An independent monitoring board recommended early termination of the PALM trial after determining that 2 of the 4 experimental therapies were linked with better rates of survival.
A clinical trial evaluating 4 experimental therapeutics for Ebola virus disease has been halted after an independent data and safety monitoring board determined 2 of the therapies were linked with better rates of survival.
The PAmoja TuLinde Maisha (PALM [together save lives]) clinical trial was launched on November 20, 2018 as part of the response to an ongoing Ebola outbreak in the Democratic Republic of the Congo (DRC).
The randomized, multicenter, controlled trial was designed to evaluate the safety and efficacy of 3 antibody-based investigational agents for the treatment of Ebola: REGN-EB3, ZMapp, and mAb114, and 1 small molecule antiviral remdesivir.
The primary objective of the trial was to compare mortality in patients with Ebola who received either REGN-EB3, mAb114, or remdesivir with those who received ZMapp in the control arm.
As of August 9, 2019, the trial had enrolled 681 patients toward an enrollment of 725 individuals from 4 treatment centers in Beni, Katwa, Butembo, and Mangina.
The trial is monitored by an independent data and safety monitoring board that meets regularly to review interim safety and efficacy data. When the board met on August 9, it recommended that the study be halted, as individuals receiving REGN-EB3 or mAb114 had a greater chance of survival compared with the other treatment arms.
Based on the preliminary findings, REGN-EB3 (Regeneron) and mAb114 (Ridgeback Biotherapeutics) will be the 2 investigational treatments administered as part of an Extension Phase to further evaluate safety until final results of the clinical trial are known. After the results are finalized, an Expanded Access Phase will be initiated using the lead therapeutic from the trial.
Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, told Contagion® that among people with low viral loads, only 6% of participants who received REGN-EB3 died and only 11% of those who received mAb-114 died. On the other hand, 33% of participants who received remdesivir and 24% of participants who received ZMapp died.
According to the National Institutes of Health (NIH), in addition to limiting therapeutics 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.
"REGN-EB3 is a 3-antibody cocktail designed with the goal of enhancing efficacy, reducing the development of viral sequences that lead to resistance, and increasing potential utility in future outbreaks as viruses continually evolve," Christos Kyratsous, PhD, vice president of research, infectious diseases and viral vector technologies at Regeneron, said in a press release. "The Regeneron rapid response infectious disease platform has the opportunity to accelerate our response to future epidemics and pandemics, and we continue to work on additional diseases that may pose a threat to public health."
The NIAID, part of the NIH, and the Institut National de Recherche Biomedicale in the DRC jointly sponsored the trial.
A press release issued by NIH indicates that final analysis of the data is expected in late September or early October and complete results will be submitted for publication in peer-reviewed medical literature as soon as possible.