Clinical Trials

MainTitle

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

This study is currently recruiting participants. (see Contacts and Locations)

Verified August 2019 by Gilead Sciences

Sponsor
Gilead Sciences


Information provided by (Responsible Party)
Gilead Sciences
ClinicalTrials.gov Identifier
NCT03472326

First received: March 8, 2018
Last updated: August 7, 2019
Last Verified: August 2019
History of Changes
Purpose

Purpose

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 Intervention Phase
HIV-1-infection

Drug : GS-9131
Drug : Placebo
Drug : BIC
Drug : TAF
Drug : ART regimen
Drug : DRV
Drug : RTV
Phase 2

Study Type: Interventional
Study Design: 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

Further study details as provided by Gilead Sciences:

Primary Outcome Measures

  • 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:
  • 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 ]
  • Proportion of Participants With Plasma HIV-1 < 0.5 log10 (copies/mL) at Week 24 [ Time Frame: Week 24 ]
  • 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 ]
  • Number of Participants With Treatment-Emergent Protease Inhibitor (PI) Mutations at the time of Virologic Failure [ Time Frame: Up to Week 24 ]
  • Number of Participants With Treatment-Emergent Integrase Strand-Transfer Inhibitor (INSTI) Mutations at the time of Virologic Failure [ Time Frame: Up to Week 24 ]

Estimated Enrollment: 68
Study Start Date: April 3, 2018
Estimated Study Completion Date: February 2021
Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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®
Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
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.

contacts and locations

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03472326

Contacts

Contact:   Gilead Clinical Study Information Center 1-833-445-3230 (GILEAD-0) GileadClinicalTrials@gilead.com

Locations

Uganda
Joint Clinical Research Centre Recruiting
Kampala, Uganda, 10005
Zimbabwe
Joint Research Ethics Committee for the University of Zimbabwe College of Health Sciences and Parirenyatwa Group of Hospitals Recruiting
Harare, Zimbabwe

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director: Gilead Study Director Gilead Sciences
More Information

More Information


Responsible Party: Gilead Sciences  
ClinicalTrials.gov Identifier: NCT03472326   History of Changes  
Other Study ID Numbers: GS-US-442-4148  
Study First Received: March 8, 2018  
Last Updated: August 7, 2019  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Additional relevant MeSH terms:
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this data on August 16, 2019
This information is provided by ClinicalTrials.gov.