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 1044 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.

Results

The New England Journal of Medicine published the results of this trial on December 12, 2019.

Results: A total of 681 patients were enrolled from November 20, 2018, to August 9, 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 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), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). 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. Four serious adverse events were judged to be potentially related to the trial drugs.

Conclusions: Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response.