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

NCT03472326 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: GS-US-442-4148
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 2

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.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Part 1 Sentinel Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Day 11

  Baseline, Day 11

• Part 1 Sentinel Cohort 2: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15

  Baseline, Day 15

• Part 1 Randomized Cohort: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15

  Baseline, Day 15

• Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24

  Week 24

• Part 2: Change From Baseline in Plasma log10 HIV-1 RNA at Week 24

  Baseline, Week 24

Study Arms (5)

Part 1 Sentinel Cohort 1: GS-9131 60 mg

EXPERIMENTAL

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

Drug: GS-9131; Drug: ARV regimen

Part 1 Sentinel Cohort 2: GS-9131 180 mg

EXPERIMENTAL

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

Drug: GS-9131; Drug: ARV regimen

Part 1: Randomized Cohort

EXPERIMENTAL

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.

Drug: GS-9131; Drug: ARV regimen

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

EXPERIMENTAL

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.

Drug: GS-9131; Drug: BIC; Drug: DRV; Drug: RTV

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

EXPERIMENTAL

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.

Drug: GS-9131; Drug: BIC; Drug: TAF

Interventions

GS-9131 DRUG

Tablet(s) administered orally once daily

Part 1 Sentinel Cohort 1: GS-9131 60 mg; Part 1 Sentinel Cohort 2: GS-9131 180 mg; Part 1: Randomized Cohort; Part 2 Sentinel Cohort 1: GS-9131 + BIC + DRV + RTV; Part 2 Sentinel Cohort 2: GS-9131 + BIC + TAF

BIC DRUG

Tablet(s) administered orally once daily

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

TAF DRUG

Tablet(s) administered orally once daily

Also known as: Vemlidy®

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

ARV regimen DRUG

ARV regimen may consist of the ARV agents containing nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI)

Part 1 Sentinel Cohort 1: GS-9131 60 mg; Part 1 Sentinel Cohort 2: GS-9131 180 mg; Part 1: Randomized Cohort

DRV DRUG

Tablet(s) administered orally once daily

Also known as: Prezista®

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

RTV DRUG

Tablet(s) administered orally once daily

Also known as: Norvir®

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

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (2)

Joint Clinical Research Centre

Kampala, 10005, Uganda

Location

Joint Research Ethics Committee for the University of Zimbabwe College of Health Sciences and Parirenyatwa Group of Hospitals

Harare, Zimbabwe

Location

MeSH Terms

Interventions

GS-9131; imidazole mustard; tenofovir alafenamide; Darunavir; Ritonavir

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles

Limitations and Caveats

The study was terminated because a majority of Sentinel Cohort 2 participants did not meet primary endpoint of HIV-1 RNA \> 0.5 log10 decrease from baseline through up to 14 days of therapy.

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2018
• First Posted: March 21, 2018
• Study Start: April 3, 2018
• Primary Completion: December 9, 2019
• Study Completion: December 9, 2019
• Last Updated: January 5, 2021
• Results First Posted: January 5, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1); ZI (1)