Background

CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey.

Methods

This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18–59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 μg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting.

Findings

Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36–48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6–59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7–261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4–92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001).

Interpretation

CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile.

Funding

Turkish Health Institutes Association.

中文翻译：

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灭活全病毒体 SARS-CoV-2 疫苗 (CoronaVac) 的功效和安全性：在土耳其进行的一项双盲、随机、安慰剂对照的 3 期试验的中期结果

背景

CoronaVac 是一种灭活的全病毒体 SARS-CoV-2 疫苗，在 1/2 期试验中已被证明在 18 岁及以上的人群中具有良好的耐受性和良好的安全性，并且对 SARS-CoV 提供了良好的体液反应-2。我们介绍了在土耳其进行的 CoronaVac 3 期临床试验的中期疗效和安全性结果。

方法

这是一项双盲、随机、安慰剂对照的 3 期试验。在土耳其的 24 个中心招募了年龄在 18-59 岁之间、没有 COVID-19 病史且 SARS-CoV-2 PCR 和抗体检测结果呈阴性的志愿者。排除标准包括（但不限于）过去 6 个月内的免疫抑制治疗（包括类固醇）、出血性疾病、无脾以及过去 3 个月内接受过任何血液制品或免疫球蛋白。K1 队列由医护人员组成（以 1:1 的比例随机分配），并且使用交互式网络响应系统将除医护人员以外的其他人招募到 K2 队列中（以 2:1 的比例随机分配）。研究疫苗是 3 μg 灭活的 SARS-CoV-2 病毒颗粒，吸附在 0·5 mL 水性悬浮液中的氢氧化铝上。参与者在第 0 天和第 14 天肌肉注射疫苗或安慰剂（由除灭活病毒外的所有疫苗成分组成）。主要疗效结果是在每个方案中第二次剂量后至少 14 天预防经 PCR 确认的症状性 COVID-19人口。在意向治疗人群中进行了安全性分析。这项研究已在 ClinicalTrials.gov (NCT04582344) 注册，并且正在进行但不再招募。

发现

在 2020 年 9 月 14 日至 2021 年 1 月 5 日期间筛选的 11 303 名志愿者中，随机分配了 10 218 名志愿者。由于方案偏差将 4 名参与者排除在疫苗组之外后，意向治疗组由 10 214 名参与者组成（疫苗组 6646 名 [65·1%] 和安慰剂组 3568 名 [34·9%] ) 和每个协议组由 10029 名参与者（6559 [65·4%] 和 3470 [34·6%]）组成，他们接受了两剂疫苗或安慰剂。在 43 天的中位随访期间（IQR 36-48），疫苗组报告了 9 例经 PCR 确认的症状性 COVID-19（每 1000 人 31·7 例 [14·6–59·3] -年），安慰剂组报告了 32 例（每 1000 人年 192·3 例 [135·7–261·1]）在第二次接种后 14 天或更长时间，疫苗效力为 83·5% （95% CI 65·4–92·1；p< 0·0001)。任何不良事件的频率在疫苗组中为 1259 (18·9%)，在安慰剂组中为 603 (16·9%) (p=0·0108)，没有死亡或 4 级不良事件。最常见的全身性不良事件是疲劳（疫苗组 546 名 [8·2%] 名参与者和安慰剂组 248 名 [7·0%] 名参与者，p=0·0228）。注射部位疼痛是最常见的局部不良事件（疫苗组为 157 [2·4%]，安慰剂组为 40 [1·1%]，p<0·0001）。

解释

CoronaVac 对经 PCR 确认的症状性 COVID-19 具有很高的疗效，具有良好的安全性和耐受性。

资金

土耳其卫生机构协会。