Johnson & Johnson Resumes Phase 3 Trial of COVID-19 Vaccine

Johnson & Johnson recently announced that it will resume recruitment in the Phase 3 ENSEMBLE trial of its COVID-19 vaccine, Ad26.COV2-S, after the independent Data Safety and Monitoring Board (DSMB) deemed it safe to do so. 

Following discussions with FDA, preparation to resume the trial in the US, including submissions for approval by Institutional Review Boards, are underway. 

Johnson & Johnson paused dosing participants in the clinical trial on October 13 after a patient experienced an unexplained illness. At the time, the company stated that the illness would be reviewed and evaluated by DSMB, as well as clinical and safety physicians. 

But after a thorough evaluation of the “serious medical event” experienced by the participant, experts did not identify a clear cause for the medical event. Johnson & Johnson noted that there is currently no evidence that the vaccine candidate caused the event. 

“Our primary goal is to ensure the safety, well-being and privacy of the participants and all those involved in our trials,” a Johnson & Johnson spokesperson said in the recent announcement. 

“Janssen is committed to respecting study participant privacy and the integrity of the clinical trial in which the study investigator and the participant are intentionally not informed (remain “blinded”) as to whether this participant received the vaccine candidate or placebo.” 

The Phase 3 ENSEMBLE trial is a randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of Ad26.COV2-S versus placebo in nearly 60,000 adults 18 years old and older.

Johnson & Johnson also noted a collaboration with the UK and Northern Ireland to launch a separate Phase 3 trial in multiple countries. The trial will explore a two-dose regimen of Ad26.COV2-S.

All studies conducted by pharmaceutical companies have prespecified guidelines, which ensure that a study may be paused or stopped if any unexpected serious adverse events related to the study product occur. 

When this happens, researchers will carefully review information and then decide when the study can re-start. 

Study sponsors make the call on study pauses, which are a common component of clinical trial protocol, while a regulatory hold of a clinical trial is a requirement by regulatory health authorities, including FDA, Johnson & Johnson stated.

At the end of September, the company found early positive results from the ongoing Phase 1/2a clinical trial of Ad26.COV2.S. 

The results showed that a single dose of Ad26.COV2.S induced a strong neutralizing antibody response and was well tolerated in almost all participants aged 18 years and older.

But local adverse events were reported in 58 percent of Cohort 1 participants and 27 percent of Cohort 3 participants, researchers said. Solicited systemic adverse events were also reported in 64 percent of Cohort 1 participants and 36 percent of Cohort 3 participants. 

Serious adverse events are not uncommon in clinical trials, Johnson & Johnson noted. And the number of these adverse events may increase in trials involving large numbers of participants.

The recent trial pause is a setback for the company, which is seemingly behind its competitors in the “vaccine race,” The New York Times reported last week.  

For example, Regeneron and Eli Lilly have already requested FDA emergency use authorizations for their promising COVID-19 products. 

But experts noted that Johnson & Johnson’s vaccine candidate has several advantages compared to others being tested in clinical trials, including that the vaccine is a single dose and does not need to be frozen, which could ease manufacturing and distribution concerns. 

“A single dose goes a long way, meaning we can treat more people,” Kartik Chandran, a virologist at Albert Einstein College of Medicine and the group’s leader, said in the report.