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)
2022; RELX Group (Netherlands); Linguagem: Inglês
10.2139/ssrn.4213351
ISSN1556-5068
AutoresFrancisco Hernández-Bernal, Maria del Carmen Ricardo-Cobas, Yenima Martín-Bauta, Ernesto Rodríguez-Martínez, Klaudia Urrutia-Pérez, Karen Urrutia-Pérez, Joel Quintana-Guerra, Zadis Navarro-Rodríguez, Marjoris Piñera-Martínez, José L. Rodríguez-Reinoso, Cristina Olimpia Chávez-Chong, Idania Baladrón-Castrillo, Grettel Melo-Suárez, Alejandro Batista-Izquierdo, Alexis R. Pupo-Micó, Ricardo L. Mora-Betancourt, Dayamí Soler-Cano, Jacqueline Bizet-Almeida, Maria C. Martínez-Rodríguez, Leonardo Lobaina-Lambert, Vivian M. Velázquez-Pérez, Jalimy Soler-Díaz, Yunaili Blanco-Garrido, Sandra Laurencio-Vallina, Tamara Meriño-Hechavarría, Norberto Carmenaty-Campos, Enri Rodríguez-Montero, Miladys Limonta-Fernández, Marel A. Valdés, Reinier Hernández-Rodríguez, Eulogio Pimentel-Vázquez, Karem M. Catasús-Álvarez, Maria V. Cabrera-Núñez, Marta Ayala-Ávila, Verena L. Muzio-González, ABDALA Group of Investigators,
Tópico(s)Hepatitis B Virus Studies
ResumoBackground: 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.Trial Registration Details: This study was registered with Cuban Public Clinical Trial Registry, RPCEC00000359.Funding Information: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.Declaration of Interests: Authors FHB, YMB, KlUP, KaUP, JQG, JLRR, IBC, GMS, MLF, MAV, RHR, KMCA, MAA, and VLMG, are employees of the Centre for Genetic Engineering and Biotechnology, Havana Network, where Abdala vaccine active ingredient is produced and the formulation was developed. The remaining authors have no conflict of interests. No honoraria, consulting fees or payments for seminar presentations, speeches or appearances have been received by any of the authors. Ethics Approval Statement: The protocol followed the guidelines of the Declaration of Helsinki and was evaluated by an ad hoc Centralized Ethics Committee, integrated by members of the Ethics and Review Committee of the Provincial Hospital “Saturnino Lora” in Santiago de Cuba (main clinical site), extended with members of the Research Ethics Committees of the Universities of Medical Sciences of Santiago de Cuba, Guantánamo and Granma, who granted ethical approval of the study. This Review Boards was made up of highly qualified medical specialists not linked to the study, as well as a member of the community. This committee followed up on the research ensuring the protection of the rights, safety and well-being of the subjects involved in the study. In addition, the Cuban Centre for State Control of Drugs, Medical Devices and Equipment approved the start of the clinical trial after considering the scientific, methodological and ethical aspects. The manuscript adheres to CONSORT reporting guidelines.
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