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

Study Overview
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Brief Summary
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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).

Official Title
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An Operationally Seamless Phase 2/3 Randomized, Open-label, Multicenter, Active-Controlled Study to Evaluate the Safety and Efficacy of Bictegravir/Lenacapavir Versus Stable Baseline Regimen in Virologically Suppressed People With HIV-1 on Stable Complex Treatment Regimens

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Bictegravir
* Drug: Lenacapavir
* Drug: BIC/LEN FDC
* Drug: Stable Baseline Regimen


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented plasma human immunodeficiency virus type-1 (HIV-1) ribonucleic acid (RNA) levels < 50 copies/mL during treatment with the baseline regimen for a minimum period of 6 months prior to the screening visit. 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). 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/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 2: Bictegravir (BIC) 75 mg + Lenacapavir (LEN) 25 mg<br>Participants will switch from their stable baseline regimen (SBR) to a regimen of BIC 75 mg plus LEN 25 mg. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC 75 mg plus LEN 25 mg starting on Day 1 up to the end of randomized treatment (ERT) visit, participants will be treated for at least 24 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN fixed dose combination (FDC) at the selected dose. | Drug: Bictegravir<br>* Tablets administered orally without regard to food<br>* Other names: GS-9883;Drug: Lenacapavir<br>* Tablets administered orally without regard to food<br>* Other names: GS-6207;|
| Experimental: Phase 2: BIC 75 mg + LEN 50 mg<br>Participants will switch from their SBR to a regimen of BIC 75 mg plus LEN 50 mg. Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC 75 mg plus LEN 50 mg starting on Day 1 up to the ERT visit, participants will be treated for at least 24 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN FDC at the selected dose. | Drug: Bictegravir<br>* Tablets administered orally without regard to food<br>* Other names: GS-9883;Drug: Lenacapavir<br>* Tablets administered orally without regard to food<br>* Other names: GS-6207;|
| Active Comparator: Phase 2: Stable Baseline Regimen (SBR)<br>Participants will continue with their SBR per prescription for up to the ERT visit, participants will be treated for at least 24 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN FDC at the selected dose. | Drug: Stable Baseline Regimen<br>* 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<br>|
| Experimental: Phase 3: BIC/LEN Fixed-dose Combination (FDC)<br>Participants will switch from their SBR to a regimen of BIC/LEN FDC (dose selection per Week 24 date from Phase 2). Participants will receive a 2-day loading dose regimen of LEN 600 mg, in addition to the daily doses of BIC/LEN FDC starting on Day 1 up to the ERT visit, participants will be treated for at least 48 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN FDC at the selected dose. | Drug: BIC/LEN FDC<br>* Tablets administered orally without regard to food<br>|
| Active Comparator: Phase 3: Stable Baseline Regimen<br>Participants will continue with their SBR per prescription for up to the ERT visit, participants will be treated for at least 48 weeks during the Randomized Period. Following Randomized Period, the participants will have an option to participate in an Extension Period to receive BIC/LEN FDC at the selected dose. | Drug: Stable Baseline Regimen<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 2: Change From Baseline in CD4 Cell Count at Week 24 |  | Baseline, Week 24 | 
| 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 | Cmax is defined as the maximum observed concentration of drug. | Day 1 up to Week 24 | 
| Phase 2: PK Parameter: AUCtau of BIC and LEN at Steady State | AUCtau is defined as the area under the concentration versus time curve over the dosing interval. | Day 1 up to Week 24 | 
| Phase 2: PK Parameter: Ctau of BIC and LEN at Steady State | Ctau is defined as the observed drug concentration at the end of the dosing interval. | Day 1 up to 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 | 
| Phase 3: Change From Baseline in CD4 Cell Count at Week 48 |  | Baseline, Week 48 | 
| Phase 3: Percentage of Participants Experiencing Treatment-emergent AEs Through Week 48 |  | First dose date up to Week 48 |