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OpenTrials
Completed

NCT Number: NCT04811040

Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir 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).

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Key information

Conditions

HIV-1 Infection

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Mills Clinical Research, Los Angeles, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Oral Lenacapavir

Drug

Tablets administered without regard to food

Other names: GS-6207

Subcutaneous Lenacapavir

Drug

Administered in the abdomen via subcutaneous injections

Other names: GS-6207

Teropavimab

Drug

Administered intravenously

Other names: 3BNC117-LS, GS-5423

Zinlirvimab

Drug

Administered intravenously

Other names: 10-1074-LS, GS-2872

Primary outcomes

  1. Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)

    Time frame: 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 outcomes

  1. 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

    Time frame: 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).

  2. Primary Cohort: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm

    Time frame: 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).

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

    Time frame: Week 26

    Anti-teropavimab antibodies positive participants are participants with positive treatment-emergent anti-drug antibody.

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

    Time frame: Week 26

    Anti-zinlirvimab antibodies positive participants are participants with positive treatment-emergent anti-drug antibody.

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

    Time frame: Baseline; Week 26

  6. Primary Cohort: Number of Participants Who Develop Treatment-Emergent Resistance to LEN, Teropavimab, and Zinlirvimab

    Time frame: 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.

  7. Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

    Time frame: 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.

  8. Primary Cohort: Pharmacokinetic (PK) Parameter: AUC0-26 of Teropavimab

    Time frame: 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.

  9. Primary Cohort: PK Parameter: AUC0-26 of Zinlirvimab

    Time frame: 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.

  10. Primary Cohort: PK Parameter: AUClast of Teropavimab

    Time frame: 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.

  11. Primary Cohort: PK Parameter: AUClast of Zinlirvimab

    Time frame: 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.

  12. Primary Cohort: PK Parameter: T1/2 of LEN

    Time frame: 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.

  13. Primary Cohort: PK Parameter: T1/2 of Teropavimab

    Time frame: 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.

  14. Primary Cohort: PK Parameter: T1/2 of Zinlirvimab

    Time frame: 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.

  15. Primary Cohort: PK Parameter: Cmax of Teropavimab

    Time frame: 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.

  16. Primary Cohort: PK Parameter: Cmax of Zinlirvimab

    Time frame: 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.

  17. Primary Cohort: PK Parameter: Tmax of Teropavimab

    Time frame: 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.

  18. Primary Cohort: PK Parameter: Tmax of Zinlirvimab

    Time frame: 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.

  19. Primary Cohort: PK Parameter: Tlast of LEN

    Time frame: 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).

  20. Primary Cohort: PK Parameter: Tlast of Teropavimab

    Time frame: 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).

  21. Primary Cohort: PK Parameter: Tlast of Zinlirvimab

    Time frame: 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).

  22. Primary Cohort: PK Parameter: C26week of LEN

    Time frame: Week 26

    C26week is the concentration at week 26.

  23. Primary Cohort: PK Parameter: C26week of Teropavimab

    Time frame: Week 26

    C26week is the concentration at week 26.

  24. Primary Cohort: PK Parameter: C26week of Zinlirvimab

    Time frame: Week 26

    C26week is the concentration at week 26.

Sponsors and collaborators

Lead sponsor

Gilead Sciences

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2022
Study completion
2023
First posted
Mar 23, 2021
Registry last updated
Jan 27, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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