A phase 3, randomised, double-blind, placebo-controlled clinical trial for adult evaluation of the efficacy and safety of a SARS-CoV-2 recombinant spike RBD protein vaccine (ABDALA-3 Study)
Authors: Hernández-Bernal Francisco , Ricardo-Cobas Maria C , Martín-Bauta Yenima , Rodríguez-Martínez Ernesto , Urrutia-Pérez Klaudia , Urrutia-Pérez Karen , Quintana-Guerra Joel , Navarro-Rodríguez Zadis , Piñera-Martínez Marjoris , Rodríguez-Reinoso José L , Chávez-Chong Cristina O , Baladrón-Castrillo Idania , Melo-Suárez Grettel , Batista-Izquierdo Alejandro , Pupo-Micó Alexis , Mora-Betancourt Ricardo , Soler-Cano Dayamí , Bizet-Almeida Jacqueline , Martínez-Rodríguez Maria C , Lobaina-Lambert Leonardo , Velázquez-Pérez Vivian M , Soler-Díaz Jalimy , Blanco-Garrido Yunaili , Laurencio-Vallina Sandra , Meriño-Hechavarría Tamara , Carmenaty-Campos Norberto , Rodríguez-Montero Enri , Limonta-Fernández Miladys , Alonso-Valdés Marel , Hernández-Rodríguez Reinier , Pimentel-Vázquez Eulogio , Catasús-Álvarez Karem M , Cabrera-Núñez Maria V , Ayala-Ávila Marta , Muzio-González Verena L ,   for the ABDALA Group of Investigators
Published: September 2022

Background

The pandemic of COVID-19 raised the urgent need of safe and efficacious vaccines against SARS-CoV-2. We evaluated the efficacy and safety of a new SARS-CoV-2 virus receptor-binding domain (RBD) vaccine.

Methods

A phase 3, multicentre, randomised, double-blind, placebo-controlled trial was carried out at 18 clinical sites in three provinces of the south-eastern region of Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1, in blocks) to two groups: placebo, and 50 µg RBD vaccine (Abdala). The product was administered intramuscularly, 0.5 mL in the deltoid region, in a three dose immunization schedule at 0-14-28 days. The organoleptic characteristics and presentations of vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained blinded during the study period. The main endpoint was to evaluate the efficacy of the Abdala vaccine in the prevention of symptomatic COVID-19. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000359.

Findings

Between March 22 to April 03, 2021, 48290 subjects were included (24144 and 21146 in the placebo and Abdala groups, respectively). The product was well tolerated. No severe adverse events with demonstrated cause-effect relationship attributable to vaccine were reported. The incidence of adverse reactions in the placebo and Abdala vaccine arms were 446/24144 (1.9%) and 615/24146 (2.5%), respectively. Adverse reactions were mostly mild, and from the injection site, which resolved in the first 24-48 hours. The Abdala vaccine efficacy against symptomatic COVID-19 was 92.28% (95% CI 85.74-95.82). In the case of mild/moderate disease the vaccine efficacy was 91.96% (84.69-95.78) and 94.46% (58.52-99.28) for the severe forms (serious/critical disease). There were five critical patients (of which four died), all in the placebo group, indicating that Abdala vaccine efficacy for both conditions was of 100%.

Interpretation

The Abdala vaccine was safe, well tolerated, and highly effective, fulfilling the WHO target product profile for COVID-19 vaccines.

Funding

Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.