Clinical Trial Center (CTC) of Iran University of Medical Sciences, Tehran, Iran.
Stem Cell Technology Research Center (STRC), Tehran, Iran.
Virol J. 2023 Jul 18;20(1):154. doi: 10.1186/s12985-023-02121-z.
We compared Fakhravac and BBIBP-Corv2 vaccines in a phase III trial.
We conducted a multicenter, parallel-group, active-control, non-inferiority clinical trial with pragmatic considerations assessing the safety and efficacy of Fakhravac and BBIBP-Corv2 vaccines. We started with two randomized double-blind arms and added two non-randomized open-label arms (based on participant preference) because of slow recruitment. The adult population received 0.5 ml (10 µg per dose) intramuscular injections of Fakhravac or BBIBP-Corv-2 vaccines 21 days apart. The primary outcome was the occurrence of PCR-positive symptomatic Covid-19 disease 14 days or more after the second injection. A 10% non-inferiority margin to the reported 72.8% efficacy of BBIBP-Corv2 was assumed. Cox proportional hazard modeling was used to estimate hazard ratios and their 95% confidence intervals.
We enrolled 24,056 adults in four groups (randomized-Fakhravac: 824, randomized-BBIBP-Corv2: 832; Non-randomized-Fakhravac: 19,429, Non-randomized-BBIBP-Corv2: 2971). All observed local and systemic adverse reactions were generally self-limited and resolved completely. We observed similar Serious Adverse Event (SAE) rates in the BBIBP-Corv2 (2.57, 95% CI 1.33-4.49) and Fakhravac (2.25, 95% CI 1.72-2.89) groups; none of which were related to the vaccines received. We recorded 9815 Medically Attendant Adverse Events (MAAE), 736 of which were categorized as somehow related. The rate of related MAAE in the Fakhravac was similar to the BBIBP-Corv2 groups (0.31 and 0.26 per 1000 person-day) in the randomized and considerably higher (0.24 and 0.07 per 1000 person-day) in the non-randomized arms. We observed 129 (35% of the 365 required by target sample size) events of PCR + symptomatic Covid-19 during four months of active follow-up in the randomized arm, demonstrating that those receiving the Fakhravac vaccine were significantly less likely (HR = 0.69; 95% CI 0.49-0.98) to be diagnosed with PCR + symptomatic Covid-19 compared with those receiving BBIBP-Corv2 vaccine. After adjusting for type I error using the O'Brien Fleming method, the Fakhravac vaccine was non-inferior to the BBIBP-Corv2 (assuming a 10% non-inferiority margin to the reported 72.8% BBIBP-Corv2 vaccine efficacy; HR < 1.35) (One-way test: HR = 0.66; 99.8% CI 0.38-1.15). In the non-randomized arm, the results were inconclusive (HR = 1.23; 95% CI 0.96-1.61). We observed 5 cases of hospitalized Covid-19 in the randomized arm, none of which occurred in the Fakhravac vaccine group. Those receiving the Fakhravac vaccine were four times less likely to go to the hospital because of a Covid-19 diagnosis (HR = 0.24; 95% CI 0.10-0.60). The vaccine efficacy of the Fakhravac vaccine is estimated to be 81.5% (95% CI 81-82.4%).
Fakhravac inactivated SARS-CoV-2 vaccine has comparable safety and efficacy to the BBIBP-Corv2 vaccine. Trial registration This study was registered with the Iranian Registry of Clinical Trials ( www.irct.ir : IRCT20210206050259N3).
我们在一项 III 期试验中比较了 Fakhravac 和 BBIBP-Corv2 疫苗。
我们进行了一项多中心、平行组、活性对照、非劣效性临床研究，考虑到实际情况评估了 Fakhravac 和 BBIBP-Corv2 疫苗的安全性和有效性。由于招募缓慢，我们开始时设有两个随机双盲臂，并增加了两个非随机开放标签臂（基于参与者的偏好）。成年人群接受 0.5 毫升（每次剂量 10µg）肌肉内注射 Fakhravac 或 BBIBP-Corv-2 疫苗，间隔 21 天。主要结局是第二次注射后 14 天或更长时间 PCR 阳性有症状的 Covid-19 疾病的发生。假设 BBIBP-Corv2 报告的 72.8%有效性的 10%非劣效性边界。使用 Cox 比例风险模型估计风险比及其 95%置信区间。
我们在四个组中招募了 24056 名成年人（随机-Fakhravac：824，随机-BBIBP-Corv2：832；非随机-Fakhravac：19429，非随机-BBIBP-Corv2：2971）。所有观察到的局部和全身不良反应通常是自限性的，完全消退。我们在 BBIBP-Corv2（2.57，95%CI 1.33-4.49）和 Fakhravac（2.25，95%CI 1.72-2.89）组中观察到相似的严重不良事件（SAE）发生率；没有一个与接受的疫苗有关。我们记录了 9815 例医学随访不良事件（MAAE），其中 736 例被归类为某种程度相关。Fakhravac 组相关 MAAE 的发生率与 BBIBP-Corv2 组相似（随机组为每 1000 人天 0.31 和 0.26，非随机组为每 1000 人天 0.24 和 0.07）。在随机臂的四个月主动随访中，我们观察到 129 例（目标样本量所需的 365 例的 35%）PCR+症状性 Covid-19 事件，这表明与接受 BBIBP-Corv2 疫苗相比，接受 Fakhravac 疫苗的人明显不太可能（HR=0.69；95%CI 0.49-0.98）被诊断为 PCR+症状性 Covid-19。使用 O'Brien Fleming 方法调整 I 型错误后，Fakhravac 疫苗与 BBIBP-Corv2 疫苗相比不劣效（假设 10%的非劣效性边界为 BBIBP-Corv2 疫苗报告的 72.8%有效性；HR<1.35）（单向检验：HR=0.66；99.8%CI 0.38-1.15）。在非随机臂中，结果不确定（HR=1.23；95%CI 0.96-1.61）。我们在随机臂中观察到 5 例住院 Covid-19 病例，其中均未发生在 Fakhravac 疫苗组。因 Covid-19 诊断而住院的 Fakhravac 疫苗接种者发生的可能性低四倍（HR=0.24；95%CI 0.10-0.60）。Fakhravac 灭活 SARS-CoV-2 疫苗的疫苗效力估计为 81.5%（95%CI 81-82.4%）。
Fakhravac 灭活 SARS-CoV-2 疫苗与 BBIBP-Corv2 疫苗具有相当的安全性和有效性。试验注册：本研究在伊朗临床试验注册中心（www.irct.ir：IRCT20210206050259N3）注册。
