Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults

Abstract

Background: The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials.

Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only. Adult participants (≥18 years of age) were randomly assigned in a 1:1 ratio to receive a total of three 25-μg doses (30 days apart) of ZF2001 or placebo. The primary end point was the occurrence of symptomatic coronavirus disease 2019 (Covid-19), as confirmed on polymerase-chain-reaction assay, at least 7 days after receipt of the third dose. A key secondary efficacy end point was the occurrence of severe-to-critical Covid-19 (including Covid-19-related death) at least 7 days after receipt of the third dose.

Results: Between December 12, 2020, and December 15, 2021, a total of 28,873 participants received at least one dose of ZF2001 or placebo and were included in the safety analysis; 25,193 participants who had completed the three-dose regimen, for whom there were approximately 6 months of follow-up data, were included in the updated primary efficacy analysis that was conducted at the second data cutoff date of December 15, 2021. In the updated analysis, primary end-point cases were reported in 158 of 12,625 participants in the ZF2001 group and in 580 of 12,568 participants in the placebo group, for a vaccine efficacy of 75.7% (95% confidence interval [CI], 71.0 to 79.8). Severe-to-critical Covid-19 occurred in 6 participants in the ZF2001 group and in 43 in the placebo group, for a vaccine efficacy of 87.6% (95% CI, 70.6 to 95.7); Covid-19-related death occurred in 2 and 12 participants, respectively, for a vaccine efficacy of 86.5% (95% CI, 38.9 to 98.5). The incidence of adverse events and serious adverse events was balanced in the two groups, and there were no vaccine-related deaths. Most adverse reactions (98.5%) were of grade 1 or 2.

Conclusions: In a large cohort of adults, the ZF2001 vaccine was shown to be safe and effective against symptomatic and severe-to-critical Covid-19 for at least 6 months after full vaccination. (Funded by the National Science and Technology Major Project and others; ClinicalTrials.gov number, NCT04646590.).

Figure 1. Screening, Randomization, Follow-up, and Analyses Performed up to the Second Data Cutoff Date of December 15, 2021.

Eight participants who had been randomly assigned to receive placebo and instead received at least one dose of ZF2001 (protocol violation) were included in the ZF2001 group in the safety analysis. Covid-19 denotes coronavirus disease 2019.

Figure 2. Kaplan–Meier Plots of the Cumulative Incidence of Symptomatic Covid-19 in the Trial Groups.

The cumulative incidence of symptomatic Covid-19, as confirmed on real-time polymerase-chain-reaction (PCR) assay, with an onset of at least 7 days after the third dose of ZF2001 or placebo (the primary end point) in the modified full analysis set for efficacy is shown at the first data cutoff date of June 30, 2021 (Panel A) and at the second data cutoff date of December 15, 2021 (Panel B). The cumulative incidence of real-time PCR–confirmed symptomatic Covid-19, with an onset after the first dose of ZF2001 or placebo, in the full analysis set for efficacy is shown at the first data cutoff date of June 30, 2021 (Panel C) and at the second data cutoff date of December 15, 2021 (Panel D). In each panel, the inset shows the same data on an enlarged y axis.

Figure 3. Adverse Events at the Second Data Cutoff Date of December 15, 2021.

Panel A shows the incidence of adverse events, both overall and according to age group, among the participants who received at least one dose of ZF2001 or placebo. Panel B shows the overall incidence of local and systemic adverse reactions. A total of 28,873 participants were included in the safety analysis set (14,448 in the ZF2001 group and 14,425 in the placebo group); 8 participants who had been randomly assigned to receive placebo and instead received at least one dose of ZF2001 (protocol violation) were included in the ZF2001 group for the safety analysis.