A Study of Teropavimab and Zinlirvimab in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection

Phase 2Active Not RecruitingNCT05729568

Gilead Sciences83 enrolled

Overview

The goal of this study is to test the effectiveness, safety, and tolerability of the combination of broadly neutralizing antibodies (bNAbs) (teropavimab (TAB; GS-5423) and zinlirvimab (ZAB; GS-2872)) with lenacapavir (LEN) in virologically suppressed adults with HIV-1 infection. The purpose of this study is to evaluate the efficacy of switching to a regimen of LEN, TAB and ZAB, versus continuing on baseline oral antiretroviral therapy (ART) as determined by the proportion of participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 50 copies/mL at Week 26.

Participants will be randomized in Treatment Groups 1 and 2 to receive LEN, TAB, and ZAB, with differing doses of TAB and ZAB between the 2 groups and in Treatment Group 3 to continue their baseline oral ART for 52 weeks. Eligible participants in Treatment Groups 1 through 3 will have the option of participating in the study extension phase to receive LEN, TAB and ZAB after completing study follow-up through Week 52. Treatment Group 2 was removed prior to dosing of all groups during Protocol Amendment 2.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV Infection

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * On stable oral antiretroviral therapy (ART) consisting of no more than 2 drug classes (with the exception of pharmacologic boosters cobicistat or ritonavir) for ≥ 1 year prior to screening visit 2. A change in ART regimen ≥ 28 days prior to screening visit 2 for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed. * No clinically significant documented historical resistance to the current ART regimen with the exception of isolated nucleoside reverse transcriptase inhibitor mutations including M184V or ≤ 2 thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y, and/or K219Q). * Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL at screening visit 2. * Documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 12 months preceding screening visit 2 (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Virologic elevations of ≥ 50 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable. * Proviral phenotypic sensitivity to both teropavimab and zinlirvimab at screening or from protocol GS-US-536-5816 within 24 months prior to screening. * Screening clusters of differentiation 4 (CD4)+ T-cell count ≥ 200 cells/μL at screening visit 2. Key Exclusion Criteria: * Comorbid condition requiring ongoing immunosuppression. * Evidence of hepatitis C virus (HCV) infection (prior infection cleared spontaneously or with treatment is acceptable) * Evidence of current hepatitis B virus (HBV) infection regardless of HBV surface antigen status, at the screening visit 2. * History of opportunistic infection or illness indicative of Stage 3 HIV disease. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (34)

Ruane Clinical Research Group, Inc.

Los Angeles, California, United States

Mills Clinical Research

Los Angeles, California, United States

UC San Diego (UCSD) AntiViral Research Center (AVRC)

San Diego, California, United States

Optimus Medical Group

San Francisco, California, United States

University of Colorado Clinical and Translational Research Center

Aurora, Colorado, United States

Outcomes

Primary Outcomes

Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) ≥ 50 Copies/mL at Week 26 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm

Percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 was analyzed using US FDA-defined snapshot algorithm, which defines a participant's virologic outcome and included participants a) who had 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 adverse event (AE) or death and had 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. Clopper-Pearson exact method was used to calculate the 95% confidence interval (CI) for the outcome measure of each treatment. Percentages were rounded off.

Time frame: Week 26

Secondary Outcomes

Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm

Time frame: Week 52

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

Percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 26 was analyzed using the US FDA-defined 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. The Clopper-Pearson exact method was used to calculate the 95% CI for the outcome measure of each treatment. Percentages were rounded off.

Time frame: Week 26

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm

Time frame: Week 52

Change From Baseline in Clusters of Differentiation 4 (CD4) + T-cell Counts at Week 26

Time frame: Baseline, Week 26

Change From Baseline in CD4+ T-cell Counts at Week 52

Time frame: Baseline, Week 52

Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

Time frame: Up to approximately 6 years

Trough Concentration at Week 26 for TAB and ZAB

Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.

Time frame: Week 26

Trough Concentration at Week 26 for LEN

Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.

Time frame: Week 26

Trough Concentration at Week 52 for TAB and ZAB

Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.

Time frame: Week 52

Trough Concentration at Week 52 for LEN

Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.

Time frame: Week 52

Pharmacokinetic (PK) Parameter: AUC0-tau for TAB and ZAB

AUC0-tau is defined as the partial area under the concentration versus time curve from time "0" to time "t".

Time frame: Up to approximately 6 years

PK Parameter: t1/2 for TAB and ZAB

t1/2 is defined as the terminal elimination half-life.

Time frame: Up to approximately 6 years

PK Parameter: Cmax for TAB and ZAB

Cmax is defined as the maximum observed concentration of drug.

Time frame: Up to approximately 6 years

PK Parameter: Cmax for LEN

Cmax is defined as the maximum observed concentration of drug.

Time frame: Up to approximately 6 years

PK Parameter: Tmax for TAB, ZAB, and LEN

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

Time frame: Up to approximately 6 years

Percentage of Participants With Treatment-emergent Anti-TAB and Anti-ZAB Antibodies

Anti-TAB and anti-ZAB antibodies incidence referred to the percentage of participants who have treatment-emergent anti-TAB and anti-ZAB antibodies among all participants evaluable for anti-drug antibody (ADA) incidence.

Time frame: Up to approximately 6 years