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 mu g 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. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
C1 [Tanriover, Mine Durusu] Hacettepe Univ, Sch Med, Dept Internal Med, Ankara, Turkey.
[Akova, Murat; Unal, Serhat] Hacettepe Univ, Sch Med, Dept Infect Dis & Clin Microbiol, Ankara, Turkey.
[Gur, Hazal] Hacettepe Univ, Sch Med, Dept Med Microbiol, Ankara, Turkey.
[Tanriover, Mine Durusu; Akova, Murat; Unal, Serhat] Hacettepe Univ, Vaccine Inst, Ankara, Turkey.
[Doganay, Hamdi Levent] Univ Hlth Sci, Istanbul Umraniye Training & Res Hosp, Istanbul Prov Hlth Directorate, Dept Gastroenterol,Turkish Republ Minist Hlth, Istanbul, Turkey.
[Guner, Hatice Rahmet; Azap, Alpay] Ankara Yildirim Beyazit Univ, Ankara City Hosp, Dept Infect Dis & Clin Microbiol, Ankara, Turkey.
[Akhan, Sila] Kocaeli Univ, Sch Med, Dept Infect Dis & Clin Microbiol, Kocaeli, Turkey.
[Kose, Sukran] Izmir Univ Hlth Sci, Tepecik Training & Res Hosp, Izmir Prov Hlth Directorate, Dept Infect Dis,Turkish Republ Minist Hlth, Izmir, Turkey.
[Erdinc, Fatma Sebnem] Ankara Numune Training & Res Hosp, Ankara Prov Hlth Directorate, Turkish Republ Minist Hlth, Dept Infect Dis, Ankara, Turkey.
[Akalin, Emin Halis] Bursa Uludag Univ, Bursa Uludag Univ Hosp, Hlth Applicat & Res Ctr, Dept Infect Dis & Clin Microbiol, Bursa, Turkey.
[Tabak, Omer Fehmi] Istanbul Univ Cerrahpasa, Cerrahpasa Med Sch, Dept Infect Dis & Clin Microbiol, Istanbul, Turkey.
[Pullukcu, Husnu] Ege Univ, Sch Med, Dept Infect Dis & Clin Microbiol, Izmir, Turkey.
[Batum, Ozgur] Univ Hlth Sci, Dr Suat Seren Chest Dis & Surg Training & Res Hos, Izmir Prov Hlth Directorate, Dept Chest Dis,Turkish Republ Minist Hlth, Izmir, Turkey.
[Yavuz, Serap Simsek] Istanbul Univ, Istanbul Sch Med, Dept Infect Dis & Clin Microbiol, Istanbul, Turkey.
[Turhan, Ozge] Akdeniz Univ, Sch Med, Dept Infect Dis & Clin Microbiol, Antalya, Turkey.
[Yildirmak, Mustafa Taner] Prof Dr Cemil Tascioglu City Hosp, Istanbul Prov Hlth Directorate, Turkish Republ Minist Hlth, Dept Infect Dis & Clin Microbiol, Istanbul, Turkey.
[Koksal, Iftihar] Acibadem Univ, Atakent Hosp, Dept Infect Dis & Clin Microbiol, Istanbul, Turkey.
[Tasova, Yesim] Cukurova Univ, Balcali Hosp, Dept Infect Dis & Clin Microbiol, Hlth Applicat & Res Ctr, Adana, Turkey.
[Korten, Volkan] Marmara Univ, Sch Med, Dept Infect Dis & Clin Microbiol, Istanbul, Turkey.
[Yilmaz, Gurdal] Karadeniz Tech Univ, Sch Med, Dept Infect Dis & Clin Microbiol, Trabzon, Turkey.
[Celen, Mustafa Kemal] Dicle Univ, Sch Med, Dept Infect Dis & Clin Microbiol, Diyarbakir, Turkey.
[Altin, Sedat] Univ Hlth Sci, Istanbul Yedikule Chest Dis & Thorac Surg Trainin, Istanbul Prov Hlth Directorate, Dept Chest Dis,Turkish Republ Minist Hlth, Istanbul, Turkey.
[Celik, Ilhami] Kayseri City Training & Res Hosp, Turkish Republ Minist Hlth, Dept Infect Dis & Clin Microbiol, Kayseri, Turkey.
[Bayindir, Yasar] Inonu Univ, Turgut Ozal Hlth Ctr, Dept Infect Dis & Clin Microbiol, Malatya, Turkey.
[Karaoglan, Ilkay] Gaziantep Univ, Sahinbey Res & Applicat Ctr, Dept Infect Dis & Clin Microbiol, Gaziantep, Turkey.
[Yilmaz, Aydin] Ataturk Chest Dis & Thorac Surg Training & Res Ho, Ankara Kecioren Sanat, Ankara Prov Hlth Directorate, Dept Chest Dis,Turkish Republ Minist Hlth, Ankara, Turkey.
[Ozkul, Aykut] Ankara Univ, Fac Vet Med, Dept Virol, Ankara, Turkey.