The single-dose adenovirus-vectored vaccine Ad26.COV2.S, which encodes the spike protein of SARS-CoV-2, is currently undergoing Phase III testing with the support of Johnson & Johnson. This randomized double-blind Phase III trial, known as ENSEMBLE, has enrolled 45,000 adult participants in multiple countries.
Johnson & Johnson has already completed a Phase I/II trial on its single-dose candidate. It says that it expects to report interim efficacy data from an analysis of the Phase III trial in early February 2021.
The primary outcome of the ENSEMBLE study is "Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19) with Seronegative Status". This primary endpoint is the same as was the case for the Pfizer and Moderna Phase III trials, which reported median vaccine efficacies of 95.0% and 94.1%, respectively. The AstraZeneca/Oxford vaccine, which is similar to the Johnson & Johnson vaccine in that it is also an adenoviral-vectored vaccine, has reported efficacy of 70.4%, though there are many issues with this final figure.
What will be the absolute efficacy of the single-dose Johnson & Johnson Ad26.COV2.S vaccine candidate according to the results of Phase III testing?
In this study, confirmed cases of COVID-19 are defined as molecularly confirmed (PCR positive) symptomatic cases of COVID-19 from 14 days post-vaccination.
This question resolves as the median estimate of the absolute vaccine efficacy of Ad26.COV2.S, , where ARU is the disease attack rate in the unvaccinated group and ARV is the disease attack rate in the vaccinated group. The disease attack rate is the proportion of virologically confirmed (PCR positive) symptomatic cases of COVID-19 (WHO, 2017). Such a finding should be presented in a peer-reviewed research article that is authored and/or supported by Johnson & Johnson. If no median estimate is provided, we will resolve this question on the mean absolute vaccine efficacy.
This question will close retroactively to the date when the interim results expected in early February are released. However, it will not resolve on the basis of that efficacy data — rather, it will resolve on the basis of the final phase III efficacy data in a published peer-reviewed article.