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

JRCT ID: jRCT2051240046

Registered date:29/05/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: HIV-1-Infection
• Date of first enrollment: 23/05/2024
• Target sample size: 546
• Countries of recruitment: US,Japan,Puerto Rico,Japan
• Study type: Interventional

Intervention(s)

Experimental: Treatment Group 1: Bictegravir (BIC)/ Lenacapavir (LEN) (75/50 mg) + Placebo to match (PTM) B/F/TAF
Blinded 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.

Experimental: Treatment Group 2: B/F/TAF (50/200/25 mg) + PTM BIC/LEN
Blinded 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.

Outcome(s)

• Primary Outcome: Proportion of Participants with HIV-1 RNA >= 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 48 ]

Secondary Outcome

-Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 48, 96 as Determined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 48, 96 ]
-Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 48 [ Time Frame: Baseline; Week 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 Algorithm [ Time Frame: Week 96 ]
-Treatment Group 1: Change from Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline; Week 96 ]
-Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) through Week 48 [ Time Frame: From first dose date up to Week 48 ]
-Treatment Group 1: Percentage of Participants Experiencing Treatment-Emergent AEs through Week 96 [ Time Frame: From first dose date up to Week 96 ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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.

Exclude 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 x upper limit of normal (ULN).
- Direct bilirubin > 1.5 x 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.

Related Information

• Primary Sponsor: Watanabe Takanobu
• Secondary ID(s): NCT06333808,2023-510022-33