Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection
- Conditions
- HIV-1 Infection
- Interventions
- Registration Number
- NCT04811040
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate the safety and tolerability of a combination of the broadly neutralizing antibodies (bNAbs) teropavimab (formerly GS-5423) and zinlirvimab (formerly GS-2872) in combination with the HIV capsid inhibitor lenacapavir (LEN).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
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On first-line antiretroviral therapy (ART) for ≥ 2 years prior to screening. A change in ART regimen ≥ 28 days prior to screening for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed
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No documented historical resistance to the current ART regimen
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Plasma HIV-1 RNA < 50 copies/mL at screening
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Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 18 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable.
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Proviral phenotypic sensitivity to both teropavimab and zinlirvimab at screening by the PhenoSense mAb Assay (Monogram Biosciences) for inclusion in the Primary Cohort; sensitivity at screening by the PhenoSense mAb Assay (Monogram Biosciences) to 1 mAb, either teropavimab or zinlirvimab, within 18 months prior to enrollment for inclusion in the optional Pilot Cohort
-- In both cohorts, teropavimab sensitivity is defined as 90% inhibitory concentration (IC90) ≤ 2 μg/mL; zinlirvimab sensitivity is defined as IC90 ≤ 2 μg/mL;
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Cluster determinant 4+ (CD4+) count nadir ≥ 350 cells/μL
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Screening CD4+ count ≥ 500 cells/μL
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Availability of a fully active alternative ART regimen, in the opinion of the investigator, in the event of discontinuation of the current ART regimen with development of resistance
Key
- Comorbid condition requiring ongoing immunosuppression
- Evidence of current hepatitis B virus (HBV) infection
- Evidence of current hepatitis C virus (HCV) infection (prior infection cleared spontaneously or with treatment is acceptable)
- 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 Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg Oral Lenacapavir Participants will receive a loading dose of 600 milligrams (mg) LEN orally on Day 1 and Day 2, along with 927 mg LEN as subcutaneous (SC) injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an intravenous (IV) infusion on Day 1. Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg Subcutaneous Lenacapavir Participants will receive a loading dose of 600 milligrams (mg) LEN orally on Day 1 and Day 2, along with 927 mg LEN as subcutaneous (SC) injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an intravenous (IV) infusion on Day 1. Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg Teropavimab Participants will receive a loading dose of 600 milligrams (mg) LEN orally on Day 1 and Day 2, along with 927 mg LEN as subcutaneous (SC) injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an intravenous (IV) infusion on Day 1. Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg Oral Lenacapavir Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1. Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg Subcutaneous Lenacapavir Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1. Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg Oral Lenacapavir Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1. Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg Subcutaneous Lenacapavir Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1. Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg Teropavimab Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1. Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg Oral Lenacapavir Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1. Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg Subcutaneous Lenacapavir Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1. Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg Teropavimab Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1. Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg Zinlirvimab Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1. Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg Zinlirvimab Participants will receive a loading dose of 600 milligrams (mg) LEN orally on Day 1 and Day 2, along with 927 mg LEN as subcutaneous (SC) injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an intravenous (IV) infusion on Day 1. Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg Zinlirvimab Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1. Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg Zinlirvimab Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1. Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg Teropavimab Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.
- Primary Outcome Measures
Name Time Method Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) Day 1 up to Week 26 A treatment emergent SAE was defined as an event that, at any dose, resulted in the following: death; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly/birth defect; a medically important event or reaction: such events may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes constituting SAEs. These events had an onset date on or after the study drug start date and prior to the last exposure date of long-acting (LA) regimen period for the LA regimen period analysis. The long acting regimen period included participants who were randomized and received at least one dose of the complete LA study drug regimen (ie, SC LEN + Teropavimab + Zinlirvimab).
- Secondary Outcome Measures
Name Time Method Primary Cohort: PK Parameter: T1/2 of Zinlirvimab Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Primary Cohort: PK Parameter: Cmax of Teropavimab Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) Cmax is defined as the maximum observed concentration of drug.
Primary Cohort: PK Parameter: T1/2 of Teropavimab Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Primary Cohort: Percentage of Participants With Human Immunodeficiency Virus- 1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 26 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm Week 26 The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 26 was analyzed using the snapshot algorithm, which defined a participant's virologic outcome and included participants who had the last available on-treatment HIV-1 RNA \< 50 copies/mL in the Week 26 analysis window. Week 26 window was between Days 176 and 224 (inclusive).
Primary Cohort: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm Week 26 The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 was analyzed using the snapshot algorithm, which defined a participant's virologic outcome and included participants a) who had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 26 analysis window; b) who did not have on-treatment HIV-1 RNA data in the Week 26 analysis window and i) discontinued study drug prior to or in the Week 26 analysis window due to lack of efficacy, or ii) discontinued study drug prior to or in the Week 26 analysis window due to AE or death and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or iii) discontinued study drug prior to or in the Week 26 analysis window due to reasons other than AE, death, or lack of efficacy and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL.
Week 26 window was between Days 176 and 224 (inclusive).Primary Cohort: Percentage of Participants With Positive Anti-Teropavimab Antibodies Week 26 Anti-teropavimab antibodies positive participants are participants with positive treatment-emergent anti-drug antibody.
Primary Cohort: Percentage of Participants With Positive Anti-zinlirvimab Antibodies Week 26 Anti-zinlirvimab antibodies positive participants are participants with positive treatment-emergent anti-drug antibody.
Primary Cohort: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 26 Baseline; Week 26 Primary Cohort: Number of Participants Who Develop Treatment-Emergent Resistance to LEN, Teropavimab, and Zinlirvimab Day 1 up to Week 26 Participants in the Resistance Analysis Population analyzed for this outcome included any participant who had received 1 dose of study drug, maintained their study drug regimen, and met one of the following virologic failure criteria:
* Participants with HIV-1 RNA \>/= 200 copies/mL on 2 consecutive visits
* Participants with HIV-1 RNA \>/= 200 copies/mL at study discontinuation or Week 26.Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) Day 1 up to Week 26 TEAEs were those adverse events that began on or after the first dose date of study drug and prior to last exposure date of LA regimen from participants who prematurely discontinued study or completed study, or any adverse events led to premature study drug discontinuation.
Primary Cohort: Pharmacokinetic (PK) Parameter: AUC0-26 of Teropavimab Predose and at End of Infusion (EOI) of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26 AUC0-26 is defined as the concentration of drug over time from Week zero to Week 26.
Primary Cohort: PK Parameter: AUC0-26 of Zinlirvimab Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26 AUC0-26 is defined as the concentration of drug over time from Week zero to Week 26.
Primary Cohort: PK Parameter: AUClast of Teropavimab Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Primary Cohort: PK Parameter: AUClast of Zinlirvimab Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Primary Cohort: PK Parameter: T1/2 of LEN Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Primary Cohort: PK Parameter: Cmax of Zinlirvimab Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) Cmax is defined as the maximum observed concentration of drug.
Primary Cohort: PK Parameter: Tmax of Teropavimab Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) Tmax is defined as the time (observed time point) of Cmax.
Primary Cohort: PK Parameter: Tmax of Zinlirvimab Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) Tmax is defined as the time (observed time point) of Cmax.
Primary Cohort: PK Parameter: Tlast of LEN Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).
Primary Cohort: PK Parameter: Tlast of Teropavimab Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).
Primary Cohort: PK Parameter: Tlast of Zinlirvimab Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55) Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).
Primary Cohort: PK Parameter: C26week of LEN Week 26 C26week is the concentration at week 26.
Primary Cohort: PK Parameter: C26week of Teropavimab Week 26 C26week is the concentration at week 26.
Primary Cohort: PK Parameter: C26week of Zinlirvimab Week 26 C26week is the concentration at week 26.
Trial Locations
- Locations (23)
Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
The Brody School of Medicine at East Carolina University, ECU Adult Specialty Care
🇺🇸Greenville, North Carolina, United States
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
Ruane Clinical Research Group Inc.
🇺🇸Los Angeles, California, United States
University of Miami Miller School of Medicine Schiff Center for Liver Disease
🇺🇸Miami, Florida, United States
Indiana CTSI Clinical Research Center
🇺🇸Indianapolis, Indiana, United States
The Crofoot Research, INC.
🇺🇸Houston, Texas, United States
One Community Health
🇺🇸Sacramento, California, United States
Icahn School of Medicine at Mount Sinai-Clinical and Translational Research Center
🇺🇸New York, New York, United States
Peter Shalit, M.D.
🇺🇸Seattle, Washington, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Midway Immunology and Research Center
🇺🇸Fort Pierce, Florida, United States
UCSD AntViral Research Center (AVRC)
🇺🇸San Diego, California, United States
Mills Clinical Research
🇺🇸Los Angeles, California, United States
Triple O Research Institute, P.A
🇺🇸West Palm Beach, Florida, United States
Mercer University, Department of Internal Medicine
🇺🇸Macon, Georgia, United States
National Institutes of Health/Clinical Center
🇺🇸Bethesda, Maryland, United States
AXCES Research Group
🇺🇸Santa Fe, New Mexico, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Central Texas Clinical Research
🇺🇸Austin, Texas, United States
Rosedale Health & Wellness
🇺🇸Huntersville, North Carolina, 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