843. The PALM Consortium: A Multicenter, Multioutbreak Randomized Controlled Trial of Ebola Virus Disease Therapeutics

Abstract

BackgroundRecent outbreaks of Ebola virus disease in the Democratic Republic of the Congo (DRC) reinforce the desperate need to establish definitively the comparative safety and efficacy of different medical countermeasures (MCM).MethodsThrough a multipartner governance framework under WHO coordination, the Institut National de Recherche Biomédicale and NIAID collaborated with clinical partners (the MOH, ALIMA, MSF) to launch a randomized controlled trial in 2018 in the North Kivu/Ituri provinces of DRC. PCR+ participants receiving enhanced supportive care are being randomized 1:1:1:1 to receive either ZMapp™ (control arm), remdesivir, mAb114, or REG-EB3 according to standard treatment regimens. Stratification is by site, country, and baseline nucleoprotein (NP) PCR cycle threshold (CT) ≤ 22 or > 22. The primary objective is a comparison of 28-day mortality relative to the control arm. The planned accrual is for 125 patients per arm. Secondary objectives include an evaluation of the comparative safety and tolerability of the 4 investigational MCMs, relative changes in viral load over time, comparisons of treatment efficacy according to baseline risk categories, 58-day mortality, RNA clearance from semen, and an assessment of the validity of drug-class comparisons, including efficacy. The study is monitored by an independent data and safety monitoring committee (DSMB).ResultsEnrollment commenced in the Ebola Treatment Unit in Beni in November, 2018, with sites in Butembo and Katwa added in early 2019. Time from study concept initiation to study start was only 3.5 months. Ongoing hurdles encountered to date include maintenance of cold chain requirements for the MCMs and marked volatility in the security situation surrounding sites affecting staff and patient safety. Despite these challenges, data quality and completed follow-up have been remarkably high and by mid-April, 2019, accrual to date (see table) had already surpassed the predefined threshold triggering an interim DSMB review.ConclusionScientifically rigorous and ethically sound clinical research can take place during disease outbreaks even within a conflict zone. Results about the relative efficacy of the evaluated investigational MCMs are pending the completion of the trial. Disclosures All Authors: No reported Disclosures.