Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.
Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.
复制标题
DOI：
10.1016/s0140-6736(21)01429-x
复制
发表时间：
2021-07-17
期刊：
影响因子：
--
通讯作者：
CoronaVac Study Group
中科院分区：
文献类型：
--
作者：
Tanriover MD;Doğanay HL;Akova M;Güner HR;Azap A;Akhan S;Köse Ş;Erdinç FŞ;Akalın EH;Tabak ÖF;Pullukçu H;Batum Ö;Şimşek Yavuz S;Turhan Ö;Yıldırmak MT;Köksal İ;Taşova Y;Korten V;Yılmaz G;Çelen MK;Altın S;Çelik İ;Bayındır Y;Karaoğlan İ;Yılmaz A;Özkul A;Gür H;Unal S;CoronaVac Study Group
CoronaVac是一种灭活的全病毒体SARS-CoV-2疫苗，在1/2期试验中显示出在18岁及以上的个体中具有良好的耐受性和良好的安全性，并提供了针对SARS-CoV-2的良好体液应答。我们介绍了CoronaVac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III期试验。在土耳其的24个中心招募了18-59岁的志愿者，他们没有COVID-19病史，SARS-CoV-2的PCR和抗体检测结果均为阴性。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、无脾和过去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组成（以1：1的比例随机分配），使用交互式网络应答系统将卫生保健工作者以外的个人招募到K2队列（以2：1的比例随机分配）。研究疫苗为3 μg灭活SARS-CoV-2病毒粒子，吸附于0.5 mL水悬液中的氢氧化铝上。受试者在第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组分组成）。主要疗效结局是在符合方案人群中，在第二次给药后至少14天预防PCR证实的症状性COVID-19。在意向治疗人群中进行安全性分析。本研究已在ClinicalTrials.gov（NCT 04582344）注册，正在进行中，但不再招募。在2020年9月14日至2021年1月5日期间筛选的11303名志愿者中，随机分配了10218名。在由于方案偏离而从疫苗组中排除了4名参与者之后，意向治疗组由10214名参与者组成（疫苗组6646例[65.1%]，安慰剂组3568例[34.9%]），符合方案组包括10029例受试者（6559 [65.4%]和3470 [34.6%]）接受了两剂疫苗或安慰剂。在43天的中位随访期内（IQR 36-48），疫苗组报告了9例PCR确认的症状性COVID-19病例（31.7例[14.6 - 59.3]/1000人-年），安慰剂组报告32例（192.3例[135.7 - 261.1]/1000人-年），疫苗效力为83.5%（95%CI 65.4 - 92.1; p<0.0001）。疫苗组和安慰剂组的任何不良事件的频率分别为1259（18.9%）和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）。CoronaVac对PCR证实的症状性COVID-19具有高疗效，具有良好的安全性和耐受性。土耳其卫生研究所（TUSEB）。
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. Health Institutes of Turkey (TUSEB).