Investigational Therapeutics for the Treatment of People With Ebola Virus Disease

NCT03719586 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 19000319-I-0003
• Study Type: interventional
• Target: 681
• Locations: 2 countries
• Sites: 2

Brief 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. ...

Conditions

Ebola Virus

Keywords

EBOV; Viral Hemorrhagic Fever; Ebola Treatment Center; Filovirus; Zaire Ebola Virus

Outcome Measures

Primary Outcomes (1)

• Mortality

  Number of Participants with Mortality by Day 28

  28 days

Secondary Outcomes (3)

• Time in Days to First Negative Ebola Virus RT-PCR in Blood.

  up to Day 28

• Viremia as Determined by CTnp Values on PCR

  Days 1, 2, 3, 4, 6, 8, 10, 14, and 28.

• Incidence of Serious Adverse Events/AEs

  up to Day 58

Study Arms (4)

A

EXPERIMENTAL

Remdesivir plus optimized Standard of Care (oSOC)

Drug: Remdesivir

B

EXPERIMENTAL

MAb114 plus optimized Standard of Care (oSOC)

Drug: MAb114

C

EXPERIMENTAL

REGN-EB3 plus optimized Standard of Care (oSOC)

Drug: REGN-EB3

Control

EXPERIMENTAL

Zmapp plus optimized Standard of Care (oSOC)

Drug: ZMapp

Interventions

ZMapp DRUG

Three doses of 50 mg/kg of body weight administered intravenously every third day beginning on Day 1

Control

Remdesivir DRUG

Administered intravenously with a loading dose on Day 1 (200 mg for adults and pediatric patients with body weight \>= 40 kg and for pediatric patients weighing \< 40 kg one loading dose of remdesivir 5 mg/kg) followed by 9 to 13 days of once-daily maintenance dosing starting on Day 2 and extending through Day 10 to 14 (100 mg for adults and pediatric patients with body weight \>= 40 kg and for pediatric patients weighing \< 40 kg remdesivir 2.5 mg/kg)

A

MAb114 DRUG

50 mg/kg of body weight administered intravenously on Day 1 as a single infusion

B

REGN-EB3 DRUG

150 mg/kg of body weight administered intravenously on Day 1 as a single infusion

C

Eligibility Criteria

• Age: Up to 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females of any age with documented positive RT-PCR in blood for acute Ebola virus infection within 3 days prior to enrollment and who have symptoms of any duration.
• Willingness of study participant to accept randomization to any assigned treatment arm.
• All males and females of childbearing potential must be willing to use effective methods of contraception, from time of enrollment until Day 58 of study.
• Must agree not to enroll in another study of an investigational agent prior to completion of Day 28 of study.
• Ability to provide informed consent personally, or by a legally acceptable representative if the patient is unable to do so.
• Patients who, in the judgment of the investigator, will be unlikely or unable to comply with the requirements of this protocol through Day 28.
• Prior treatment with any investigational antiviral drug therapy against Ebola virus infection within 5 half-lives or 30 days, whichever is longer, prior to enrollment. (Patients who have received an experimental (or, in future, potentially a licensed) immunization against Ebola virus remain eligible.)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Ebola Treatment Centers throughout the DRC

Kinshasa Gombe, Democratic Republic of the Congo

Location

Related Publications (2)

• 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.

  PMID: 33217357 DERIVED

• 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.

  PMID: 31774950 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hemorrhagic Fevers, Viral

Interventions

ZMapp; remdesivir; ansuvimab; atoltivimab, maftivimab, and odesivimab-ebgn drug combination

Condition Hierarchy (Ancestors)

RNA Virus Infections; Virus Diseases; Infections

Limitations and Caveats

By design, efficacy comparisons between the 3 investigational treatment arms and the ZMapp control arm were always restricted to those time periods when both ZMapp and the study drug were available, and there were brief periods when ZMapp became unavailable, accounting for why the total numbers compared between the arms are sometimes lower than the total number of enrolled patients. Also, the REGN-EB3 arm started enrolling later than the other three arms due to a protocol modification.

Results Point of Contact

• Title: Dr. Richard T. Davey, Jr., M.D., U.S. study PI
• Organization: NIAID/NIH

rdavey@niaid.nih.gov

301-496-8029

Study Officials

• Richard T Davey, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2018
• First Posted: October 25, 2018
• Study Start: November 21, 2018
• Primary Completion: September 9, 2019
• Study Completion: August 18, 2020
• Last Updated: September 8, 2021
• Results First Posted: September 8, 2021

Record last verified: 2020-11

Locations

DE (1); US (1)