Safety, Tolerability and Immunogenicity of an Inactivated SARS-CoV-2 Vaccine (CoronaVac) in Healthy Children and Adolescents: A Randomised, Double-Blind, and Placebo-Controlled, Phase 1/2 Clinical Trial

Abstract

Background: The COVID-19 vaccine for children and adolescents, who are indispensable populations to curb the pandemic, would protect this population against rare severe COVID-19 and infectious conditions. Here we aimed to assess the safety, tolerability and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in children and adolescents aged 3-17 years old. Methods: We did a randomised, double-blind, placebo-controlled phase 1/2 clinical trial of CoronaVac in healthy children and adolescents aged 3-17 years old in Zanhuang (Hebei, China). Vaccine (in 0 ·5ml aluminum hydroxide adjuvant) or placebo (adjuvant only) was given by intramuscular injection in two doses (day 0 and day 28). We conducted phase 1 trial in 71 participants with an age de-escalation in tree groups and dose-escalation in two blocks (1.5ug or 3ug per injection). Within each block, participants were randomly assigned (3:1) using block randomisation to receive CoronaVac or placebo. In phase 2, participants were randomly assigned (2:2:1) using block randomisation to receive either CoronaVac at 1.5ug or 3ug per dose, or placebo. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint was seroconversion rate at 28 days after the second injection and its GMT as the secondary endpoint. This study is ongoing and is registered with ClinicalTrials.gov (NCT04551547).Findings: Between October 31 and December 2, 2020, 72 participants were enrolled in phase 1, and between December 12 and December 30, 2020, 480 participants were enrolled in phase 2. 500 participants received at least one dose of vaccine or placebo (n=71 for phase 1 and n=479 for phase 2; safety population). In the combined safety profile of phase 1 and phase 2, any adverse reactions within 28 days after injection occurred in 56 (26%) of 219 participants in the 1·5ug group, 63 (29%) of 217 in the 3ug group and 27 (24%) of 114 in the placebo group, without significant difference. Most adverse reactions were mild and moderate in severity and injection site pain (73[13%]) of 550 participants was the most frequently reported event. As of March 12, 2021, only one serious adverse event has been reported, which was considered unrelated to vaccination. In phase 1, seroconversion after the second dose was observed in 27 of 27 participants (100·0% [95%CI 87·3-100·0]) in the 1·5ug groups and 26 of 26 participants (100·0% [86·8-100·0]) in the 3ug group, with the geometric mean titers of 55·0 (95%CI 38·9-77·9) and 117·4 (87·8-157·0). In phase 2, seroconversion was seen in 180 of 186 participants (96·8% [93·1-98·8]) in the 1·5ug group and 180 of 180 participants (100·0% [98·0-100·0]) in the 3ug group, with the geometric mean titers of 86·4 (73·9-101·0) and 142·2 (124·7-162·1). There were no detectable antibody responses in the placebo groups. Interpretation: CoronaVac was well tolerated and induced strong neutralising antibody responses in children and adolescents aged 3-17 years. The study has provided solid safety and immunogenicity data to support the further study and use of CoronaVac in children and adolescents.Trial Registration: NCT04551547Funding Statement: Chinese National Key Research and Development Program and Beijing Science and Technology Program.Declaration of Interests: QG and XL are employees of Sinovac Life Sciences Co., Ltd. YS, WY and LW are employees of Sinovac Biotech Ltd. All other authors declare no competing interests.Ethics Approval Statement: The clinical trial protocol and informed consent form were approved by the Ethics Committee of Hebei CDC (IRB2020-005).