Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in Virologically Suppressed People 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 oral weekly islatravir (ISL) in combination with lenacapavir (LEN) in virologically suppressed people with HIV (PWH) at Week 24.

Official Title
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A Phase 2 Randomized, Open-Label, Active-Controlled Study Evaluating the Safety and Efficacy of an Oral Weekly Regimen of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: ISL
* Drug: LEN
* Drug: B/F/TAF


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for ≥ 24 weeks at screening. Documented plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) for ≥ 24 weeks before and at screening. Plasma HIV-1 RNA < 50 copies/mL at screening. Key Exclusion Criteria: History of prior virologic failure while receiving treatment for HIV-1. Prior use of, or exposure to, islatravir (ISL) or lenacapavir (LEN). Active, serious infections requiring parenteral therapy < 30 days before randomization. Active or occult hepatitis B virus (HBV) coinfection, defined as hepatitis B core antibody (HBcAb) positive, hepatitis B surface antigen (HBsAg) positive, or HBV deoxyribonucleic acid (DNA) positive as determined by the central laboratory. Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA. Any of the following laboratory values at screening: Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula CD4+ T-cells < 200 cells/mm^3 (Cohort 1); CD4+ T-cells < 350 cells/mm^3 (cohort 2). Absolute lymphocyte count < 900 cells/mm^3 (cohort 2). Individuals of childbearing potential (as defined in protocol) who have a positive serum pregnancy test at screening or positive urine and serum pregnancy tests at Day 1 prior to study drug administration. Individuals who plan to continue breastfeeding during the study. Documented historical or screening resistance reports showing nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) or non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs) resistance mutations in reverse transcriptase, including M184V/I (Cohort 2). 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: ISL+LEN<br>Participants will receive the following for at least 48 weeks: Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg) Day 2: LEN only oral 600 mg (2 x 300 mg) Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg (2 x 1 mg) | Drug: ISL<br>* Capsules administered orally without regard to food<br>Drug: LEN<br>* Tablets administered orally without regard to food<br>* Other names: GS-6207;|
| Experimental: B/F/TAF<br>Participants will receive the following for at least 48 weeks: bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily After 48 weeks, participants will switch from B/F/TAF to ISL+LEN Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg) Day 2: LEN only oral 600 mg (2 x 300 mg) Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study. | Drug: ISL<br>* Capsules administered orally without regard to food<br>Drug: LEN<br>* Tablets administered orally without regard to food<br>* Other names: GS-6207;Drug: B/F/TAF<br>* Tablets administered orally 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 |
| --- | --- | --- |
| Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US Food and Drug Administration (FDA)-defined Snapshot Algorithm |  | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm |  | Week 12 | 
| Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm |  | Week 48 | 
| Proportions of Participants With HIV-1 RNA < 50 copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm |  | Week 12 | 
| Proportions of Participants With HIV-1 RNA < 50 copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm |  | Week 24 | 
| Proportions 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 12 |  | Baseline, Week 12 | 
| Change From Baseline in CD4+ Cell Count at Week 24 |  | Baseline, Week 24 | 
| Change From Baseline in CD4+ Cell Count at Week 48 |  | Baseline, Week 48 | 
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation |  | Up to 5 years | 
| Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL) and Lenacapavir (LEN) | Cmax is defined as the maximum observed concentration of drug. | Day 1 up to Week 36 | 
| PK Parameter: Tmax of ISL and LEN | Tmax is defined as the time (observed time point) of Cmax. | Day 1 up to Week 36 | 
| PK Parameter: Ctau of ISL and LEN | Ctau is defined as the observed drug concentration at the end of the dosing interval. | Day 1 up to Week 36 | 
| PK Parameter: AUCtau of ISL and LEN | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | Day 1 up to Week 36 | 
| PK Parameter: t1/2 of ISL and LEN | t1/2 is defined as the estimate of the terminal elimination half-life of the drug. | Day 1 up to Week 36 |