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
- Conditions
- HIV-1-infection
- Interventions
- Drug: Failing ARV RegimenDrug: 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
- 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.
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)
Mills Clinical Research
🇺🇸Los Angeles, California, United States
Emory Hospital Midtown Infectious Disease Clinic
🇺🇸Atlanta, Georgia, United States
North Texas Infectious Diseases Consultants, P.A.
🇺🇸Dallas, Texas, United States
Maple Leaf Research/Maple Leaf Medical Clinic
🇨🇦Toronto, Ontario, Canada
AIDS Healthcare Foundation - South Beach
🇺🇸Miami Beach, Florida, United States
Gary J. Richmond, M.D., P.A.
🇺🇸Fort Lauderdale, Florida, United States
Floridian Clinical Research
🇺🇸Hialeah, Florida, United States
Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Vancouver ID Research and Care Centre Society
🇨🇦Vancouver, British Columbia, Canada
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Helen Joseph Hospital
🇿🇦Johannesburg, South Africa
The Ottawa Hospital
🇨🇦Ottawa, Canada
Midland Florida Clinical Research Center, LLC
🇺🇸DeLand, Florida, United States
Durban International Clinical Research Site, Enhancing Care Foundation
🇿🇦Durban, South Africa
Eisenhower Health Center at Rimrock
🇺🇸Palm Springs, California, United States
Triple O Research Institute, P.A.
🇺🇸West Palm Beach, Florida, United States
Southampton Healthcare, Inc.
🇺🇸Saint Louis, Missouri, United States
The Miriam Hospital
🇺🇸Providence, Rhode Island, United States
Midway Immunology and Research Center
🇺🇸Fort Pierce, Florida, United States
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Washington Health Institute
🇺🇸Washington, District of Columbia, United States
Hôpital Bichat-Claude Bernard
🇫🇷Paris, France
Howard Brown Health Center
🇺🇸Chicago, Illinois, United States
University of Naples Federico II
🇮🇹Bergamo, Italy
UOC Malattie Infettive - ASST Spedali Civili Di Brescia - Piazzale Spedali Civili 1
🇮🇹Brescia, Italy
Clinique de médecine urbaine du Quartier Latin
🇨🇦Montreal, Quebec, Canada
Clinical Alliance for Research and Education - Infectious Diseases, LLC (CARE-ID)
🇺🇸Annandale, Virginia, United States
National Hospital Organization Nagoya Medical Center
🇯🇵Nagoya, Japan
Vx Pharma
🇿🇦Pretoria, South Africa
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
AIDS Arms, Inc. DBA Prism Health North Texas
🇺🇸Dallas, Texas, United States
Northstar Healthcare
🇺🇸Chicago, Illinois, United States
Hospital Dr. Salvador Bienvenido Gautier
🇩🇴Santo Domingo, Dominican Republic
U.O.C. Malattie Infettive - Fondazione Policlinico Universitario A. Gemelli IRCCS
🇮🇹Rome, Italy
Perinatal HIV Research Unit (PHRU)
🇿🇦Soweto, South Africa
Hôpital Saint-Louis
🇫🇷Paris, France
Hôpital Saint-Antoine
🇫🇷Paris, France
New York-Presbyterian/Queens
🇺🇸Flushing, New York, United States
North Shore University Hospital/Division of Infectious Diseases
🇺🇸Manhasset, New York, United States
Divisione di Malattie Infettive, IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
Hospital Universitari Germans Trías i Pujol
🇪🇸Badalona, Spain
Faculty of Medicine Ramathibodi Hospital, Mahidol University
🇹🇭Bangkok, Thailand
Universitätsklinikum Frankfurt, Medizinische Klinik II
🇩🇪Frankfurt, Hesse, Germany
Bamrasnaradura Infectious Diseases Institute
🇹🇭Nonthaburi, Thailand
Thai Red Cross AIDS Research Center
🇹🇭Bangkok, Thailand
Faculty of Medicine Siriraj Hospital, Mahidol University
🇹🇭Bangkok, Thailand
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Faculty of Medicine, Khon Kaen University
🇹🇭Khon Kaen, Thailand
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Kaohsiung Veterans General Hospital
🇨🇳Kaohsiung, Taiwan
Far Eastern Memorial Hospital
🇨🇳New Taipei City, Taiwan
Taoyuan General Hospital, Ministry of Health and Welfare
🇨🇳Taoyuan City, Taiwan
U.O.C. IMMUNODEFICIENZE VIRALI - Istituto Nazionale Malattie Infettive Lazzaro Spallanzani IRCCS
🇮🇹Roma, Italy
Universitätsklinikum Essen, Klinik für Dermatologie und Venerologie
🇩🇪Essen, Germany
Ruane Clinical Research Group Inc
🇺🇸Los Angeles, California, United States
Atlanta ID Group, PC
🇺🇸Atlanta, Georgia, United States
Atrium Health- Infectious Disease Consultants
🇺🇸Charlotte, North Carolina, United States
1265 Union Avenue, 8 East
🇺🇸Memphis, Tennessee, United States
St Hope Foundation
🇺🇸Bellaire, Texas, United States
DCOL Center for Clinical Research
🇺🇸Longview, Texas, United States
Hôpital Sainte-Marguerite
🇫🇷Marseille, France
Instituto Dominicano de Estudios Virologicos (IDEV)
🇩🇴Santo Domingo, Dominican Republic
ICH Study Center GmbH & Co. KG
🇩🇪Hamburg, Germany
Tokyo Medical University Hospital
🇯🇵Tokyo, Japan
National Hospital Organization Osaka National Hospital
🇯🇵Osaka, Japan
Center Hospital of the National Center for Global Health and Medicine
🇯🇵Tokyo, Japan
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Chatham County Health Department
🇺🇸Savannah, Georgia, United States
St. Joseph's Hospital Comprehensive Research Institute
🇺🇸Tampa, Florida, United States
One Community Health
🇺🇸Sacramento, California, United States
Yale University; School of Medicine
🇺🇸New Haven, Connecticut, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Jacobi Medical Center
🇺🇸Bronx, New York, United States
Central Texas Clinical Research
🇺🇸Austin, Texas, United States
The Crofoot Research Center, INC.
🇺🇸Houston, Texas, United States