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

Phase 1
Completed
Conditions
Ebola Virus Infection
Interventions
Other: A/Current Standard of Care Alone
Drug: B/Current Standard of Care Plus ZMapp
Registration Number
NCT02363322
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief 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.

Detailed 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 & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
72
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
A/Current Standard of Care AloneA/Current Standard of Care AloneA/Current Standard of Care Alone: Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting
B/Current Standard of Care Plus ZMappB/Current Standard of Care Plus ZMappB/Current Standard of Care Plus ZMapp: ZMapp (Trademark) + Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting. ZMapp 50mg/kg IV administered every third day for 3 infusions.
B/Current Standard of Care Plus ZMappA/Current Standard of Care AloneB/Current Standard of Care Plus ZMapp: ZMapp (Trademark) + Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting. ZMapp 50mg/kg IV administered every third day for 3 infusions.
Primary Outcome Measures
NameTimeMethod
Mortality28 days

Death at Day 28

Secondary Outcome Measures
NameTimeMethod
Plasma Viral Load28 days

Time to viral clearance

Number of Participants With ZMapp Infusion-related Adverse Events10 Days

Adverse events related to ZMapp infusions

Trial Locations

Locations (11)

National Institutes of Health Clinical Center, 9000 Rockville Pike

🇺🇸

Bethesda, Maryland, United States

CTE Forecariah

🇬🇳

Forecariah, Guinea

International Medical Corps (IMC) Lunsar

🇸🇱

Port Loko, Sierra Leone

Adventist Development and Relief Ebola Treatment Unit

🇸🇱

Waterloo, Sierra Leone

Monrovia Medical Unit

🇱🇷

Monrovia, Liberia

Police Training School 1 (PTS1), Western Rural District

🇸🇱

Freetown, Sierra Leone

ELWA III Hospital

🇱🇷

Paynesville, Liberia

International Medical Corps (IMC) Kambia

🇸🇱

Kambia, Sierra Leone

Emergency Ebola Treatment Unit

🇸🇱

Goderich, Sierra Leone

Police Training School 2

🇸🇱

Hastings, Sierra Leone

Chinese Friendship Hospital

🇸🇱

Jui, Sierra Leone

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