Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial.

University of the Philippines Manila, Ermita, Manila, Philippines. Clover Biopharmaceuticals, Cambridge, MA, USA. Duke University Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. Oxford Vaccine Group, University of Oxford, Oxford, UK. Manila Doctors Hospital, Manila, Philippines. Asian Hospital and Medical Center, Alabang, Muntinlupa, Philippines. Global Research in Infectious Diseases, Singapore. Centro de Estudios en Infectología Pediátrica, Universidad Del Valle Clínica Imbanaco, Cali, Colombia. Clinica De La Costa, Barranquilla, Atlantico, Colombia. Hospital Universidad del Norte, Barranquilla, Colombia. Center of Attention in Medical Research, Bogotá, Colombia. Faculty of Health Sciences at the University of Caldas, Manizales, Colombia. Policlínico Social del Norte, Bogotá, Colombia. Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. D'Or Institute for Research and Education, Rio de Janeiro, Brazil. Federal University of Rio Grande do Norte, Natal, Brazil. Infectious Diseases Division, Universidade Federal de Santa Maria, Rio Grande do Sul, Brazil. Atena Institute of Clinical Research, Rio Grande do Norte, Natal, Brazil. University of the East Ramon Magsaysay Memorial Medical Center, Quezon City, Philippines. Far Eastern University Hospital - Nicanor Reyes Medical Foundation, Quezon City, Philippines. Las Pinas Doctors Hospital, Las Pinas City, Philippines. De La Salle Medical and Health Sciences Institute, Cavite City, Philippines. Tropical Disease Foundation, Cavite City, Philippines. Infection Control Service, St Luke's Medical Center, Taguig, Philippines. Anima Research Center, Alken, Belgium. Clinic of Infectious Diseases, CUB-Hôpital Erasme, Bruxelles, Belgium. Pulmonology Department, CHU Universite Catholique de Louvain Namur Site Sainte-Elisabeth, Namur, Belgium. Soweto Clinical Trials Centre, Johannesburg, South Africa. Wits Clinical Research, Soweto, Johannesburg, South Africa. DJW Research, Noordheuwel, Krugersdorp, Gauteng, South Africa. Dr JM Engelbrecht Trial Site, Vergelegen Mediclinic, Western Cape, South Africa. Independent Advisor, Stuart, FL, USA. Division of Paediatrics, University of Western Australia, Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute and Perth Children's Hospital, Perth, WA, Australia. Independent Advisor, New York, NY, USA. Clover Biopharmaceuticals, Chengdu, China. Global Research in Infectious Diseases, Rio de Janeiro, Brazil. Electronic address: clemens.ralf@outlook.com.

Lancet (London, England). 2022;(10323):461-472

Abstract

BACKGROUND A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019. METHODS This ongoing phase 2 and 3 double-blind, placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition, at 31 sites in five countries (Belgium, Brazil, Colombia, Philippines, and South Africa). The participants were randomly assigned 1:1 using a centralised internet randomisation system to receive two 0·5 mL intramuscular doses of SCB-2019 (30 μg, adjuvanted with 1·50 mg CpG-1018 and 0·75 mg alum) or placebo (0·9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart. All study staff and participants were masked, but vaccine administrators were not. Primary endpoints were vaccine efficacy, measured by RT-PCR-confirmed COVID-19 of any severity with onset from 14 days after the second dose in baseline SARS-CoV-2 seronegative participants (the per-protocol population), and the safety and solicited local and systemic adverse events in the phase 2 subset. This study is registered on EudraCT (2020-004272-17) and ClinicalTrials.gov (NCT04672395). FINDINGS 30 174 participants were enrolled from March 24, 2021, until the cutoff date of Aug 10, 2021, of whom 30 128 received their first assigned vaccine (n=15 064) or a placebo injection (n=15 064). The per-protocol population consisted of 12 355 baseline SARS-CoV-2-naive participants (6251 vaccinees and 6104 placebo recipients). Most exclusions (13 389 [44·4%]) were because of seropositivity at baseline. There were 207 confirmed per-protocol cases of COVID-19 at 14 days after the second dose, 52 vaccinees versus 155 placebo recipients, and an overall vaccine efficacy against any severity COVID-19 of 67·2% (95·72% CI 54·3-76·8), 83·7% (97·86% CI 55·9-95·4) against moderate-to-severe COVID-19, and 100% (97·86% CI 25·3-100·0) against severe COVID-19. All COVID-19 cases were due to virus variants; vaccine efficacy against any severity COVID-19 due to the three predominant variants was 78·7% (95% CI 57·3-90·4) for delta, 91·8% (44·9-99·8) for gamma, and 58·6% (13·3-81·5) for mu. No safety issues emerged in the follow-up period for the efficacy analysis (median of 82 days [IQR 63-103]). The vaccine elicited higher rates of mainly mild-to-moderate injection site pain than the placebo after the first (35·7% [287 of 803] vs 10·3% [81 of 786]) and second (26·9% [189 of 702] vs 7·4% [52 of 699]) doses, but the rates of other solicited local and systemic adverse events were similar between the groups. INTERPRETATION Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant. FUNDING Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations.

Methodological quality

Metadata