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

Gilead Sciences

Status and phase: Completed; Phase 1

Conditions: HIV-1 Infection

Treatments: Drug: Zinlirvimab; Drug: Teropavimab; Drug: Oral Lenacapavir; Drug: Subcutaneous Lenacapavir

Study type: Interventional

Funder types: Industry

Identifiers

NCT04811040

GS-US-536-5816

Details and patient eligibility

About

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).

Enrollment: 32 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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32 participants in 4 patient groups

Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg

Experimental group

Description:

Participants will receive a loading dose of 600 milligrams (mg) LEN orally on Day 1 and Day 2, along with 927 mg LEN as subcutaneous (SC) injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an intravenous (IV) infusion on Day 1.

Treatment:

Drug: Subcutaneous Lenacapavir

Drug: Oral Lenacapavir

Drug: Teropavimab

Drug: Zinlirvimab

Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg

Experimental group

Description:

Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.

Treatment:

Drug: Subcutaneous Lenacapavir

Drug: Oral Lenacapavir

Drug: Teropavimab

Drug: Zinlirvimab

Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg

Experimental group

Description:

Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1.

Treatment:

Drug: Subcutaneous Lenacapavir

Drug: Oral Lenacapavir

Drug: Teropavimab

Drug: Zinlirvimab

Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg

Experimental group

Description:

Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1.

Treatment:

Drug: Subcutaneous Lenacapavir

Drug: Oral Lenacapavir

Drug: Teropavimab

Drug: Zinlirvimab