Now Reading
Bharat Biotech’s Covaxin Phase 3 Trial Paper Published, Finally

Bharat Biotech’s Covaxin Phase 3 Trial Paper Published, Finally

In this illustrative photograph, vials labelled ‘Covaxin’ are seen on a table. Photo: Reuters

  • Bharat Biotech had its paper describing Covaxin’s phase 3 trial finally published by The Lancet on November 11.
  • The paper reiterates the principal conclusions of the preprint paper of the trial that Bharat Biotech researchers had uploaded in July 2021.
  • Notably, the published paper refutes Bharat Biotech chairman Krishna Ella’s claim that a trial participant’s death was due to suicide.
  • The paper also describes gaps in what we know about Covaxin and what we don’t know well enough, and the need for more research.

New Delhi: On November 11, The Lancet journal published a long-awaited paper – describing the phase 3 trial of Covaxin, the COVID-19 vaccine manufactured by Hyderabad-based Bharat Biotech.

The published paper repeats the principal conclusions of the preprint paper that the trial researchers had uploaded in July 2021 – that Covaxin has an efficacy of 77.8% against symptomatic infections of the ‘original’ strain of the novel coronavirus.

The figure was slightly higher among participants younger than 60 years and lower by almost 10 percentage points among those older than 60.

What the paper leaves out could be just as instructive. For example, on November 10, Bharat Biotech chairman Krishna Ella had said at a public event that a trial participant who had died in Bhopal did so by suicide. The newly published paper, however, rules out this possibility.

Specifically, the paper states that 15 trial participants died during the course of the trial. Not one of them has been officially attributed to the vaccine.

Ella’s comment was about the vaccine trial site at People’s Hospital, Bhopal, where people were tricked into participating in the trial. One of these participants later died, casting doubt on whether data from the site could be included in the overall analysis without crossing ethical boundaries.

In all, the phase 3 trial enrolled 25,573 participants – divided (almost) equally into two groups: one that received the vaccine (treatment group) and one that received the placebo (control group).

According to the paper, five participants in the treatment group – due to cerebellar haemorrhage, haemorrhagic stroke, ovarian cancer, sudden cardiac death and COVID-19. Ten participants in the control group died because of alcohol overdose, myocardial infarction, cardiac arrest with underlying hypertension and COVID-19.

Both the paper and an independent commentary, also published by The Lancet, have said Covaxin was safe and well-tolerated among participants. The known side effects aside, they said the shot didn’t elicit any serious life-treating allergic reactions during the trial.

The Drug Controller General of India (DCGI) had approved Covaxin for public use in “clinical trial mode” on January 3, 2021 – at a time when the phase 3 trial was yet to reach even its first endpoint (a threshold, such as the number of COVID-19 cases among participants, that would signal the trial can yield meaningful insights).

The DCGI had said then that the vaccine was “110% safe”. Other government scientists and officials also touted Covaxin’s various purported benefits over other vaccines available at the time – including that it could be stored in a ‘regular’ refrigerator and that it could be more effective against newer strains of the virus – to justify approving it.

The paper published in The Lancet reiterates Covaxin’s safety and easy storage.

On the flip side, Covaxin’s phase 3 trial was limited to 25 hospitals around India; there were no trial sites outside India, contrary to the trials of other major vaccines, including Covishield. This limited the vaccine’s assessment to a limited population, the independent commentary read.

Second, the paper admits, “The study population also lacked ethnic and racial diversity, highlighting the importance of evaluating the efficacy of BBV152 (Covaxin) in other populations.”

Bharat Biotech had planned a trial in Brazil but had to abandon it due to “exacerbating conditions” there – presumably the corruption scandal that erupted around Brazil’s efforts to import Covaxin from India.

The paper also states that since pregnant women, people living with HIV and people with severe comorbidities were excluded from the trial, more studies will have to be conducted before approving the vaccine’s use among members of these groups.

The phase 3 trial’s primary outcome was the number of COVID-19 infections 14 days after participants had received both doses. The secondary outcome was the vaccine’s ability to prevent the occurrence of severe COVID-191.

The researchers recorded that 16 people had severe COVID-19 during the trial – one in the treatment group and 15 in the control group, yielding an efficacy of 93.4%, which was more than Covaxin’s efficacy on the primary outcome.

However, the efficacy plummeted to 63.6% against asymptomatic infections of COVID-19 – even if this finding may not be reliable.

In large clinical trials, researchers seldom arrive at single-point measurements of various variables. Instead, the measurements can vary across a range called the confidence interval (CI). The narrower a CI is, the more reliable the measurement is said to be. The phase 3 trial paper published in The Lancet, however, specified a wide CI for Covaxin’s efficacy against asymptomatic infections.

Therefore, the paper writes, researchers will have to conduct more studies to assess Covaxin’s performance against asymptomatic infections.

It’s notable that none of the vaccines approved against COVID-19 have thus far demonstrated efficacy against asymptomatic infection in a clinical trial. The Pfizer-BioNTech vaccine may be the first among equals here: it has been “associated with decreased asymptomatic SARS-CoV-2 infections in health-care workers,” the paper itself says.

“Generally, the apparent protection against severe COVID-19 is most crucial, but the capability of preventing asymptomatic infection would also protect against mild disease, transmission and eventually might lead to a reduction in subsequent cases of severe COVID-19,”  the independent commentary reads.

Similarly, the paper’s authors – led by Raches Ella, project lead, COVID-19 vaccines at Bharat Biotech – write that they conducted “preliminary” analyses of Covaxin versus the virus’s variants of concern.

They reported that the vaccine had a similar efficacy against the alpha variant (B.1.1.7) as it did against the ‘original’, wild-type strain (B.1), but lower efficacy against the beta (B.1.351), gamma (P.1) and delta (B.1.617.2) variants.

Against the delta variant in particular – currently the dominant strain in India – Ella & co. wrote that Covaxin had an efficacy of 65.2%, and that they would have to conduct more studies to ascertain these findings.

The commentary also concluded:

The next step for studies of BBV152 should be a focus on monitoring for epidemiological variations in SARS-CoV-2 and the long-term vaccine efficacy against symptomatic COVID-19 and asymptomatic infection to identify whether the vaccine provides ongoing protection when any [variant of concern] replacement (other than [those] investigated in this study) has occurred.

  1. At least one of the following symptoms: clinical signs at rest that are indicative of severe systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic or neurological dysfunction; admission to an ICU; or death

Scroll To Top