A Study of GS-5423 and GS-2872 in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection
- Conditions
- HIV Infections
- Interventions
- Drug: Antiretroviral Therapy
- Registration Number
- NCT05729568
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The goal of this study is to test the effectiveness, safety, and tolerability of the combination of broadly neutralizing antibodies (bNAbs) (teropavimab (formerly GS-5423) and zinlirvimab (formerly GS-2872)) with lenacapavir (LEN) in virologically suppressed adults with HIV-1 infection.
The purpose of this study is to evaluate the efficacy of switching to a regimen of LEN, teropavimab, and zinlirvimab, versus continuing on baseline oral antiretroviral therapy (ART) as determined by the proportion of participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 50 copies/mL at Week 26.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 83
- On stable oral antiretroviral therapy (ART) consisting of no more than 2 drug classes (with the exception of pharmacologic boosters cobicistat or ritonavir) for ≥ 1 year prior to screening visit 2. A change in ART regimen ≥ 28 days prior to screening visit 2 for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed.
- No clinically significant documented historical resistance to the current ART regimen with the exception of isolated nucleoside reverse transcriptase inhibitor mutations including M184V or ≤ 2 thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y, and/or K219Q).
- Plasma HIV-1 RNA < 50 copies/mL at screening visit 2.
- Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 12 months preceding screening visit 2 (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Virologic elevations of ≥ 50 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable.
- Proviral pheynotypic sensitivity to both teropavimab and zinlirvimab at screening or from protocol GS-US-536-5816 within 24 months prior to screening.
- Screening CD4+ T-cell count ≥ 200 cells/μL at screening visit 2.
Key
- Comorbid condition requiring ongoing immunosuppression.
- Evidence of hepatitis C virus (HCV) infection (prior infection cleared spontaneously or with treatment is acceptable)
- Evidence of current hepatitis B virus (HBV) infection regardless of HBV surface antigen status, at the screening visit 2.
- History of opportunistic infection or illness indicative of Stage 3 HIV disease.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Extension Phase: ART Lenacapavir Injection Participants who complete study through Week 52 with HIV-1 RNA \< 50 copies/mL and in the absence of confirmed virologic rebound (VR) throughout the randomized phase of the study will be given the option to participate in the extension phase and receive the study drugs of LEN, teropavimab, and zinlirvimab at the dose specified for randomized phase until after completion of the primary analysis (unless modified based on the data monitoring committee (DMC) analysis), up to approximately 5 years. Treatment with study drug will begin at Week 52 and at that time the baseline oral ART will be discontinued. Extension Phase: ART Lenacapavir Tablet Participants who complete study through Week 52 with HIV-1 RNA \< 50 copies/mL and in the absence of confirmed virologic rebound (VR) throughout the randomized phase of the study will be given the option to participate in the extension phase and receive the study drugs of LEN, teropavimab, and zinlirvimab at the dose specified for randomized phase until after completion of the primary analysis (unless modified based on the data monitoring committee (DMC) analysis), up to approximately 5 years. Treatment with study drug will begin at Week 52 and at that time the baseline oral ART will be discontinued. Randomized Phase: Lenacapavir (LEN) + Teropavimab Dose A + Zinlirvimab Dose B Lenacapavir Tablet Participants will receive oral LEN 600mg, subcutaneous (SC) LEN 927 mg, teropavimab Dose A, and zinlirvimab Dose B on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. The last treatment regimen will include SC LEN + teropavimab Dose A + zinlirvimab Dose B. Extension Phase: LEN + Teropavimab Dose A + Zinlirvimab Dose B Lenacapavir Injection At Week 52, participants who receive the study drug of LEN, teropavimab, zinlirvimab, and complete study through Week 52 with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL will be given the option to participate in the study extension phase, where they will continue to receive their randomized study drugs treatment regimen until after completion of the primary analysis (unless modified based on the data monitoring committee (DMC) analysis), up to approximately 5 years. Extension Phase: LEN + Teropavimab Dose A + Zinlirvimab Dose B Teropavimab At Week 52, participants who receive the study drug of LEN, teropavimab, zinlirvimab, and complete study through Week 52 with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL will be given the option to participate in the study extension phase, where they will continue to receive their randomized study drugs treatment regimen until after completion of the primary analysis (unless modified based on the data monitoring committee (DMC) analysis), up to approximately 5 years. Randomized Phase: Lenacapavir (LEN) + Teropavimab Dose A + Zinlirvimab Dose B Teropavimab Participants will receive oral LEN 600mg, subcutaneous (SC) LEN 927 mg, teropavimab Dose A, and zinlirvimab Dose B on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. The last treatment regimen will include SC LEN + teropavimab Dose A + zinlirvimab Dose B. Randomized Phase: Antiretroviral Therapy (ART) Antiretroviral Therapy Participants will continue their baseline oral ART through Week 52. Randomized Phase: Lenacapavir (LEN) + Teropavimab Dose A + Zinlirvimab Dose B Lenacapavir Injection Participants will receive oral LEN 600mg, subcutaneous (SC) LEN 927 mg, teropavimab Dose A, and zinlirvimab Dose B on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. The last treatment regimen will include SC LEN + teropavimab Dose A + zinlirvimab Dose B. Randomized Phase: Lenacapavir (LEN) + Teropavimab Dose A + Zinlirvimab Dose B Zinlirvimab Participants will receive oral LEN 600mg, subcutaneous (SC) LEN 927 mg, teropavimab Dose A, and zinlirvimab Dose B on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. The last treatment regimen will include SC LEN + teropavimab Dose A + zinlirvimab Dose B. Extension Phase: ART Teropavimab Participants who complete study through Week 52 with HIV-1 RNA \< 50 copies/mL and in the absence of confirmed virologic rebound (VR) throughout the randomized phase of the study will be given the option to participate in the extension phase and receive the study drugs of LEN, teropavimab, and zinlirvimab at the dose specified for randomized phase until after completion of the primary analysis (unless modified based on the data monitoring committee (DMC) analysis), up to approximately 5 years. Treatment with study drug will begin at Week 52 and at that time the baseline oral ART will be discontinued. Extension Phase: LEN + Teropavimab Dose A + Zinlirvimab Dose B Zinlirvimab At Week 52, participants who receive the study drug of LEN, teropavimab, zinlirvimab, and complete study through Week 52 with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL will be given the option to participate in the study extension phase, where they will continue to receive their randomized study drugs treatment regimen until after completion of the primary analysis (unless modified based on the data monitoring committee (DMC) analysis), up to approximately 5 years. Extension Phase: ART Zinlirvimab Participants who complete study through Week 52 with HIV-1 RNA \< 50 copies/mL and in the absence of confirmed virologic rebound (VR) throughout the randomized phase of the study will be given the option to participate in the extension phase and receive the study drugs of LEN, teropavimab, and zinlirvimab at the dose specified for randomized phase until after completion of the primary analysis (unless modified based on the data monitoring committee (DMC) analysis), up to approximately 5 years. Treatment with study drug will begin at Week 52 and at that time the baseline oral ART will be discontinued.
- Primary Outcome Measures
Name Time Method Proportion of Participants with Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) ≥ 50 copies/mL at Week 26 as Determined by the United States Food and Drug Administration (US FDA)-defined Snapshot Algorithm Week 26
- Secondary Outcome Measures
Name Time Method Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm Week 52 Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm Week 52 Trough Concentration at Week 26 for GS-5423, GS-2872, and LEN Week 26 Trough Concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.
Trough Concentration at Week 52 for GS-5423, GS-2872, and LEN Week 52 Trough Concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.
PK Parameter: AUClast for GS-5423, GS-2872, and LEN First dose date up to end of study (Up to approximately 6 years) AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.
PK Parameter: Cmax for GS-5423, GS-2872, and LEN First dose date up to end of study (Up to approximately 6 years) Cmax is defined as the maximum observed concentration of drug.
Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm Week 26 PK Parameter: Tmax for GS-5423, GS-2872, and LEN First dose date up to end of study (Up to approximately 6 years) Tmax is defined as the time (observed time point) of Cmax.
Proportion of Participants with Treatment-emergent Anti-GS-5423 Antibodies Up to end of study (Up to approximately 6 years) Proportion of Participants with Treatment-emergent Anti-GS-2872 Antibodies Up to end of study (Up to approximately 6 years) Change from Baseline in Clusters of Differentiation 4 (CD4)+ T-cell Counts at Week 26 Baseline, Week 26 Change from Baseline in Clusters of Differentiation 4 (CD4)+ T-cell Counts at Week 52 Baseline, Week 52 Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) First dose date up to end of study (Up to approximately 6 years) Pharmacokinetic (PK) Parameter: AUC0-t for GS-5423, GS-2872, and LEN First dose date up to end of study (Up to approximately 6 years) AUC0-t is defined as the partial area under the concentration versus time curve from time "0" to time "t".
PK Parameter: t1/2 for GS-5423, GS-2872, and LEN First dose date up to end of study (Up to approximately 6 years) t1/2 is defined as the terminal elimination half-life.
Trial Locations
- Locations (33)
Ruane Clinical Research Group, Inc.
🇺🇸Los Angeles, California, United States
Can Community Health Care
🇺🇸Fort Lauderdale, Florida, United States
Emory University Hospital Midtown Infectious Disease Clinic
🇺🇸Atlanta, Georgia, United States
Prisma Health - Clinical Research Unit
🇺🇸Columbia, South Carolina, United States
Regional Center for Infectious Disease Research
🇺🇸Greensboro, North Carolina, United States
UC San Diego (UCSD) AntiViral Research Center (AVRC)
🇺🇸San Diego, California, United States
Mills Clinical Research
🇺🇸Los Angeles, California, United States
Midland Florida Clinical Research Center, LLC
🇺🇸DeLand, Florida, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Midway Immunology and Research Center
🇺🇸Fort Pierce, Florida, United States
Triple O Research Institute, P.A.
🇺🇸West Palm Beach, Florida, United States
Infectious Disease Specialists of Atlanta
🇺🇸Decatur, Georgia, United States
Southhampton Healthcare, Inc
🇺🇸Saint Louis, Missouri, United States
AXCES Research Group, LLC
🇺🇸El Paso, Texas, United States
The Brody School of Medicine at East Carolina University
🇺🇸Greenville, North Carolina, United States
Rosedale Health and Wellness
🇺🇸Huntersville, North Carolina, United States
St Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
AIDS Arms, Inc. DBA Prism Health North Texas
🇺🇸Dallas, Texas, United States
Central Texas Clinical Research
🇺🇸Austin, Texas, United States
The Crofoot Research Center, INC
🇺🇸Houston, Texas, United States
Clinical Alliance for Research & Education, Infectious Diseases LLC (CARE-ID)
🇺🇸Annandale, Virginia, United States
Holdsworth House Medical Practice
🇦🇺Sydney, New South Wales, Australia
East Sydney Doctors
🇦🇺Darlinghurst, New South Wales, Australia
Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Clinical Research Puerto Rico
🇵🇷San Juan, Puerto Rico
Maple Leaf Research/Maple Leaf Medical Clinic
🇨🇦Toronto, Canada
Optimus Medical Group
🇺🇸San Francisco, California, United States
Duke University Health Center
🇺🇸Durham, North Carolina, United States
University of Colorado Clinical and Translational Research Center
🇺🇸Aurora, Colorado, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Yale University; School of Medicine; AIDS Program
🇺🇸New Haven, Connecticut, United States
NC TraCS Institute - CTRC; University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States