Study to Evaluate the Safety and Efficacy of Lenacapavir in Combination With Other Antiretroviral Agents in People Living With HIV

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy of lenacapavir (formerly GS-6207) containing regimens in people living with human immunodeficiency virus (HIV) (PLWH).

Official Title
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A Phase 2 Randomized, Open Label, Active Controlled Study Evaluating the Safety and Efficacy of Long-acting Capsid Inhibitor GS-6207 in Combination With Other Antiretroviral Agents in People Living With HIV

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Oral Lenacapavir
* Drug: F/TAF
* Drug: Subcutaneous Lenacapavir
* Drug: TAF
* Drug: BIC
* Drug: B/F/TAF


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Antiretroviral (ARV) naive with no use of any ARV within one month of screening. Use of pre-exposure prophylaxis (PrEP) (any duration), post-exposure prophylaxis (PEP) (any duration), or HIV-1 treatment (< 10 days therapy total) > 1 month prior to screening is permitted HIV-1 ribonucleic acid (RNA) ≥ 200 copies/mL at screening Cluster Determinant 4+ (CD4+) cell count ≥ 200 cells/microliter at screening Key Exclusion Criteria: Current Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) 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: Lenacapavir, F/TAF, and TAF<br>Induction: Participants will receive oral lenacapavir 600 mg, 600 mg, and 300 mg at Days 1, 2, and 8, respectively. Participants will also begin oral daily emtricitabine/tenofovir alafenamide (F/TAF) 200/25mg from Day 1 onwards for a total of 28 weeks. On Day 15 participants will receive subcutaneous (SC) lenacapavir 927 mg. Maintenance: Participants will receive SC lenacapavir 927 mg at Week 28 and every 26 weeks. Participants will discontinue oral daily F/TAF 200/25 mg at Week 28 and begin taking oral daily TAF 25 mg. May require oral weekly bridging if an SC injection of GS-6207 cannot be administered for any reason within the protocol visit window. Participants willing to continue the study beyond Week 80 will continue to receive SC lenacapavir 927 mg every 6 months (26 weeks) and oral daily TAF 25 mg from Week 80 onwards. | Drug: Oral Lenacapavir<br>* Tablets administered without regard to food<br>* Other names: GS-6207;Drug: F/TAF<br>* Tablets administered without regard to food<br>* Other names: Descovy®;Drug: Subcutaneous Lenacapavir<br>* Administered in the abdomen via subcutaneous injections<br>* Other names: GS-6207;Drug: TAF<br>* Tablets administered without regard to food<br>|
| Experimental: Lenacapavir, F/TAF, and BIC<br>Induction: Participants will receive oral lenacapavir 600 mg, 600 mg, and 300 mg at Days 1, 2, and 8, respectively. Participants will also begin oral daily F/TAF 200/25 mg from Day 1 onward for a total of 28 weeks. On Day 15 participants will receive SC lenacapavir 927 mg. Maintenance: Participants will receive SC lenacapavir 927 mg at Week 28 and every 26 weeks. Participants will discontinue oral daily F/TAF 200/25 mg at Week 28 and begin oral daily bictegravir (BIC) 75 mg. May require oral weekly bridging if an SC injection of GS-6207 cannot be administered for any reason within the protocol visit window. Participants willing to continue the study beyond Week 80 will continue to receive SC lenacapavir 927 mg every 6 months (26 weeks) and oral daily bictegravir (BIC) 75 mg from Week 80 onwards. | Drug: Oral Lenacapavir<br>* Tablets administered without regard to food<br>* Other names: GS-6207;Drug: F/TAF<br>* Tablets administered without regard to food<br>* Other names: Descovy®;Drug: Subcutaneous Lenacapavir<br>* Administered in the abdomen via subcutaneous injections<br>* Other names: GS-6207;Drug: BIC<br>* Tablets administered without regard to food<br>|
| Experimental: Lenacapavir and F/TAF<br>Participants will receive oral lenacapavir 600 mg at Day 1 and Day 2. On Day 3, participants will begin oral daily lenacapavir 50 mg. Participants will begin oral daily F/TAF 200/25 mg from Day 1 onwards. Participants willing to continue the study beyond Week 80 will continue to receive oral daily lenacapavir 50 mg and oral daily F/TAF 200/25 mg from Week 80 onwards. | Drug: Oral Lenacapavir<br>* Tablets administered without regard to food<br>* Other names: GS-6207;Drug: F/TAF<br>* Tablets administered without regard to food<br>* Other names: Descovy®;|
| Active Comparator: B/F/TAF<br>Participants will receive oral daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg at Day 1 and throughout their participation in the study. | Drug: B/F/TAF<br>* Tablets administered without regard to food<br>* Other names: Biktarvy®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 54 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 54 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 54 window was between Day 323 and 413 (inclusive). | Week 54 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 28 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 28 window was between Days 176 and 231 (inclusive). | Week 28 | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 38 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Week 24 window was between Days 232 and 322 (inclusive). | Week 38 | 
| Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm |  | Week 80 | 
| Change From Baseline in Log10 HIV-1 RNA at Week 28 |  | Baseline; Week 28 | 
| Change From Baseline in Log10 HIV-1 RNA at Week 38 |  | Baseline; Week 38 | 
| Change From Baseline in Log10 HIV-1 RNA at Week 54 |  | Baseline; Week 54 | 
| Change From Baseline in Log10 HIV-1 RNA at Week 80 |  | Baseline; Week 80 | 
| Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 28 |  | Baseline; Week 28 | 
| Change From Baseline in CD4+ Cell Count at Week 38 |  | Baseline; Week 38 | 
| Change From Baseline in CD4+ Cell Count at Week 54 |  | Baseline; Week 54 | 
| Change From Baseline in CD4+ Cell Count at Week 80 |  | Baseline; Week 80 | 
| Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. | First dose date up to 54 weeks | 
| Percentage of Participants Who Experienced Laboratory Abnormalities | Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline visit, up to last exposure date for participants who permanently discontinued study drug, or the last available date in the database snapshot for participants who were still on treatment at the time of an interim analysis. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening. | First dose date up to 54 weeks | 
| Pharmacokinetics (PK) of TAF (Tenofovir Alafenamide)and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) on Day 1 | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2) and at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1 | 
| PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) on Day 1 | Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1 | 
| PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) on Day 1 | Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 and 2 on Day 1. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1 | 
| PK of TFV: Last Observed Quantifiable Concentration of the Drug (Clast) on Day 1 | Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK sub study analysis was conducted for Group 1 and 2 on Day 1. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1 | 
| PK of TAF and TFV: AUClast at Weeks 16, 22, or 28 | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | 
| PK of TAF and TFV: Cmax at Weeks 16, 22, or 28 | Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | 
| PK of TAF and TFV: Tmax at Weeks 16, 22, or 28 | Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TAF and TFV were summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | 
| PK of TFV: Clast at Weeks 16, 22, or 28 | Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 15 participants in the treatment group receiving oral LEN (Treatment Group 3). Key PK parameters of TFV was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. For each participant, PK samples were taken at only one of the three possible visits: Weeks 16, 22, or 28. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | 
| PK of TAF: AUClast at Week 38 | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | 
| PK of TAF: Cmax at Week 38 | Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | 
| PK of TAF: Tmax at Week 38 | Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). Key PK parameters of TAF was summarized for participants in the PK Sub study Analysis Set by treatment group, analyte and visit. PK substudy analysis was conducted for Group 1 at Week 38. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | 
| PK of Tenofovir Diphosphate (TFV-DP): AUClast at Weeks 4, 10, 16, or 22 | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A peripheral blood mononuclear cell (PBMC) substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. | 0 hours (Predose) and at 1, 2, and 6 hours postdose | 
| PK of TFV-DP: Cmax at Weeks 4, 10, 16, or 22 | Cmax is defined as the maximum observed concentration of drug. A PBMC substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. | 0 hours (Predose) and at 1, 2, and 6 hours postdose | 
| PK of TFV-DP: Tmax at Weeks 4, 10, 16, or 22 | Tmax is defined as the time (observed time point) of Cmax. A PBMC substudy was conducted in a total of approximately 15 participants in Treatment Groups 1 and 2. For each participant, PK samples were taken at only one of the four possible visits: Weeks 4, 10, 16, or 22. A 12-hour postdose sample was collected, if possible. The PK results were combined and summarized without regard to specific study visit within the range of prespecified study visits. | 0 hours (Predose) and at 1, 2, and 6 hours postdose | 
| PK of Bictegravir (BIC): AUClast at Week 38 | AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | 
| PK of BIC: Cmax at Week 38 | Cmax is defined as the maximum observed concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | 
| PK of BIC: Tmax at Week 38 | Tmax is defined as the time (observed time point) of Cmax. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose | 
| PK of BIC: Clast at Week 38 | Clast is defined as the last observable concentration of drug. A PK substudy was conducted in at least 10 participants in each of the treatment groups receiving SC LEN (Treatment Groups 1 and 2). At Week 38, samples were analyzed for BIC only in Treatment Group 2. | 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose |