Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine: A Randomized Clinical Trial

Abstract

ImportanceThe protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown. ObjectiveTo evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults. Design, Setting, and ParticipantsA multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021. InterventionsIn cohort 1, 2 doses of FINLAY-FR-2 (n=13857) or placebo (n=3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2plus1 dose of FINLAY-FR-1A (n=4340) or 3 placebo doses (n=1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection. Main Outcomes and MeasuresThe primary outcome was polymerase chain reaction-confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed. ResultsIn cohort 1 a total 17319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1 men in the vaccine group and 59.1 men in the placebo group; cohort 2 included 59.8 men in the vaccine group and 59.9 in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2) cases of COVID-19 occurred in the vaccine group and 221 (6.1) in the placebo group (vaccine efficacy: 49.7; 95 CI, 40.8-57.3) vs 75 (1.6) and 51 (4.3) in cohort 2 (vaccine efficacy: 64.9; 95 CI, 49.7-59.5). The incidence of serious adverse events was lower than 0.1, with no vaccine-related deaths. Conclusions and RelevanceIn this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19-related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price. Trial Registrationisrctn.org Identifier: IRCT20210303050558N1 This randomized clinical trial evaluates the efficacy and safety of the FINLAY-FR-2 and FINLAY-FR-1A COVID-19 vaccines in the Iranian population.