Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV

Phase 2Active Not RecruitingNCT05052996

Gilead Sciences142 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

142

Conditions

HIV-1 Infection

Interventions

ISLDRUG

Capsules administered orally without regard to food

LENDRUG

Tablets administered orally without regard to food

B/F/TAFDRUG

Tablets administered orally without regard to food

ISL/LEN FDC

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (44)

Outcomes

Primary Outcomes

Percentage 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

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 24 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 the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off.

Time frame: Week 24

Secondary Outcomes

Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 12 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 the applicable study drug discontinuation status. Week 12 window was between Day 71 and 105 (inclusive). Percentages were rounded off.

Time frame: Week 12

Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 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 the applicable study drug discontinuation status. Week 48 window was between Day 316 and 378 (inclusive). Percentages were rounded off.

Time frame: Week 48

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 12 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 the applicable study drug discontinuation status. Week 12 window was between Day 71 and 105 (inclusive). Percentages were rounded off.

Data from ClinicalTrials.gov

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Tablets administered orally without regard to food

Pacific Oaks Medical Group

Beverly Hills, California, United States

Ruane Clinical Research Group, Inc

Los Angeles, California, United States

Mills Clinical Research

Los Angeles, California, United States

Hoag Medical Group - Newport Beach

Newport Beach, California, United States

BIOS Clinical Research

Palm Springs, California, United States

Optimus Medical Group

San Francisco, California, United States

Public Health Institute at Denver Health

Denver, Colorado, United States

Vivent Health

Denver, Colorado, United States

Washington Health Institute

Washington D.C., District of Columbia, United States

The George Washington University Medical Faculty Associates Inc.

Washington D.C., District of Columbia, United States

...and 34 more locations

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 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 the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off.

Time frame: Week 24

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 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 the applicable study drug discontinuation status. Week 48 window was between Day 316 and 378 (inclusive). Percentages were rounded off.

Time frame: Week 48

Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12

Time frame: Baseline and Week 12

Change From Baseline in CD4+ Cell Count at Week 24

Time frame: Baseline and Week 24

Change From Baseline in CD4+ Cell Count at Week 48

Time frame: Baseline and Week 48

Percentage of Participants Experiencing Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation

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. Percentages were rounded off.

Time frame: Up to 5 years

Cohort 1: Plasma Concentrations for ISL

Time frame: Anytime postdose at Week 4

Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL)

Cmax was defined as the maximum observed concentration of drug.

Time frame: Anytime post dose on Day 1 and at either Week 12 or Week 18

Cohort 2: PK Parameter: Tmax of ISL

Tmax was defined as the time (observed time point) of Cmax.

Time frame: Anytime post dose on Day 1 and at either Week 12 or Week 18

Cohort 2: PK Parameter: Ctau of ISL

Ctau was defined as the observed drug concentration at the end of the dosing interval.

Time frame: Anytime post dose at either Week 12 or Week 18

Cohort 2: PK Parameter: AUCtau of ISL

AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Time frame: Anytime post dose at either Week 12 or Week 18

Plasma Concentrations for LEN

Time frame: Anytime postdose at Week 4

Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN

Cmax was defined as the maximum observed concentration of drug.

Time frame: Anytime post dose on Day 1, Day 2 and at either Week 12 or 18

Cohort 2: PK Parameter: Tmax of LEN

Tmax is defined as the time (observed time point) of Cmax.

Time frame: Anytime post dose on Day 1, Day 2 and at either Week 12 or Week 18

Cohort 2: PK Parameter: Ctau of LEN

Ctau was defined as the observed drug concentration at the end of the dosing interval.

Time frame: Anytime post dose at either Week 12 or Week 18

Cohort 2: PK Parameter: AUCtau of LEN

AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Time frame: Anytime post dose at either Week 12 or Week 18