NCT02818582

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

Completed Phase 2 Results posted Last updated 15 February 2022

What this trial tests

Phase 2 trial testing GS-5734 in Ebola in 38 participants. Completed in 31 August 2020.

Timeline

1 July 2016

Primary endpoint
31 August 2020

31 August 2020

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	38
Start date	1 July 2016
Primary completion	31 August 2020
Estimated completion	31 August 2020
Sites	2 locations across Liberia, Guinea

Drugs / interventions tested

• GS-5734 — full drug profile →
• Placebo Comparator

Conditions studied

• Ebola — all drugs for Ebola →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 18 to 99, male only, with Ebola. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Assay Negativity Rate (ANR) for Ebola Virus During the Treatment Phase Primary · Treatment Phase (assessed at days 4, 8, 11, 16, 20, 24, & 28)

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.

Group	Value	95% CI
GS-5734 100mg Given Intravenously Daily for 5 Days	0.85	± 0.24
Normal Saline Given Intravenously Daily for 5 Days	0.76	± 0.3

Mean Assay Negativity Rate (ANR) for Ebola Virus During the Follow-up Phase Primary · Follow-up phase (assessed on weeks 8, 12, 16, 20, & 24)

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.

Group	Value	95% CI
GS-5734 100mg Given Intravenously Daily for 5 Days	0.96	± 0.1
Normal Saline Given Intravenously Daily for 5 Days	0.81	± 0.29

Mean Assay Negativity Rate (ANR) for Ebola Virus During the Treatment Phase Secondary · Treatment Phase (assessed on days 4, 8, 11, 16, 20, 24, & 28)

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.

Group	Value	95% CI
GS-5734 100mg Given Intravenously Daily for 5 Days	0.86	± 0.24
Normal Saline Given Intravenously Daily for 5 Days	0.86	± 0.19

Mean Assay Negativity Rate (ANR) for Ebola Virus During the Treatment Phase Secondary · Treatment Phase (assessed on days 4, 8, 11, 16, 20, 24, & 28)

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.

Group	Value	95% CI
GS-5734 100mg Given Intravenously Daily for 5 Days	0.79	± 0.25
Normal Saline Given Intravenously Daily for 5 Days	0.28	± 0.35

Mean Assay Negativity Rate (ANR) for Ebola Virus During the Follow-up Phase Secondary · Follow-up phase (assessed on weeks 8, 12, 16, 20, & 24)

Mean assay negativity rate (ANR) of semen samples collected during the follow-up phase - 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.

Group	Value	95% CI
GS-5734 100mg Given Intravenously Daily for 5 Days	0.95	± 0.12
Normal Saline Given Intravenously Daily for 5 Days	0.9	± 0.19

Mean Assay Negativity Rate (ANR) for Ebola Virus During the Follow-up Phase Secondary · Follow-up phase (assessed on weeks 8, 12, 16, 20, & 24)

Mean assay negativity rate (ANR) of semen samples collected during the follow-up phase - 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.

Group	Value	95% CI
GS-5734 100mg Given Intravenously Daily for 5 Days	1	± 0
Normal Saline Given Intravenously Daily for 5 Days	0.33	± 0.23

Mean Change From Baseline in ALT Value Secondary · Treatment phase - Day 1

Mean change from baseline in alanine transaminase (ALT) value at day 1

Group	Value	95% CI
GS-5734 100mg Given Intravenously Daily for 5 Days	3.6	± 11.94
Normal Saline Given Intravenously Daily for 5 Days	-2.22	± 7.48

Mean Change From Baseline in ALT Value Secondary · Treatment phase - Day 2

Mean change from baseline in alanine transaminase (ALT) value at day 2

Group	Value	95% CI
GS-5734 100mg Given Intravenously Daily for 5 Days	2.25	± 11.61
Normal Saline Given Intravenously Daily for 5 Days	-0.56	± 7.25

Mean Change From Baseline in ALT Value Secondary · Treatment phase - Day 3

Mean change from baseline in alanine transaminase (ALT) value at day 3

Group	Value	95% CI
GS-5734 100mg Given Intravenously Daily for 5 Days	4.05	± 12.25
Normal Saline Given Intravenously Daily for 5 Days	10.28	± 18.05

Mean Change From Baseline in ALT Value Secondary · Treatment phase - Day 4

Mean change from baseline in alanine transaminase (ALT) value at day 4

Group	Value	95% CI
GS-5734 100mg Given Intravenously Daily for 5 Days	8.45	± 13.2
Normal Saline Given Intravenously Daily for 5 Days	11.78	± 20.74

Mean Change From Baseline in ALT Value Secondary · Treatment phase - Day 5

Mean change from baseline in alanine transaminase (ALT) value at day 5

Group	Value	95% CI
GS-5734 100mg Given Intravenously Daily for 5 Days	13.15	± 14.64
Normal Saline Given Intravenously Daily for 5 Days	9.22	± 14.97

Mean Change From Baseline in ALT Value Secondary · Treatment phase - Day 8

Mean change from baseline in alanine transaminase (ALT) value at day 8

Group	Value	95% CI
GS-5734 100mg Given Intravenously Daily for 5 Days	21.45	± 21.09
Normal Saline Given Intravenously Daily for 5 Days	4.89	± 7.88

Adverse events — posted to ClinicalTrials.gov

Time frame: 24 Weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

GS-5734 100mg Given Intravenously Daily for 5 Days

Serious: 0/20 (0%)

Deaths: 0/20

Normal Saline Given Intravenously Daily for 5 Days

Serious: 0/18 (0%)

Deaths: 0/18

Other adverse events (19 terms — click to expand)

Reaction	System	GS-5734 100mg Given Intrav…	Normal Saline Given Intrav…
Decreased appetite	Metabolism and nutrition disorders	—	—
Headache	Nervous system disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Infusion site pain	General disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Dizziness	Cardiac disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—
Eye pain	Eye disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Tendon pain	Musculoskeletal and connective tissue disorders	—	—
Tremor	Nervous system disorders	—	—
Ecchymosis	Skin and subcutaneous tissue disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—

Data from ClinicalTrials.gov NCT02818582 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19.
   Eastman RT, Roth JS, Brimacombe KR, Simeonov A, et al · · 2020 · cited 595× · PMID 32483554 · DOI 10.1021/acscentsci.0c00489
2. The ProTide Prodrug Technology: From the Concept to the Clinic.
   Mehellou Y, Rattan HS, Balzarini J. · · 2018 · cited 225× · PMID 28792763 · DOI 10.1021/acs.jmedchem.7b00734
3. Remdesivir against COVID-19 and Other Viral Diseases.
   Malin JJ, Suárez I, Priesner V, Fätkenheuer G, et al · · 2020 · cited 202× · PMID 33055231 · DOI 10.1128/cmr.00162-20
4. The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold.
   Yates MK, Seley-Radtke KL. · · 2019 · cited 160× · PMID 30529089 · DOI 10.1016/j.antiviral.2018.11.016
5. Innovation and trends in the development and approval of antiviral medicines: 1987-2017 and beyond.
   Chaudhuri S, Symons JA, Deval J. · · 2018 · cited 136× · PMID 29758235 · DOI 10.1016/j.antiviral.2018.05.005
6. Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies.
   Singh AK, Singh A, Singh R, Misra A. · · 2020 · cited 110× · PMID 32428865 · DOI 10.1016/j.dsx.2020.05.018
7. A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir.
   Liang C, Tian L, Liu Y, Hui N, et al · · 2020 · cited 68× · PMID 32563812 · DOI 10.1016/j.ejmech.2020.112527
8. Remdesivir: From Ebola to COVID-19.
   Santoro MG, Carafoli E. · · 2021 · cited 45× · PMID 33388129 · DOI 10.1016/j.bbrc.2020.11.043