Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV
- Registration Number
- NCT05052996
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 142
- 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
-
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
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CD4+ T-cells < 200 cells/mm^3 (Cohort 1); CD4+ T-cells < 350 cells/mm^3 (cohort 2).
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Absolute lymphocyte count < 900 cells/mm^3 (cohort 2).
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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.
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Individuals who plan to continue breastfeeding during the study.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 (ISL+LEN) ISL Participants will receive the following for at least 48 weeks: * Day 1 and Day 2: ISL 40 and LEN 600 mg * Day 8 and weekly thereafter (ie, every 7 days): ISL 20 mg and LEN 300 mg Cohort 1 (ISL+LEN) LEN Participants will receive the following for at least 48 weeks: * Day 1 and Day 2: ISL 40 and LEN 600 mg * Day 8 and weekly thereafter (ie, every 7 days): ISL 20 mg and LEN 300 mg Cohort 1 (B/F/TAF to ISL+LEN) ISL Participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily for at least 48 weeks After 48 weeks, participants will switch from B/F/TAF to ISL+LEN * ISL 40 and LEN 600 mg on Day 1 and Day 2 * ISL 20 mg and LEN 300 mg weekly Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study. Cohort 1 (B/F/TAF to ISL+LEN) LEN Participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily for at least 48 weeks After 48 weeks, participants will switch from B/F/TAF to ISL+LEN * ISL 40 and LEN 600 mg on Day 1 and Day 2 * ISL 20 mg and LEN 300 mg weekly Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study. Cohort 1 (B/F/TAF to ISL+LEN) B/F/TAF Participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily for at least 48 weeks After 48 weeks, participants will switch from B/F/TAF to ISL+LEN * ISL 40 and LEN 600 mg on Day 1 and Day 2 * ISL 20 mg and LEN 300 mg weekly Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study. Cohort 2 (ISL+LEN) LEN 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 Cohort 2 (B/F/TAF to ISL+LEN) LEN Participants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks 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. Cohort 2 (B/F/TAF to ISL+LEN) B/F/TAF Participants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks 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. Cohort 2 (ISL+LEN) ISL 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 Cohort 2 (B/F/TAF to ISL+LEN) ISL Participants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks 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.
- Primary Outcome Measures
Name Time Method 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 Week 24 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in CD4+ Cell Count at Week 48 Baseline and Week 48 Percentage of Participants Experiencing Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation Up to 5 years 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.
Cohort 2: PK Parameter: Ctau of ISL Anytime post dose at either Week 12 or Week 18 Ctau was defined as the observed drug concentration at the end of the dosing interval.
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm Week 12 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.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm Week 12 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.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm Week 48 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.
Change From Baseline in CD4+ Cell Count at Week 24 Baseline and Week 24 Cohort 1: Plasma Concentrations for ISL Anytime postdose at Week 4 Cohort 2: PK Parameter: AUCtau of ISL Anytime post dose at either Week 12 or Week 18 AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Cohort 2: PK Parameter: Tmax of LEN Anytime post dose on Day 1, Day 2 and at either Week 12 or Week 18 Tmax is defined as the time (observed time point) of Cmax.
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm Week 48 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.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm Week 24 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.
Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12 Baseline and Week 12 Cohort 2: PK Parameter: Tmax of ISL Anytime post dose on Day 1 and at either Week 12 or Week 18 Tmax was defined as the time (observed time point) of Cmax.
Plasma Concentrations for LEN Anytime postdose at Week 4 Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL) Anytime post dose on Day 1 and at either Week 12 or Week 18 Cmax was defined as the maximum observed concentration of drug.
Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN Anytime post dose on Day 1, Day 2 and at either Week 12 or 18 Cmax was defined as the maximum observed concentration of drug.
Cohort 2: PK Parameter: Ctau of LEN Anytime post dose at either Week 12 or Week 18 Ctau was defined as the observed drug concentration at the end of the dosing interval.
Cohort 2: PK Parameter: AUCtau of LEN Anytime post dose at either Week 12 or Week 18 AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Trial Locations
- Locations (44)
Ruane Clinical Research Group, Inc
🇺🇸Los Angeles, California, United States
Mills Clinical Research
🇺🇸Los Angeles, California, United States
Emory University Hospital Midtown Infectious Disease Clinic
🇺🇸Atlanta, Georgia, United States
Atlanta ID Group, PC
🇺🇸Atlanta, Georgia, United States
The George Washington University Medical Faculty Associates Inc.
🇺🇸Washington, District of Columbia, United States
Hoag Medical Group - Newport Beach
🇺🇸Newport Beach, California, United States
Philadelphia FIGHT Community Health Centers
🇺🇸Philadelphia, Pennsylvania, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
AccessHealth MA
🇺🇸Boston, Massachusetts, United States
Peter Shalit, M.D.
🇺🇸Seattle, Washington, United States
Schiff Center for Liver Diseases/University of Miami
🇺🇸Miami, Florida, United States
The Crofoot Research Center, INC
🇺🇸Houston, Texas, United States
Huntridge Family Clinic
🇺🇸Las Vegas, Nevada, 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
Pacific Oaks Medical Group
🇺🇸Beverly Hills, California, United States
BIOS Clinical Research
🇺🇸Palm Springs, California, United States
Washington Health Institute
🇺🇸Washington, District of Columbia, United States
CAN Community Health Care, Inc.
🇺🇸Fort Lauderdale, Florida, United States
Floridian Clinical Research
🇺🇸Miami Lakes, Florida, United States
Midway Immunology and Research Center
🇺🇸Fort Pierce, Florida, United States
JEM Research Institute
🇺🇸Lake Worth, Florida, United States
Metro Infectious Disease Consultants
🇺🇸Decatur, Georgia, United States
Chatham County Health Department
🇺🇸Savannah, Georgia, United States
Howard Brown Health Center
🇺🇸Chicago, Illinois, United States
Northstar Healthcare
🇺🇸Chicago, Illinois, United States
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
Indiana CTSI Clinical Research Center
🇺🇸Indianapolis, Indiana, United States
Hennepin Healthcare HCMC
🇺🇸New Brighton, Minnesota, United States
Southampton Healthcare, Inc.
🇺🇸Saint Louis, Missouri, United States
AXCES Research Group
🇺🇸Santa Fe, New Mexico, United States
ID Care
🇺🇸Hillsborough, New Jersey, United States
New York-Presbyterian Queens
🇺🇸Flushing, New York, United States
AIDS Arms Inc
🇺🇸Dallas, Texas, United States
Community Health Care
🇺🇸Tacoma, Washington, United States
MultiCare Rockwood Main Clinic
🇺🇸Spokane, Washington, United States
North Texas Infectious Diseases Consultants, P.A.
🇺🇸Dallas, Texas, United States
Penn Medicine: Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
NC TraCS Institute - CTRC: University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Central Texas Clinical Research, LLC
🇺🇸Austin, Texas, United States
John A. Burns School of Medicine, University of Hawaii Clinics at Kaka'ako
🇺🇸Honolulu, Hawaii, United States
Jacobi Medical Center
🇺🇸Bronx, New York, United States