Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02363322
Recruitment Status : Completed
First Posted : February 16, 2015
Results First Posted : May 14, 2019
Last Update Posted : June 5, 2019
Sponsor:
Collaborators:
The Ministry of Health and Social Welfare, Liberia
The Ministry of Health and Sanitation, Sierra Leone
Institut National de la Santé Et de la Recherche Médicale, France
The Ministry of Health and Public Hygiene, Guinea
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Tracking Information
First Submitted Date  ICMJE February 13, 2015
First Posted Date  ICMJE February 16, 2015
Results First Submitted Date  ICMJE August 7, 2018
Results First Posted Date  ICMJE May 14, 2019
Last Update Posted Date June 5, 2019
Actual Study Start Date  ICMJE March 13, 2015
Actual Primary Completion Date December 31, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 19, 2019)
Mortality [ Time Frame: 28 days ]
Death at Day 28
Original Primary Outcome Measures  ICMJE
 (submitted: February 13, 2015)
Mortality [ Time Frame: 28 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2019)
  • Number of Participants With ZMapp Infusion-related Adverse Events [ Time Frame: 10 Days ]
    Adverse events related to ZMapp infusions
  • Plasma Viral Load [ Time Frame: 28 days ]
    Time to viral clearance
Original Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2015)
  • Clinical and virology effects of experimental treatment [ Time Frame: 28 days ]
  • Adverse Events [ Time Frame: Throughout ]
  • Plasma Viral Load [ Time Frame: Throughout ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Putative Investigational Therapeutics in the Treatment of Patients With Known Ebola Infection
Official Title  ICMJE A Multicenter Randomized Safety and Efficacy Study of Putative Investigational Therapeutics in the Treatment of Patients With Known Ebola Infection
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ebola Virus Infection
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Active Comparator: A/Current Standard of Care Alone
    A/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
    Intervention: Other: A/Current Standard of Care Alone
  • Experimental: B/Current Standard of Care Plus ZMapp

    B/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.

    Interventions:
    • Drug: B/Current Standard of Care Plus ZMapp
    • Other: A/Current Standard of Care Alone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 4, 2018)
72
Original Estimated Enrollment  ICMJE
 (submitted: February 13, 2015)
1000
Actual Study Completion Date  ICMJE December 31, 2017
Actual Primary Completion Date December 31, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Guinea,   Liberia,   Sierra Leone,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02363322
Other Study ID Numbers  ICMJE 150083
15-I-0083 ( Other Identifier: NIH Office of Protocol Services )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE
  • The Ministry of Health and Social Welfare, Liberia
  • The Ministry of Health and Sanitation, Sierra Leone
  • Institut National de la Santé Et de la Recherche Médicale, France
  • The Ministry of Health and Public Hygiene, Guinea
Investigators  ICMJE
Principal Investigator: Richard T Davey, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP