Protocol No: ECCT/21/06/06 Date of Protocol: 18-05-2021

Study Title:

A parallel-group, Phase III, multi-stage, modified double-blind, multi-armed study to assess the efficacy, safety, and immunogenicity of two SARS-CoV-2 Adjuvanted
Recombinant Protein Vaccines (monovalent and bivalent) for prevention against COVID-19 in adults 18 years of ageand older

Study Objectives:

Key Primary objectives
Primary Efficacy: To assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTMAS03
vaccines for the prevention of symptomatic COVID-19 occurring ≥ 14 days after the second injection.
Primary Safety: To assess the safety of the CoV2 preS dTM-AS03 vaccines compared to placebo throughout the study

Laymans Summary:

This is a Phase 3 study (efficacy study) of two experimental vaccines against SARS-CoV-2. The full names are:
1. Monovalent: SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, monovalent D614 (CoV2 preS dTMAS03 [D614])
2. Bivalent: SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, bivalent D614/B.1.351 (CoV2 preS dTM-AS03 [D614 + B.1.351])

This study is also known as “VAT00008” or “CoVPN 3005.”

The study vaccine is developed by Sanofi Pasteur, a company that produces vaccines against other diseases such as diphtheria, tetanus, pertussis, meningitis and
influenza.

The vaccine will be manufactured using the same technology as is used to make an influenza vaccine that is licensed in the US for the prevention of influenza in
adults, marketed as Flublok®.

The study will enroll about 37,500 participants globally.

The purpose of the study is to learn if:

The study vaccines can prevent symptomatic COVID-19 illness                                                                                                                                                                           The vaccines are safe                                                                                                                                                                                                                                           The vaccines make people too uncomfortable                                                                                                                                                                                                       The study vaccines can prevent infection with SARS-CoV-2                                                                                                                                                                                 The sudy vaccines can prevent severe COVID-19 illness and hospitalization

An outbreak of severe respiratory illness by this virus began in Wuhan city, China in December 2019. It was described as Coronavirus disease 2019 (COVID-19) which is a respiratory disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak rapidly escalated leading to WHO declaring it a Pandemic in March 2020. Since then, public health measures of isolation, quarantine, social distancing to contain the spread of the virus have been used to stop the spread of the virus. Despite these measures, by 11 May 2020 the virus had been detected in 192 countries. The burden has been catastrophic: As at 2 may 2021, there were more than 3.1 million deaths and over 151 million confirmed cases worldwide. In the same time, more than 3.3 million cases, and 82 thousand deaths were reported in Africa. In Kenya, as of 10 May 2021, more than 163,620 cases and 2,907 deaths were reported.

The clinical profile of the illness caused by SARS-CoV-2, is variable. The majority of cases are mild or individuals may have no symptoms. Among those with symptoms, typical presentation includes fever, cough, and shortness of breath. The severe manifestations include acute respiratory failure requiring intensive care unit (ICU) admission and some cases result in death. While mostly self-limited, symptoms such as fatigue and dyspnea appear to persist in many individuals for up to 2 months after illness onset despite viral clearance. Adults over 50 years of age and individuals with chronic medical conditions like diabetes and hypertension are at a higher risk of severe disease and death.

In response to the disease, vaccines have been developed and rollout began. However, new variants of the virus have emerged. They were originally named after the country in which they were first detected but have now been renamed thus:(the alpha (B.1.1.7) variant, Beta (B.1.351) variant, the Gamma (P.1) variant, the Delta (B.1.617) variant). These variants have now spread from their countries of origin, been detected in other countries around the world and early study data has shown that vaccines are not equally effective against the emerging variants.

Sanofi Pasteur initiated development of vaccine using a coronavirus protein (SARS-CoV-2 Spike (S) protein). After reviewing phase 1 and II study data, this phase III study-VAT00008, is designed to investigate how well two Recombinant vaccines (monovalent vaccine-containing one variant & bivalent vaccine-containing two variants) protect people from developing symptoms when infected by the corona virus and how safe they are when administered by intramuscular injectionin adults who are at least 18 years of aged by comparing their action to that of a placebo (this is a substance that looks like the vaccine but has no action on the body).

The study will be conducted in two stages among about 21 046 people. Stage one will enroll about 10160 people (5080 will receive vaccine and 5080 will receive placebo) and stage two will enroll about 10886 people (half will receive vaccine and half will receive placebo). Based on decisions of the Study Oversight Group (OG), participants will be invited upon consent to continue participation as part of an unblinded crossover / booster study design. The participant unblinding and consent will trigger the end of the initial double-blind primary series design and the start of the Crossover / Booster design, which includes a primary series vaccination for initial placebo recipients (i.e., crossover vaccination) and a booster for both initial placebo and vaccine recipients (i.e., booster vaccination).

Butere site expects to enroll approximately 420 out of the 429 participants who remain active in the study protocol version 5.0 dated 08 Sep 2021.

Abstract of Study:

Background
SARS-CoV-2 is a novel coronavirus that emerged in the human population and has led to a pandemic of acute respiratory disease named COVID-19. The burden of SARS-CoV-2
morbidity and mortality has been catastrophic with greater than 2.8 million deaths recorded since first emerging in December 2019 among over 131.9 million confirmed cases
(as of 06 April 2021) (2). In many locations, the rapid emergence of COVID-19 has overwhelmed the capacity of health systems to provide care for COVID-19-affected
patients, let alone unaffected patients. Interventions to reduce transmission through reduction of population contact (also called social distancing) has had profound
economic consequences. Safe and effective vaccines with sufficient supply would be vital to address the significant medical and societal burden caused by the pandemic.
The CoV2 preS dTM-AS03 vaccines developed by Sanofi Pasteur utilize a recombinant protein approach in combination with an oil-in-water adjuvant, AS03 provided by
GlaxoSmithKline (GSK). The CoV2 preS dTM-AS03 vaccines belong to the pharmacotherapeutic group of “covid19 vaccines”. The vaccines contain recombinant S protein,
stabilized to maintain native prefusion trimer configuration as present on the viral envelope. The purpose of the study is to assess the efficacy, safety, and immunogenicity of
two CoV2 preS dTM-AS03 vaccines (monovalent and bivalent) in adults 18 years of age and older in a multi-stage approach.
Methods
This study is designed to maximize representation of the broader population by minimizing exclusionary eligibility criteria and allowing the participation of individuals with a
broad range of medical conditions, including controlled HIV infection, Hepatitis B and Hepatitis C, and conditions associated with an increased risk of severe COVID-19. It is
also designed to be inclusive of other subpopulations affected by COVID-19, including older adults as well as ethnic and racial minorities. Participants will be screened for
eligibility criteria at the time of inclusion and then randomized to either the investigational vaccine or placebo in a 1:1 ratio in each stage. • Stage 1: eligible participants will
be randomized to receive either 2 injections of CoV2 preS dTM-AS03 (D614) vaccine or Placebo 1 (participants who receive the placebo as part of Stage 1) administered 21
days apart • Stage 2: eligible participants will be randomized to receive 2 injections of either CoV2 preS dTM-AS03 (D614 + B.1.351) vaccine or Placebo 2 (participants who
receive placebo as part of Stage 2) administered 21 days apart. Randomization will be stratified by age groups (18-59 years of age and 60 years of age and older), baseline
SARS-CoV-2 rapid serodiagnostic test positivity, and site. In the event that the enrollment in Stage 1 overlaps with enrollment of Stage 2, participants will continue to be
randomly allocated to one of the investigational vaccine groups and their matched placebo group in a 1:1 ratio.
Approximately 37 430 participants are planned to be enrolled (8000 per study intervention group in Stage 1 and 10 715 per study intervention group in Stage 2)The duration
of the study for each participant will be 365 days post-last injection (ie, approximately 386 days total). The study includes 8 visits at D01, D22, D43, D78, D134, D202, D292,
and D387. Participants will be contacted once a week over the entire duration of the study to inquire about the development of symptoms of COVID-19-like-illness and to
remind participants to contact study staff if they experience symptoms of COVID-19-like illness. Additional visits and procedures are included for participants with verified
COVID-19-like illness.