce the risk of fever). 
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7 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal 
7.1 
Discontinuation of Study Intervention 
7.1.1 
Temporary contraindications 
The following is a temporary contraindication to blood draw BL0002 at Visit 2: 
1) Receipt of oral or injectable antibiotic therapy within 72 hours prior to blood draw. 
Note: If a participant receives oral or injectable antibiotic therapy within 3 days prior to the blood 
draw, the Investigator will postpone that blood draw until it has been 3 days since the participant 
last received oral or injectable antibiotic therapy. Postponement must still be within the timeframe 
for blood draw. If postponement would result in the sample collection falling outside this 
timeframe, the blood sample should be collected without postponement, and it should be 
documented appropriately (in source document and CRF) that the sample was taken less than 
3 days after stopping antibiotic treatment. 
7.2 
Participant Discontinuation/Withdrawal from the Study 
• 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. This is expected to be uncommon. 
• 
The reason for withdrawal should be clearly documented in the source documents and in 
the CRF: Adverse Event, Lost to Follow-up, Protocol Deviation, or Withdrawal by 
participant. 
• 
The participant will be permanently discontinued both from the study intervention and 
from the study at that time. 
• 
If the participant withdraws consent for disclosure of future information, the Sponsor 
may retain and continue to use any data collected before such a withdrawal of consent. 
• 
If a participant withdraws consent, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records. 
• 
Withdrawn participants will not be replaced. 
Follow-up of Discontinuations 
For participants who have prematurely terminated the study, the site should attempt to contact 
them and complete all scheduled safety follow-ups, except if they specified that they do not want 
to be contacted again and it is documented in the source document. 
For participants where the reason for early termination is lost to follow-up, the site will not 
attempt to obtain further safety information. See Section 7.3 for definition of “lost to follow-up”. 
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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 is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the site for a required study 
visit or cannot be contacted as planned in the SoA: 
• 
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant 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 (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods), or at least to determine his/her health status while fully respecting 
his/her rights. These contact attempts should be documented in the participant’s medical 
record. 
• 
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 10.1. 
8 
Study Assessments and Procedures 
• 
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed. 
• 
Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study intervention. 
• 
Adherence to the study design requirements, including those specified in the SoA, 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 
screening failure, as applicable. 
Blood samples will be collected as described in the SoA table (Section 1.3). 
The maximum amount of blood collected from each participant over the duration of the study, 
including any extra assessments that may be required, will not exceed 40 mL. Repeat or 
unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
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Guidance and information for the sample collection, preparation, storage, and shipment are 
provided in the Operating Guidelines. 
8.1 
Efficacy and Immunogenicity Assessments 
8.1.1 
Efficacy Assessments 
No clinical efficacy data will be obtained in the study. 
8.1.2 
Immunogenicity Assessments 
Multiplexed opsonophagocytic killing assay (MOPA) 
This method will be performed on BL0001 and BL0002 collected on D01 and D31 respectively. 
Assays will be performed by PPD (a CRO laboratory), Richmond (VA), USA. 
Pneumococcal capsular polysaccharide – electro-chemiluminescent assay (PnPS-ECL) 
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This method will be performed on BL0001 and BL0002 collected on D01 and D31 respectively. 
Assays will be performed by Sanofi Pasteur Global Clinical Immunology (GCI), Swiftwater (PA), 
USA. 
8.2 
Safety Assessments 
This section presents safety assessments other than adverse events which are presented in 
Section 8.3. 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1 
Medical History 
Prior to enrollment, participants will be assessed for pre-existing conditions and illnesses, both 
past and ongoing. Any such conditions will be documented in the source document. Significant 
(clinically relevant) medical history (reported as diagnosis) including conditions/illnesses for 
which the participant is or has been followed by a physician or conditions/illnesses that could 
resume during the course of the study or lead to an SAE or to a repetitive outpatient care will be 
collected in the CRF. 
8.2.2 
Physical Examinations 
At Visit 1, the Investigator or a delegate will perform a physical examination based on medical 
history and including evaluation of the following body systems: general appearance, skin, head, 
eyes, ears, nose, throat, heart, lungs abdomen, musculoskeletal, extremities, neurological and 
lymph nodes examination. A targeted physical examination may also be performed at Visit 2, as 
necessary. Information will be recorded in the source document. 
Temperature measurement will be done during the physical examination before vaccination and 
recorded in the source document. 
8.2.3 
Vital Signs 
Axillary pre-vaccination temperature will be systematically collected by the investigator on the 
source document. Tympanic, skin, and temporal artery thermometers must not be used. 
8.2.4 
Clinical Safety Laboratory Assessments 
Urine pregnancy testing will be performed in women of childbearing potential before vaccination. 
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8.3 
Adverse Events and Serious Adverse Events 
The definitions of an AE, SAE, and the different categories of AEs can be found in 
Appendix 10.3. 
AEs will be reported by the participants to the investigator, then by the investigator to the 
Sponsor. 
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 for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the participant to discontinue the study (see Section 7). 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information 
Immediate Post-vaccination Observation Period 
Participants will be kept under observation for 30 minutes after vaccination to ensure their safety. 
The post-vaccination observation should be documented in the source document and immediate 
events will be recorded at D01 in the eCRF. 
Reactogenicity 
Solicited injection site reactions will be collected from D01 to D08 after vaccination. 
Solicited systemic reactions will be collected from D01 to D08 after vaccination. 
The solicited injection site reactions and systemic reactions that are pre-listed in the diary cards 
and CRF, together with the intensity scales, are presented in Appendix 10.3.5.1.1. 
Unsolicited Non-serious Adverse Events 
Unsolicited non-serious adverse events will be collected from D01 to D31 after vaccination. 
The intensity grading scale for unsolicited non-serious adverse events is presented in 
Appendix 10.3.5.1.2. 
Adverse Events of Special Interest (AESIs) 
AESIs will be collected throughout the study period, from D01 until 6 months after vaccination. 
See Section 8.3.6 for the list of AESIs. 
SAEs 
Information on SAEs will be collected and assessed throughout the study, from D01 until 6 
months after vaccination. 
Medical occurrences that begin before the start of study intervention but after obtaining informed 
consent will not be recorded on the AE section of the CRF. 
All SAEs will be recorded and reported to the Sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 10.3. The investigator will 
submit any updated SAE data to the Sponsor within 24 hours of it being available. 
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Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time after a 
participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study intervention or study participation, the investigator must promptly notify the 
Sponsor. 
8.3.2 
Method of Detecting AEs and SAEs 
Individual diary cards, specifically designed for this study by the Sponsor and provided to the 
study sites, will be given to study participants for the recording of daily safety information. These 
diary cards will include pre-listed terms and intensity scales as well as areas for free text to 
capture additional safety information or other relevant details. Participants will also be provided 
with rulers for measuring the size of injection site reactions, and with standard digital 
thermometers for measuring daily temperatures. To ensure consistency of reporting, the study 
sites will instruct participants on how to correctly use these tools. 
At specified intervals, the Investigator or an authorized designee will interview the participants to 
collect the information recorded in the diary card, and will attempt to clarify anything that is 
incomplete or unclear. All clinical study information gathered by the study site will be reported 
electronically by the Investigator or authorized designee using a web-based CRF. Any information 
that was not documented in the diary card will first be captured in the source document and then 
reported electronically. 
The 6-month follow-up will be done by interviewing participants over the telephone using a 
questionnaire to capture SAEs and AESIs, if applicable. 
The method of recording, evaluating, and assessing causal relationship of AE and SAE and the 
procedures for completing and transmitting SAE reports are provided in Appendix 10.3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.3.3 
Follow-up of AEs and SAEs 
Unless a participant refuses further contact, each participant who experiences an AE (whether 
serious or non-serious) during the study must be followed until the condition resolves, becomes 
stable, or becomes chronic (even after the end of the participant’s participation in the study) if 
either of the following is true: 
• The AE is considered by the Investigator to be related to the study intervention administered 
• The AE caused the discontinuation of the participant from the study or from vaccination 
The Investigator will inform the Sponsor of the date of final disappearance of the event or the date 
of “chronicity” establishment. 
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8.3.4 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the Sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards 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/IEC, and investigators. 
• 
For all studies except those investigating medical devices investigator safety reports must 
be prepared for suspected unexpected serious adverse reactions (SUSAR) according to 
local regulatory requirements and Sponsor policy and forwarded to investigators as 
necessary. 
• 
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (eg, summary or listing of SAEs) from the Sponsor will 
review and then file it and will notify the IRB/IEC, if appropriate according to local 
requirements. 
8.3.5 
Pregnancy 
Pregnancy is an exclusion criterion for enrollment in this study, but a participant could potentially 
become pregnant during her participation. 
• 
Details of all pregnancies in female participants will be collected after the start of study 
intervention and until delivery by the investigator and recorded in the Pregnancy CRF. 
Any data collected after CRF lock will be transmitted to the pharmacovigilance 
department on the paper form. 
• 
If a pregnancy is reported, the investigator should inform the Sponsor within 1 month of 
learning of the pregnancy and should follow the procedures outlined in Appendix 10.4. 
• 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6 
Adverse Events of Special Interest 
An AESI is an event for which ongoing monitoring and rapid communication by the Investigator 
to the Sponsor must be done. AESI will be collected throughout the study. AESI include the 
following: 
• Anaphylaxis defined as per the Brighton collaboration case definition (28). 
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8.4 
Treatment of Overdose 
Since the study intervention is administered by a health care professional, it is unlikely that 
overdose by injection occurs. 
However, in the event of an overdose, the Investigator should: 
1) Contact the Medical Monitor immediately. 
2) Closely monitor the participant for any AE/SAE. 
3) Document the quantity of the excess of the overdose in the source documents. 
8.5 
Pharmacokinetics 
Pharmacokinetics parameters are not evaluated in this study. 
8.6 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.7 
Genetics 
Genetics are not evaluated in this study. 
8.8 
Biomarkers 
No other biomarkers than those described in the immunogenicity assessments section 
(Section 8.1.2) are evaluated in this study. 
8.9 
Immunogenicity Assessments 
See Section 8.1.2. 
8.10 Medical Resource Utilization and Health Economics 
Medical Resource Utilization and Health Economics parameters are not evaluated in this study. 
9 
Statistical Considerations 
9.1 
Statistical Hypotheses 
No hypotheses will be tested. The analyses will be descriptive. 
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9.2 
Sample Size Determination 
There are no statistically powered hypotheses in this study thus no formal sample size 
computation. The number of participants is judged sufficient to provide useful immunogenicity 
and safety data on the 3 SP0202 formulations, Prevnar 13 and Pneumovax 23. 
The sample size was set to approximatively 150 participants per vaccine group and 
approximatively 75 by age group. Assuming a drop-out rate of approximatively 15%, a total of 
128 participants by vaccine group (Per Protocol Analysis Set [PPAS]) are expected. 
The expected precision of estimation for quantitative data is as follows (PPAS) - the maximum 
distance from the log10 mean to the limits of 95% CI is equal to 0.173 for single mean and 0.246 
for difference in means of two groups (when the standard deviation is 1). 
 
Standard 
deviation 
N 
evaluable 
Distance between 
log10 mean and 
95%CI limits for 
a single mean 
Distance between 2 
groups difference in 
log10 means and 
95%CI limits 
Distance between 
GMT and 
95%CI limits for 
a single mean 
Distance from 
GMT ratio 
between 2 groups 
to 95%CI upper 
limit 
0.5 
128 
0.087 
0.123 
1.22 
1.33 
0.6 
128 
0.104 
0.148 
1.27 
1.41 
0.7 
128 
0.121 
0.172     
1.32 
1.49 
0.8 
128 
0.139 
0.197     
1.38 
1.57 
0.9 
128 
0.156 
0.222     
1.43 
1.67 
1 
128 
0.173 
0.246     
1.49 
1.76 
9.3 
Populations for Analyses 
The following populations are defined: 
Population 
Description 
Randomized 
All participants with data in the CRF 
Safety Analysis Set (SafAS) 
Participants who have received the study vaccine. All participants will 
have their safety analyzed according to the vaccine they actually 
received. 
Safety data recorded for a vaccine received out of the protocol design 
will be excluded from the analysis (and listed separately). 
Full analysis set (FAS) 
Subset of randomized participants who received at least 1 dose of the 
study vaccine and had a valid post-vaccination blood sample result. 
Participants will be analyzed according to the intervention to which they 
were randomized. 
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Per-protocol analysis set 
(PPAS) 
Subset of the FAS. Participants presenting with at least one of the 
following relevant protocol deviations will be excluded from the PPAS: 
• 
Participant did not meet all protocol-specified inclusion criteria or 
met at least one of the protocol-specified exclusion criteria  
• 
Participant did not receive vaccine 
• 
Participant received a vaccine other than the one that he / she was 
randomized to receive 
• 
Preparation and / or administration of vaccine was not done as per-
protocol 
• 
Participant did not provide the post-dose serology sample at V2 in 
the proper time window or a post-dose serology sample was not 
drawn 
• 
Participant received a protocol-prohibited therapy / medication / 
vaccine) 
In addition to the reasons listed above, participants will also be 
excluded from the PPAS if their Visit 02 / post-vaccination serology 
sample did not produce a valid test result (ie, results for all antigens are 
missing). 
In the event of a local or national immunization program with a 
pandemic influenza vaccine, participants who receive 1 or more doses 
of a pandemic influenza vaccine at any time during the study will not be 
withdrawn from the study. 
9.4 
Statistical Analyses 
The statistical analysis plan (SAP) will be finalized prior to database lock and it will include a 
more technical and detailed description of the statistical analyses described in this section. This 
section is a summary of the planned statistical analyses of the most important endpoints. 
9.4.1 
General Considerations 
All analyses will be descriptive. 
For immunogenicity data, assuming that log10 transformation of the titers / concentrations and 
titers / concentrations ratio follows a normal distribution, first, the mean and 95% confidence 
intervals (CIs) will be calculated on log10 (titers / concentrations; titers / concentrations ratio) 
using the usual calculation for normal distribution, then antilog transformations will be applied to 
the results of calculations, to compute geometric mean titers / concentrations (GMTs / GMCs) and 
geometric mean of the individual titer / concentration ratios (GMTRs / GMCRs) and their 
95% CIs. 
The 95% CIs of ratio of GMTs / GMCs between 2 groups will be computed from the difference of 
log 10 transformed means of titers/concentrations using normal approximation. 
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The 95% CIs of point estimates will be calculated using the exact binomial distribution 
(Clopper-Pearson method (29)) for proportions. 
Generally, no replacement of missing data will be done. 
9.4.2 
Safety Analyses 
Safety analyses will be performed on the SafAS and presented by group and by age group for 
summary tables (main endpoints). The main parameters will be described with 95% CI. At least 
number and percentages of participants will be presented after vaccine injection reporting any: 
• Immediate unsolicited systemic AEs 
• Solicited injection site reactions and solicited systemic reactions occurring within 7 days after 
the day of injection (D1 to D8) according to presence, time of onset, intensity (Grade 1, Grade 
2, or Grade 3), number of days of presence and action taken 
• Unsolicited AEs occurring within 30 days after injection by system organ class (SOC) and 
preferred term (PT), relationship, intensity, time of onset, and duration 
• All SAEs occurring throughout the study by SOC and PT, relationship and seriousness criteria 
• All AESIs occurring throughout the study by SOC and PT and relationship 
No replacement of missing data will be done. Nevertheless, missing relationship will be 
considered as related at the time of statistical analysis. 
9.4.3 
Immunogenicity Analyses 
All immunogenicity analyses will be performed on the PPAS and presented by group and age 
group. Additional immunogenicity analyses will be performed on the FAS. 
The point estimates and their 95% CI of at least the following parameters will be presented before 
and 1-month post-vaccination for each pneumococcal serotype specific OPA titers and IgG 
concentrations: 
• GMT/GMC of serotype specific titers/concentrations 
• 
GM of titers/ concentrations ratio (post- / pre-vaccination) 
Differences in terms of ratio of GMTs/GMCs between 2 groups (ie, any SP0202 formulations and 
Prevnar 13 or Pneumovax 23) post-vaccination will be presented. 
Reverse cumulative distribution curves (RCDCs) of individual concentrations/titers will be 
presented for all serotypes at pre and post-vaccination. 
Missing data will not be imputed. No test or search for outliers will be performed. 
For the calculation of GMTs / GMCs and percentage above cut-offs, any pre-vaccination or 
post-vaccination value reported as < LLOQ will be converted to a value of 0.5 LLOQ. 
For the calculation of GMTR / GMCR, any pre-vaccination value reported as < LLOQ will be 
converted to LLOQ, and any post-vaccination value reported as < LLOQ will be converted to a 
titer of 0.5 LLOQ when only either the numerator or the denominator is < LLOQ. If both 
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numerator and denominator are < LLOQ, then both will be converted in the same way so that the 
increase is defined as 1. 
Any value reported as > ULOQ (upper limit of quantitation) will be converted to ULOQ. 
9.4.4 
Other Analyses 
Any further analyses will be described in the SAP. 
9.5 
Interim Analyses 
This study will not include an early safety data review. However, participant safety will be 
continuously monitored by the Sponsor’s internal safety review committee (SMT) which includes 
safety signal detection at any time during the study. The analyses for SMT will be blinded and 
descriptive therefore no statistical adjustment is necessary. 
A DMC will review continuously related AESIs and related SAEs up the 6-month follow-up. In 
addition, a first DMC safety analysis on data collected on at least 150 participants up to D31 
(30 days after injection) will be conducted in an unblinded manner by an external independent 
statistician to Sanofi and won’t be communicated to the Sponsor. The DMC will also review the 
unblinded safety data collected up to D31 on all participants. The analyses for this scope will be 
descriptive so no statistical adjustment is necessary. 
A statistical analysis of the safety and immunogenicity objectives up to V02 (Day 31) will be 
conducted once data on all participants are available and an interim database lock has been 
conducted. The blind will be broken for the analysis and kept at the Sponsor level until the 6-
month follow-up completion. No statistical adjustment is necessary because no hypotheses will be 
tested. A final analysis will be conducted once the 6-month safety data has been collected and the 
final database lock has occurred. 
If the V01-V02 immunogenicity data release is planned at the time or after the 6-month safety 
data availability, only one database lock and one analysis including all data may be conducted. 
The SAP will describe the planned analyses in greater detail. 
9.6 
Data Monitoring Committee (DMC) 
A DMC has been implemented to oversee the safety data of the SP0202 clinical program and will 
be utilized throughout this study. The committee will assess the safety data in an unblinded 
manner. This includes the related AESIs and related SAEs review on ongoing basis, as well as 
safety profile of each SP0202 formulation prior to database lock. 
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10 Supporting Documentation and Operational Considerations 
10.1 Appendix: Regulatory, Ethical, and Study Oversight Considerations 
Note: The term “participant” is used throughout this protocol. However, the term “subject” will be 
used in the CRF in order to comply with the Clinical Data Interchange Standards Consortium 
(CDISC) requirements. 
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 Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines 
• 
Applicable ICH Good Clinical Practice (GCP) Guidelines 
• 
Applicable laws and regulations (eg, data protection law as General Data Protection 
Regulation [GDPR]) 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, 
advertisements) must be submitted to an IRB/IEC by the Investigator or the Sponsor 
(according to local regulations) and reviewed and approved by the IRB/IEC before the study is 
initiated 
• Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, 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/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
• 
Determining whether an incidental finding (as per Sanofi policy) should be returned to a 
participant and, if it meets the appropriate criteria, to ensure the finding is returned (an 
incidental finding is a previously undiagnosed medical condition that is discovered 
unintentionally and is unrelated to the aims of the study for which the tests are being 
performed). The following should be considered when determining the return of an 
incidental finding: 
• The return of such information to the study participant (and/or his/her designated 
healthcare professional, if so designated by the participant) is consistent with all 
applicable national, state, or regional laws and regulations in the country where the 
study is being conducted, and 
• The finding reveals a substantial risk of a serious health condition or has 
reproductive importance, AND has analytical validity, AND has clinical validity. 
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• The participant in a clinical study has the right to opt out of being notified by the 
Investigator of such incidental findings. In the event that the participant has opted 
out of being notified and the finding has consequences for other individuals, eg, the 
finding relates to a communicable disease, Investigators should seek independent 
ethical advice before determining next steps. 
• In case the participant has decided to opt out, the Investigator must record in the 
site medical files that she/he does not want to know about such findings. 
• 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• 
Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical 
studies (if applicable), and all other applicable local regulations 
10.1.2 Financial Disclosure 
Information related to financial disclosure is described in the Investigator’s contract. 
10.1.3 Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to the participant 
or his/her legally authorized representative and answer all questions regarding the study. 
• Participants must be informed that their participation is voluntary. Participants will be required 
to sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center. 
• The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF. 
• The actual ICF used at each center may differ, depending on local regulations and IEC / IRB 
requirements. However, all versions must contain the standard information found in the 
sample ICF provided by the Sponsor. Any change to the content of the ICF must be approved 
by the Sponsor and the IEC / IRB prior to the form being used. 
• If new information becomes available that may be relevant to the participant’s willingness to 
continue participation in the study, this will be communicated to him / her in a timely manner. 
Such information will be provided via a revised ICF or an addendum to the original ICF. 
• Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the participant or the participant’s legally authorized 
representative. 
The ICF will contain a specific section that addresses the use of remaining mandatory samples for 
optional exploratory research. The investigator or authorized designee will explain to each 
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participant the objectives of the exploratory research. Participants will be told that they are free to 
refuse to participate and may withdraw their consent at any time and for any reason during the 
storage period. 
Recruitment Procedures 
Before the start of the trial, the Investigator or a sub-investigator will contact an appropriate pool 
of potential participants and invite them to participate in the study. The site will ensure that any 
advertisements used to recruit participants (eg, letters, pamphlets, posters) are submitted to Sanofi 
Pasteur prior to submission to the IEC / IRB for approval. 
10.1.4 Data Protection and Future Use of Stored Samples 
• All personal data collected related to participants, Investigators, or any person involved in the 
study, which may be included in the Sponsor’s databases, shall be treated in compliance with 
all applicable laws and regulations including the GDPR. Data collected must be adequate, 
relevant and not excessive, in relation to the purposes for which they are collected. Each 
category of data must be properly justified and in line with the study objective. 
• Participants race and ethnicity will be collected in this study because these data are required 
by regulatory agencies (eg, on African-American population for the Food and Drug 
Administration). 
• Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names 
or any information which would make the participant identifiable will not be transferred to the 
Sponsor. 
• The participant must be informed that his/her 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 as described in the informed consent. 
• The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
• When archiving or processing personal data pertaining to the Investigator and/or to the 
participants, the Sponsor shall take all appropriate measures to safeguard and prevent access to 
this data by any unauthorized third party. 
• Participant data will be used for this study and in support of the whole drug development 
program for the Investigational Product, including negotiations with payers and publication of 
results. 
• Any unused part of the serum samples will be securely stored by Sanofi Pasteur for up to 25 
years after the end of the study. These samples are being retained in long-term storage to 
support answers to regulatory questions related to the product’s licensure and the potential 
revalidation of the study results. 
The other biological samples collected to qualify the participant for inclusion in the study or to 
monitor his/her health are dedicated for immediate use. In case they are not completely used 
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up, they will be destroyed at the latest at the end of the study or after the time requested by 
local law. 
In addition, participants will be asked to indicate in the ICF whether they will permit the 
future use of any unused stored serum samples for other tests. If they refuse permission, the 
samples will not be used for any testing other than that directly related to this study. If they 
agree to this use, they will not be paid for giving permission. Anonymity of samples will be 
ensured. The aim of any possible future research is unknown today, and may not be related to 
this particular study. It may be to improve the knowledge of vaccines or infectious diseases, or 
to improve existing tests or develop new tests to assess vaccines. Human genetic tests will 
never be performed on these samples without specific individual informed consent. 
10.1.5 Committees Structure 
This study will not include an early safety data review. However, participant safety will be 
continuously monitored by the Sponsor. A blinded review will be performed by the Sponsor 
during the Safety Management Team (SMT) meeting which includes safety signal detection at any 
time during the study. Two unblinded reviews by a Data Monitoring Committee (DMC) will also 
be conducted. 
10.1.6 Dissemination of Clinical Study Data 
Sanofi shares information about clinical trials and results on publicly accessible websites, based 
on company commitments, international and local legal and regulatory requirements, and other 
clinical trial disclosure commitments established by pharmaceutical industry associations.  These 
websites include clinicaltrials.gov, EU clinical trial register (eu.ctr), and sanofi.com, as well as 
some national registries. 
In addition, results from clinical trials in patients are required to be submitted to peer-reviewed 
journals following internal company review for accuracy, fair balance, and intellectual property. 
For those journals that request sharing of the analyzable data sets that are reported in the 
publication, interested researchers are directed to submit their request to 
clinicalstudydatarequest.com. 
Individual participant data and supporting clinical documents are available for request at 
clinicalstudydatarequest.com. While making information available we continue to protect the 
privacy of participants in our clinical trials. Details on data sharing criteria and process for 
requesting access can be found at this web address: clinicalstudydatarequest.com. 
10.1.7 Data Quality Assurance 
• All participant data relating to the study will be recorded on 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. 
• The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
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• The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
• Monitoring details describing strategy (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, remote, or on-site monitoring) are provided in the Monitoring 
Plan. 
• The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
• The Sponsor assumes accountability for actions delegated to other individuals (eg, Contract 
Research Organizations). 
• 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 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
• Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 25 years after the signature of the final study report 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. 
10.1.8 Source Documents 
“Source data” are the data contained in source documents. Source documents are original 
documents or certified copies, and include, but are not limited to, diary cards, medical and 
hospital records, screening logs, informed consent / assent forms, telephone contact logs, and 
worksheets. 
• 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’s site. 
• Data entered in the CRF that are transcribed 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. 
Detailed guidance and information are provided in the Operating Guidelines. 
10.1.9 Study and Site Start and Closure 
Details on which clinical supplies are provided by the Sponsor or the site are described in the 
Operating Guidelines. 
The study start date is considered the date of the first visit planned in the SoA of the first 
participant. 
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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 either destroyed or returned to the Sponsor, all samples are shipped to the appropriate 
laboratories, the study-site has all the documents necessary for archiving and a study-site closure 
visit has been performed. A form will be submitted to IRB to close out the study once all site 
closeouts have been completed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or investigator may include but are not 
limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor's procedures, or 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 IECs/IRBs, the regulatory authorities, and any contract research organization(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. 
10.1.10 Publication Policy 
Information related to publication policy is described in the Investigator’s contract. 
10.2 Appendix: Clinical Laboratory Tests 
A urine human chorionic gonadotropin (hCG) pregnancy test (as needed for women of 
childbearing potential) will be performed before vaccination. 
10.3 Appendix: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
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10.3.1 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 signs measurements), including those 
that worsen from baseline, considered clinically significant in the medical and scientific 
judgment of the investigator (ie, not related to progression of underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
• New conditions 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/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae. 
 
Events NOT Meeting the AE Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be 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 pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
 
Other Definitions 
Adverse Reaction: 
All noxious and unintended responses to a study intervention related to any dose should be 
considered adverse reactions (AR). 
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(The phrase “responses to a study intervention” means that a causal relationship between a 
study intervention and an AE is at least a reasonable possibility) 
Immediate Event/Reaction: 
Immediate events are recorded to capture medically relevant unsolicited systemic AEs 
(including those related to the study intervention administered) that occur within the first 30 
minutes after vaccination. 
Injection Site Reaction: 
An injection site reaction is an AR at and around the injection site. Injection site reactions are 
commonly inflammatory reactions. They are considered to be related to the study intervention 
administered. 
Systemic AE/AR: 
Systemic AEs are all AEs that are not injection or administration site reactions. They therefore 
include systemic manifestations such as headache, fever, as well as localized or topical 
manifestations that are not associated with the vaccination or administration site (eg, erythema 
that is localized but that is not occurring at the injection site). 
Systemic AEs assessed as related to study intervention are referred as systemic ARs. 
Adverse Event of Special Interest (AESI): 
An adverse event of special interest (serious or non-serious) is one of scientific and medical 
concern specific to the Sponsor’s study intervention or program, for which ongoing monitoring 
and rapid communication by the investigator to the Sponsor can be appropriate. Such an event 
might warrant further investigation in order to characterize and understand it. Depending on the 
nature of the event, rapid communication by the study Sponsor to other parties (eg, regulators) 
might also be warranted. 
Reactogenicity / Solicited Reactions 
A solicited reaction is an “expected” adverse reaction (sign or symptom) observed and reported 
under the conditions (nature and onset) pre-listed in the protocol and CRF (eg, injection site 
pain or headache occurring between the day of vaccination and the next 7 days). 
By definition, solicited reactions are considered as being related to the study intervention 
administered. 
For injectable vaccines, solicited reactions can either be solicited injection site reactions or 
solicited systemic reactions. 
Unsolicited AE/AR 
An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions, 
ie, pre-listed in the CRF in terms of diagnosis and/or onset window post-vaccination. For 
example, varicella or a solicited term such as headache starting after the solicited observation 
period (headache starting on Day 10 post-vaccination in the case where headache occurring 
between the day of vaccination and the next 7 days is pre-listed in the protocol and CRF as a 
solicited reaction). 
An unsolicited AR is an unsolicited AE that is considered related to study intervention. 
Unsolicited AEs includes both serious (SAEs) and non-serious unsolicited AEs. 
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10.3.2 Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
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, which 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 detained (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. 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent 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) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Other important medical event 
• Medical or scientific judgment should be exercised in deciding whether expedited reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
health of the participant or may require intervention to prevent one of the other outcomes 
listed in the above definition. These important medical events should also usually be 
considered serious. 
• 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, 
or development of drug dependency or drug abuse, new-onset diabetes or autoimmune 
disease. 
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Note: Serious and severe are not synonymous. The term severe is often used to describe the 
intensity of a specific event as corresponding to Grade 3. This is not the same as serious, which is 
based on participant / event outcome or action criteria usually associated with events that pose a 
threat to a participant’s life or functioning. 
10.3.3 Recording and Follow-Up of AE and/or SAE 
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics 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 the Sponsor in lieu of completion of the CRF pages. 
• There may be instances when copies of medical records for certain cases are requested by 
the Sponsor. 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 the 
Sponsor. 
• 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 Causal Relationship 
By convention, all AEs reported at the injection site (whether solicited or unsolicited) and all 
solicited systemic AEs are considered to be related to the study intervention (see definition in 
Section 6 and therefore are referred to as reactions and do not require the Investigator’s opinion 
on relatedness. 
• Causal relationship of unsolicited systemic AEs and SAEs will be recorded as follows: 
• 
For non-serious unsolicited systemic AEs (except for non-serious AESIs), relationship 
to study intervention will usually be assessed by the Investigator only.  
• 
For SAEs and non-serious AESIs, relationship to study intervention will be assessed 
by both the Investigator and the Sponsor. Sponsor assessment is entered in the GPV 
database only.  
• 
For SAEs only, the causal relationship to study procedures (related/not related to study 
procedures) will be assessed by both the Investigator and the Sponsor. Sponsor 
assessment is entered in the GPV database only. 
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• The Investigator will assess the causal relationship between each unsolicited systemic AE 
and the study intervention administereda as either not related or related, based on the 
following definitions: 
• 
Not related – The AE is clearly / most probably caused by other etiologies such as an 
underlying condition, therapeutic intervention, or concomitant therapy; or the delay 
between vaccination and the onset of the AE is incompatible with a causal relationship; 
or the AE started before the vaccination 
• 
Related – There is a “reasonable possibility” that the AE was caused by the study 
intervention administered, meaning that there is evidence or arguments to suggest a 
causal relationship 
• The investigator will use clinical judgment to determine the relationship. 
• 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/SAE and has provided an assessment of causal relationship. 
• 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 causal relationship for every event before the 
initial transmission of the SAE data to the Sponsor. 
• The investigator may change his/her opinion of causal relationship in light of follow-up 
information and send a SAE follow-up report with the updated causal relationship 
assessment. 
• The causal relationship assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
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 causal relationship of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
                                                 
a Study intervention administered can correspond to either the investigational product or other products when no 
investigational product is administered at the visit 
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• If a participant dies during participation in the study or during a recognized follow-up 
period, when available the investigator will provide the Sponsor with a copy of any 
post-mortem findings including histopathology. 
• New or updated information will be recorded in the originally completed CRF. 
• The investigator will submit any updated SAE data to the Sponsor within 24 hours of 
receipt of the information. 
• Adverse events likely to be related to the study intervention, whether serious or not, that 
persist at the end of the study will be followed up by the Investigator until their complete 
disappearance or the stabilization of the participant’s condition. The Investigator will 
inform the Sponsor of the date of final disappearance of the event or the date of “chronicity” 
establishment. 
10.3.4 Reporting of SAEs 
SAE Reporting to the Sponsor via an Electronic Data Collection Tool 
• The primary mechanism for reporting an SAE to the Sponsor 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) in order to report the event within 24 hours. The site will enter the 
SAE data into the electronic system as soon as it becomes 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). 
• Details regarding SAE reporting can be found in the Operating Guidelines. 
 
SAE Reporting to the Sponsor via Paper CRF 
• The SAE paper CRF can be sent to the Sponsor by one of the following means: 
• 
By fax, to the following number: 570-957-2782 
• 
In PDF format to the following e-mail address, using a method of transmission that 
includes password protection: PV.outsourcing@sanofi.com 
• 
By express mail, to the following address:  
Sanofi Pasteur Inc.  
Reception and Triage – Case Management 
Global Pharmacovigilance 
Mail Drop: 45D38, Discovery Drive 
Swiftwater, PA 18370 
 
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Safety Emergency Call 
If, as per the Investigator's judgment, a participant experiences a medical emergency, the 
Investigator may contact the Sponsor's RMO for advice on how to address any study-related 
medical question or problem. If the RMO is not available, then the Investigator may contact the 
Call Center—available 24 hours a day, 7 days a week—that will forward all safety emergency 
calls to the appropriate primary or back-up Sanofi Pasteur contact, as needed. The toll-free 
contact information for the Call Center is provided in the Operating Guidelines. 
This process does not replace the need to report an SAE. The Investigator is still required to 
follow the protocol-defined process for reporting SAEs to the GPV Department. 
In case of emergency code-breaking, the Investigator is required to follow the code-breaking 
procedures described in Section 6.3.2. 
10.3.5 Assessment of Intensity 
The investigator will make an assessment of intensity for each AE reported during the study. An 
intensity grade will be assigned to each AE. The intensity grading scales used in this study are 
adapted from the “FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, September 2007”. 
10.3.5.1 Tables for Clinical Abnormalities 
10.3.5.1.1 Solicited AR Intensity Grading Scale 
 
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Table 10.1: Solicited injection site reactions: terminology, definitions, and intensity scales 
CRF term 
(MedDRA lowest 
level term [LLT]) 
Injection site pain 
Injection site erythema 
Injection site swelling  
Diary card term 
Pain 
Redness 
Swelling 
Definition 
Pain either present spontaneously or when 
the injection site is touched or injected limb 
is mobilized 
Presence of a redness including the 
approximate point of needle entry 
Swelling at or near the injection site 
Swelling or edema is caused by a fluid 
infiltration in tissue or cavity and, 
depending on the space available for the 
fluid to disperse, swelling may be either soft 
(typically) or firm (less typical) to touch and 
thus can be best described by looking at the 
size of the swelling 
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Intensity scale* 
CRF: 
Grade 1: A type of adverse event that is 
usually transient and may require only 
minimal treatment or therapeutic 
intervention. The event does not generally 
interfere with usual activities of daily living. 
Grade 2: A type of adverse event that is 
usually alleviated with additional 
therapeutic intervention. The event 
interferes with usual activities of daily 
living, causing discomfort but poses no 
significant or permanent risk of harm to the 
research participant. 
Grade 3: A type of adverse event that 
interrupts usual activities of daily living, or 
significantly affects clinical status, or may 
require intensive therapeutic intervention. 
Diary card: 
Grade 1: No interference with usual 
activities 
Grade 2: Some interference with usual 
activities 
Grade 3: Significant; prevents usual 
activities 
Grade 1: ≥ 25 to ≤ 50 mm 
Grade 2: ≥ 51 to ≤ 100 mm 
Grade 3: > 100 mm 
Grade 1: ≥ 25 to ≤ 50 mm 
Grade 2: ≥ 51 to ≤ 100 mm 
Grade 3: > 100 mm 
MedDRA: Medical Dictionary for Regulatory Activities 
* For the subjective reaction of pain, participants will record the intensity level (Grade 1, 2, or 3) in the diary card. For the measurable reactions of redness and swelling, they will 
record just the size of the reaction, and the classification as Grade 1, 2, or 3 will be assigned at the time of the statistical analysis 
 
 
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Table 10.2: Solicited systemic reactions: terminology, definitions, and intensity scales 
CRF term 
(MedDRA 
lowest level 
term [LLT]) 
Fever 
Headache 
Malaise 
Myalgia 
Arthralgia 
Shivering 
Diary card 
term 
Temperature 
Headache 
Feeling unwell 
Muscle aches and 
pains 
Joint pain 
Chills 
Definition 
Elevation of 
temperature to 
≥°38.0°C (≥ 100.4°F) 
Pain or discomfort in 
the head or scalp. 
Does not include 
migraine. 
General ill feeling. 
Malaise is a 
generalized feeling of 
discomfort, illness, or 
lack of well-being 
that can be associated 
with a disease state. It 
can be accompanied 
by a sensation of 
exhaustion or 
inadequate energy to 
accomplish usual 
activities. 
Muscle aches and 
pains are common 
and can involve more 
than one muscle at the 
same time. Muscle 
pain can also involve 
the soft tissues that 
surround muscles. 
These structures, 
which are often 
referred to as 
connective tissues, 
include ligaments, 
tendons, and fascia 
(thick bands of 
tendons). 
Does not apply to 
muscle pain at the 
injection site which 
should be reported as 
injection site pain. 
Pain in a joint or 
joints 
Sensation of cold 
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Intensity 
scale* 
Grade 1: ≥ 38.0°C to 
≤ 38.4°C, 
or ≥ 100.4°F to 
≤ 101.1°F 
CRF: 
Grade 1: A type of 
adverse event that is 
usually transient and 
may require only 
minimal treatment or 
therapeutic 
intervention. The 
event does not 
generally interfere 
with usual activities 
of daily living. 
CRF: 
Grade 1: A type of 
adverse event that is 
usually transient and 
may require only 
minimal treatment or 
therapeutic 
intervention. The 
event does not 
generally interfere 
with usual activities 
of daily living. 
CRF: 
Grade 1: A type of 
adverse event that is 
usually transient and 
may require only 
minimal treatment or 
therapeutic 
intervention. The 
event does not 
generally interfere 
with usual activities 
of daily living. 
CRF: 
Grade 1: A type of 
adverse event that is 
usually transient and 
may require only 
minimal treatment or 
therapeutic 
intervention. The 
event does not 
generally interfere 
with usual activities 
of daily living. 
CRF: 
Grade 1: A type of 
adverse event that is 
usually transient and 
may require only 
minimal treatment or 
therapeutic 
intervention. The 
event does not 
generally interfere 
with usual activities 
of daily living. 
 
Grade 2: ≥ 38.5°C to 
≤ 38.9°C, 
or ≥ 101.2°F to 
≤ 102.0°F 
Grade 2: A type of 
adverse event that is 
usually alleviated 
with additional 
therapeutic 
intervention. The 
event interferes with 
usual activities of 
daily living, causing 
discomfort but poses 
no significant or 
permanent risk of 
harm to the research 
participant. 
Grade 2: A type of 
adverse event that is 
usually alleviated 
with additional 
therapeutic 
intervention. The 
event interferes with 
usual activities of 
daily living, causing 
discomfort but poses 
no significant or 
permanent risk of 
harm to the research 
participant. 
Grade 2: A type of 
adverse event that is 
usually alleviated 
with additional 
therapeutic 
intervention. The 
event interferes with 
usual activities of 
daily living, causing 
discomfort but poses 
no significant or 
permanent risk of 
harm to the research 
participant. 
Grade 2: A type of 
adverse event that is 
usually alleviated 
with additional 
therapeutic 
intervention. The 
event interferes with 
usual activities of 
daily living, causing 
discomfort but poses 
no significant or 
permanent risk of 
harm to the research 
participant. 
Grade 2: A type of 
adverse event that is 
usually alleviated 
with additional 
therapeutic 
intervention. The 
event interferes with 
usual activities of 
daily living, causing 
discomfort but poses 
no significant or 
permanent risk of 
harm to the research 
participant. 
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Grade 3: ≥ 39.0°C 
or ≥ 102.1°F 
Grade 3: A type of 
adverse event that 
interrupts usual 
activities of daily 
living, or significantly 
affects clinical status, 
or may require 
intensive therapeutic 
intervention. 
Diary card: 
Grade 1: No 
interference with 
usual activities 
Grade 2: Some 
interference with 
usual activities 
Grade 3: Significant; 
prevents usual 
activities 
Grade 3: A type of 
adverse event that 
interrupts usual 
activities of daily 
living, or significantly 
affects clinical status, 
or may require 
intensive therapeutic 
intervention. 
Diary card: 
Grade 1: No 
interference with 
usual activities 
Grade 2: Some 
interference with 
usual activities 
Grade 3: Significant; 
prevents usual 
activities 
Grade 3: A type of 
adverse event that 
interrupts usual 
activities of daily 
living, or significantly 
affects clinical status, 
or may require 
intensive therapeutic 
intervention. 
Diary card: 
Grade 1: No 
interference with 
usual activities 
Grade 2: Some 
interference with 
usual activities 
Grade 3: Significant; 
prevents usual 
activities 
Grade 3: A type of 
adverse event that 
interrupts usual 
activities of daily 
living, or significantly 
affects clinical status, 
or may require 
intensive therapeutic 
intervention. 
Diary card: 
Grade 1: No 
interference with 
usual activities 
Grade 2: Some 
interference with 
usual activities 
Grade 3: Significant; 
prevents usual 
activities 
Grade 3: A type of 
adverse event that 
interrupts usual 
activities of daily 
living, or significantly 
affects clinical status, 
or may require 
intensive therapeutic 
intervention. 
Diary card: 
Grade 1: No 
interference with 
usual activities 
Grade 2: Some 
interference with 
usual activities 
Grade 3: Significant; 
prevents usual 
activities 
MedDRA: Medical Dictionary for Regulatory Activities 
* For all reactions but fever, participants will record the intensity level (Grade 1, 2, or 3) in the diary card. For fever, they will record the body temperature, and the classification as 
Grade 1, 2, or 3 will be assigned at the time of the statistical analysis based on the unit used to measure the temperature and the intensity scale. 
 
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Important notes for the accurate assessment of temperature: 
Participants are to measure body temperature once per day, preferably always at the same time. 
The optimal time for measurement is the evening, when body temperature is the highest. 
Temperature is also to be measured at the time of any apparent fever. The observed daily 
temperature and the route of measurement are to be recorded in the diary card, and the highest 
temperature will be recorded by the site in the CRF. The preferred route for this study is axillary. 
10.3.5.1.2 Unsolicited AE Intensity Grading Scale 
For measurable unsolicited AEs that are part of the list of solicited reactions, the corresponding 
scale for solicited reactions will be used (see Section 10.3.5.1.1). 
All other unsolicited AEs will be classified according to the following intensity scale: 
• Grade 1 
• 
CRF: A type of adverse event that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with usual 
activities of daily living. 
• 
Diary card: No interference with usual activities. 
• Grade 2 
• 
CRF: A type of adverse event that is usually alleviated with additional therapeutic 
intervention. The event interferes with usual activities of daily living, causing discomfort 
but poses no significant or permanent risk of harm to the research participant. 
• 
Diary card: Some interference with usual activities. 
• Grade 3 
• 
CRF: A type of adverse event that interrupts usual activities of daily living, or 
significantly affects clinical status, or may require intensive therapeutic intervention. 
• 
Diary card: Significant; prevents usual activities. 
10.4 Appendix: Collection of Pregnancy Information 
DEFINITIONS: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP 
1) Premenarchal 
2) Premenopausal female with 1 of the following: 
• 
Documented hysterectomy 
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• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry. 
Note: Documentation can come from the site personnel’s: review of the participant’s medical 
records, medical examination, or medical history interview. 
3) Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
• 
A high follicle stimulating hormone (FSH) level in the postmenopausal range may 
be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, confirmation with more than one FSH measurement is 
required. 
• 
Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
COLLECTION OF PREGNANCY INFORMATION 
Female Participants who become pregnant 
• The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. The initial information together with the 
contraceptive method if any will be recorded on the appropriate form and submitted to the 
Sponsor within 1 month of learning of a participant's pregnancy. 
• The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate and the information will 
be forwarded to the Sponsor. Generally, follow-up will not be required for longer than 6 to 
8 weeks beyond the estimated delivery date, but will be in accordance with local regulations. 
Any termination of pregnancy will be reported, regardless of fetal status (presence or absence 
of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
• A spontaneous abortion (occurring at <22 weeks gestational age) or still birth (occurring at 
>22 weeks gestational age) is always considered to be an SAE and will be reported as such. 
• Any post-study pregnancy related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the Sponsor as described in Section 8.3.4. While the 
investigator is not obligated to actively seek this information in former study participants, he 
or she may learn of an SAE through spontaneous reporting. 
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• In case of pregnancy during the primary series and if at least 1 dose of the study vaccine(s) has 
been administered, the participant will not be discontinued from the study, but no further 
vaccination will be administered until after delivery (if applicable and still within the study 
vaccination window). However, the participant will be followed for safety assessment (and 
may be followed for immunogenicity assessment, if applicable). 
10.5 Appendix: Risk-based Approach 
ICH E6-R2 guideline for GCP is introducing the « risk-based approach » concept which permits 
to focus efforts on what is critical for a study and most specifically on Critical Data and Critical 
Processes. Critical data and processes are defined for the study with associated risks in the Study 
Risk Management Plan. 
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10.6 Appendix: Abbreviations 
AE 
 
Adverse Events 
AESI  
Adverse events of special interest 
AR 
 
Adverse reactions 
CRF  
Case report form 
DMC  
Data Monitoring Committee 
FAS 
 
Full analysis set 
FSH 
 
Follicle stimulating hormone 
GCI 
 
Global Clinical Immunology 
GCP  
Good Clinical Practice 
GDPR  
General Data Protection Regulation 
GPV  
Global Pharmacovigilance 
HRT  
Hormonal replacement therapy 
IB 
 
Investigator’s Brochure 
ICF 
 
informed consent form 
ICH 
 
International Council for Harmonization 
IEC 
 
Independent Ethics Committees 
IgG 
 
immunoglobulin G 
IMP 
 
Investigational Medicinal Product 
IPD 
 
invasive pneumococcal disease 
IRB 
 
Institutional Review Boards 
IRT 
 
Interactive Response Technology 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOPA 
multiplex opsonophagocytic assay 
NIMP  
Non- Investigational Medicinal Product; 
PCV  
pneumococcal conjugate vaccine 
PPAS  
Per-protocol analysis set 
PPSV  
pneumococcal polysaccharide vaccine 
PT 
 
preferred term 
RMO  
Responsible Medical Officer 
SAE  
Serious adverse events 
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SafAS  
Safety Analysis Set 
SAP 
 
Statistical analysis plan 
SOC  
system organ class 
SMT  
Safety Management Team 
SoA 
 
Schedule of Activities 
TBD  
to be determined 
WHO  
World Health Organization 
WOCBP 
Woman of Childbearing Potential 
yo 
 
year old 
 
 
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10.7 Appendix: Protocol Amendment History 
The Protocol Amendment Rationale for the current amendment is located directly before the 
Table of Contents. 
 
 
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11 References 
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Clutterbuck EA, Lazarus R, Yu LM, Bowman J, Bateman EA, Diggle L, et al. 
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Geno KA, Gilbert GL, Song JY, Skovsted IC, Klugman KP, Jones C, et al. Pneumococcal 
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Klugman KP, Black S, Dagan R, Malley R, Whitney CG. Pneumococcal conjugate vaccine 
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Weiser JN, Ferreira DM, Paton JC. Streptococcus pneumoniae: transmission, colonization 
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Grabenstein JD, Klugman KP. A century of pneumococcal vaccination research in 
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Tregnaghi MW, Saez-Llorens X, Lopez P, Abate H, Smith E, Posleman A, et al. Efficacy 
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Miller E, Andrews NJ, Waight PA, Slack MP, George RC. Herd immunity and serotype 
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Flasche S, Van Hoek AJ, Goldblatt D, Edmunds WJ, O'Brien KL, Scott JA, et al. The 
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Wroe PC, Lee GM, Finkelstein JA, Pelton SI, Hanage WP, Lipsitch M, et al. 
Pneumococcal carriage and antibiotic resistance in young children before 13-valent conjugate 
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Lewnard JA, Hanage WP. Making sense of differences in pneumococcal serotype 
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Stockmann C, Ampofo K, Pavia AT, Blaschke AJ, Mason EO, Presson AP, et al. Clinical 
and Epidemiological Evidence of the Red Queen Hypothesis in Pneumococcal Serotype 
Dynamics. Clin Infect Dis. 2016;63(5):619-26. 
26. 
Jones CH, Zhang G, Nayerhoda R, Beitelshees M, Hill A, Rostami P, et al. Comprehensive 
vaccine design for commensal disease progression. Sci Adv. 2017;3(10):e1701797. 
27. 
Freedman MS, Hunter P, Ault K, Kroger A. Advisory Committee on Immunization 
Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older - United 
States, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(5):133-5. 
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Rüggeberg JU, Gold MS, Bayas J-M, Blum MD, Bonhoeffer J, Friedlander S, et al. 
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12 Sponsor Signature Page 
 
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Document Number
CLI_00308030
Version Number
3.0
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Approver Name
Date
(Universal Time)
Reason for Signature
Approval
Approval
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