Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir (GS-6207) 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;

• 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 Cohorts: Lenacapavir (LEN), Teropavimab, Zinlirvimab Dose C; Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose C followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose C.	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 Cohorts: LEN, Teropavimab, Zinlirvimab Dose D; Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose D followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose D.	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: Optional Cohorts: Lenacapavir (LEN), Teropavimab, Zinlirvimab Dose C; Optional cohort included participants from primary cohort who could not qualify for primary cohort at the study start. Participants in optional cohort will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose C followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose C.	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: Optional Cohorts: LEN, Teropavimab, Zinlirvimab Dose D; Optional cohort included participants screened for primary cohort but could not qualify for primary cohort at the study start. Participants in optional cohort will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose D followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose D.	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	Time Frame
Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)	First dose date up to Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm		Week 26
Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm		Week 26
Proportion of Participants With Positive Anti-Teropavimab Antibodies		Week 26
Proportion of Participants With Positive Anti-zinlirvimab Antibodies		Week 26
Change from Baseline in CD4+ Cell Count at Week 26		Baseline; Week 26
Proportion of Participants Who Develop Treatment-Emergent Resistance to Lenacapvir (LEN), Teropavimab, and Zinlirvimab		Day 1 up to Week 26
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs)		First dose date up to Week 26
Pharmacokinetic (PK) Parameter: AUC0-t of Teropavimab, and Zinlirvimab, and LEN	AUC0-t is defined as the concentration of drug over time from time zero to time "t".	Day 1 up to Week 52
PK Parameter: AUClast of Teropavimab, and Zinlirvimab, and LEN	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Day 1 up to Week 52
PK Parameter: T1/2 of Teropavimab, and Zinlirvimab, and LEN	T1/2 is defined as the estimate of the terminal elimination half-life of the drug.	Day 1 up to Week 52
PK Parameter: Cmax of Teropavimab, and Zinlirvimab, and LEN	Cmax is defined as the maximum observed concentration of drug.	Day 1 up to Week 52
PK Parameter: Tmax of Teropavimab, and Zinlirvimab, and LEN	Tmax is defined as the time (observed time point) of Cmax.	Day 1 up to Week 52
PK Parameter: Tlast of Teropavimab, and Zinlirvimab, and LEN	Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).	Day 1 up to Week 52
PK Parameter: Ct of Teropavimab, and Zinlirvimab, and LEN	Ct is the concentration at a particular time (t).	Day 1 up to Week 52

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2021
• Primary Completion (Actual): April 18, 2023
• Study Completion (Actual): October 17, 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): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Urogenital Diseases; Genital Diseases; 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