An independent monitoring board has recommends the early termination of Ebola Therapeutics Trial in DRC Because of Favorable Results with Two of Four Candidates.
The Pamoja Tulinde Maisha (PALM [together save lives]) study is a randomized, controlled trial of four investigational agents (ZMapp, remdesivir, mAb114 and REGN-EB3) for the treatment of patients with Ebola virus disease.
The study began on November 20, 2018 in the Democratic Republic of the Congo (DRC) as part of the emergency response to an ongoing Ebola outbreak in the North Kivu and Ituri Provinces.
The trial which enrolled 681 patients toward an enrollment total of 725 started in August 9, 2019. Patients were enrolled at four Ebola Treatment Centers (ETCs) in Beni, Katwa, Butembo and Mangina and the trial was overseen by staff from the Institut National de Recherche Biomédicale (INRB); the DRC Ministry of Health; and three medical humanitarian organizations: the Alliance for International Medical Action (ALIMA), the International Medical Corps (IMC), and Médecins Sans Frontières (MSF).
The trial is monitored by an independent Data and Safety Monitoring Board (DSMB) that meets periodically to review interim safety and efficacy data and to make recommendations to the study team and the sponsors.
As a result of their August 9, 2019 review, the DSMB recommended that the study be stopped and that all future patients be randomized to receive either REGN-EB3 or mAb114 in what is being considered an extension phase of the study.
This recommendation was based on the fact that an early stopping criterion in the protocol had been met by one of the products, REGN-EB3. The preliminary results in 499 study participants indicated that those individuals receiving REGN-EB3 or mAb114 had a greater chance of survival compared to those participants in the other two arms.
The principal investigators of the study, its statistician and its co-sponsors accepted this recommendation, and the ETC staff at the sites were promptly informed. In addition to limiting future patient randomizations to REGN-EB3 and mAb114, patients who were randomized to ZMapp or remdesivir in the last 10 days now have the option, at the discretion of their treating physician, to receive either REGN-EB3 or mAb114.
According to the US National Institute of Allergy and Infectious Diseases (NIAID), while the final analysis of the data can occur only after all the data are generated and collected (likely late September/early October 2019), the DSMB and the study leadership felt the preliminary analysis of the existing data was compelling enough to recommend and implement these changes in the trial immediately.
NIAD states the complete results will be submitted for publication in the peer-reviewed medical literature as soon as possible.
The study is co-sponsored and funded by the INRB and the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. National Institutes of Health; carried out by an international research consortium coordinated by the World Health Organization (WHO); and supported by four pharmaceutical companies (MappBio, Gilead, Regeneron, and Ridgeback Biotherapeutics).