HIV-1-infection
Conditions
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.
Interventions
DRUGBictegravir
Tablets administered orally without regard to food
DRUGLenacapavir
Tablets administered orally without regard to food
DRUGB/F/TAF
Tablets administered orally without regard to food
Tablets administered orally without regard to food
DRUGPlacebo to match BIC/LEN
Tablets administered orally without regard to food
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Participants will be randomized in parallel in one of two treatment groups during the Blinded Phase. Participants in both treatment groups will be given the option to continue BIC/LEN FDC treatment during the Open-Label Phase.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Treatment Group 1: Percentage of Participants Experiencing Treatment-Emergent AEs through Week 96 | From 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 Algorithm | Week 48 |
| Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 48 | Baseline; Week 48 |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) through Week 48 | From first dose date up to Week 48 |
| Treatment Group 1: Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 96 as Determined by US FDA-defined Snapshot Algorithm | Week 96 |
| Treatment Group 1: Change from Baseline in CD4 Cell Count at Week 96 | Baseline; Week 96 |
| 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 | Week 96 |
Countries
Argentina, Australia, Canada, Dominican Republic, Germany, Italy, Japan, Mexico, Puerto Rico, South Korea, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed