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

GS-US-536-5816

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).

2021-04-08

2023-04-18

2023-10-17

Completed

Early phase I

32

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; * 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.

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2023-10-27