Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People With HIV-1

Phase 3

Active, not recruiting

• Conditions: HIV-1-infection
• Interventions: Drug: ISL/LEN; Drug: B/F/TAF; Drug: PTM B/F/TAF; Drug: PTM ISL/LEN

• Registration Number: NCT06630286
• Lead Sponsor: Gilead Sciences

Brief Summary

The goal of this clinical study is to learn about the safety and efficacy of switching to once weekly tablet of islatravir/lenacapavir (ISL/LEN) regimen versus continuing standard treatment of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (PWH) who are virologically suppressed (HIV-1 RNA levels \< 50 copies/mL) on B/F/TAF for ≥ 6 months prior to screening.

The primary objective is to evaluate the efficacy of switching to oral weekly ISL/LEN tablet regimen versus continuing B/F/TAF in virologically suppressed PWH at Week 48.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-10-04
• Study First Submitted QC: 2024-10-04
• Study First Posted: 2024-10-08
• Study Start: 2024-10-09
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-08
• Last Update Posted: 2025-07-10
• Primary Completion: 2026-04
• Study Completion: 2030-08-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 609

Inclusion Criteria

• HIV-1 RNA < 50 copies/mL for ≥ 6 months before screening, as documented by:

  1. One HIV-1 RNA < 50 copies/mL immediately preceding the 24 week period prior to screening.
  2. Within 24 weeks prior to screening, if HIV-1 RNA results are available, all levels must be < 50 copies/mL.
  3. During the 6 to 12 months period prior to screening, transient detectable viremia ≥ 50 copies/mL is acceptable ("blip"), as long as it is not confirmed on 2 consecutive visits.

• Plasma HIV-1 RNA levels < 50 copies/mL at screening.

• Individuals are receiving B/F/TAF for ≥ 6 months prior to screening and willing to continue until Day 1.

• Individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception.

Key

Exclusion Criteria

• Prior virologic failure.

• Prior use of, or exposure to ISL or LEN.

• Active, serious infections requiring parenteral therapy within 30 days before randomization.

• Active tuberculosis infection.

• Acute hepatitis within 30 days before randomization.

• Hepatitis B virus (HBV) infection as determined below at the screening visit:

  1. Positive HBV surface antigen OR
  2. Positive HBV core antibody and negative HBV surface antibody. Note: individuals found to be susceptible to HBV infection (eg negative hepatitis B surface antibody at the screening visit, regardless of prior HBV vaccination history) should be recommended to receive HBV vaccination.

• Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA. Note: individuals with prior/inactive HCV infection (defined as undetectable HCV RNA) may be enrolled.

• Any of the following laboratory values at screening:

  1. Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula
  2. Alanine aminotransferase > 5 x upper limit of normal (ULN)
  3. Direct bilirubin > 1.5 x ULN
  4. Platelets < 50,000/μL
  5. Hemoglobin < 8.0 g/dL

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Blinded Phase: ISL/LEN + Placebo-to-Match (PTM) B/F/TAF	ISL/LEN	Participants will receive an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive PTM B/F/TAF once daily from Day 1 up to Week 96.
Blinded Phase: ISL/LEN + Placebo-to-Match (PTM) B/F/TAF	PTM B/F/TAF	Participants will receive an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive PTM B/F/TAF once daily from Day 1 up to Week 96.
Blinded Phase: PTM ISL/LEN + B/F/TAF	B/F/TAF	Participants will receive an initial dose of PTM ISL/LEN (Dose A), followed by once weekly PTM ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive B/F/TAF (50/200/25 mg) once daily up from Day 1 up to Week 96.
Blinded Phase: PTM ISL/LEN + B/F/TAF	PTM ISL/LEN	Participants will receive an initial dose of PTM ISL/LEN (Dose A), followed by once weekly PTM ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive B/F/TAF (50/200/25 mg) once daily up from Day 1 up to Week 96.
Open- Label Extension (OLE) Phase	ISL/LEN	After the end of Blinded Phase at Week 96, if safety and efficacy of ISL/LEN are demonstrated following review of unblinded data, all participants will be given an option to enter the open-label extension phase to receive ISL/LEN in an extension phase until ISL/LEN becomes available or until the sponsor elects to discontinue the study, whichever occurs first. Participants receiving ISL/LEN and PTM B/F/TAF during the blinded phase will continue to take ISL/LEN weekly. Participants receiving B/F/TAF and PTM ISL/LEN during the blinded phase will take an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards.

Primary Outcome Measures

Name	Time	Method
Proportion of Participants with HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the United States (US) Food and Drug Administration (FDA)-Defined Snapshot Algorithm	Week 48

Secondary Outcome Measures

Name	Time	Method
Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Weeks 48 as Determined by the US FDA-Defined Snapshot Algorithm	Week 48
Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the US FDA-Defined Snapshot Algorithm	Week 96
Proportion of Participants with HIV-1 RNA < 50 Copies/mL at Weeks 96 as Determined by the US FDA-Defined Snapshot Algorithm	Week 96
Change From Baseline in Cluster of Differentiation 4 (CD4) T-Cell Count at Weeks 48	Week 48
Change From Baseline in CD4 T-Cell Count at Weeks 96	Week 96
Proportion of Participants Discontinuing ISL/LEN due to Treatment-Emergent Adverse Events (TEAEs)	Day 1 up to Week 48

Trial Locations

Locations (103)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Pueblo Family Physicians; 🇺🇸 Phoenix, Arizona, United States

Kaiser Permanente Southern California; 🇺🇸 Los Angeles, California, United States

Ruane Clinical Research Group, Inc; 🇺🇸 Los Angeles, California, United States

Mills Clinical Research; 🇺🇸 Los Angeles, California, United States

BIOS Clinical Research; 🇺🇸 Palm Springs, California, United States

Optimus Medical Group; 🇺🇸 San Francisco, California, United States

Vivent Health; 🇺🇸 Denver, Colorado, United States

University of Colorado- Anschutz Medical Campus - PPDS; 🇺🇸 Denver, Colorado, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

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