Investigational Therapeutics for the Treatment of People With Ebola Virus Disease

Summary

Background: Ebola virus can cause serious illness or death. No medicines are approved to treat it. Researchers need to test new medicines to see if they help people recover from Ebola and are safe to give. They need to test the drugs and compare them in a controlled way. Researchers want to test 4 drugs with people who have Ebola and are in treatment centers. Objective: To study the safety and effectiveness of 4 drugs for people with Ebola virus. Eligibility: People of any age with Ebola infection who are in treatment centers Design: Participants will be screened with questions, medical history, and blood tests. Participants will be randomly assigned to get 1 of 3 study drugs: * ZMapp by IV over about 4 hours. It will be given 3 times, 3 days apart. * Remdesivir by IV over about 1 hour. It will be given once a day for 10 days. * Mab114 by IV for 30-60 minutes. It will be given 1 time. * REGN-EB3 by IV for about 2 hours. It will be given 1 time. For at least a week, participants will stay in isolation in a clinic. They will: * Get supportive care and be monitored * Have a small plastic tube (IV) put in an arm vein for several days to give fluids and collect blood. * Get their study drug. * Be monitored for disease signs and drug side effects. They may get medicines for side effects. * Have blood and urine tests. Participants will stay in the clinic until they finish the study drug and are well enough to leave. Participants will have 2 follow-up visits over 2 months. They will answer questions and give blood and semen samples. ...

Timeline

Start

2018-11-21

Primary completion

2019-09-09

Completion

2020-08-18

Outcome

Met primary endpoint

paper death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007) PMID 31774950 ↗

release “the PALM Trial was stopped early following a pre-specified interim analysis that showed the superiority of Inmazeb in preventing death versus two other investigational treatments.” regeneron.com ↗

release “a randomized, controlled trial evaluating four investigational therapies for Ebola virus infection was stopped early because REGN-EB3 was superior to ZMapp in preventing death.” regeneron.com ↗

release “REGN-EB3, a triple-antibody cocktail, demonstrated superior efficacy compared to the ZMapp control arm across multiple measures, including the primary endpoint of mortality at day 28” regeneron.com ↗

release “REGN-EB3 was shown to save lives in the PALM trial” regeneron.com ↗

release “REGN-EB3 crossed the pre-specified superiority threshold for preventing death compared to the control arm, ZMapp®.” regeneron.com ↗

Publications

• Ottoni MP, Ricciardone JD, Nadimpalli A, Singh S, Katsomya AM, Pokoso LM, Petrucci R. Ebola-negative neonates born to Ebola-infected mothers after monoclonal antibody therapy: a case series. Lancet Child Adolesc Health. 2020 Dec;4(12):884-888. doi: 10.1016/S2352-4642(20)30278-9.
• Mulangu S, Dodd LE, Davey RT Jr, Tshiani Mbaya O, Proschan M, Mukadi D, Lusakibanza Manzo M, Nzolo D, Tshomba Oloma A, Ibanda A, Ali R, Coulibaly S, Levine AC, Grais R, Diaz J, Lane HC, Muyembe-Tamfum JJ; PALM Writing Group; Sivahera B, Camara M, Kojan R, Walker R, Dighero-Kemp B, Cao H, Mukumbayi P, Mbala-Kingebeni P, Ahuka S, Albert S, Bonnett T, Crozier I, Duvenhage M, Proffitt C, Teitelbaum M, Moench T, Aboulhab J, Barrett K, Cahill K, Cone K, Eckes R, Hensley L, Herpin B, Higgs E, Ledgerwood J, Pierson J, Smolskis M, Sow Y, Tierney J, Sivapalasingam S, Holman W, Gettinger N, Vallee D, Nordwall J; PALM Consortium Study Team. A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. N Engl J Med. 2019 Dec 12;381(24):2293-2303. doi: 10.1056/NEJMoa1910993. Epub 2019 Nov 27.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Ansuvimab	Monoclonal antibody	50 mg/kg	Intravenous
Subject	REGN-EB3	Monoclonal antibody	150 mg/kg	Intravenous
Subject	Remdesivir	Small molecule	2.5 mg/kg	Intravenous
Subject	Remdesivir	Small molecule	100 mg	Intravenous
Subject	ZMapp	Monoclonal antibody	50 mg/kg	Intravenous

Indications