The Indian Council of Medical Research’s (ICMR) announcement that a vaccine for Covid-19 by Hyderabad-based Bharat Biotech International Ltd (BBIL) will be launched on August 15 has left the vaccine company and experts equally baffled.
In its clinical trial protocol registered with the Clinical Trial Registry of India (CTRI), BBIL has said the estimated duration of the trial is at least 15 months. So what has changed the situation? Why the hurry?
On Thursday, ICMR Director-General Balram Bhargava wrote in a communication to 13 institutes — including AIIMS in New Delhi and Patna — that all approvals and clinical trial processes need to be “fast tracked”, and that “non-compliance” would be viewed seriously. Enrolment of healthy volunteers should be initiated no later than July 7, the letter said.
BBIL had planned Phase 1 and 2 of randomised double-blind multi-centre clinical trials to evaluate the vaccine’s safety, adverse reactions, degree to which volunteers can tolerate adverse reactions. and immunogenicity (the ability of the vaccine to provoke an immune response).
It has sent vials of the vaccine candidate to the Central Research Institute (CRI) in Kasauli, Himachal Pradesh, for quality check. “We are still awaiting clearances from the CRI, Kasauli, where three batches of our vaccine candidate are being tested. This is the pre-clinical development stage. It beats us how the ICMR has made this announcement for a launch,” a company official told BusinessLine .
“To my knowledge, such an accelerated development pathway has not been done ever for any kind of vaccine, even for the ones being tried out in other countries. Even with accelerated timelines, this seems really rushed, and hence with potential risks and inadequate attention to process,” said Anant Bhan, a bio-ethics expert. Queries sent to Bhargava about his communication did not elicit a reply.
BBIL had earlier said that volunteers could be recruited for its proposed trial from July 13. So, the ICMR’s ambitious deadline has put the company in a spot. Company officials reckon that it is not easy to enrol up to 1,125 volunteers on whom the vaccine will be tested in two phases. Typically, volunteers administered a vaccine are observed for close to six months.
“It is tough to find health volunteers who have not had virologically confirmed Covid-19. Even after they are administered the dose, they will have to be asked to be careful so that they don’t contract the infection. If they do, then new volunteers will have to be found and enrolled,” the company official explained.
The trial process
In Phase 1 trial, 375 healthy volunteers aged 18-55 years will be enrolled, and most will receive two intramuscular doses of BBV152 vaccine, while others will receive Japanese Encephalitis Vaccine (JENVAC). This is in order to compare the effect of BBV152 vaccine on its potential to boost antibodies against the virus with those that receive JENVAC.
The group will be divided in a 4:1 ratio, where for every four persons who receive BBV152 vaccine in the test group, one will receive a JENVAC in the control group. The BBV152 and JENVAC doses will be administered in a gap of 14 days in the test and control groups, respectively.
Once 50 participants from 125 in the first group complete seven days of vaccination, and a data safety monitoring board recommends progression, the other two groups of 125 participants each will be taken on board.
After close to a month of this process, the progression to Phase 2 with 750 health volunteers aged 12-65 years will be considered, and the process of studying them will last six months, according to CTRI protocol.