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

Phase 3 Double-blind Multicenter Randomized Active-Controlled Study to Evaluate the Safety and Efficacy of Bictegravir/Lenacapavir Versus Biktarvy® (Bictegravir/Emtricitabine/Tenofovir Alafenamide) in Virologically Suppressed People With HIV-1

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.

Key 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.