| Protocol No: | ECCT/21/11/03 | Date of Protocol: | 08-09-2021 |
| 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 age and older |
| Study Objectives: | A. Efficacy Objectives: 1. To assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for the prevention of symptomatic COVID-19 occurring ≥ 14 days after the second injection. 2. To assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for the prevention of symptomatic COVID-19 occurring ≥ 14 days after the first injection. 3. To assess, in all participants regardless of prior SARS-CoV-2 infection, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for:
4. To assess, in participants who are SARS-CoV-2 non-naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for:
5. To assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for the prevention of asymptomatic SARS-CoV-2 infection. 6. To assess the impact of the CoV2 preS dTM-AS03 vaccines in the reduction of viral burden and shedding among participants with symptomatic COVID-19. 7. To assess, in all participants regardless of prior SARS-CoV-2 infection and in participants who are SARS-CoV-2 non-naïve and naïve, clinical efficacy of the CoV2 preS dTM-AS03 vaccines for:
8. To assess the durability of clinical efficacy of the CoV2 preS dTM-AS03 vaccines over time in SARS-CoV-2 naïve participants against:
9. To assess the durability of clinical efficacy of the CoV2 preS dTM-AS03 vaccines over time in all participants and by prior SARS-CoV-2 infection (naïve and non-naïve) for:
10. To assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for the prevention of symptomatic COVID-19 occurring ≥ 7 days after the second injection. 11. To assess the durability of vaccine efficacy post-crossover in all participants and by prior SARS-CoV-2 infection (naïve and non-naïve). 12. To assess the durability of vaccine efficacy post-crossover in participants who are SARS-CoV-2 naïve. B. Immunogenicity Objectives: 1. To compare the neutralizing antibody response 21 days after last vaccination (D43) to the D614G variant between the monovalent and bivalent vaccines in SARS-CoV-2 naïve and non-naïve participants in the Random Immunogenicity Subcohort. 2. To compare the neutralizing antibody response 21 days after last vaccination (D43) to the Beta (B.1.351) variant between the monovalent and bivalent vaccines in SARS-CoV-2 naïve and non-naïve participants in the Random Immunogenicity Subcohort. 3. To compare the neutralizing antibody response 21 days after last vaccination (D43) to the Beta (B.1.351) variant in the bivalent vaccine group and the neutralizing antibody response to the D614G variant in the monovalent vaccine group in SARS-CoV-2 naïve and non-naïve participants in the Random Immunogenicity Subcohort. 4. To describe the neutralizing antibody profile at D01, D22, D43, D78, D134, D202, D292, and D387 in each study group for participants in the Random Immunogenicity Subcohort. 5. To describe the neutralizing antibody profile at D01, D22, D43, D78, D134, D202, D292, and D387 in each study group for participants aged 18‑25 years in the Random Immunogenicity Subcohort. 6. To describe the association of neutralizing antibody responses and the risk of symptomatic COVID-19. 7. To describe the association of neutralizing antibody responses and the risk of SARS-CoV-2 infection. 8. To describe the association of neutralizing antibody responses and the risk of other COVID-19 disease endpoints. 9. To evaluate the immunological correlates of risk and correlates of protection against symptomatic COVID-19, SARS-CoV-2 infection, and other COVID-19 disease endpoints. C. Safety Objectives: 1. To describe the frequency and spectrum of disease in episodes of symptomatic COVID‑19 in SARS-CoV-2 non-naïve adults in each study group. 2. To assess the safety of the CoV2 preS dTM-AS03 vaccines compared to placebo in participants aged 18‑25 years throughout the study. |
| Laymans Summary: | 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 with 2 stages. It is designed to demonstrate clinical efficacy of each of the two SARS-CoV-2 recombinant protein vaccines (monovalent and bivalent) with AS03 adjuvant in preventing the occurrence of symptomatic COVID-19 with onset at least 14 days after the second injection of the vaccine in SARS-CoV-2 naïve individuals. This is aimed at generating data required for approval of each of the vaccines for use in prevention against SARS-CoV-2 infection and disease in adults. Additionally, data collected during this study is planned to support future development in other populations (eg, pediatrics, pregnant women). VAT00008 will be a Phase III, randomized, modified double-blind, placebo-controlled, multi-stage, multi center, multi-country study. In Stage 1, the AS03 adjuvanted monovalent vaccine with the prefusion S protein from the prototype (D614) variant will be evaluated against a placebo control. In Stage 2, the AS03 adjuvanted bivalent vaccine with prefusion S protein from the prototype and South African Beta variant (D614 + B.1.351) will be assessed against a placebo control. Both stages are considered independent to enable generation of data to support licensure of each candidate vaccines (i.e., the monovalent and bivalent vaccine). The primary endpoint of the study will be occurrences of symptomatic COVID-19 among the studied population. |
| Abstract of Study: | Broad Objective: 1. Efficacy: To assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTM-AS03 vaccines for the prevention of symptomatic COVID-19 occurring ≥ 14 days after the second injection. 2. Safety: To assess the safety of the CoV2 preS dTM-AS03 vaccines compared to placebo throughout the study. Specific Objectives: 1. Efficacy: To assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV-2 preS dTM-AS03 vaccines for prevention of the following occurring ≥ 14 days after the second injection: Prevention of SARS-CoV-2 infection and Prevention of severe COVID-19. 2. Safety: To describe the frequency and spectrum of disease in episodes of symptomatic COVID-19 in SARS-CoV-2 non-naïve adults in each group 3. Immunogenicity: To compare the neutralizing antibody response 21 days after last vaccination (D43) to the: · D614G variant between the monovalent and bivalent vaccines in SARS-CoV-2 naïve and non-naïve participants in the Random Immunogenicity Subcohort. · B.1.351 variant between the monovalent and bivalent vaccines in SARS-CoV-2 naïve and non-naïve participants in the Random Immunogenicity Subcohort. · B.1.351 strain in the bivalent vaccine group and the neutralizing antibody response to the D614G variant in the monovalent vaccine group in SARS-CoV-2 naïve and non-naïve participants in the Random Immunogenicity Subcohort.
In participants regardless of prior SARS-CoV-2 infection and in SARSCoV-2 non-naïve and naïve participants: · To describe the neutralizing antibody profile for participants in the Random Immunogenicity Subcohort. · To describe the association of neutralizing antibody responses and the risk of symptomatic COVID-19, SARS-CoV-2 infection, other COVID-19 disease endpoints. · To evaluate the immunological correlates of risk and correlates of protection against symptomatic COVID19, SARS-CoV-2 infection, other COVID-19 disease endpoints.
Study setting: This will be a multi-center, multi-country trial. In Kenya, 14 sites, including the Fountain Projects and Research Office Clinical Research Centre (FOPRO-CRC) at Fountain Health Care Hospital in Eldoret, Kenya will be involved. Study design: Phase 3, Randomized, Modified Double-Blind, Placebo Controlled Study. Study population: Adults 18 years of age and older. Number of participants to be engaged: A total of approximately 21 046 participants are planned to be enrolled (5080 per study intervention group in Stage 1 and 5443 per study intervention group in Stage 2). A total of 50 participants will be enrolled at the FOPRO-CRC site. Main study procedures: VAT00008 will be a Phase III, randomized, modified double-blind, placebo-controlled, multi-stage, multi‑center, multi-country study 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 with 2 stages. In Stage 1, the AS03 adjuvanted monovalent vaccine with the prefusion S protein from the prototype (D614) variant will be evaluated against a placebo control. In Stage 2, the AS03 adjuvanted bivalent vaccine with prefusion S protein from the prototype and South African Beta variant (D614 + B.1.351) will be assessed against a placebo control. Both stages are considered independent to enable generation of data to support licensure of each candidate vaccines (i.e., the monovalent and bivalent vaccine). The primary endpoint of the study will be occurrences of symptomatic COVID-19 among the studied population.
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