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

Gilead Sciences

Status and phase: Terminated; Phase 2

Conditions: HIV-1-infection

Treatments: Drug: ARV regimen; Drug: RTV; Drug: GS-9131; Drug: TAF; Drug: BIC; Drug: DRV

Study type: Interventional

Funder types: Industry

Identifiers

NCT03472326

GS-US-442-4148

Details and patient eligibility

About

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.

Enrollment: 21 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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21 participants in 5 patient groups

Part 1 Sentinel Cohort 1: GS-9131 60 mg

Experimental group

Description:

Treatment experienced participants will receive GS-9131 60 mg in addition to their current failing ARV regimen for a period of 10 days.

Treatment:

Drug: ARV regimen

Drug: GS-9131

Part 1 Sentinel Cohort 2: GS-9131 180 mg

Experimental group

Description:

Treatment experienced participants will receive GS-9131 180 mg in addition to their current failing ARV regimen for a period of 14 days.

Treatment:

Drug: ARV regimen

Drug: GS-9131

Part 1: Randomized Cohort

Experimental group

Description:

Participants will be randomized in 1:1:1:1 so as to receive GS-9131 in 3 active dose levels up to a maximum of 180 mg or Placebo to match GS-9131 in addition to their current failing ARV regimen for a period of 14 days in Part 1.

Treatment:

Drug: ARV regimen

Drug: GS-9131

Part 2 Sentinel Cohort 1: GS-9131 + BIC + DRV + RTV

Experimental group

Description:

Participants who complete dosing in Sentinel Cohort 1 of Part 1 and show a reduction in plasma HIV RNA \> 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinue their current failing regimen will receive an optimized regimen consisting of GS-9131 60 mg + bictegravir (BIC) 30 mg + darunavir (DRV) 800 mg + ritonavir (RTV) 100 mg for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 60 mg + BIC 75 mg + tenofovir alafenamide (TAF) 25 mg, for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurs first.

Treatment:

Drug: DRV

Drug: GS-9131

Drug: BIC

Drug: RTV

Part 2 Sentinel Cohort 2: GS-9131 + BIC + TAF

Experimental group

Description:

Participants who complete dosing in Sentinel Cohort 2 of Part 1 and show a reduction in plasma HIV RNA \> 0.5 log10 from their pre-GS-9131 baseline value at Day 15 and discontinue their current failing regimen will receive an optimized regimen consisting of GS-9131 180 mg + BIC 75 mg + TAF 25 mg, for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 180 mg + BIC 75 mg + TAF 25 mg, for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurs first.

Treatment:

Drug: TAF

Drug: GS-9131

Drug: BIC