Randomized Controlled Trial
Study population and setting
This multicenter parallel randomized double-blinded study randomized participants to either placebo (aluminum adjuvant alone), WIV04 vaccine, or HB02 vaccine (both are inactivated SARS-CoV-2 vaccine with aluminum adjuvant from Sinopharm pharmaceutical company) in 1:1:1 ratio with two doses 21 days apart. The study included participants from the United Arab Emirates, Bahrain, Egypt, and Jordan. Randomization was stratified by study site using a block size of 15. Patients with confirmed SARS, MERS infection or positive SARS-CoV-2 PCR, acute respiratory illness, HIV, leukemia, lymphoma, an autoimmune disease, history of bleeding disorders or were on anti-tuberculosis treatments and pregnant women were excluded. The primary outcome was laboratory-confirmed symptomatic COVID-19 at least 14 days after the second dose. Cases were defined as mild, moderate, severe or critical according to the definition of National Health Commission of China. Vaccine efficacy was assessed using different population sets as follows: 1) participants who were PCR negative at enrollment, were randomized, received at least one treatment dose and had at least one follow up visit; 2) participants who were randomized, received at least one treatment dose and had least one follow up visit regardless of baseline PCR; 3) all participants who were PCR negative at baseline who received two treatment doses and at least one follow up visit; and 4) all participants who received two treatment doses and at least one follow up visit, regardless of baseline PCR. Subsequent analysis limited to those who were compliant to their protocol assignments were also conducted. The results presented are from the second interim analysis after a data lock on Dec 20,2021 when 142 cases of SARS-CoV-2 infection were identified in two of the study sites (UAE and Bahrain).
Summary of Main Findings
A total of 40,111 participants were randomized into the three arms. The mean age of study participants was 36.2 years (more than 97 percent below the age of 60 years), 84-85 % male, and the mean body mass index was 26-27 kg/m2. Only 5% had evidence of SARS-CoV-2 infection at study enrollment. The median duration of follow-up was 77 days (1-121 days) after two weeks of the second dose. A total of 142 cases of symptomatic COVID-19 were identified 2 weeks after the second dose (95 in the placebo arm; 26 in the WIV04 arm; 21 in the HB02 arm), representing the following incidence rates per 1,000 person-years: 44.4, 95%CI 36.6-54.6 (placebo), 12.1, 95%CI 8.3-17.8 (WIV04) and 9.8, 95%CI 6.4-15 (Hb02). Vaccine efficacy was 78.1% (95%CI 64.8-86.3) for HB02 and 72.8% (95%CI 58.1-82.4) for WIV04. Two cases of severe infection were identified in the placebo group compared to zero cases in both vaccine groups. . There were no differences in solicited or unsolicited adverse events reported among the three groups.
Since this is a randomized double-blinded study, biases due to selection or outcome ascertainment were unlikely to impact the study results. Symptomatic cases were adjudicated by two independent masked committees, further minimizing the risk of ascertainment bias. The study included more than 40,000 participants with multiple racial backgrounds, which strengthens the study’s external validity.
The mean age of the study participants was 36.1 years and the majority of participants were male, with no symptomatic COVID-19 infection in people over age 60 years, which limits generalizability. No data pertaining to comorbidities were reported in the main manuscript or in the supplementary material. While balance between the study groups in regard to medical conditions is expected due to randomization and the large sample size, generalizing the study results to other settings might be limited if the study population was generally free of comorbidities. While the study included participants with multiple racial backgrounds, it included three sites in only two countries (UAE and Bahrain) which may limit generalizing results to settings where the SARS-CoV-2 transmission rates could be different. The median duration of the follow up was 3 months after the second dose, which limits inferences on vaccine efficacy beyond this period. The study didn’t address the efficacy of the WIV04 or HB02 vaccines against any of the new variant strains.
This study presents interim analyses from the first trial to evaluate the efficacy of two inactivated SARS-CoV-2 vaccines against symptomatic COVID-19 disease.
This review was posted on: 11 July 2021