GS-5734 to Assess the Antiviral Activity, Longer-Term Clearance of Ebola Virus, and Safety in Male Ebola Survivors With Evidence of Ebola Virus Persistence in Semen
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ClinicalTrials.gov Identifier: NCT02818582 |
Recruitment Status :
Completed
First Posted : June 29, 2016
Last Update Posted : September 30, 2020
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Tracking Information | |||||
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First Submitted Date ICMJE | June 28, 2016 | ||||
First Posted Date ICMJE | June 29, 2016 | ||||
Last Update Posted Date | September 30, 2020 | ||||
Actual Study Start Date ICMJE | July 1, 2016 | ||||
Actual Primary Completion Date | August 31, 2020 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | GS-5734 to Assess the Antiviral Activity, Longer-Term Clearance of Ebola Virus, and Safety in Male Ebola Survivors With Evidence of Ebola Virus Persistence in Semen | ||||
Official Title ICMJE | PREVAIL IV: Double-Blind, Randomized, Two-Phase, Placebo-Controlled, Phase II Trial of GS-5734 to Assess the Antiviral Activity, Longer-Term Clearance of Ebola Virus, and Safety in Male Ebola Survivors With Evidence of Ebola Virus Persistence in Semen | ||||
Brief Summary | Background: Some people have Ebola virus in their body for months after they recover from Ebola virus disease. Some may have health problems from the virus while others are fine. These people may be able to pass the virus to others. There are currently no drugs for people who have survived Ebola virus disease but still have the virus in their body. A new drug, GS-5734, might help get rid of Ebola virus in semen. Objective: To test if GS-5734 helps get rid of Ebola virus in semen and is safe for humans. Eligibility: Men who participated in the Ebola survivor study (PREVAIL III) and have evidence of the Ebola virus in their semen Design: Participants will be screened with: Questions Physical exam Eye exam Blood tests 2 semen samples if they have not had it tested recently Participants must live near the study site in Liberia for 6 months. Participants will be put into 1 of 2 study groups. They will have an infusion of either GS-5734 or a placebo every day for 5 days. A plastic tube is put into an arm vein. The infusion lasts 1 hour. Participants will be observed for 1 hour after. They will provide a semen sample on infusion day 4. After the infusions, participants will have 5 visits in the first month, then 1 per month for 5 more months. These include giving a blood and semen sample. Blood tests are performed before and after each infusion and the last visit (5 month visit) will also include an eye exam. When the study is over, if the study drug works and is safe, participants who got the placebo can get the study drug. |
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Detailed Description | With the unprecedented size of the recent 2014-2016 West African Ebola outbreak, the scientific community is learning a great deal about the psychological and physical consequences of Ebola, Ebola viral persistence in survivors, risk of Ebola disease relapse in survivors, and the potential for survivors to transmit the virus to others. Data from PREVAIL III has demonstrated that persistence of Ebola virus in the semen of male survivors is common. In addition to Ebola virus persistence, Ebola relapse causing clinical disease has been well documented. There are no licensed therapies for the treatment of Ebola virus disease nor for the clearance of persistent Ebola virus in survivors. A safe, effective therapy that can reduce and/or eliminate persistent Ebola virus from semen would reduce the risk of transmission and enable male survivors to resume normal sexual relations without fear of harming loved ones. The mechanism underlying Post-Ebola Syndrome is as yet unknown, but improvement in Post-Ebola signs and symptoms resulting from GS-5734 treatment would be an added benefit. This study is a double-blind, randomized, two-phase (treatment and longer-term follow-up), two- arm trial of GS-5734 versus placebo among male Ebola survivors with persistent Ebola virus RNA in their semen. Participants are randomized 1:1 to receive either 100 mg of GS-5734 or placebo once daily by intravenous catheter for 5 days. Informed by transaminase elevations in prior Phase I studies in normal healthy subjects, a risk-mitigation strategy includes a built-in dose de-escalation. Participants will be stratified by country and on the basis of one versus two positive semen samples for Ebola virus RNA using the Cepheid GeneXpert platform assessed within 42 days prior to study enrollment. The early DSMB review in August 2016 concluded there was no need for a cohort dose reduction. The protocol expanded to Guinea in October 2017, where the outbreak ended later. Currently there is an outbreak in the Democratic Republic of the Congo where the study team may evaluate conducting this study following the completion of the outbreak. Antiviral activity, as well as safety and tolerability, will be assessed during the treatment phase. Longer-term clearance of Ebola virus will be assessed during the 5-month follow-up phase. Primary analyses for the assessment of antiviral activity in the treatment phase will focus on the assay negativity rate (ANR; percentage of genital samples that are negative for Ebola) over the first 28 days of the study, as well as clinical and laboratory adverse events. A sample is considered negative by PCR if the test result is undetectable. Primary analysis for the follow-up phase will focus on the ANR collected monthly from months 2 to 6. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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Condition ICMJE | Ebola | ||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Completed | ||||
Actual Enrollment ICMJE |
38 | ||||
Original Estimated Enrollment ICMJE |
120 | ||||
Actual Study Completion Date ICMJE | August 31, 2020 | ||||
Actual Primary Completion Date | August 31, 2020 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Individuals must meet all of the following criteria to be eligible for study participation:
EXCLUSION CRITERIA: Individuals meeting any of the following criteria will be excluded from study participation:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 99 Years (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 | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT02818582 | ||||
Other Study ID Numbers ICMJE | 999916137 16-I-N137 |
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Has Data Monitoring Committee | Not Provided | ||||
U.S. FDA-regulated Product |
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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 | Not Provided | ||||
Investigators ICMJE |
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PRS Account | National Institutes of Health Clinical Center (CC) | ||||
Verification Date | October 2019 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |