Randomized Controlled Trial of Ebola Virus Disease Therapeutics in the Democratic Republic of the Congo

International Medical Corps was part of the PALM/Pamoja Tulinde Maisha (“Together Save Lives” in the Kiswahili language) Consortium study team that conducted a trial of four investigational therapies for EVD in the DRC, where an outbreak began in August 2018. The four investigational therapies for EVD used in this trial were intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114 and the triple monoclonal antibody REGN-EB3. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase– polymerase-chain-reaction assay were enrolled and randomly assigned to the four groups in a 1:1:1:1 ratio. A total of 681 patients were enrolled from November 2018 to August 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial. The recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 33.5% of patients in the REGN-EB3 group and 35.1% of patients in the MAb114 group, as compared with 49.7% of patients in the ZMapp group and 53.1% in the Remdesivir group. The findings suggest that both MAb114 and REGN-EB3 were better than ZMapp in reducing deaths from EVD. The trial also found that a shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. The successful conclusion of this very challenging trial showed that it is possible to conduct scientifically and ethically sound clinical research during disease outbreaks, even in conflict zones, and can help inform the outbreak response.

Start Date:2018

End Date:2019

Partners: Brown University
Médecins sans Frontières (MSF)
Alliance for International Medical Action (ALIMA)
National Institute of Allergy and Infectious Diseases/ US National Institutes of Health
WHO Geneva
PALM consortium members
Institut National de Recherche Biomédicale
Democratic Republic of Congo Ministry of Health

Donors: National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)

Publications: The New England Journal of Medicine