Efficacy and Safety of a COVID-19 Inactivated Vaccine in Healthcare Professionals in Brazil: The PROFISCOV Study

Abstract

Background: Vaccines are urgently needed to tackle the unprecedented morbidity and mortality of COVID-19. Administration of inactivated viruses are the common and mature platform of developing new vaccines. CoronaVac is an inactivated vaccine that has undergone preclinical tests and phase I/II clinical trials.

Methods: We conducted a randomised, double-blind, placebo-controlled phase 3 clinical trial with CoronaVac among healthy healthcare professionals in 16 centres in Brazil. Participants received two doses of vaccine (3 μg in 0.5 mL) vaccine or placebo at day 0 and 14. The primary efficacy endpoint was the number of symptomatic COVID-19 cases confirmed by RT-PCR 14 days after the second dose of the vaccine. Prevention of disease severity was a major secondary efficacy endpoint, and adverse events incidence up to seven days after immunization was the primary safety outcome. The trial was registered at ClinicalTrials.gov, NCT04456595.

Findings: Between July 21 and Dec 16, 2020, 12 396 participants were enrolled and received at least one vaccine or placebo dose. There were 9,823 participants who received the two doses and were followed for at least 14 days and had, therefore, reached the final efficacy analysis. There were 253 confirmed COVID-19 cases in the cohort: 85 cases (11.0/100 person-year) among 4,953 participants in the vaccine group, and 168 cases (22·3/100 person-year) among 4,870 participants in the placebo group. The primary efficacy against symptomatic COVID-19 was 50·7% (95%CI 36·0-62·0). The secondary efficacy against cases requiring assistance (score ≥3) and moderate and severe cases (score ≥4) were 83·7% (95%CI 58·0-93.7) and 100% (95%CI 56·4-100.0) respectively. All 6 cases of severe COVID-19 occurred in the placebo group. The incidence of adverse reactions, which was mainly pain at the administration site, was higher in the vaccine group (77·1%) than in the placebo group (66·4%). There were 67 serious adverse events reported by 64 participants and all were determined to be unrelated to vaccination, including two fatal cases. In a subset of participants, neutralizing antibody assays showed similar seroconversion and geometric mean titres against B.1.128, P.1, and P.2 variants.

Interpretation: A phase 3 clinical trial conducted in healthcare professionals in Brazil demonstrated that the inactivated CoronaVac vaccine has a good safety profile and is efficacious against any symptomatic SARS-CoV-2 infections and highly protective against moderate and severe COVID-19.

Note:
Trial Registration: The trial was registered at ClinicalTrials.gov, NCT04456595.

Funding Statement: Fundação Butantan, Instituto Butantan, and São Paulo Research Foundation - FAPESP (Grants 2020/10127-1 and 2020/06409-1).

Declaration of Interests: Instituto Butantan is non-profit public research institute that is part of the Secretary of Health of the State of São Paulo and acted as sponsor of the study and is Market Authorization Holder of CoronaVac in Brazil under authorization of Sinovac Life Sciences. Ricardo Palacios, Ana Paula Batista, Camila Nascimento Santos Albuquerque, Elizabeth Gonzalez Patiño, Joane do Prado Santos, Mônica Tilli Reis Pessoa Conde and Roberta de Oliveira Piorelli are full-time employees of Fundação Butantan, a non-profit organization supporting activities from Instituto Butantan. Viviane Fongaro Botosso is full-time researcher at Instituto Butantan. None of us received shares or any kind monetary compensation linked to the distribution of CoronaVac in Brazil, or have any share or financial interests in Sinovac Life Sciences or parent companies. The other investigators of the study in Brazil Ana Lúcia Lyrio de Oliveira, André Machado de Siqueira, Cor Jesus Fernandes Fontes, Danise Senna Oliveira, Eduardo Barbosa Coelho, Esper Georges Kallás, Fabiano Ramos, Fábio Eudes Leal, Francisco Hideo Aoki, Gecilmara Cristina Salviato Pileggi, Gustavo Adolfo Sierra Romero, Luis Fernando Aranha Camargo, Luiz Carlos Pereira Junior, Maurício Lacerda Nogueira, Mauro Martins Teixeira, Sonia Mara Raboni, and Danielle Bruna Leal de Oliveira received shares or any kind monetary compensation linked to the distribution of CoronaVac in Brazil, or have any share or financial interests in Sinovac Life Sciences or parent companies. Gang Zeng and Qianqian Xin are full-time employees of Sinovac Biotech Co. Ltd.

Ethic Approval Statement: The study complied with ICH Good Clinical Practices and Brazilian ethical and regulatory guidelines, and was approved by the Brazilian National Research Ethics Council - CONEP - (CAAE 34634620.1.1001.0068) and the Brazilian National Regulatory Agency - ANVISA - (CE 47/2020).

Keywords: Brazil, COVID-19, COVID-19 Vaccine, Inactivated Vaccines, Phase III Clinical Trial, Randomised controlled trial, protocol