| Protocol No: | ECCT/21/06/08 | 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 |
| 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 age and older as a primary series and open-label extension to assess immunogenicity, safety, efficacy of a monovalent booster dose of SARS-CoV2 Adjuvanted Recombinant Protein Vaccine | |
| 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
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| Laymans Summary: | This is a Phase 3 study (efficacy study) of two experimental vaccines against SARS-CoV-2. The full names are:
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 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 study vaccines can prevent severe COVID-19 illness and hospitalization |
| 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.
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| 25 | Unblinded Crossover / Booster All participants in Stage 1 and Stage 2 will be unblinded and informed of the results of the study. Study Investigators will discuss the possibility of receiving the (authorized/approved) vaccines available to them outside of the study. Based on decisions of the Study 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 (ie, crossover vaccination) and a booster for both initial placebo and vaccine recipients (ie, booster vaccination). Non-naïve participants who initially received placebo and are 18-59 years of age will be offered the opportunity to receive the investigational CoV2 preS dTM-AS03 monovalent (D614) vaccine if authorized/approved vaccines are not available or if they choose not to receive an authorized/approved vaccine series. Naïve participants 18-59 years of age and all participants ≥ 60 years of age who initially received placebo will be recommended to receive an authorized/approved vaccination series. |