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

NCT04811040 | Completed Phase 1 Results FDA Drug

• 1 other identifier: GS-US-536-5816
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 23

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).

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (24)

• 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

• 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

• Primary Cohort: Percentage of Participants With Positive Anti-Teropavimab Antibodies

  Week 26

• Primary Cohort: Percentage of Participants With Positive Anti-zinlirvimab Antibodies

  Week 26

• Primary Cohort: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 26

  Baseline; Week 26

Study Arms (4)

Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg

EXPERIMENTAL

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; Drug: Subcutaneous Lenacapavir; Drug: Teropavimab; Drug: Zinlirvimab

Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg

EXPERIMENTAL

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; Drug: Subcutaneous Lenacapavir; Drug: Teropavimab; Drug: Zinlirvimab

Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg

EXPERIMENTAL

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; Drug: Subcutaneous Lenacapavir; Drug: Teropavimab; Drug: Zinlirvimab

Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg

EXPERIMENTAL

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; Drug: Subcutaneous Lenacapavir; Drug: Teropavimab; Drug: Zinlirvimab

Interventions

Oral Lenacapavir DRUG

Tablets administered without regard to food

Also known as: GS-6207

Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg; Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg; Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg; Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg

Subcutaneous Lenacapavir DRUG

Administered in the abdomen via subcutaneous injections

Also known as: GS-6207

Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg; Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg; Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg; Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg

Teropavimab DRUG

Administered intravenously

Also known as: 3BNC117-LS, GS-5423

Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg; Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg; Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg; Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg

Zinlirvimab DRUG

Administered intravenously

Also known as: 10-1074-LS, GS-2872

Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg; Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg; Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg; Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \-- 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (23)

Ruane Clinical Research Group Inc.

Los Angeles, California, 90036, United States

Location

Mills Clinical Research

Los Angeles, California, 90069, United States

Location

One Community Health

Sacramento, California, 95811, United States

Location

UCSD AntViral Research Center (AVRC)

San Diego, California, 92103, United States

Location

Yale University; School of Medicine; AIDS Program

New Haven, Connecticut, 06510, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34982, United States

Location

University of Miami Miller School of Medicine Schiff Center for Liver Disease

Miami, Florida, 33136, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Triple O Research Institute, P.A

West Palm Beach, Florida, 33407, United States

Location

Mercer University, Department of Internal Medicine

Macon, Georgia, 31201, United States

Location

Indiana CTSI Clinical Research Center

Indianapolis, Indiana, 46202, United States

Location

National Institutes of Health/Clinical Center

Bethesda, Maryland, 20892, United States

Location

Be Well Medical Center

Berkley, Michigan, 48072, United States

Location

AXCES Research Group

Santa Fe, New Mexico, 87505, United States

Location

Icahn School of Medicine at Mount Sinai-Clinical and Translational Research Center

New York, New York, 10029, United States

Location

NC TraCS Institute-CTRC; University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

The Brody School of Medicine at East Carolina University, ECU Adult Specialty Care

Greenville, North Carolina, 27834, United States

Location

Rosedale Health & Wellness

Huntersville, North Carolina, 28078, United States

Location

Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Central Texas Clinical Research

Austin, Texas, 78705, United States

Location

The Crofoot Research, INC.

Houston, Texas, 77098, United States

Location

Peter Shalit, M.D.

Seattle, Washington, 98104, United States

Location

Related Publications (7)

• 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.

  BACKGROUND

• 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.

  PMID: 38307098 BACKGROUND

• 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

  BACKGROUND

• 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

  BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 39298557 BACKGROUND

• Eron JJ, Cook PP, Mehrotra ML, Huang H, Caskey M, Crofoot GE, Gorgos L, VanderVeen LA, Zheng Y, Collins SE, Osiyemi OO, Brinson C, DeJesus E. Lenacapavir Plus 2 Broadly Neutralizing Antibodies, Teropavimab and Zinlirvimab, for People With HIV-1 Highly Susceptible to Either Teropavimab or Zinlirvimab. J Infect Dis. 2025 Jul 11;231(6):1440-1444. doi: 10.1093/infdis/jiaf159.

  PMID: 40176256 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

lenacapavir

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Clinical pharmacologist and sponsor are not masked to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2021
• First Posted: March 23, 2021
• Study Start: April 8, 2021
• Primary Completion: June 9, 2022
• Study Completion: October 26, 2023
• Last Updated: January 27, 2025
• Results First Posted: January 27, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (23)