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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

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ClinicalTrials.gov Identifier: NCT03472326
Recruitment Status : Terminated (GS-9131 did not meet the targeted antiviral response)
First Posted : March 21, 2018
Results First Posted : January 5, 2021
Last Update Posted : January 5, 2021
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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.


Condition or disease Intervention/treatment Phase
HIV-1-infection Drug: GS-9131 Drug: BIC Drug: TAF Drug: ARV regimen Drug: DRV Drug: RTV Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : April 3, 2018
Actual Primary Completion Date : December 9, 2019
Actual Study Completion Date : December 9, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Part 1 Sentinel Cohort 1: GS-9131 60 mg
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
Tablet(s) administered orally once daily

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

Experimental: Part 1 Sentinel Cohort 2: GS-9131 180 mg
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
Tablet(s) administered orally once daily

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

Experimental: Part 1: Randomized Cohort
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
Tablet(s) administered orally once daily

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

Experimental: Part 2 Sentinel Cohort 1: GS-9131 + BIC + DRV + RTV
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
Tablet(s) administered orally once daily

Drug: BIC
Tablet(s) administered orally once daily

Drug: DRV
Tablet(s) administered orally once daily
Other Name: Prezista®

Drug: RTV
Tablet(s) administered orally once daily
Other Name: Norvir®

Experimental: Part 2 Sentinel Cohort 2: GS-9131 + BIC + TAF
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
Tablet(s) administered orally once daily

Drug: BIC
Tablet(s) administered orally once daily

Drug: TAF
Tablet(s) administered orally once daily
Other Name: Vemlidy®




Primary Outcome Measures :
  1. Part 1 Randomized Cohort: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 15 [ Time Frame: 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.


Secondary Outcome Measures :
  1. Part 1 Sentinel Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Day 11 [ Time Frame: Baseline, Day 11 ]
  2. Part 1 Sentinel Cohort 2: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15 [ Time Frame: Baseline, Day 15 ]
  3. Part 1 Randomized Cohort: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15 [ Time Frame: Baseline, Day 15 ]
  4. Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24 [ Time Frame: 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.

  5. Part 2: Change From Baseline in Plasma log10 HIV-1 RNA at Week 24 [ Time Frame: Baseline, Week 24 ]
  6. Part 2: Change From Baseline in CD4+ Cell Count at Week 24 [ Time Frame: Baseline, Week 24 ]
  7. Part 2: Number of Participants With Treatment Emergent Nucleos(t)Ide Reverse Transcriptase Inhibitor (NRTI) Mutations at the Time of Virologic Failure [ Time Frame: From first dose up to Week 24 ]
    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.

  8. Part 2: Number of Participants With Treatment Emergent Protease Inhibitor (PI) Mutations at the Time of Virologic Failure [ Time Frame: From first dose up to Week 24 ]
    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.

  9. Part 2: Number of Participants With Treatment Emergent Integrase Strand Transfer Inhibitor (INSTI) Mutations at the Time of Virologic Failure [ Time Frame: From first dose up to Week 24 ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03472326


Locations
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Uganda
Joint Clinical Research Centre
Kampala, Uganda, 10005
Zimbabwe
Joint Research Ethics Committee for the University of Zimbabwe College of Health Sciences and Parirenyatwa Group of Hospitals
Harare, Zimbabwe
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol  [PDF] November 1, 2018
Statistical Analysis Plan  [PDF] March 3, 2020

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT03472326    
Other Study ID Numbers: GS-US-442-4148
First Posted: March 21, 2018    Key Record Dates
Results First Posted: January 5, 2021
Last Update Posted: January 5, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Darunavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents