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Efficacy of GS-9131 Functional Monotherapy in HIV-1-Infected Adults Failing a Nucleos(t)Ide Reverse Transcriptase Inhibitor-Containing Regimen

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03472326
Recruitment Status : Terminated (GS-9131 did not meet the targeted antiviral response)
First Posted : March 21, 2018
Last Update Posted : April 28, 2020
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 compared to placebo-to-match (PTM) GS-9131, each administered once daily with the existing failing antiretroviral (ARV) regimen.

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: Placebo Drug: BIC Drug: TAF Drug: ART 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
Treatment experienced participants will receive open label GS-9131 60 mg (2 x 30 mg tablets) once daily + current failing antiretroviral therapy (ART) regimen for 10 days
Drug: GS-9131
Tablet(s) administered orally once daily. Dose for the open-label extension will be determined following review of the safety, efficacy and available PK data of the Randomized Cohort in Part 1 from Part 2.

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

Experimental: Part 1: Sentinel Cohort 2
Treatment experienced participants will receive open-label GS-9131 180 mg (6 x 30 mg tablets) once daily + current failing ART for 14 days.
Drug: GS-9131
Tablet(s) administered orally once daily. Dose for the open-label extension will be determined following review of the safety, efficacy and available PK data of the Randomized Cohort in Part 1 from Part 2.

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

Experimental: Randomized Cohort (Treatment Arm A: GS-9131)
Participants will receive GS-9131 up to 180 mg once daily + current failing ART regimen for 14 days
Drug: GS-9131
Tablet(s) administered orally once daily. Dose for the open-label extension will be determined following review of the safety, efficacy and available PK data of the Randomized Cohort in Part 1 from Part 2.

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

Experimental: Part 1: Randomized Cohort (Treatment Arm B: GS-9131)
Participants will receive GS-9131 up to 180 mg once daily + current failing ART regimen for 14 days
Drug: GS-9131
Tablet(s) administered orally once daily. Dose for the open-label extension will be determined following review of the safety, efficacy and available PK data of the Randomized Cohort in Part 1 from Part 2.

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

Experimental: Part 1: Randomized Cohort (Treatment Arm C: GS-9131)
Participants will receive GS-9131 up to 180 mg once daily + current failing ART regimen for 14 days
Drug: GS-9131
Tablet(s) administered orally once daily. Dose for the open-label extension will be determined following review of the safety, efficacy and available PK data of the Randomized Cohort in Part 1 from Part 2.

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

Experimental: Part 1: Randomized Cohort (Treatment Arm D: GS-9131 Placebo)
Participants will receive GS-9131 placebo + current failing ART regimen for 14 days
Drug: Placebo
Placebo-to-match (PTM) GS-9131 tablets

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

Experimental: Part 2: GS-9131 60 mg + BIC + DRV + RTV Regimen
Participants from Treatment Sentinel Cohort 1 in Part 1 will receive GS-9131 60 mg (2 x 30 mg tablet) + bictegravir (BIC) + darunavir (DRV) + ritonavir (RTV) for 24 weeks
Drug: GS-9131
Tablet(s) administered orally once daily. Dose for the open-label extension will be determined following review of the safety, efficacy and available PK data of the Randomized Cohort in Part 1 from Part 2.

Drug: BIC
30 mg tablet(s) administered orally once daily

Drug: DRV
800 mg tablet(s) administered orally once daily
Other Name: Prezista®

Drug: RTV
100 mg tablet(s) administered orally once daily
Other Name: Norvir®

Experimental: Part 2: GS-9131 up to 180 mg + BIC + TAF Regimen
Participants from Sentinel Cohort 2 and Randomized Cohort (A-D) in Part 1 will receive GS-9131 up to 180 mg + BIC + TAF for 24 weeks
Drug: GS-9131
Tablet(s) administered orally once daily. Dose for the open-label extension will be determined following review of the safety, efficacy and available PK data of the Randomized Cohort in Part 1 from Part 2.

Drug: BIC
30 mg tablet(s) administered orally once daily

Drug: TAF
25 mg tablet(s) administered orally once daily
Other Name: Vemlidy®

Experimental: Open-label Extension Phase
Participants in Part 2 may have the option to receive open-label GS-9131 + BIC + TAF for an additional 24 weeks or until the product becomes accessible to participants through an access program, or until Gilead elects to discontinue the study in that country, whichever occurs first.
Drug: GS-9131
Tablet(s) administered orally once daily. Dose for the open-label extension will be determined following review of the safety, efficacy and available PK data of the Randomized Cohort in Part 1 from Part 2.

Drug: BIC
30 mg tablet(s) administered orally once daily

Drug: TAF
25 mg tablet(s) administered orally once daily
Other Name: Vemlidy®




Primary Outcome Measures :
  1. Proportion of Participants With Plasma HIV-1 RNA Decrease From Baseline Exceeding 0.5 log10 (copies/mL) at Day 15 in the Randomized Cohort in Part 1 [ Time Frame: Day 15 ]

Secondary Outcome Measures :
  1. Change From Baseline in Plasma log10 HIV-1 RNA (copies/mL) at Day 11 for Sentinel Cohort 1 and Day 15 for Sentinel Cohort 2 and the Randomized Cohort in Part 1 [ Time Frame: Baseline to Day 11 and Day 15 ]
  2. Proportion of Participants With Plasma HIV-1 < 0.5 log10 (copies/mL) at Week 24 [ Time Frame: Week 24 ]
  3. Number of Participants With Treatment-Emergent Nucleoside/Nucleotide Reverse Transcriptase Inhibitor (NRTI) Mutations at the time of Virologic Failure [ Time Frame: Up to Week 24 ]
  4. Number of Participants With Treatment-Emergent Protease Inhibitor (PI) Mutations at the time of Virologic Failure [ Time Frame: Up to Week 24 ]
  5. Number of Participants With Treatment-Emergent Integrase Strand-Transfer Inhibitor (INSTI) Mutations at the time of Virologic Failure [ Time Frame: Up to Week 24 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 antiretroviral (ARV) regimen that contains 2 NRTIs and a non-NRTI (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

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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
Last Update Posted: April 28, 2020
Last Verified: April 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