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

NCT02818582 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 99991613716-I-N137
• Study Type: interventional
• Target: 38
• Locations: 2 countries
• Sites: 2

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.

Conditions

Ebola

Keywords

Liberia; Guinea

Outcome Measures

Primary Outcomes (2)

• Mean Assay Negativity Rate (ANR) for Ebola Virus During the Treatment Phase

  Mean assay negativity rate (ANR) of semen samples collected during the treatment phase on days 4, 8, 11, 16, 20, 24, \& 28. Average of all time points for negative values were compiled for the collected assay values. Negativity rate per participant was calculated using all time points by calculating the number of negative results over total number of time points (7). The assay negativity rate was averaged over all participants to get the mean assay negativity rate.

  Treatment Phase (assessed at days 4, 8, 11, 16, 20, 24, & 28)

• Mean Assay Negativity Rate (ANR) for Ebola Virus During the Follow-up Phase

  Mean assay negativity rate (ANR) of semen samples collected during the follow-up phase on weeks 8, 12, 16, 20, \& 24. Average of all time points for negative values were compiled for the collected assay values. Negativity rate per participant was calculated using all time points by calculating the number of negative results over total number of time points (5). The assay negativity rate was averaged over all participants to get the mean assay negativity rate.

  Follow-up phase (assessed on weeks 8, 12, 16, 20, & 24)

Secondary Outcomes (257)

• Mean Assay Negativity Rate (ANR) for Ebola Virus During the Treatment Phase

  Treatment Phase (assessed on days 4, 8, 11, 16, 20, 24, & 28)

• Mean Assay Negativity Rate (ANR) for Ebola Virus During the Follow-up Phase

  Follow-up phase (assessed on weeks 8, 12, 16, 20, & 24)

• Mean Change From Baseline in ALT Value

  Treatment phase - Day 1

• Mean Change From Baseline in ALT Value

  Treatment phase - Day 2

• Mean Change From Baseline in ALT Value

  Treatment phase - Day 3

Study Arms (2)

GS-5734 100mg given intravenously daily for 5 days

ACTIVE COMPARATOR

Male Ebola survivors with persistent Ebola virus in their semen were given GS-5734 100mg intravenously daily for 5 days

Drug: GS-5734

Normal saline intravenously for 5 days

PLACEBO COMPARATOR

Male Ebola survivors with persistent Ebola virus in their semen were given normal saline intravenously daily for 5 days

Other: Placebo Comparator

Interventions

GS-5734 DRUG

Daily GS-5734 delivered intravenously (IV) for 5 days

GS-5734 100mg given intravenously daily for 5 days

Placebo Comparator OTHER

Placebo delivered intravenously (IV) for 5 days.

Normal saline intravenously for 5 days

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals must meet all of the following criteria to be eligible for study participation:
• Men more than or equal to 18 years of age.
• One of two semen samples with Ebola virus RNA detection (defined as a positive PCR for NP or GP using the GeneXpert assay within 42 days prior to randomization).
• Willingness to be available for study evaluations for 6 months.
• Willingness to allow storage of biological samples.
• Willingness to be followed by a Participant Tracker.
• Willingness to refrain from alcohol consumption for study days -7 to 14.
• Willingness to comply with MOH \& CDC guidance on using a condom for sexual activity and at least through week 24 of the study.

You may not qualify if:

• Individuals meeting any of the following criteria will be excluded from study participation:
• Estimated glomerular filtration rate less than 60 mL/min/1.73m\^2
• History of significant renal disease
• History of significant liver disease
• Evidence of liver disease on physical exam such as ascites
• Aspartate transaminase (AST) or alanine transaminase (ALT), greater than the upper limit of normal, a prothrombin time 1.1 times greater than the upper limits of normal, normal, or a total bilirubin \> 1.5 times the upper limits of normal(per Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity tables version 2.0 Nov. 2014).
• Presence of Grade 2 or higher abnormalities for: low hemoglobin, low white blood count (WBC), low platelets, or low or high potassium (per DAIDS toxicity tables version 2.0 Nov. 2014).
• Presence of greater than Grade 2 abnormalities for low or high sodium (per DAIDS toxicity tables version 2.0 Nov. 2014).
• Any condition that, in the opinion of the investigator, would compromise the safety of the study subject or staff, or would prevent proper conduct of the study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Gilead Sciences: collaborator

Study Sites (2)

Partnership of Clinical Research in Guinea (PREGUI) / Centre National de Formation et de Recherche en Santé Rurale de Mafèrinyah

Forécariah, Maferinyah, Guinea

Location

JFK Hospital Partnership for Research for Vaccines and Infectious Diseases in Liberia (PREVAIL)

Monrovia, FWA00021658, Liberia

Location

Related Publications (4)

• de Vries DH, Rwemisisi JT, Musinguzi LK, Benoni TE, Muhangi D, de Groot M, Kaawa-Mafigiri D, Pool R. The first mile: community experience of outbreak control during an Ebola outbreak in Luwero District, Uganda. BMC Public Health. 2016 Feb 16;16:161. doi: 10.1186/s12889-016-2852-0.

  PMID: 26883621 BACKGROUND

• Bwaka MA, Bonnet MJ, Calain P, Colebunders R, De Roo A, Guimard Y, Katwiki KR, Kibadi K, Kipasa MA, Kuvula KJ, Mapanda BB, Massamba M, Mupapa KD, Muyembe-Tamfum JJ, Ndaberey E, Peters CJ, Rollin PE, Van den Enden E, Van den Enden E. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis. 1999 Feb;179 Suppl 1:S1-7. doi: 10.1086/514308.

  PMID: 9988155 BACKGROUND

• Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011 Mar 5;377(9768):849-62. doi: 10.1016/S0140-6736(10)60667-8.

  PMID: 21084112 BACKGROUND

• Higgs ES, Gayedyu-Dennis D, Fischer Ii WA, Nason M, Reilly C, Beavogui AH, Aboulhab J, Nordwall J, Lobbo P, Wachekwa I, Cao H, Cihlar T, Hensley L, Lane HC. PREVAIL IV: A Randomized, Double-Blind, 2-Phase, Phase 2 Trial of Remdesivir vs Placebo for Reduction of Ebola Virus RNA in the Semen of Male Survivors. Clin Infect Dis. 2021 Nov 16;73(10):1849-1856. doi: 10.1093/cid/ciab215.

  PMID: 33709142 DERIVED

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola

Interventions

remdesivir

Condition Hierarchy (Ancestors)

Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections

Results Point of Contact

• Title: Higgs, Elizabeth
• Organization: National Institute of Allergy and Infectious Diseases

ehiggs@niaid.nih.gov

+1 301 768 3947

Study Officials

• Elizabeth S Higgs, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2016
• First Posted: June 29, 2016
• Study Start: July 1, 2016
• Primary Completion: August 31, 2020
• Study Completion: August 31, 2020
• Last Updated: February 15, 2022
• Results First Posted: February 15, 2022

Record last verified: 2019-10

Locations

LI (1); GU (1)