A Study of GS-5423 and GS-2872 in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection

Gilead Sciences

Status and phase: Active, not recruiting; Phase 2

Conditions: HIV Infections

Treatments: Drug: Lenacapavir Tablet; Drug: Zinlirvimab; Drug: Antiretroviral Therapy; Drug: Teropavimab; Drug: Lenacapavir Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT05729568

GS-US-536-5939

Details and patient eligibility

About

The goal of this study is to test the effectiveness, safety, and tolerability of the combination of broadly neutralizing antibodies (bNAbs) (teropavimab (formerly GS-5423) and zinlirvimab (formerly 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, teropavimab, and zinlirvimab, 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.

Enrollment: 83 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 HIV-1 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 pheynotypic sensitivity to both teropavimab and zinlirvimab at screening or from protocol GS-US-536-5816 within 24 months prior to screening.
• Screening 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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83 participants in 4 patient groups

Randomized Phase: Lenacapavir (LEN) + Teropavimab Dose A + Zinlirvimab Dose B

Experimental group

Description:

Participants will receive oral LEN 600mg, subcutaneous (SC) LEN 927 mg, teropavimab Dose A, and zinlirvimab Dose B on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. The last treatment regimen will include SC LEN + teropavimab Dose A + zinlirvimab Dose B.

Treatment:

Drug: Lenacapavir Injection

Drug: Teropavimab

Drug: Zinlirvimab

Drug: Lenacapavir Tablet

Randomized Phase: Antiretroviral Therapy (ART)

Experimental group

Description:

Participants will continue their baseline oral ART through Week 52.

Treatment:

Drug: Antiretroviral Therapy

Extension Phase: LEN + Teropavimab Dose A + Zinlirvimab Dose B

Experimental group

Description:

At Week 52, participants who receive the study drug of LEN, teropavimab, zinlirvimab, and complete study through Week 52 with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL will be given the option to participate in the study extension phase, where they will continue to receive their randomized study drugs treatment regimen until after completion of the primary analysis (unless modified based on the data monitoring committee (DMC) analysis), up to approximately 5 years.

Treatment:

Drug: Lenacapavir Injection

Drug: Teropavimab

Drug: Zinlirvimab

Extension Phase: ART

Experimental group

Description:

Participants who complete study through Week 52 with HIV-1 RNA \< 50 copies/mL and in the absence of confirmed virologic rebound (VR) throughout the randomized phase of the study will be given the option to participate in the extension phase and receive the study drugs of LEN, teropavimab, and zinlirvimab at the dose specified for randomized phase until after completion of the primary analysis (unless modified based on the data monitoring committee (DMC) analysis), up to approximately 5 years. Treatment with study drug will begin at Week 52 and at that time the baseline oral ART will be discontinued.

Treatment:

Drug: Lenacapavir Injection

Drug: Teropavimab

Drug: Zinlirvimab

Drug: Lenacapavir Tablet