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
Condition: Ebola
MeSH terms: Hemorrhagic Fever, Ebola
Study type: Interventional
Phase: Phase 2

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.
    

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 Data Safety and
      Monitoring Board (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.
    

Intervention name(s): GS-5734; Placebo Comparator
Intervention type(s): Drug; Other
Intervention description(s): Daily GS-5734 delivered intravenously (IV) for 5 days; Placebo delivered intravenously (IV) for 5 days.
Intervention MeSH terms: Remdesivir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Liberia; Guinea