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Study to Evaluate the Safety and Efficacy of Teropavimab and GS-2872 in Combination With Lenacapavir (GS-6207) in Virologically Suppressed Adults With HIV-1 Infection

Sponsor
Gilead Sciences (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04811040
Collaborator
(none)
41
Enrollment
23
Locations
2
Arms
31.8
Anticipated Duration (Months)
1.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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 GS-2872 in combination with the HIV capsid inhibitor lenacapavir (LEN).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
41 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Masking Description:
Clinical pharmacologist and sponsor are not masked to treatment assignment.
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Apr 8, 2021
Actual Primary Completion Date :
Jun 9, 2022
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Lenacapavir (LEN), teropavimab, GS-2872 Dose C

Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + GS-2872 Dose C followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + GS-2872 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: GS-2872
    Administered intravenously
    Other Names:
  • 10-1074-LS

    		•
    Experimental: LEN, teropavimab, GS-2872 Dose D

    Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + GS-2872 Dose D followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + GS-2872 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: GS-2872
    Administered intravenously
    Other Names:
  • 10-1074-LS

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) [First dose date up to Week 26]

    Secondary Outcome Measures

    1. Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm [Week 26]

    2. Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm [Week 26]

    3. Proportion of Participants With Positive Anti-Teropavimab Antibodies [Week 26]

    4. Proportion of Participants With Positive Anti-GS-2872 Antibodies [Week 26]

    5. Change from Baseline in CD4+ Cell Count at Week 26 [Baseline; Week 26]

    6. Proportion of Participants Who Develop Treatment-Emergent Resistance to Lenacapvir (LEN), Teropavimab, and GS-2872 [Day 1 up to Week 26]

    7. Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) [First dose date up to Week 26]

    8. Pharmacokinetic (PK) Parameter: AUC0-t of Teropavimab, and GS-2872, and LEN [Day 1 up to Week 52]

      AUC0-t is defined as the concentration of drug over time from time zero to time "t".

    9. PK Parameter: AUClast of Teropavimab, and GS-2872, and LEN [Day 1 up to Week 52]

      AUClast is defined as the concentration of drug from time zero to the last observable concentration.

    10. PK Parameter: T1/2 of Teropavimab, and GS-2872, and LEN [Day 1 up to Week 52]

      T1/2 is defined as the estimate of the terminal elimination half-life of the drug.

    11. PK Parameter: Cmax of Teropavimab, and GS-2872, and LEN [Day 1 up to Week 52]

      Cmax is defined as the maximum observed concentration of drug.

    12. PK Parameter: Tmax of Teropavimab, and GS-2872, and LEN [Day 1 up to Week 52]

      Tmax is defined as the time (observed time point) of Cmax.

    13. PK Parameter: Tlast of Teropavimab, and GS-2872, and LEN [Day 1 up to Week 52]

      Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).

    14. PK Parameter: Ct of Teropavimab, and GS-2872, and LEN [Day 1 up to Week 52]

      Ct is the concentration at a particular time (t).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 GS-2872 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 GS-2872, 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; GS-2872 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.

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT04811040
    Other Study ID Numbers:
    • GS-US-536-5816
    First Posted:
    Mar 23, 2021
    Last Update Posted:
    Jul 5, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Infections
    Communicable Diseases
    HIV Infections

    Study Results

    No Results Posted as of Jul 5, 2022