Study to Evaluate the Safety and Efficacy of Lenacapavir (GS-6207) in Combination With an Optimized Background Regimen (OBR) in Heavily Treatment Experienced Participants Living With HIV-1 Infection With Multidrug Resistance

Phase 2

Active, not recruiting

Conditions: HIV-1-infection

Interventions: Drug: Oral Lenacapavir
Drug: Subcutaneous Lenacapavir
Drug: Oral Lenacapavir Placebo
Drug: Failing ARV Regimen
Drug: Optimized Background Regimen (OBR)

Registration Number: NCT04150068

Lead Sponsor: Gilead Sciences

Brief Summary: The primary objective of this study is to evaluate the antiviral activity of lenacapavir (formerly GS-6207) administered as an add-on to a failing regimen (functional monotherapy) in people with human immunodeficiency virus (HIV) (PWH) with multi-drug resistance (MDR).

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 72

Inclusion Criteria

Adult aged ≥ 18 years (at all sites) or adolescent aged ≥ 12 and weighing ≥ 35 kg (at sites in North America and Dominican Republic)
Currently receiving a stable failing ARV regimen for > 8 weeks
Have HIV-1 RNA ≥ 400 copies/mL at screening
Have multidrug resistance (resistance to ≥2 agents from ≥3 of the 4 main classes of ARV)
Have no more than 2 fully active ARV remaining from the 4 main classes that can be effectively combined to form a viable regimen
Able and willing to receive an OBR together with lenacapavir
No Hepatitis C virus (HCV) ongoing infection

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1A: Lenacapavir	Oral Lenacapavir	Participants with HIV-1 ribonucleic acid (RNA) ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at Cohort Selection visit compared with screening visit will receive oral lenacapavir (LEN) 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive subcutaneous (SC) LEN 927 mg and will initiate an optimized background regimen (OBR) at Day 1 SC Visit (14 days after the first dose of oral LEN). Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
Cohort 1A: Lenacapavir	Subcutaneous Lenacapavir	Participants with HIV-1 ribonucleic acid (RNA) ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at Cohort Selection visit compared with screening visit will receive oral lenacapavir (LEN) 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive subcutaneous (SC) LEN 927 mg and will initiate an optimized background regimen (OBR) at Day 1 SC Visit (14 days after the first dose of oral LEN). Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
Cohort 1A: Lenacapavir	Failing ARV Regimen	Participants with HIV-1 ribonucleic acid (RNA) ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at Cohort Selection visit compared with screening visit will receive oral lenacapavir (LEN) 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive subcutaneous (SC) LEN 927 mg and will initiate an optimized background regimen (OBR) at Day 1 SC Visit (14 days after the first dose of oral LEN). Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
Cohort 1A: Lenacapavir	Optimized Background Regimen (OBR)	Participants with HIV-1 ribonucleic acid (RNA) ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at Cohort Selection visit compared with screening visit will receive oral lenacapavir (LEN) 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive subcutaneous (SC) LEN 927 mg and will initiate an optimized background regimen (OBR) at Day 1 SC Visit (14 days after the first dose of oral LEN). Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
Cohort 1B: Placebo to Lenacapavir	Failing ARV Regimen	Participants with HIV-1 RNA ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR. Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue study in the country.
Cohort 1B: Placebo to Lenacapavir	Optimized Background Regimen (OBR)	Participants with HIV-1 RNA ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR. Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue study in the country.
Cohort 2: Lenacapavir	Oral Lenacapavir	Participants with a ≥ 0.5 log10 copies/mL HIV-1 RNA decline at the Cohort Selection Visit compared with the screening visit or with HIV-1 RNA \< 400 copies/mL or if Cohort 1 is fully enrolled will receive oral LEN 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, and will initiate an OBR on Day 1 in Oral Lead-in Period (Baseline to Day 14); followed by Maintenance Period where participants will receive SC LEN 927 mg at Day 1 SC Visit (14 days after the first dose of oral LEN) while continuing their OBR. Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
Cohort 2: Lenacapavir	Optimized Background Regimen (OBR)	Participants with a ≥ 0.5 log10 copies/mL HIV-1 RNA decline at the Cohort Selection Visit compared with the screening visit or with HIV-1 RNA \< 400 copies/mL or if Cohort 1 is fully enrolled will receive oral LEN 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, and will initiate an OBR on Day 1 in Oral Lead-in Period (Baseline to Day 14); followed by Maintenance Period where participants will receive SC LEN 927 mg at Day 1 SC Visit (14 days after the first dose of oral LEN) while continuing their OBR. Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.
Cohort 1B: Placebo to Lenacapavir	Oral Lenacapavir	Participants with HIV-1 RNA ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR. Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue study in the country.
Cohort 1B: Placebo to Lenacapavir	Oral Lenacapavir Placebo	Participants with HIV-1 RNA ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR. Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue study in the country.
Cohort 1B: Placebo to Lenacapavir	Subcutaneous Lenacapavir	Participants with HIV-1 RNA ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR. Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue study in the country.
Cohort 2: Lenacapavir	Subcutaneous Lenacapavir	Participants with a ≥ 0.5 log10 copies/mL HIV-1 RNA decline at the Cohort Selection Visit compared with the screening visit or with HIV-1 RNA \< 400 copies/mL or if Cohort 1 is fully enrolled will receive oral LEN 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, and will initiate an OBR on Day 1 in Oral Lead-in Period (Baseline to Day 14); followed by Maintenance Period where participants will receive SC LEN 927 mg at Day 1 SC Visit (14 days after the first dose of oral LEN) while continuing their OBR. Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants in Cohort 1 Achieving a Reduction of ≥ 0.5 log10 Copies/mL in Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) From Baseline to the End of Functional Monotherapy Period	Baseline up to Day 1 SC Visit (14 days after the first dose of oral lencapavir) or Day 15

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 50 Copies/mL at Week 52 Based on the US FDA-defined Snapshot Algorithm	Week 52
Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 200 Copies/mL at Week 52 Based on the US FDA-defined Snapshot Algorithm	Week 52
Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 50 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm	Week 26 (26 weeks after first dose of subcutaneous lenacapavir)	The percentage of participants in cohort 1 with plasma HIV-1 RNA \< 50 copies/mL at Week 26 was analyzed using the United States Food and Drug Administration (US FDA)-defined 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.
Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 200 Copies/mL From the First SC Dose of Lenacapavir Based on the US FDA-defined Snapshot Algorithm	Week 156
Percentage of Participants in Cohort 1 With Plasma HIV-1 RNA < 200 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm	Week 26 (26 weeks after first dose of subcutaneous lenacapavir)	The percentage of participants in cohort 1 with plasma HIV-1 RNA \< 200 copies/mL at Week 26 was analyzed using the US FDA-defined 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.
Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 50 Copies/mL From the First SC Dose of Lenacapavir Based on the US FDA-defined Snapshot Algorithm	Week 156
Percentage of Participants in Combined Cohorts 1 and 2 With Plasma HIV-1 RNA < 50 Copies/mL From the First Subcutaneous (SC) Dose of Lenacapavir Based on the US FDA-defined Snapshot Algorithm	Week 104

Trial Locations

Locations (75): Ruane Clinical Research Group Inc
🇺🇸
Los Angeles, California, United States
Mills Clinical Research
🇺🇸
Los Angeles, California, United States
Eisenhower Health Center at Rimrock
🇺🇸
Palm Springs, California, United States
One Community Health
🇺🇸
Sacramento, California, United States
Yale University; School of Medicine
🇺🇸
New Haven, Connecticut, United States
Washington Health Institute
🇺🇸
Washington, District of Columbia, United States
Midland Florida Clinical Research Center, LLC
🇺🇸
DeLand, Florida, United States
Gary J. Richmond, M.D., P.A.
🇺🇸
Fort Lauderdale, Florida, United States
Midway Immunology and Research Center
🇺🇸
Fort Pierce, Florida, United States
Floridian Clinical Research
🇺🇸
Hialeah, Florida, United States
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Ruane Clinical Research Group Inc
🇺🇸Los Angeles, California, United States