Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey; Hacettepe University Vaccine Institute, Ankara, Turkey.
Department of Gastroenterology, Turkish Republic Ministry of Health, İstanbul Provincial Health Directorate, University of Health Sciences İstanbul Ümraniye Training and Research Hospital, İstanbul, Turkey.
Lancet. 2021 Jul 17;398(10296):213-222. doi: 10.1016/S0140-6736(21)01429-X. Epub 2021 Jul 8.
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.
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.
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).
CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile.
Turkish Health Institutes Association.
科兴新冠疫苗是一种已灭活的完整病毒 SARS-CoV-2 疫苗，在 1/2 期临床试验中，18 岁及以上人群中显示出良好的耐受性和安全性，对 SARS-CoV-2 产生良好的体液免疫应答。我们报告了科兴新冠疫苗在土耳其进行的 3 期临床试验的中期疗效和安全性结果。
这是一项双盲、随机、安慰剂对照的 3 期临床试验。在土耳其的 24 个中心，招募了 18-59 岁无 COVID-19 病史、SARS-CoV-2 PCR 和抗体检测均为阴性的志愿者。排除标准包括（但不限于）过去 6 个月内接受免疫抑制治疗（包括类固醇）、出血性疾病、脾切除和过去 3 个月内接受任何血液制品或免疫球蛋白。K1 队列由卫生保健工作者（按 1:1 的比例随机分组）组成，其他非卫生保健工作者也被招募到 K2 队列（按 2:1 的比例随机分组），使用交互式网络响应系统。研究疫苗为 3μg 已灭活 SARS-CoV-2 病毒颗粒吸附于氢氧化铝，悬浮于 0.5ml 水性溶液中。参与者在第 0 天和第 14 天接受疫苗或安慰剂（除已灭活病毒外，包含所有疫苗成分）肌内注射。主要疗效终点为在第二剂疫苗接种后至少 14 天，在方案人群中预防 PCR 确诊的有症状 COVID-19。安全性分析在意向治疗人群中进行。本研究在 ClinicalTrials.gov （NCT04582344）注册，目前正在进行中，但不再招募。
在 2020 年 9 月 14 日至 2021 年 1 月 5 日筛选的 11303 名志愿者中，有 10218 名被随机分配。由于 4 名疫苗组参与者违反方案，排除了 4 名参与者后，意向治疗组包括 10214 名参与者（疫苗组 6646 例[65.1%]，安慰剂组 3568 例[34.9%]），方案治疗组包括 10029 名参与者（疫苗组 6559 例[65.4%]，安慰剂组 3470 例[34.6%]），他们均接受了两剂疫苗或安慰剂。在中位随访期 43 天（IQR 36-48）期间，疫苗组报告了 9 例 PCR 确诊的有症状 COVID-19（每 1000 人年 31.7 例[14.6-59.3]），安慰剂组报告了 32 例（每 1000 人年 192.3 例[135.7-261.1]），第二剂疫苗接种后 14 天或更长时间，疫苗效力为 83.5%（95%CI 65.4-92.1；p<0.0001）。疫苗组发生任何不良事件的频率为 1259 例（18.9%），安慰剂组为 603 例（16.9%）（p=0.0108），无死亡或 4 级不良事件。最常见的全身不良事件是疲劳（疫苗组 546 例[8.2%]，安慰剂组 248 例[7.0%]，p=0.0228）。注射部位疼痛是最常见的局部不良事件（疫苗组 157 例[2.4%]，安慰剂组 40 例[1.1%]，p<0.0001）。
科兴新冠疫苗对 PCR 确诊的有症状 COVID-19 具有高疗效，安全性和耐受性良好。
土耳其卫生研究所协会。
