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Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With Biktarvy

Phase 3
Active, not recruiting
Conditions
HIV-1-infection
Interventions
Drug: B/F/TAF
Drug: Placebo to match B/F/TAF
Drug: Placebo to match BIC/LEN
Registration Number
NCT06333808
Lead Sponsor
Gilead Sciences
Brief Summary

The goal of this clinical study is to learn more about the effects of switching to the study drugs, bictegravir (BIC)/lenacapavir (LEN), fixed-dose combination (FDC) versus current therapy bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) FDC in people living with HIV-1 (PWH).

The primary objective of this study is to learn how effective it is to switch to BIC/LEN FDC tablets versus continuing on B/F/TAF FDC tablets in virologically suppressed PWH.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
577
Inclusion Criteria
  • Currently receiving B/F/TAF for at least 6 months prior to screening.
  • If plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) measurements in the last 6 months prior to screening are available, all levels must be < 50 copies/mL.
  • At least one documented HIV-1 RNA level measured between 6 and 12 months (± 2 months) prior to screening. This and any other HIV-1 RNA measurements documented in this period must be < 50 copies/mL.
  • Plasma HIV-1 RNA levels < 50 copies/mL at screening.
  • No documented or suspected resistance to BIC (including integrase strand-transfer inhibitor resistant (INSTI-R) mutations T66A/I/K, E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene).
  • No documented or suspected resistance to tenofovir alafenamide (TAF) (TAF; mutations K65R, K65N, K70E, Q151M or T69 insertion, or ≥ 3 of the following thymidine analog mutations [M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R] in the reverse transcriptase gene).
  • Estimated glomerular filtration rate ≥ 30 mL/min according to the Cockcroft-Gault formula for creatinine clearance.

Key

Exclusion Criteria
  • Positive serum pregnancy test or pregnant at screening or a positive pregnancy test prior to Day 1 randomization.

  • Breastfeeding (nursing).

  • Prior use of, or exposure to, LEN.

  • Active, serious infections (other than HIV-1) requiring parenteral therapy < 30 days prior to randomization.

  • Active tuberculosis infection.

  • Acute hepatitis < 30 days before randomization.

  • Chronic hepatitis B virus (HBV) infection, as determined by either:

    • Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit.
    • Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit.
  • Known hypersensitivity to the study drug, its metabolites, or any formulation excipient.

  • History of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).

  • Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant as determined by the investigator.

  • Active malignancy requiring acute systemic therapy.

  • Any of the following laboratory values at screening:

    • Alanine aminotransferase > 5 × upper limit of normal (ULN).
    • Direct bilirubin > 1.5 × ULN.
    • Platelets < 50,000/mm^3.
    • Hemoglobin < 8.0 g/dL.
  • Requirement for ongoing therapy with or prior use of any prohibited medications listed in the protocol.

  • Participation or planned participation in any other clinical study (including observational studies) without prior approval from the sponsor.

  • Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements.

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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Treatment Group 1: Bictegravir (BIC)/ Lenacapavir (LEN) (75/50 mg) + PTM B/F/TAFLenacapavirBlinded Phase: Participants will switch from bictegravir/emtricitabine/tenofovir (B/F/TAF) FDC tablets to BIC/LEN (75/50 mg) FDC tablets and placebo-to-match (PTM) B/F/TAF. Participants will receive a 2-day oral loading dose of LEN 600 mg on Day 1 and on Day 2, in addition to the daily doses of BIC/LEN FDC tablet starting on Day 1 up to end of blinded treatment (EBT) visit. Open-label (OL) Phase: Following treatment in the Blinded Phase, participants from Treatment Group 1 will receive BIC/LEN FDC tablets through Week 48 in the Open-label Phase. At the OL Week 48 visit, participants from Treatment Group 1 will be given the option to continue to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
Treatment Group 2: B/F/TAF (50/200/25 mg) + PTM BIC/LENLenacapavirBlinded Phase: Participants will continue with their B/F/TAF (50/200/25 mg) FDC tablets and start PTM BIC/LEN tablets on Day 1. Participants will receive PTM LEN tablets for 2 days (2 PTM LEN tablets on Day 1 and on Day 2. The blinded phase will continue until the EBT visit. Open Label Phase: Participants in Treatment Group 2 who complete the EBT visit will be given the option to enter the OL phase to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
Treatment Group 2: B/F/TAF (50/200/25 mg) + PTM BIC/LENB/F/TAFBlinded Phase: Participants will continue with their B/F/TAF (50/200/25 mg) FDC tablets and start PTM BIC/LEN tablets on Day 1. Participants will receive PTM LEN tablets for 2 days (2 PTM LEN tablets on Day 1 and on Day 2. The blinded phase will continue until the EBT visit. Open Label Phase: Participants in Treatment Group 2 who complete the EBT visit will be given the option to enter the OL phase to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
Treatment Group 2: B/F/TAF (50/200/25 mg) + PTM BIC/LENPlacebo to match BIC/LENBlinded Phase: Participants will continue with their B/F/TAF (50/200/25 mg) FDC tablets and start PTM BIC/LEN tablets on Day 1. Participants will receive PTM LEN tablets for 2 days (2 PTM LEN tablets on Day 1 and on Day 2. The blinded phase will continue until the EBT visit. Open Label Phase: Participants in Treatment Group 2 who complete the EBT visit will be given the option to enter the OL phase to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
Treatment Group 1: Bictegravir (BIC)/ Lenacapavir (LEN) (75/50 mg) + PTM B/F/TAFPlacebo to match B/F/TAFBlinded Phase: Participants will switch from bictegravir/emtricitabine/tenofovir (B/F/TAF) FDC tablets to BIC/LEN (75/50 mg) FDC tablets and placebo-to-match (PTM) B/F/TAF. Participants will receive a 2-day oral loading dose of LEN 600 mg on Day 1 and on Day 2, in addition to the daily doses of BIC/LEN FDC tablet starting on Day 1 up to end of blinded treatment (EBT) visit. Open-label (OL) Phase: Following treatment in the Blinded Phase, participants from Treatment Group 1 will receive BIC/LEN FDC tablets through Week 48 in the Open-label Phase. At the OL Week 48 visit, participants from Treatment Group 1 will be given the option to continue to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
Treatment Group 1: Bictegravir (BIC)/ Lenacapavir (LEN) (75/50 mg) + PTM B/F/TAFBictegravirBlinded Phase: Participants will switch from bictegravir/emtricitabine/tenofovir (B/F/TAF) FDC tablets to BIC/LEN (75/50 mg) FDC tablets and placebo-to-match (PTM) B/F/TAF. Participants will receive a 2-day oral loading dose of LEN 600 mg on Day 1 and on Day 2, in addition to the daily doses of BIC/LEN FDC tablet starting on Day 1 up to end of blinded treatment (EBT) visit. Open-label (OL) Phase: Following treatment in the Blinded Phase, participants from Treatment Group 1 will receive BIC/LEN FDC tablets through Week 48 in the Open-label Phase. At the OL Week 48 visit, participants from Treatment Group 1 will be given the option to continue to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
Treatment Group 2: B/F/TAF (50/200/25 mg) + PTM BIC/LENBictegravirBlinded Phase: Participants will continue with their B/F/TAF (50/200/25 mg) FDC tablets and start PTM BIC/LEN tablets on Day 1. Participants will receive PTM LEN tablets for 2 days (2 PTM LEN tablets on Day 1 and on Day 2. The blinded phase will continue until the EBT visit. Open Label Phase: Participants in Treatment Group 2 who complete the EBT visit will be given the option to enter the OL phase to receive BIC/LEN FDC tablets until the conclusion of the OL Phase.
Primary Outcome Measures
NameTimeMethod
Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot AlgorithmWeek 48
Secondary Outcome Measures
NameTimeMethod
Treatment Group 1: Change from Baseline in CD4 Cell Count at Week 96Baseline; Week 96
Treatment Group 1: Percentage of Participants Experiencing Treatment-Emergent AEs through Week 96From first dose date up to Week 96
Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot AlgorithmWeek 48
Treatment Group 1: Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot AlgorithmWeek 96
Treatment Group 1: Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 96 as Determined by US FDA-defined Snapshot AlgorithmWeek 96
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) through Week 48From first dose date up to Week 48
Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 48Baseline; Week 48

Trial Locations

Locations (102)

Pueblo Family Physicians

🇺🇸

Phoenix, Arizona, United States

Be Well Medical Center

🇺🇸

Berkeley, California, United States

Pacific Oaks Medical Group

🇺🇸

Beverly Hills, California, United States

Ruane Clinical Research Group Inc.

🇺🇸

Los Angeles, California, United States

Alta Bates Summit Medical Center, Summit Campus, East Bay Advanced Care

🇺🇸

Oakland, California, United States

BIOS Clinical Research

🇺🇸

Palm Springs, California, United States

UCSD Anti Viral Research Centre (AVRC)

🇺🇸

San Diego, California, United States

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

🇺🇸

Torrance, California, United States

Mills Clinical Research

🇺🇸

West Hollywood, California, United States

Public Health Institute at Denver Health

🇺🇸

Denver, Colorado, United States

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Pueblo Family Physicians
🇺🇸Phoenix, Arizona, United States

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