tetano
Editor, Senior Moderator
N Engl J Med
. 2022 May 4.
doi: 10.1056/NEJMoa2202261. Online ahead of print.
Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults
Lianpan Dai[SUP] 1 [/SUP], Lidong Gao[SUP] 1 [/SUP], Lifeng Tao[SUP] 1 [/SUP], Sri R Hadinegoro[SUP] 1 [/SUP], Musabaev Erkin[SUP] 1 [/SUP], Zhifang Ying[SUP] 1 [/SUP], Peng He[SUP] 1 [/SUP], Rodman T Girsang[SUP] 1 [/SUP], Hugo Vergara[SUP] 1 [/SUP], Javed Akram[SUP] 1 [/SUP], Hindra I Satari[SUP] 1 [/SUP], Tanwir Khaliq[SUP] 1 [/SUP], Ume Sughra[SUP] 1 [/SUP], Ana P Celi[SUP] 1 [/SUP], Fangjun Li[SUP] 1 [/SUP], Yan Li[SUP] 1 [/SUP], Zhiwei Jiang[SUP] 1 [/SUP], Dilbar Dalimova[SUP] 1 [/SUP], Jaloliddin Tuychiev[SUP] 1 [/SUP], Shahlo Turdikulova[SUP] 1 [/SUP], Aamer Ikram[SUP] 1 [/SUP], Nancy Flores Lastra[SUP] 1 [/SUP], Fan Ding[SUP] 1 [/SUP], Mahendra Suhardono[SUP] 1 [/SUP], Eddy Fadlyana[SUP] 1 [/SUP], Jinghua Yan[SUP] 1 [/SUP], Zhongyu Hu[SUP] 1 [/SUP], Changgui Li[SUP] 1 [/SUP], Ibrokhim Y Abdurakhmonov[SUP] 1 [/SUP], George F Gao[SUP] 1 [/SUP], ZF2001 Global Trial Group
Affiliations
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.).
. 2022 May 4.
doi: 10.1056/NEJMoa2202261. Online ahead of print.
Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults
Lianpan Dai[SUP] 1 [/SUP], Lidong Gao[SUP] 1 [/SUP], Lifeng Tao[SUP] 1 [/SUP], Sri R Hadinegoro[SUP] 1 [/SUP], Musabaev Erkin[SUP] 1 [/SUP], Zhifang Ying[SUP] 1 [/SUP], Peng He[SUP] 1 [/SUP], Rodman T Girsang[SUP] 1 [/SUP], Hugo Vergara[SUP] 1 [/SUP], Javed Akram[SUP] 1 [/SUP], Hindra I Satari[SUP] 1 [/SUP], Tanwir Khaliq[SUP] 1 [/SUP], Ume Sughra[SUP] 1 [/SUP], Ana P Celi[SUP] 1 [/SUP], Fangjun Li[SUP] 1 [/SUP], Yan Li[SUP] 1 [/SUP], Zhiwei Jiang[SUP] 1 [/SUP], Dilbar Dalimova[SUP] 1 [/SUP], Jaloliddin Tuychiev[SUP] 1 [/SUP], Shahlo Turdikulova[SUP] 1 [/SUP], Aamer Ikram[SUP] 1 [/SUP], Nancy Flores Lastra[SUP] 1 [/SUP], Fan Ding[SUP] 1 [/SUP], Mahendra Suhardono[SUP] 1 [/SUP], Eddy Fadlyana[SUP] 1 [/SUP], Jinghua Yan[SUP] 1 [/SUP], Zhongyu Hu[SUP] 1 [/SUP], Changgui Li[SUP] 1 [/SUP], Ibrokhim Y Abdurakhmonov[SUP] 1 [/SUP], George F Gao[SUP] 1 [/SUP], ZF2001 Global Trial Group
Affiliations
- PMID: 35507481
- DOI: 10.1056/NEJMoa2202261
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.).