Putative Investigational Therapeutics in the Treatment of Patients With Known Ebola Infection

Ebola Virus Infection Clinical Trial

Official title:

A Multicenter Randomized Safety and Efficacy Study of Putative Investigational Therapeutics in the Treatment of Patients With Known Ebola Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02363322
• Other study ID #: 150083
• Secondary ID: 15-I-0083
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 13, 2015
• Est. completion date: December 31, 2017

Study information

• Verified date: June 2018
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background:

• Ebola is a viral infection that can spread quickly and causes life-threatening disease. Right now there is an Ebola outbreak in many countries in West Africa. There are no approved treatments for Ebola. But possible treatments are being developed. Researchers need to study these treatments to see if they help people get better.

Objective:

• To identify possible Ebola treatments. Also, to learn if adding 1 or more experimental drugs to advanced Ebola care can reduce the risk of death.

Eligibility:

• People who have recently been diagnosed with Ebola, usually by a test called the Polymerase Chain Reaction (PCR), and have been hospitalized in an isolation unit for treatment.

Design:

• Participants will be randomly assigned to Group A or B. Both groups will get advanced level care. One group will also get an experimental drug.

• Participants may have blood tests. They may have another PCR test.

• Researchers will try to learn how the participant got Ebola.

• Participants put in the experimental drug group may start taking medicine within 24 hours of enrollment. It may be given by mouth or intravenously. Additional doses may be needed.

• Participants may have a series of timed blood tests over the first 24 to 48 hours after they take the medicine.

• Blood will be drawn frequently. Other body fluids (urine, stool, vaginal fluid, etc.) may also be collected.

• Participants will be followed for up to 60 days. They may be evaluated for any long-term effects of the experimental treatment(s). They may be asked to return for 1 or more outpatient visits.

• For consenting participants, follow-up will be extended for up to one full year past Day 58 with contact/visits every 1-3 months to assess for a history of signs or symptoms potentially consistent with late onset of virologic relapse syndrome.

Description:

Ebolaviruses (EBOV) are members of the Filoviridae and are known primarily as the underlying cause of severe viral hemorrhagic fevers with disturbingly high case fatality rates. Between 1994 and the present, there have been many EBOV outbreaks affecting mostly central Africa, with 2 large outbreaks in 1995 in Kikwit, Democratic Republic of Congo (DRC), and in Gulu, Uganda in 2000-2001. However, the 2014 West African outbreak significantly exceeds all previous outbreaks in geographic range, number of patients affected, and in disruption of typical activities of civil society.

There is strong consensus that the most important element necessary to improve survival from Ebola infection is the provision of full hemodynamic support in the form of aggressive fluid replacement, ability to diagnose and correct severe metabolic derangements, and other standards of modern medical care available in resource-rich environments. However, against this background, a small series of investigational agents or interventions have also been proposed as putative antiviral strategies of potential utility in treating this infection. Unfortunately, phase 1/2 data supporting the safety and efficacy of these agents is generally lacking, and thus there should be equipoise as to which, if any, of these interventions should be utilized in the treatment of severe infection.

In this multicenter randomized trial, we propose a flexible trial design with frequent interim monitoring to facilitate early elimination of poorly performing treatments as well as the introduction of new candidate therapies. The trial allows for a series of pairwise comparisons of novel interventions against a background of optimized medical care, with the goal of determining whether one or more of these interventions can improve the mortality over that achievable through optimized standard-of- care (oSOC) alone. The primary endpoint of this trial will be comparative mortality at Day 28, with a number of secondary endpoints that hopefully will generate generalizable knowledge about the relative safety and antiviral activity of these adjunctive interventions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: December 31, 2017
• Est. primary completion date: December 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

• INCLUSION CRITERIA:

• Males or females with documented positive PCR for Ebola virus infection within 10 days of enrollment

• Willingness of study participant to accept randomization to any assigned treatment arm

• Access to oSOC

• All males and females of childbearing potential, must be willing to use highly effective methods of contraception [e.g. absolute abstinence from potentially reproductive sexual activity, hormonal, surgical or multiple barrier/combined], from time of enrollment for the duration of study participation.

• Must agree not to enroll in another study of an investigational agent prior to completion of last required protocol visit (Day 58)

• Ability to provide informed consent personally, or by a legally-authorized [per applicable local laws and regulations] representative [LAR] if the patient is unable to do so.

EXCLUSION CRITERIA:

• Any medical condition that, in the opinion of the site investigator, would place the patient at an unreasonably increased risk through participation in this study, including any past or concurrent conditions that would preclude randomization to one or more of the assigned treatment arms.

• Prior treatment with any investigational antiviral drug therapy against Ebola infection other than experimental vaccines, within 5 half-lives or 30 days, whichever is longer, prior to enrollment

Related Conditions & MeSH terms

• Communicable Diseases
• Ebola Virus Infection
• Hemorrhagic Fever, Ebola
• Infection
• Virus Diseases

Intervention

Drug:
• B/Current Standard of Care Plus ZMapp
Triple monoclonal cocktail of antibodies against Zaire species of Ebola virus

Other:
• A/Current Standard of Care Alone
Optimized standard of care for Ebola virus infection

Locations

Country	Name	City	State
Guinea	CTE Forecariah	Forecariah
Liberia	Monrovia Medical Unit	Monrovia
Liberia	ELWA III Hospital	Paynesville
Sierra Leone	Police Training School 1 (PTS1), Western Rural District	Freetown
Sierra Leone	Emergency Ebola Treatment Unit	Goderich
Sierra Leone	Police Training School 2	Hastings
Sierra Leone	Chinese Friendship Hospital	Jui
Sierra Leone	International Medical Corps (IMC) Kambia	Kambia
Sierra Leone	International Medical Corps (IMC) Lunsar	Port Loko
Sierra Leone	Adventist Development and Relief Ebola Treatment Unit	Waterloo
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (5)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Institut National de la Santé Et de la Recherche Médicale, France, The Ministry of Health and Public Hygiene, Guinea, The Ministry of Health and Sanitation, Sierra Leone, The Ministry of Health and Social Welfare, Liberia

Countries where clinical trial is conducted

United States,  Guinea,  Liberia,  Sierra Leone, 

References & Publications (3)

Joffe S. Evaluating novel therapies during the Ebola epidemic. JAMA. 2014 Oct 1;312(13):1299-300. doi: 10.1001/jama.2014.12867. — View Citation

Kanapathipillai R. Ebola virus disease--current knowledge. N Engl J Med. 2014 Sep 25;371(13):e18. doi: 10.1056/NEJMp1410741. — View Citation

Piot P, Muyembe JJ, Edmunds WJ. Ebola in west Africa: from disease outbreak to humanitarian crisis. Lancet Infect Dis. 2014 Nov;14(11):1034-1035. doi: 10.1016/S1473-3099(14)70956-9. Epub 2014 Oct 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality	Death at Day 28	28 days
Secondary	Number of Participants With ZMapp Infusion-related Adverse Events	Adverse events related to ZMapp infusions	10 Days
Secondary	Plasma Viral Load	Time to viral clearance	28 days

External Links

•   NIH Clinical Center Detailed Web Page