New Delhi: Bharat Biotech, the Hyderabad-based firm that has developed the indigenous Covid vaccine candidate Covaxin, is still thousands of volunteers short of its target for its ongoing Phase 3 trials.
Trial sites conducting the study on the vaccine say the company has given them an indicative deadline of 31 December to complete the recruitment of volunteers, but some claim it is unlikely they will be able to do so.
On 22 December, Bharat Biotech announced it had recruited 13,000 volunteers — a little over half of the total 25,800 volunteers needed — since the study was launched on 11 November. Speaking to ThePrint Thursday, a company representative said another couple of thousand have been recruited in the days since. They, however, denied that Bharat Biotech has asked volunteer recruitment to be completed by any particular date.
Bharat Biotech is one of three companies looking to secure emergency-use authorisation in India, where no vaccine has been approved for use so far.
The vaccine’s Phase 2 trial has found it to be safe with no serious adverse events, according to a non-peer-reviewed study released earlier this week, but it needs to undergo extensive Phase 3 trials before it can be cleared for use on the public.
The basic difference between Phase 2 and 3 trials — both involving human subjects — is that the latter requires a far wider pool of participants to get a clearer, more accurate picture of vaccine efficacy and safety.
‘As soon as possible’
As of Thursday, Covaxin, a joint initiative between Bharat Biotech and the Indian Council of Medical Research, was being studied at 26 trial sites around the country.
Speaking to ThePrint, principal investigators at several sites said the company had conveyed to them verbally at a virtual meeting that they should aim to complete volunteer recruitment by 31 December, although not at the cost of proper procedure.
Bharat Biotech meets with the principal investigators of trial sites virtually at least once a week to be apprised of the situation on ground as well as to provide support to the trial sites.
“In a virtual meeting, we were asked to complete volunteer recruitment by the 31st — as soon as possible. Trial sites that had completed their initial target were given more volunteers to recruit. Most places have finished with 1,000 volunteers,” said Dr Dhananjay Lad, managing director of Goa-based CROM Clinical research, which is helping two trial sites with recruitment.
The vaccine follows a two-dose schedule, given 28 days apart. By the 31st, the investigators said, Bharat Biotech hopes all volunteers are given at least the first shot. The investigators said it isn’t a hard deadline, but described it as ambitious nevertheless.
“We were initially given a target of 1,000, which we completed by the first week of December itself. They asked us to do it for 500 more volunteers, but we refused because it was too much for us,” added Dr Mohammed Shameem, principal investigator at Aligarh Muslim University, a trial site.
“We have started with the second dose of the vaccine. Managing documentation and follow-up would have become a challenge if we took on more volunteers,” he said.
A principal investigator at a site in South India said recruiting more volunteers will take time.
“The sponsor is a sponsor, so they want to finish the trial as soon as possible, but safety comes first. We have already finished with 1,000 volunteers at our site and have been asked to recruit 500 more, but it will take time,” added the investigator, who did not wish to be named.
“We may not be able to meet the deadline. People are coming, but it is happening slowly. We can’t speed up at the cost of safety, so we will finish recruitment with all precautions,” the investigator said.
Another investigator from an eastern state said they “are all trying our best to be done with the recruitment process soon”.
“It was told to us that the sooner it is done, the better, and we were not asked to compromise anything. There is no vaccine hesitancy, but we will have to spread the word faster and people will have to volunteer faster if we are to finish by the 31st,” the investigator added.
Dr N.T. Awad, a principal investigator at Lokmanya Tilak Municipal Medical College and General hospital, Mumbai, said, “We joined the trial late, and it will be a challenge for us to complete (recruitment) by the 31st because volunteers are not coming forward in large numbers. They did make a request to complete the recruitment soon, but it will be difficult for us.”
Seeking emergency-use authorisation
On 7 December, Bharat Biotech sought emergency-use authorisation of Covaxin through an application to the Modi government’s Subject Expert Committee, which advises regulator Drugs Controller General of India on approvals for new drugs and vaccines. However, it was advised to return with data from the ongoing Phase 3 trial.
According to the trial design, available with the Clinical Trial Registry of India, the trial will conclude after a total of 130 participants turn Covid-19 positive, with safety to be monitored for a further 12-month duration.
A first and second formal interim analysis will take place when one-third and two-thirds of the participants turn PCR-positive.
The purpose of this analysis is to compare the number of positive cases in the vaccine arm with the placebo arm, to ascertain the vaccine’s efficacy.
An internal analysis of the vaccine’s immunogenicity will take place by day 56 of the trial, or by early January 2021. This analysis will take place on a subset of 600 participants, 450 of whom will be from the vaccine arm, and 150 from the placebo arm.
“The Immunogenicity study will assess the immune response of a 2-dose regimen of BBV152B vaccine through geometric mean titers (GMTs) by neutralizing antibody, S-protein, and RBD specific anti-IgG binding titer in a subset of 600 (450 vaccine: 150 control) participants, across three consecutive manufacturing lots,” says a brief summary of the trial design.
“Data generated through Day 56 (Month 2) will be unblinded only to the biostatistician for evaluation of immune responses in the Immunogenicity subset,” the summary adds.
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