A new trial evaluating the efficacy of investigational therapeutics mAb114, remdesivir, and ZMapp has launched in the Democratic Republic of the Congo.
In the wake of the largest Ebola outbreak in the history of the Democratic Republic of the Congo (DRC), an international team of investigators have launched first-ever multidrug trial for Ebola treatment which will include individuals affected by the devasting outbreak in the North Kivu Province.
More than 160 individuals in this outbreak have been treated with investigational therapies from companies such as Regeneron Pharmaceuticals, Inc and Gilead Sciences, under an ethical framework called the Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI).
“Until now, patients have been treated under a compassionate use protocol, with drugs that showed promise and had a good safety profile in laboratory conditions,” Tedros Adhanom Ghebreyesus, MD, World Health Organization (WHO) Director-General said in a recent statement. “The giant step the DRC is taking now will bring clarity about what works best, and save many lives in years to come. We hope to one day say that the death and suffering from Ebola is behind us.”
The randomized controlled trial, which will evaluate the effectiveness and safety of multiple investigational therapeutics, is being coordinated by the WHO and led and sponsored by the DRC’s National Institute for Biomedical Research (INRB), in partnership with the DRC Ministry of Health, the National Institute of Allergy and Infectious Diseases (NIAID), The Alliance for International Medical Action and other groups.
The trial is currently enrolling patients of all ages with confirmed Ebola virus disease at a treatment center in the Beni health zone. The trial is expected to expand to additional treatment centers and health zones throughout the DRC in the future.
Participants will be randomly assigned to receive 1 of the investigational treatments by intravenous infusion. The treatments include mAb114, a single monoclonal antibody developed by NIAID, with early support from the INRB; remdesivir (also known as GS-5734), an antiviral drug developed by Gilead Sciences, Inc; and a monoclonal antibody cocktail treatment ZMapp, developed by Mapp Biopharmaceutical Inc. The international investigators also have a plan to amend the trial to include evaluating REGN-EB3 (also known as REGN3470-3471-3479), a monoclonal antibody cocktail developed by Regeneron Pharmaceuticals, Inc.
While the participants recover from Ebola, onsite clinicians will monitor their symptoms and collect blood samples. Once they have fully recovered, participants will be permitted to leave the treatment center but will be asked to return 2 months later for follow-up and additional bloodwork.
ZMapp is the only investigational therapeutic that was tested in an efficacy trial—during the 2014-2016 Ebola outbreak in West Africa—however, efficacy could not be definitively established at that time due to a small number of trial participants.
In October the WHO convened a meeting of the international investigators, drug developers, and partners in the trial to agree on a framework that will continue the trial into the next Ebola outbreak. By continuing the trial, data will accumulate to help investigators draw conclusions across multiple outbreaks about the currently available drugs, something not currently collected under the MEURI protocol. The investigators hope to enroll 112 patients per arm, potentially over multiple outbreaks.
“This clinical trial marks a significant and important step forward for the DRC and our international partners,” Jean-Jacques Muyembe-Tamfum, MD, PhD, director general of the INRB who is the co-principal investigator of the study, said in a statement. “We are eager to learn more about each of these investigational treatments as we continue to work tirelessly to identify new cases, trace contacts and control the spread of disease.”