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 two cohorts in the study: the efficacy-safety cohort, and the efficacy-extended safety-immunogenicity cohort. Approximately 3000 participants will be enrolled into the efficacy-extended safety-immunogenicity cohort accounting for about 5% of the total participants in each country. Globally, participants  ≥ 60 years old will account for about 10% of all enrolled subjects.  However, for ethical reasons, only participants aged below 58 years will be recruited in Kenya in view of the country’s role out of AstraZeneca COVID vaccine to people aged 58 years and above. In addition, individuals meeting the criteria for the Kenya’s Ministry of Health AstraZeneca COVID-19 vaccination will be excluded from recruitment into the trial. All the participants will receive three doses of either study vaccine or placebo on Day 0, Day 21, Day 42 in a ratio of 1:1. The efficacy will be evaluated in all vaccinated participants, All vaccinated participants will be followed up to monitor incidence of SAEs, MAAEs and AESIs and to evaluate reactogenicity of the vaccine will be evaluated in both cohorts. Participants will be selected based on their voluntariness. 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 three clinical trials sites participating in this trial in Kenya. These are KAVI-Institute of Clinical Research at University of Nairobi which will recruit 400 participants, and Moi Teaching and Referral Hospital in Eldoret and KEMRI Kilifi which will each recruit 300 participants, bringing the total number of participants in Kenya to 1,000. All the sites in Kenya will only participate in the efficacy-extended safety-immunogenicity cohort arm of the trial 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 eight planned site visits on Day -7-Day 0, Day 0, Day 21, Day 42, 28 days, 3 months, 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 while ensuring both pre-test and post-test counselling is given before and after the test, test SARS-CoV-2 RT-PCR of NP and 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. The participants will be instructed on how to measure their oral temperature and swelling at the injections site, as well as how to record any symptoms in their e-diary or diary card. 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). Further details are outlined in Section 3.7 and 5.1.

Site visits will be conducted on 28 days, 3 months, 6 months and 12 months after completion of 3 vaccination doses during which blood sample will also be collected as detailed in Section 3.8 and 3.9.

Participants should contact the investigator immediately if they notice any signs or symptoms related to COVID-19. If a participant 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.