Clinical trial NCT03472326: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HIV-1-infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2018-03-21
Enrollment: 21
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1 Randomized Cohort: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 15
timeFrame: Day 15
Secondary outcomes:
measure: Part 1 Sentinel Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Day 11
timeFrame: Baseline, Day 11
measure: Part 1 Sentinel Cohort 2: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15
timeFrame: Baseline, Day 15
measure: Part 1 Randomized Cohort: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15
timeFrame: Baseline, Day 15
measure: Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24
timeFrame: Week 24
measure: Part 2: Change From Baseline in Plasma log10 HIV-1 RNA at Week 24
timeFrame: Baseline, Week 24
measure: Part 2: Change From Baseline in CD4+ Cell Count at Week 24
timeFrame: Baseline, Week 24
measure: Part 2: Number of Participants With Treatment Emergent Nucleos(t)Ide Reverse Transcriptase Inhibitor (NRTI) Mutations at the Time of Virologic Failure
timeFrame: From first dose up to Week 24
measure: Part 2: Number of Participants With Treatment Emergent Protease Inhibitor (PI) Mutations at the Time of Virologic Failure
timeFrame: From first dose up to Week 24
measure: Part 2: Number of Participants With Treatment Emergent Integrase Strand Transfer Inhibitor (INSTI) Mutations at the Time of Virologic Failure
timeFrame: From first dose up to Week 24
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre
city: Harare
country: Zimbabwe
facility: Joint Research Ethics Committee for the University of Zimbabwe College of Health Sciences and Parirenyatwa Group of Hospitals
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: