Investigators attached with the phase III trial of Bharat Biotech’s Covaxin said that while they have at least four months of data to assess safety and immunogenicity from phase I/II trials, they are yet to gather statistical data on its efficacy from phase III trial.
The Drug Controller General of India (DCGI)-Central Drug Standards Control Organisation (CDSCO) on Sunday gave restricted emergency approval for Covaxin and Serum Institute of India’s Covishield.
“I am surprised the DCGI made an overnight decision based on subject expert committee’s (SEC) recommendation. Ideally DCGI reviews the documents recommended by SEC and that can take a few days,” said Dr Dhananjay Lad, attached with Redkar Hospital and Research Centre, Goa, a site for phase I/II and now phase III trial of Covaxin.
Lad said the vaccine was found to be “extremely safe” for use in Phase I and II except for mild adverse reactions like fever and pain at site for a day. “A vaccine has to be measured for safety as well as efficacy. Covaxin has ability to induce an immune response but for how long we don’t know. The phase III trials are ongoing and we will get answers once recruitment is over and data is analysed,” he said.
Covaxin is an inactivated virus developed in public private partnership between ICMR, NIV and Bharat Biotech. Bharat Biotech began phase I/II human trial in July and commenced phase III trial in November across 26 sites to cover 25,800 participants. It has recruited 22,500 so far, but only around 10,000 have received both doses, while the rest have only got the first dose, several investigators confirmed.
Dr Mohammad Shameem, an investigator with Aligarh Muslim University, said their hospital site is the first to recruit all 1,000 participants for Phase III trials. “By Monday, we will complete the second dose of all participants. But we can only start studying the efficacy 42-45 days after the first dose. That is 15 days from now.”
In Mumbai, Sion hospital has recruited less than 200 of 1,000 participants and started giving second doses last week.
Grant Government Medical College, Mumbai, has recruited close to 500 of the 1,000 participants. “We began the second dose last week. Till now only 83 have been given both doses,” said Dr Dinesh Dhodi from the pharmacology department.
“We have not seen severe adverse reactions in our participants but we have refrained from recruiting people with uncontrolled diabetes or blood pressure. We need to wait for DCGI to issue conditions of approval for this vaccine. I believe only those with controlled comorbidity can be given the vaccine for now.”
In AIIMS Patna, Dr Chandramani Singh said they have given the first dose to 1,177 participants but only a few have got the second dose. “It will take a few weeks before we start studying efficacy,” he said.
Dr Venkata Rao from the Institute of Medical Sciences and SUM Hospital in Jajapur, also a trial site, said the pandemic called for an emergency decision. “This is just a conditional approval. Full approval will only come after phase III results.”
Rao said that apart from animal studies, phase I and II studies, Bharat Biotech has carried out a ‘neutralisation assay’ which is essentially testing blood sample of the participant for virus exposure. “All this has shown good results. In such a situation we don’t have to wait for efficacy results,” Rao added.
An efficacy result assesses whether the vaccine protects a person from Covid-19 infection. While phase I and II look at safety and immunogenicity, phase III draws data on efficacy.
“We have clinical data from phase I and II but it is not statistically significant to measure efficacy. That is why a large-scale phase III trial is important,” said Dr Savita Verma, from PGIMS, Chandigarh, which has recruited 450 participants and given the second dose to 350 participants. It has to recruit 550 more participants.
Dr Prabhakar Reddy, from Nizam’s Institute of Medical Sciences, which has so far recruited 1,600 subjects in phase I, II and III, said they have immunogenicity data on 250 participants. “In Phase 1 /2 we found 70 per cent developed immunogenicity,” he said.
The All India Drug Action Network has questioned the approval. “It is not clear if there is any scientific basis to claim that Covaxin will be effective in the context of infection by mutant strain when its efficacy has not been established and is currently unknown against any strain of virus,” it said in a statement.
In Sir Ganga Ram Hospital, efficacy in phase III is being evaluated and second dosing has begun. Investigator Dr Anupam Sachdeva refused to comment further. Dr Suman Kanungo, from ICMR-National Institute of Cholera and Enteric Diseases in Kolkata, and Dr Akshata from Vydehi Institute of Medical Sciences and Research Centre in Bengaluru, too, refused to comment over efficacy studies at their site.
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