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

Gilead Sciences32 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

HIV-1 Infection

Interventions

Oral LenacapavirDRUG

Tablets administered without regard to food

Subcutaneous LenacapavirDRUG

Administered in the abdomen via subcutaneous injections

TeropavimabDRUG

Administered intravenously

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (23)

Outcomes

Primary Outcomes

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).

Time frame: Day 1 up to Week 26

Secondary Outcomes

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).

Time frame: 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).

Data from ClinicalTrials.gov

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Administered intravenously

Ruane Clinical Research Group Inc.

Los Angeles, California, United States

Mills Clinical Research

Los Angeles, California, United States

One Community Health

Sacramento, California, United States

UCSD AntViral Research Center (AVRC)

San Diego, California, United States

Yale University; School of Medicine; AIDS Program

New Haven, Connecticut, United States

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

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

Miami, Florida, United States

Orlando Immunology Center

Orlando, Florida, United States

Triple O Research Institute, P.A

West Palm Beach, Florida, United States

Mercer University, Department of Internal Medicine

Macon, Georgia, United States

...and 13 more locations

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

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

Time frame: 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.

Time frame: Week 26

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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.