COVID-19 is a contagious disease caused by the SARS-CoV-2 virus that has quickly infected many people all over the world and continues to be a major public health concern. The symptoms can last from several days to 2 or more weeks. Older adults and people with long-term health problems, especially of the lungs and heart, are at higher risk of having complications than young healthy children and adults. COVID-19 may sometimes cause severe problems such as pneumonia (a lung infection) and serious trouble breathing, which can lead to a hospital stay and can cause death. There are currently several vaccines that have been shown to protect against COVID-19 disease that have been approved/authorized and are being given to people in many countries. The purpose of this study is to determine if the 2 COVID-19 study vaccines are safe and protect against infection and illness caused by the virus. The COVID-19 study vaccines contain “antigen(s)” and “adjuvant”. Antigens can trigger the body’s immune system to produce antibodies that fight disease. Antibodies are proteins in the blood which are part of your immune system. The antigen in the study vaccine is the spike protein that has been copied from the SARS-CoV-2 virus. The study vaccines are not made from the actual SARS-CoV-2 virus. It is impossible for the study vaccines to give you a SARS-CoV-2 infection or COVID-19 illness. Also, they cannot cause you to give the SARS-CoV-2 virus to someone else. Adjuvants are ingredients added to help a vaccine work better by increasing the immune response. The adjuvant in this study is called AS03. How well the study vaccines protect against infection and illness also depends on the similarity between the virus variant(s) that are circulating in the community. When viruses replicate, they can mutate, like making a spelling mistake, including changes to the spike protein. These changed viruses are known as variants. Variants are versions of the virus that have enough mutations to behave differently from the original version of the virus. Vaccines are called monovalent if they contain 1 antigen or bivalent if they contain 2 antigens. This study will test a monovalent vaccine and a bivalent vaccine. The monovalent vaccine uses the spike protein antigen from the original virus that started the pandemic. This antigen is being used in currently approved/authorized COVID 19 vaccines. The bivalent vaccine has the antigen from the original virus, like the monovalent vaccine, and adds another antigen from a variant that was first found in South Africa (known as the Beta variant), which is now circulating in many parts of the world. Both the monovalent and bivalent vaccines will be given with the AS03 adjuvant. Participants will get 1 of the 2 study vaccines or a placebo. Placebo is an injection that does not contain any antigen or adjuvant or other active ingredients. In this study, the placebo will be sterile salt water. We will compare the results from people who got the placebo to the results from people who got the study vaccines to see if the study vaccines work to protect against infection with the virus, including different circulating variants, and COVID-19 disease, and are safe.

This is a parallel, multi-centre, multi-country, multi-stage Phase 3 placebo-controlled clinical trial in adults 18 years of age and older. Blinding is a modified double-blind (observer-blind) whereby participants, outcome assessors, investigators, laboratory personnel are blinded to the vaccine group assignment. Sponsor study staff and those administering the study intervention and those preparing the study intervention, are not blinded. Although the trial will be conducted in 2 stages with Stage 1 testing the monovalent vaccine COV2 preS dTM-ASO3 (D614) and Stage 2 testing the bivalent COV2 preS dTM-ASO3 (D614+B.1.351) vaccine, KAVI-Institute of Clinical Research will only take part in Stage 2 of the trial since Stage 1 of the trial is already completed. Approximately 250 participants will be enrolled at the KAVI-KNH site. Participants will be screened for eligibility at the time of inclusion and then be randomized to receive either the investigational vaccine CoV2 preS dTM-AS03 (D614 + B.1.351) or the Placebo. All participants will receive 2 injections given 3 weeks apart: the first injection will be at D01 (Vaccination [VAC] 1) and the second injection will be at D22 (VAC2). Reactogenicity subset: A subset of participants, 25% of the study population will be randomly allocated to the reactogenicity subset to collect solicited AEs for 7 days after each vaccination and nonserious unsolicited AEs up to 21 days after the second vaccination.