This study is about a vaccine for COVID-19. COVID-19 is a respiratory infection that has spread around the world. The infection is caused by a virus called SARS-CoV-2. From now on, we will call it “the COVID-19 virus”. People can catch the virus by breathing the air near people who are infected. They may also get the virus by touching something that has the virus on it and then touching their eyes, nose, or mouth. Keeping distance from others, wearing a mask, and frequent hand washing are important ways to prevent infection. COVID-19 infection causes a wide range of health issues. Some people show no symptoms, while others experience serious medical problems and need a ventilator to help them breathe. Many people have died from the virus. In the end, the best protection against COVID-19 will be an effective vaccine. That is what this research study is about. Everyone’s body has an immune system- special cells that act together to fight viruses and other invaders. The study vaccine is designed to help prepare the immune system to fight the real COVID-19 virus if it enters the body.

This Phase III study is a global multicentre, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy, safety, and immunogenicity of the recombinant COVID-19 vaccine (Sf9 cells) in 40,000 participants aged 18 years and older who do not have known history of SARS-CoV-2 infection but whose locations or circumstances put them at appreciable risk of acquiring COVID-19 or SARS-CoV-2 infection. Globally, there will be three cohorts in the study: the efficacy-safety cohort, the efficacy-extended safety cohort, and the efficacy-extended safety-immunogenicity cohort. The efficacy will be evaluated in all vaccinated participants, including population in the efficacy-safety cohort, the efficacy-extended safety cohort, and the efficacy-extended safety-immunogenicity cohort. All vaccinated participants will also be followed up to monitor incidence of SAEs, MAAEs and AESIs. The reactogenicity of the vaccine will be evaluated in the efficacy-extended safety cohort and the efficacy-extended safety-immunogenicity cohort. KAVI-Institute for Clinical Research will recruit 400 clinical trial participants. All the participants will be in the efficacy-extended safety-immunogenicity cohort, and will receive three doses of either the vaccine or placebo on Day 0, Day 21, Day 42 in a ratio of 1:1. This cohort will undergo additional visits to collect immunogenicity data associated with receiving the recombinant COVID-19 vaccine (Sf9 cells) and to analyse the infection status. There will be at least seven planned site visits on Day -7-Day 0, Day 0, Day 21, Day 42, 28 days, 6 months and 12 months after completion of 3 vaccination doses. The first site visit will be the screening visit (Day -7-Day 0), and will be held within 7 days prior to the enrolment visit (Day 0). During the screening visit, study staff will obtain written informed consent from the participants, record medical history, review inclusion and exclusion criteria, test HIV antibody, test SARS-CoV-2 RT-PCR of NP or OP swab, and do urine pregnancy test in women of child-bearing potential etc. At enrolment visit (Day 0), blood sample will be collected from the participants to establish baseline immunogenicity levels. Participants will then be randomized to either the placebo or study vaccine group and receive their vaccination. The participant and investigators will remain blinded to the assigned group. Participants are required to stay at the study site for at least 30 minutes after vaccination to monitor for any vaccine-related AE. All participants will be contacted weekly to be reminded to report any signs or symptoms of COVID-19 to study staff. Participants will be contacted by the site weekly by phone or short text messaging (sms) to answer questions about whether they have SAEs, MAAEs or AESIs. The reporting and monitoring of any participant’s illness are consistent with meeting the primary efficacy objective. If a participant becomes ill, they will be asked to immediately proceed to the site designated by their local study team where they will be assessed and treated as deemed appropriate. Participants will be given an e-diary or paper diary card to record solicited AEs within 7 days after each vaccination dose and to record unsolicited AEs within 21 days after the first dose and the second dose, and within 28 days after the third vaccination dose. Study staff will review the completed e-diary or diary card of participants in these cohorts at their next site visit. Data collected from e-diaries and diary cards will be uploaded into the electronic data capture (EDC). Site visits will be conducted on 28 days, 6 months and 12 months after completion of 3 vaccination doses during which blood sample will also be collected . Participants should contact the investigator immediately if they notice any signs or symptoms related to COVID-19.If a participant in these three cohorts demonstrates signs or symptoms of COVID-19, an unplanned site visit may occur for evaluation and possible treatment. After an electronic follow-up visit, if for any reason, the investigator would like to conduct a site visit, they may do this at their discretion.