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) plus lenacapavir (LEN), versus current therapy (Phase 2) and BIC/LEN fixed-dose combination (FDC) versus current therapy (Phase 3) in people living with HIV (PWH).
Interventions
DRUGBictegravir
Tablets administered orally without regard to food
DRUGLenacapavir
Tablets administered orally without regard to food
DRUGBIC/LEN FDC
Tablets administered orally without regard to food
DRUGStable Baseline Regimen
SBR will include a combination of antiretroviral (ARV) regimen. ARV regimen may include the following, except for participants taking a single tablet regimen or taking a complete parenteral regimen (Cabenuva). * Nucleos(t)ide Reverse Transcriptase Inhibitors: * Abacavir * Emtricitabine * Lamivudine * Tenofovir alafenamide * Tenofovir disoproxil fumarate * Zidovudine * Non-Nucleosite Reverse Transcriptase Inhibitors: * Delavirdine * Efavirenz * Nevirapine * Rilpivirine * Doravirine * Integrase Inhibitors: * Bictegravir * Cabotegravir * Dolutegravir * Elvitegravir * Raltegravir * Protease Inhibitors: * Atazanavir * Darunavir * Fosamprenavir * Indinavir * Lopinavir * Nelfinavir * Saquinavir * Tipranavir * Chemokine Co-receptor 5 (CCR5) Antagonist: * Maraviroc * Fusion Inhibitors: * Enfuvirtide * gp120 Attachment Inhibitor: * Fostemsavir * Anti-CD4 Monoclonal Antibodies: * Ibalizumab-uiyk
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * If plasma HIV-1 RNA measurements in the 6 months prior to screening are available, all levels must be \< 50 copies/mL. * At least one documented plasma 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. * Currently receiving a complex antiretroviral (ARV) regimen due to previous viral resistance, or intolerance, or contraindication to existing single-tablet regimens (STR), and on this regimen for at least 6 months prior to the screening visit. The criteria to define a complex regimen in this study are as follows: * A regimen containing a boosted protease inhibitor or a nonnucleos(t)ide reverse transcriptase inhibitor (NRTI) plus at least 1 other third agent (ie, an agent from a class other than NRTIs) (eg, bictegravir/emtricitabine/tenofovir alafenamide (coformulated; Biktarvy®)(BVY) + darunavir/cobicistat, BVY + etravirine), or * A regimen of ≥ 2 pills/day, or a regimen requiring dosing more than once daily, or * A regimen containing parenteral agent(s) (excluding a complete long-acting injectable regimen, such as intramuscular cabotegravir plus rilpivirine) as well as oral agents. * No documented or suspected resistance to bictegravir (BIC). * Estimated glomerular filtration rate ≥ 15 mL/min according to the Cockcroft-Gault formula for creatinine clearance (CLcr) who are not on renal replacement therapy. Key
Exclusion criteria
* Prior use of, or exposure to, lenacapavir (LEN) * Active tuberculosis infection * Chronic hepatitis B virus (HBV) infection Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm | Week 24 |
| Phase 3: 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 | Description |
|---|---|---|
| Phase 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (AEs) Through Week 24 | First dose date up to Week 24 | — |
| Phase 2: Pharmacokinetic (PK) Parameter: Cmax of Bictegravir (BIC) and Lenacapavir (LEN) at Steady State | Day 1 up to Week 24 | Cmax is defined as the maximum observed concentration of drug. |
| Phase 2: PK Parameter: AUCtau of BIC and LEN at Steady State | Day 1 up to Week 24 | AUCtau is defined as the area under the concentration versus time curve over the dosing interval. |
| Phase 2: PK Parameter: Ctau of BIC and LEN at Steady State | Day 1 up to Week 24 | Ctau is defined as the observed drug concentration at the end of the dosing interval. |
| Phase 3: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm | Week 48 | — |
| Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm | Week 24 | — |
| Phase 3 (BIC/LEN 75 mg/50 mg FDC): Proportion of Participants from With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm | Week 96 | — |
| Phase 3 (BIC/LEN 75 mg/50 mg FDC): Change From Baseline in CD4 Cell Count at Week 96 | Baseline, Week 96 | — |
| Phase 3: Percentage of Participants Experiencing Treatment-emergent AEs Through Week 48 | First dose date up to Week 48 | — |
| Phase 3 (BIC/LEN 75 mg/50 mg FDC): Proportion of Participants from Experiencing Treatment-emergent AEs Through Week 96 | Week 96 | — |
| Phase 3: Change From Baseline in CD4 Cell Count at Week 48 | Baseline, Week 48 | — |
| Phase 2: Change From Baseline in CD4 Cell Count at Week 24 | Baseline, Week 24 | — |
Countries
Argentina, Australia, Canada, Dominican Republic, France, Germany, Italy, Japan, Puerto Rico, South Africa, South Korea, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed