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Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials
- Source :
- JAMA
- Publication Year :
- 2020
- Publisher :
- American Medical Association, 2020.
-
Abstract
- Importance A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. Objective To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. Interventions In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 μg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 μg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). Design, setting, and participants Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. Main outcomes and measures The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. Conclusions and relevance In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. Trial registration Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.
- Subjects :
- Adult
Male
medicine.medical_specialty
COVID-19 Vaccines
Adolescent
Pneumonia, Viral
Dose-Response Relationship, Immunologic
Aluminum Hydroxide
Antibodies, Viral
01 natural sciences
Injections, Intramuscular
law.invention
03 medical and health sciences
Young Adult
Betacoronavirus
0302 clinical medicine
Immunogenicity, Vaccine
Randomized controlled trial
Adjuvants, Immunologic
Double-Blind Method
law
Internal medicine
Propiolactone
medicine
Humans
030212 general & internal medicine
0101 mathematics
Adverse effect
Pandemics
Randomized Controlled Trials as Topic
business.industry
SARS-CoV-2
Immunogenicity
Viral Vaccine
010102 general mathematics
COVID-19
Viral Vaccines
General Medicine
Preliminary Communication
Interim analysis
Antibodies, Neutralizing
Clinical trial
Vaccination
Vaccines, Inactivated
Inactivated vaccine
Female
business
Coronavirus Infections
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- JAMA
- Accession number :
- edsair.doi.dedup.....f5762b5bc83bbcd16d93fe060b865ba9