A Study of Teropavimab and Zinlirvimab 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 Infection

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

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 (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.

Full description

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.

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 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.

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 Treatment Group 1: LEN + TAB + ZAB

Experimental group

Description:

Participants will receive loading dose of lenacapavir (LEN) 600 mg tablets, orally, on Day 1 and Day 2. They will receive LEN 927 mg subcutaneous (SC) injection along with teropavimab (TAB) 2550 mg intravenous (IV) infusion and zinlirvimab (ZAB) 2550 mg IV infusion on Day 1 and every 6 months (Q6M) up to Week 52 in the Randomized Phase.

Treatment:

Drug: Zinlirvimab

Drug: Teropavimab

Drug: Lenacapavir Tablet

Drug: Lenacapavir Injection

Randomized Phase Treatment Group 3: SBR

Experimental group

Description:

Participants in Stay on Baseline Regimen (SBR) group will continue their baseline oral antiretroviral therapy (ART) up to Week 52. ART included drugs like bictegravir/emtricitabine/tenofovir alafenamide, darunavir/cobicistat/emtricitabine/tenofovir alafenamide, dolutegravir/abacavir lamivudine, and rilpivirine/emtricitabine/tenofovir alafenamide, administered as per standard of care.

Treatment:

Drug: Antiretroviral Therapy

Extension Phase: Treatment Group 1: LEN + TAB + ZAB

Experimental group

Description:

At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL will be given the option to participate in the study extension phase. In the study extension phase, participants will continue to receive their randomized study drugs every 26 weeks.

Treatment:

Drug: Zinlirvimab

Drug: Teropavimab

Drug: Lenacapavir Injection

Extension Phase Treatment Group 3: SBR

Experimental group

Description:

At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL and in the absence of confirmed virologic rebound throughout the Randomized Phase of the study will be given the option to participate in the Extension Phase to switch from oral ART to LEN, TAB and ZAB, every 26 weeks at the dose specified for Treatment Group 1.

Treatment:

Drug: Zinlirvimab

Drug: Teropavimab

Drug: Lenacapavir Tablet

Drug: Lenacapavir Injection