Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection

A Phase 1b Randomized, Blinded, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Broadly Neutralizing Antibodies (bNAbs) GS-5423 and GS-2872 in Combination With Capsid Inhibitor Lenacapavir (GS-6207) in Virologically Suppressed Adults With HIV-1 Infection

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).

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: Oral Lenacapavir; Drug: Subcutaneous Lenacapavir; Drug: Teropavimab; Drug: Zinlirvimab

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90069
      • Mills Clinical Research
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group Inc.
    • Sacramento, California, United States, 95811
      • One Community Health
    • San Diego, California, United States, 92103
      • UCSD AntViral Research Center (AVRC)
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University; School of Medicine; AIDS Program
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine Schiff Center for Liver Disease
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A
  • Georgia
    • Macon, Georgia, United States, 31201
      • Mercer University, Department of Internal Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana CTSI Clinical Research Center
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health/Clinical Center
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Axces Research Group
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai-Clinical and Translational Research Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • NC TraCS Institute-CTRC; University of North Carolina at Chapel Hill
    • Greenville, North Carolina, United States, 27834
      • The Brody School of Medicine at East Carolina University, ECU Adult Specialty Care
    • Huntersville, North Carolina, United States, 28078
      • Rosedale Health & Wellness
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Houston, Texas, United States, 77098
      • The Crofoot Research, INC.
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• 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
• No documented historical resistance to the current ART regimen
• Plasma HIV-1 RNA < 50 copies/mL at screening
• 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.

• 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;

• Cluster determinant 4+ (CD4+) count nadir ≥ 350 cells/μL
• Screening CD4+ count ≥ 500 cells/μL
• 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 Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg; 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.	Drug: Oral Lenacapavir; Tablets administered without regard to food; Other Names: GS-6207; Drug: Subcutaneous Lenacapavir; Administered in the abdomen via subcutaneous injections; Other Names: GS-6207; Drug: Teropavimab; Administered intravenously; Other Names: 3BNC117-LS; GS-5423; Drug: Zinlirvimab; Administered intravenously; Other Names: 10-1074-LS; GS-2872
Experimental: Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg; 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.	Drug: Oral Lenacapavir; Tablets administered without regard to food; Other Names: GS-6207; Drug: Subcutaneous Lenacapavir; Administered in the abdomen via subcutaneous injections; Other Names: GS-6207; Drug: Teropavimab; Administered intravenously; Other Names: 3BNC117-LS; GS-5423; Drug: Zinlirvimab; Administered intravenously; Other Names: 10-1074-LS; GS-2872
Experimental: Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg; 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.	Drug: Oral Lenacapavir; Tablets administered without regard to food; Other Names: GS-6207; Drug: Subcutaneous Lenacapavir; Administered in the abdomen via subcutaneous injections; Other Names: GS-6207; Drug: Teropavimab; Administered intravenously; Other Names: 3BNC117-LS; GS-5423; Drug: Zinlirvimab; Administered intravenously; Other Names: 10-1074-LS; GS-2872
Experimental: Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg; 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.	Drug: Oral Lenacapavir; Tablets administered without regard to food; Other Names: GS-6207; Drug: Subcutaneous Lenacapavir; Administered in the abdomen via subcutaneous injections; Other Names: GS-6207; Drug: Teropavimab; Administered intravenously; Other Names: 3BNC117-LS; GS-5423; Drug: Zinlirvimab; Administered intravenously; Other Names: 10-1074-LS; GS-2872

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)	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).	Day 1 up to Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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).	Week 26
Primary Cohort: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm	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).	Week 26
Primary Cohort: Percentage of Participants With Positive Anti-Teropavimab Antibodies	Anti-teropavimab antibodies positive participants are participants with positive treatment-emergent anti-drug antibody.	Week 26
Primary Cohort: Percentage of Participants With Positive Anti-zinlirvimab Antibodies	Anti-zinlirvimab antibodies positive participants are participants with positive treatment-emergent anti-drug antibody.	Week 26
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	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.	Day 1 up to Week 26
Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	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.	Day 1 up to Week 26
Primary Cohort: Pharmacokinetic (PK) Parameter: AUC0-26 of Teropavimab	AUC0-26 is defined as the concentration of drug over time from Week zero to Week 26.	Predose and at End of Infusion (EOI) of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26
Primary Cohort: PK Parameter: AUC0-26 of Zinlirvimab	AUC0-26 is defined as the concentration of drug over time from Week zero to Week 26.	Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26
Primary Cohort: PK Parameter: AUClast of Teropavimab	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	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)
Primary Cohort: PK Parameter: AUClast of Zinlirvimab	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	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)
Primary Cohort: PK Parameter: T1/2 of LEN	T1/2 is defined as the estimate of the terminal elimination half-life of the drug.	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)
Primary Cohort: PK Parameter: T1/2 of Teropavimab	T1/2 is defined as the estimate of the terminal elimination half-life of the drug.	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)
Primary Cohort: PK Parameter: T1/2 of Zinlirvimab	T1/2 is defined as the estimate of the terminal elimination half-life of the drug.	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)
Primary Cohort: PK Parameter: Cmax of Teropavimab	Cmax is defined as the maximum observed concentration of drug.	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)
Primary Cohort: PK Parameter: Cmax of Zinlirvimab	Cmax is defined as the maximum observed concentration of drug.	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)
Primary Cohort: PK Parameter: Tmax of Teropavimab	Tmax is defined as the time (observed time point) of Cmax.	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)
Primary Cohort: PK Parameter: Tmax of Zinlirvimab	Tmax is defined as the time (observed time point) of Cmax.	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)
Primary Cohort: PK Parameter: Tlast of LEN	Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).	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)
Primary Cohort: PK Parameter: Tlast of Teropavimab	Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).	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)
Primary Cohort: PK Parameter: Tlast of Zinlirvimab	Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).	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)
Primary Cohort: PK Parameter: C26week of LEN	C26week is the concentration at week 26.	Week 26
Primary Cohort: PK Parameter: C26week of Teropavimab	C26week is the concentration at week 26.	Week 26
Primary Cohort: PK Parameter: C26week of Zinlirvimab	C26week is the concentration at week 26.	Week 26

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Eron JJ, Cook PP, Mehrotra ML, Huang H, Caskey M, Crofoot GE, DeJesus E, Gorgos L, VanderVeen LA, Osiyemi OO, Brinson C, Collins SE. Lenacapavir Plus bNAbs for People with HIV and Susceptibility to Either Teropavimab or Zinlirvimab [Oral]. Conference on Retroviruses and Opportunistic Infections (CROI); 2024 3-6 March, Denver, CO.
• Eron JJ, Little SJ, Crofoot G, Cook P, Ruane PJ, Jayaweera D, VanderVeen LA, DeJesus E, Zheng Y, Mills A, Huang H, Waldman SE, Ramgopal M, Gorgos L, Collins SE, Baeten JM, Caskey M. Safety of teropavimab and zinlirvimab with lenacapavir once every 6 months for HIV treatment: a phase 1b, randomised, proof-of-concept study. Lancet HIV. 2024 Mar;11(3):e146-e155. doi: 10.1016/S2352-3018(23)00293-X. Epub 2024 Jan 30.
• Eron J, Little SJ, Crofoot G, Cook P, Ruane PJ, Jayaweera D, DeJesus E, Walkman SE, Mehrotra ML, VanderVeen L, Huang H, Collins S, Baeten J, Caskey M. Lenacapavir with bNAbs Teropavimab (GS-5423) and Zinlirvimab (GS-2872) Dosed Every 6 Months in People with HIV [Oral 193]. Conference on Retroviruses and Opportunistic Infections (CROI); 2023 19-22 February, Seattle, WA
• Selzer L, VanderVeen LA, Parvangada A, Martin R, Collins SE, Mehrotra M, Callebaut C. Susceptibility Screening to bNAbs Teropavimab (GS-5423) and Zinlirvimab (GS-2872) in ART-Suppressed Participants [Poster]. Conference on Retroviruses and Opportunistic Infections (CROI); 2023 19-22 February; Seattle, WA
• Lisa Selzer, Sally Demirdjian, Ross Martin, Brie Falkard, Sean E. Collins, Joseph Eron, Laurie A. VanderVeen, Christian Callebaut. Resistance analyses during treatment of lenacapavir with broadly neutralizing antibodies in people with HIV (Poster WEPEB146) AIDS 2024; Munich, Germany
• Selzer L, VanderVeen LA, Parvangada A, Martin R, Collins SE, Mehrotra M, Callebaut C. Susceptibility Screening of HIV-1 Viruses to Broadly Neutralizing Antibodies, Teropavimab and Zinlirvimab, in People With HIV-1 Suppressed by Antiretroviral Therapy. J Acquir Immune Defic Syndr. 2025 Jan 1;98(1):64-71. doi: 10.1097/QAI.0000000000003528.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2021
• Primary Completion (Actual): June 9, 2022
• Study Completion (Actual): October 26, 2023

Study Registration Dates

• First Submitted: March 19, 2021
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Immune System Diseases; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; Infections; Communicable Diseases
• Other Study ID Numbers: GS-US-536-5816

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No