Study to Evaluate the Efficacy of GS-9131 Functional Monotherapy in Human Immunodeficiency Virus (HIV)-1-Infected Adults Failing a Nucleos(t)Ide Reverse Transcriptase Inhibitor-Containing Regimen With Nucleos(t)Ide Reverse Transcriptase Inhibitor Resistant Virus

HIV-1-infection Clinical Trial

Official title:

A Phase 2 Study to Evaluate the Efficacy of GS-9131 Functional Monotherapy in HIV-1-Infected Adults Failing a Nucleos(t)Ide Reverse Transcriptase Inhibitor-Containing Regimen With Nucleos(t)Ide Reverse Transcriptase Inhibitor Resistant Virus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03472326
• Other study ID #: GS-US-442-4148
• Status: Terminated
• Phase: Phase 2
• Start date: April 3, 2018
• Est. completion date: December 9, 2019

Study information

• Verified date: December 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the short-term antiviral potency of GS-9131 functional monotherapy compared to placebo-to-match (PTM) GS-9131, each administered once daily with the existing failing antiretroviral (ARV) regimen as demonstrated by the proportion of participants achieving human immunodeficiency virus ribonucleic acid (HIV-1 RNA) > 0.5 log10 decreases from baseline after up to 14 days of therapy in HIV-1 positive, ARV treatment experienced adult participants with nucleos(t)ide resistant virus. This is a two-part study. Part 1 consists of three cohorts: 2 Sentinel Cohorts and 1 Randomized Cohort. Eligible participants from Part 1 will proceed to Part 2 followed by an optional open-label extension.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: December 9, 2019
• Est. primary completion date: December 9, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Plasma HIV-1 RNA = 500 copies/mL at screening Visit
• Currently taking a failing ARV regimen that contains 2 NRTIs and a NNRTI
• No prior or current ARV regimens containing integrase inhibitor (INSTI) or protease inhibitor (PI)
• Screening genotype must show at least the protocol defined resistance mutation profile

Key Exclusion Criteria:

• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1
• Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
• Use of an investigational drug other than the study drug
• Individuals with chronic hepatitis B virus (HBV) infection are not permitted to participate
• Active tuberculosis infection NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• GS-9131
Tablet(s) administered orally once daily
• BIC
Tablet(s) administered orally once daily
• TAF
Tablet(s) administered orally once daily
• ARV regimen
ARV regimen may consist of the ARV agents containing nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI)
• DRV
Tablet(s) administered orally once daily
• RTV
Tablet(s) administered orally once daily

Locations

Country	Name	City	State
Uganda	Joint Clinical Research Centre	Kampala
Zimbabwe	Joint Research Ethics Committee for the University of Zimbabwe College of Health Sciences and Parirenyatwa Group of Hospitals	Harare

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

Uganda,  Zimbabwe, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 Randomized Cohort: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 15	The criteria for analyzing percentage of participants with plasma HIV-1 RNA > 0.5 log10 decrease from baseline in randomized cohort was at least 50% of the participants should achieve HIV-1 RNA > 0.5 log10 decrease from baseline in the Part 1 sentinel cohort 2.	Day 15
Secondary	Part 1 Sentinel Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Day 11		Baseline, Day 11
Secondary	Part 1 Sentinel Cohort 2: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15		Baseline, Day 15
Secondary	Part 1 Randomized Cohort: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15		Baseline, Day 15
Secondary	Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.	Week 24
Secondary	Part 2: Change From Baseline in Plasma log10 HIV-1 RNA at Week 24		Baseline, Week 24
Secondary	Part 2: Change From Baseline in CD4+ Cell Count at Week 24		Baseline, Week 24
Secondary	Part 2: Number of Participants With Treatment Emergent Nucleos(t)Ide Reverse Transcriptase Inhibitor (NRTI) Mutations at the Time of Virologic Failure	Treatment emergent virological failure was defined as an event with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of the study drug. Virologic failure was defined as virologic rebound or as suboptimal virologic response in relation to pre-GS-9131 baseline plasma HIV-1 RNA levels. Virological rebound was defined as if participant at any visit after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA = 50 copies/mL, or a >1 log10 increase in HIV-1 RNA from the nadir which was subsequently confirmed at the following scheduled or unscheduled visit. Suboptimal virologic response was defined as plasma HIV-1 RNA = 200 copies/mL and reduction in HIV-1 RNA = 1 log10 from pre-GS-9131 baseline at the Week 8 visit with confirmation at the next scheduled or unscheduled visit.	From first dose up to Week 24
Secondary	Part 2: Number of Participants With Treatment Emergent Protease Inhibitor (PI) Mutations at the Time of Virologic Failure	Treatment emergent virological failure was defined as an event with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of the study drug. Virologic failure was defined as virologic rebound or as suboptimal virologic response in relation to pre-GS-9131 baseline plasma HIV-1 RNA levels. Virological rebound was defined as if participant at any visit after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA = 50 copies/mL, or a >1 log10 increase in HIV-1 RNA from the nadir which was subsequently confirmed at the following scheduled or unscheduled visit. Suboptimal virologic response was defined as plasma HIV-1 RNA = 200 copies/mL and reduction in HIV-1 RNA = 1 log10 from pre-GS-9131 baseline at the Week 8 visit with confirmation at the next scheduled or unscheduled visit.	From first dose up to Week 24
Secondary	Part 2: Number of Participants With Treatment Emergent Integrase Strand Transfer Inhibitor (INSTI) Mutations at the Time of Virologic Failure	Treatment emergent virological failure was defined as an event with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of the study drug. Virologic failure was defined as virologic rebound or as suboptimal virologic response in relation to pre-GS-9131 baseline plasma HIV-1 RNA levels. Virological rebound was defined as if participant at any visit after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA = 50 copies/mL, or a >1 log10 increase in HIV-1 RNA from the nadir which was subsequently confirmed at the following scheduled or unscheduled visit. Suboptimal virologic response was defined as plasma HIV-1 RNA = 200 copies/mL and reduction in HIV-1 RNA = 1 log10 from pre-GS-9131 baseline at the Week 8 visit with confirmation at the next scheduled or unscheduled visit.	From first dose up to Week 24