The COVID-19 vaccine developed by Janssen, a Johnson & Johnson subsidiary, leveraging its AdVac® technology platform, is temporarily paused, 20 days after the initiation of its Phase 3 Trial ENSEMBLE. It is currently the biggest phase–III COVID-19 trial with a participant pool of 60,0000 and shows great promise as a single-shot vaccine, which would ease distribution and access across different countries including LMICs.
The trial instated a pause on account of an unexplained illness observed in a participant, to comply with its scientific and ethical principles as well as honor its commitment towards transparency while meeting the regulatory standards. The unexplained illness is currently under review, with the ENSEMBLE independent Data Safety Monitoring Board (DSMB) and internal clinical and safety physicians evaluating it. The DSMB will also check if the illness caused is due to the placebo or vaccine.
The Company stated that adverse events, especially in large cohort sizes, are expected and according to its prespecified guidelines, in cases of any unexpected Serious Adverse Event (SAE), the study must be paused and reported to review the medical details before resuming the study. It also pointed out the difference between a pause and a regulatory hold, as the study sponsor implements the former while the latter is a requirement by a regulatory authority, increasing its graveness.
Prior to the pause, Johnson & Johnson announced approval by the European Commission of an Advance Purchase Agreement allowing Janssen to supply 200 million doses of the vaccine to European Union Member states and securing an option to avail 200 million additional doses.
In light of various speculations revolving around the government’s propaganda in clinical trials, questioning trial’s transparency by underplaying the importance of clinical trials’ duration, many companies including Janssen, Moderna, AstraZeneca, and Pfizer released clinical study protocols to such assuage concerns.
Another vaccine trial that was paused is of the AZD122, jointly developed by AstraZeneca and Oxford University. While trials have resumed in UK and few other sites, it continues to be on hold in the USA. US based Inovio’s vCOVID-19 vaccine trial was also put on partial halt last month regarding concerns associated with the vaccine delivery device. Such pauses are not uncommon in larger phase-III trials but with the level of uncertainty surrounding vaccine success and development timeline, it is crucial to de-risk multiple candidates and distributing the risk of clinical trial failure proportionately across candidates. Such de-risking is now being furthered by the WHO COVAX Facility and is a promising move towards ensuring timely and equitable vaccine access. We have discussed in depth about the COVID-19 vaccine progress and various procurement mechanisms being put in place in our monthly blog here.