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Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial

2021; Elsevier BV; Volume: 398; Issue: 10317 Linguagem: Inglês

10.1016/s0140-6736(21)02000-6

1474-547X

Raches Ella, Siddarth Reddy, William C. Blackwelder, Varsha Potdar, Pragya D. Yadav, Vamshi Sarangi, Sanjay Kumar, Suman Kanungo, Sanjay Rai, Prabhakar Reddy, Savita Verma, Chandramani Singh, Sagar Vivek Redkar, Satyajit Mohapatra, Anil Kumar Pandey, Pajanivel Ranganadin, Raghvendra Gumashta, Manish Multani, Shameem Mohammad, Parul Bhatt, Laxmi Kumari, Gajanan Sapkal, Nivedita Gupta, Priya Abraham, Samiran Panda, Sai Prasad, Balram Bhargava, Krishna M. Ella, Krishna Mohan Vadrevu, Pradeep Aggarwal, V. Aglawe, Abdullhameed May Ali, Nitin Anand, N. Awad, Varun Bafna, G. Balasubramaniyam, Archana Bandkar, P Basha, V. Bharge, Amit Bhate, Sameer Bhate, V. Bhavani, Ramesh Bhosale, DV Chalapathy, C. Chaubal, Deepak Chaudhary, Arun B. Chavan, Parth Desai, Dinesh Dhodi, Siddhartha Dutta, Rakesh Garg, Kapil Garg, Melvin George, Pankaj Goyal, Randeep Guleria, Sneh Lata Gupta, Mansi Jain, Mansi Jain, Sonal Jindal, Manju Kalra, Shashi Kant, Pooja Khosla, Prasad S. Kulkarni, Pradeep Kumar, Y Kumar, A. S. Majumdar, PritiLokesh Meshram, Vaibhav Mishra, Satyajit Mohanty, Julie McCulloh Nair, Shivam Pandey, Samir Kumar x Dr. Samir Kumar Panigrahi, Bapugouda Sahebagouda Patil, Vrunda More Patil, Prashant Rahate, Vino S. Raj, Sunita Ramanand, Kiran Rami, Balaji Ramraj, S. Rane, Venkatarao Epari, N. Mallikarjuna Rao, R. Raphael, Goutham Reddy, Vivek Redkar, Sagar Vivek Redkar, Ashutosh Sachdeva, Jayanta Saha, Jyotiranjan Sahoo, Prakash Sampath, A. Savith, Mihir Shah, S. Lokesh, Rajeev Sharma, Priyanka Sharma, Deepak Sharma, Akhil Kant Singh, Jasdeep Singh, Prateek Singh, S. Sivaprakasam, Suresh Subramaniam, D. Sudheer, Saira S Tandon, Muhammad Tariq, Vijay Tripathi, M. Vable, Rahul J Verma, Swagat Waghmare,

SARS-CoV-2 detection and testing

BackgroundWe report the clinical efficacy against COVID-19 infection of BBV152, a whole virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) in Indian adults.MethodsWe did a randomised, double-blind, placebo-controlled, multicentre, phase 3 clinical trial in 25 Indian hospitals or medical clinics to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Adults (age ≥18 years) who were healthy or had stable chronic medical conditions (not an immunocompromising condition or requiring treatment with immunosuppressive therapy) were randomised 1:1 with a computer-generated randomisation scheme (stratified for the presence or absence of chronic conditions) to receive two intramuscular doses of vaccine or placebo administered 4 weeks apart. Participants, investigators, study coordinators, study-related personnel, the sponsor, and nurses who administered the vaccines were masked to treatment group allocation; an unmasked contract research organisation and a masked expert adjudication panel assessed outcomes. The primary outcome was the efficacy of the BBV152 vaccine in preventing a first occurrence of laboratory-confirmed (RT-PCR-positive) symptomatic COVID-19 (any severity), occurring at least 14 days after the second dose in the per-protocol population. We also assessed safety and reactogenicity throughout the duration of the study in all participants who had received at least one dose of vaccine or placebo. This report contains interim results (data cutoff May 17, 2021) regarding immunogenicity and safety outcomes (captured on days 0 to 56) and efficacy results with a median of 99 days for the study population. The trial was registered on the Indian Clinical Trials Registry India, CTRI/2020/11/028976, and ClinicalTrials.gov, NCT04641481 (active, not recruiting).FindingsBetween Nov 16, 2020, and Jan 7, 2021, we recruited 25 798 participants who were randomly assigned to receive BBV152 or placebo; 24 419 received two doses of BBV152 (n=12 221) or placebo (n=12 198). Efficacy analysis was dependent on having 130 cases of symptomatic COVID-19, which occurred when 16 973 initially seronegative participants had at least 14 days follow-up after the second dose. 24 (0·3%) cases occurred among 8471 vaccine recipients and 106 (1·2%) among 8502 placebo recipients, giving an overall estimated vaccine efficacy of 77·8% (95% CI 65·2–86·4). In the safety population (n=25 753), 5959 adverse events occurred in 3194 participants. BBV152 was well tolerated; the same proportion of participants reported adverse events in the vaccine group (1597 [12·4%] of 12 879) and placebo group (1597 [12·4%] of 12 874), with no clinically significant differences in the distributions of solicited, unsolicited, or serious adverse events between the groups, and no cases of anaphylaxis or vaccine-related deaths.InterpretationBBV152 was highly efficacious against laboratory-confirmed symptomatic COVID-19 disease in adults. Vaccination was well tolerated with no safety concerns raised in this interim analysis.FundingBharat Biotech International and Indian Council of Medical Research.