Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated

Phase 2

Active, not recruiting

• Conditions: HIV-1-infection
• Interventions: Drug: GS-1720; Drug: Bictegravir/emtricitabine/tenofovir alafenamide; Drug: GS-1720/GS-4182 FDC; Drug: GS-4182; Drug: Placebo to Match BVY; Drug: Placebo to Match GS1720/GS-4182 FDC

• Registration Number: NCT06613685
• Lead Sponsor: Gilead Sciences

Brief Summary

The goal of this clinical study is to learn more about the experimental drugs GS-1720 (an oral, long-acting integrase strand transfer inhibitor (INSTI)) and GS-4182 (a prodrug of Lenacapavir (LEN)); to compare the combination of GS-1720 and GS-4182 with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (Biktarvy), to see if the combination of GS-1720 and GS-4182 is safe and if it works for treating human immunodeficiency virus type 1 (HIV-1) infection in treatment-naive people with HIV-1 (PWH).

This study has two phases: Phase 2 and Phase 3.

The primary objectives of this study are:

Phase 2: To evaluate the efficacy of oral weekly GS-1720 coadministered with GS-4182 versus continuing Biktarvy (BVY) in treatment-naive PWH at Week 24.

Phase 3: To evaluate the efficacy of oral weekly GS-1720/GS-4182 fixed-dose combination (FDC) tablet regimen versus continuing BVY in treatment-naive PWH at Week 48.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-09-23
• Study First Submitted QC: 2024-09-23
• Study First Posted: 2024-09-26
• Study Start: 2024-10-21
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-02
• Last Update Posted: 2025-06-05
• Primary Completion: 2029-01
• Study Completion: 2030-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 675

Inclusion Criteria

• HIV-1 RNA ≥ 500 copies/mL at screening.
• Antiretroviral (ARV) treatment-naive, except the use of oral pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or F/TAF, up to 1 month prior to screening.

Key

Exclusion Criteria

• Prior use of any long acting parenteral antiretrovirals (ARVs) such as monoclonal antibodies, broadly neutralizing antibodies targeting HIV-1, LEN, injectable cabotegravir (including oral cabotegravir lead-in), and/or injectable rilpivirine.

• Documented resistance to the integrase strand-transfer inhibitor class, specifically, resistance-associated mutations E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene.

• Any of the following laboratory values at screening:

  1. CD4 cell count < 200 cells/mm3 at screening.
  2. Estimated glomerular filtrations arate < 60 mL/min according to the Modification of Diet in Renal Disease formula.
  3. Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) > 1.5 × upper limit of normal (ULN).
  4. Direct bilirubin > 1.5 × ULN.
  5. Platelets count < 50,000 cells/mm3.
  6. Hemoglobin < 8.0 g/dL.

• Active or occult hepatitis B virus infection.

• Active hepatitis C virus infection.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 2: GS-1720 + GS-4182 (Treatment Group 1)	GS-4182	Participants will receive a 1-day loading dose of GS-1720 (1300 mg) and GS-4182 (600 mg) on Day 1.Thereafter, participants will take weekly doses of single agent GS-1720 (650 mg) and GS-4182 (300 mg) coadministered for at least 48 weeks.
Phase 2: GS-1720 + GS-4182 (Treatment Group 1)	GS-1720	Participants will receive a 1-day loading dose of GS-1720 (1300 mg) and GS-4182 (600 mg) on Day 1.Thereafter, participants will take weekly doses of single agent GS-1720 (650 mg) and GS-4182 (300 mg) coadministered for at least 48 weeks.
Phase 2: B/F/TAF (Treatment Group 2)	Bictegravir/emtricitabine/tenofovir alafenamide	Participants will receive B/F/TAF (50/200/25 mg) daily for at least 48 weeks.
Phase 2 Extension Phase: GS-1720/GS-4182 Fixed-dose Combination (FDC)	GS-1720/GS-4182 FDC	At the end of the randomized treatment, Phase 2 participants will be given the option to participate in the Extension Phase. Phase 2 Treatment Group 1 will switch to GS-1720/GS-4182 FDC (650/300 mg) weekly. Phase 2 Treatment Group 2 will receive a loading dose of GS-1720/GS-4182 FDC (1300 mg/600 mg) on Extension Phase Day 1, then GS-1720/GS-4182 FDC (650/300 mg) weekly. Participants who choose to enter the Extension Phase will receive GS-1720/GS-4182 FDC tablets until the product becomes available or until Gilead Sciences elects to discontinue the study, whichever occurs first.
Phase 3: GS-1720/GS-4182 FDC + Placebo to Match (PTM) B/F/TAF (Treatment Group 1)	GS-1720/GS-4182 FDC	Participants will receive a 1-day loading dose of GS-1720/GS-4182 FDC on Day 1. Thereafter, participants will receive GS-1720/GS-4182 FDC tablets weekly + PTM B/F/TAF once daily. Participants will receive treatment for at least 96 weeks.
Phase 3: GS-1720/GS-4182 FDC + Placebo to Match (PTM) B/F/TAF (Treatment Group 1)	Placebo to Match BVY	Participants will receive a 1-day loading dose of GS-1720/GS-4182 FDC on Day 1. Thereafter, participants will receive GS-1720/GS-4182 FDC tablets weekly + PTM B/F/TAF once daily. Participants will receive treatment for at least 96 weeks.
Phase 3: B/F/TAF + PTM GS-1720/GS-4182 FDC (Treatment Group 2)	Bictegravir/emtricitabine/tenofovir alafenamide	Participants will receive oral B/F/TAF daily along with PTM GS-1720/GS-4182 FDC weekly for at least 96 weeks. Additionally, participants will receive a 1-day loading dose of PTM GS-1720/GS-4182 on Day 1.
Phase 3: B/F/TAF + PTM GS-1720/GS-4182 FDC (Treatment Group 2)	Placebo to Match GS1720/GS-4182 FDC	Participants will receive oral B/F/TAF daily along with PTM GS-1720/GS-4182 FDC weekly for at least 96 weeks. Additionally, participants will receive a 1-day loading dose of PTM GS-1720/GS-4182 on Day 1.
Phase 3 Extension Phase: GS-1720/GS-4182 Fixed-dose Combination (FDC)	GS-1720/GS-4182 FDC	After the end of blinded treatment, Phase 3 participants will be given the option to participate in the Extension Phase. Phase 3 Treatment Group 1 will continue to receive GS-1720/GS-4182 FDC weekly while PTM B/F/TAF will be discontinued. Phase 3 Treatment Group 2 will switch to receive GS-1720/GS-4182 FDC tablets weekly. Participants in Treatment Group 2 will also receive a 1-day loading dose of GS-1720/GS-4182 FDC on Extension Phase Day 1. Participants who choose to enter the Phase 3 Extension Phase will receive GS-1720/GS-4182 FDC tablets until the product becomes available or until Gilead Sciences elects to discontinue the study, whichever occurs first.

Primary Outcome Measures

Name	Time	Method
Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the United States (US) Food and Drug Administration (FDA)-defined Snapshot Algorithm	Week 24
Phase 3: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm	Week 48

Secondary Outcome Measures

Name	Time	Method
Phase 2: Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 12	Baseline, Week 12
Phase 2: Change From Baseline in CD4 Cell Count at Week 48	Baseline, Week 48
Phase 2: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) Through Week 12	First dose date up to Week 12
Phase 2: Percentage of Participants Experiencing TEAEs Through Week 24	First dose date up to Week 24
Phase 2: Percentage of Participants Experiencing TEAEs Through Week 48	First dose date up to Week 48
Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 12	First dose date up to Week 12
Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48	First dose date up to Week 48
Phase 2: Pharmacokinetic (PK) Parameter: Cmax of GS-1720 and Lenacapavir (LEN), as Applicable	Day 1 up to Week 24	Cmax is defined as the maximum observed concentration of drug.
Phase 2: PK Parameter: Tmax of GS-1720 and LEN, as Applicable	Day 1 up to Week 24	Tmax is defined as the time (observed time point) of Cmax.
Phase 2: PK Parameter: Ctau of GS-1720 and LEN, as Applicable	Day 1 up to Week 24	Ctau is defined as the observed drug concentration at the end of the dosing interval.
Phase 2: PK Parameter: AUCtau of GS-1720 and LEN, as Applicable	Day 1 up to Week 24	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Phase 3: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm	Week 96
Phase 3: Change From Baseline in log10 HIV-1 RNA at Week 48	Baseline, Week 48
Phase 3: Change From Baseline in CD4 Cell Count at Week 96	Baseline, Week 96
Phase 3: Percentage of Participants Experiencing TEAEs Through Week 48	First dose date up to Week 48
Phase 3: Percentage of Participants Experiencing TEAEs Through Week 96	First dose date up to Week 96
Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 96	First dose date up to Week 96
Phase 2: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm	Week 12
Phase 2: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm	Week 48
Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 12	Baseline, Week 12
Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 24	Baseline, Week 24
Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 48	Baseline, Week 48
Phase 2: Change From Baseline in CD4 Cell Count at Week 24	Baseline, Week 24
Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 24	First dose date up to Week 24
Phase 3: Change From Baseline in log10 HIV-1 RNA at Week 96	Baseline, Week 96
Phase 3: Change From Baseline in CD4 Cell Count at Week 48	Baseline, Week 48
Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48	First dose date up to Week 48

Trial Locations

Locations (57)

UAB 1917 Research Clinic; 🇺🇸 Birmingham, Alabama, United States

The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center; 🇺🇸 Torrance, California, United States

Mills Clinical Research; 🇺🇸 West Hollywood, California, United States

Georgetown University Medical School; 🇺🇸 Washington, District of Columbia, United States

Midland Florida Clinical Research Center, LLC; 🇺🇸 DeLand, Florida, United States

Midway Immunology and Research Center; 🇺🇸 Fort Pierce, Florida, United States

Floridian Clinical Research, LLC; 🇺🇸 Miami Lakes, Florida, United States

Orlando Immunology Center; 🇺🇸 Orlando, Florida, United States

Triple O Research Institute, P.A.; 🇺🇸 West Palm Beach, Florida, United States

Emory University Hospital Midtown Infectious Disease Clinic; 🇺🇸 Atlanta, Georgia, United States

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