Clinical trial NCT05729568: A Study of GS-5423 and GS-2872 in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection
Official title: A Phase 2 Randomized, Open-label Study to Evaluate the Safety and Efficacy of Broadly Neutralizing Antibodies (bNAbs) GS-5423 and GS-2872 in Combination With the Capsid Inhibitor Lenacapavir as Long-Acting Treatment Dosed Every 6 Months in Virologically Suppressed Adults With HIV-1 Infection
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2023-02-15
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Proportion 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
timeFrame: Week 26
Secondary outcomes:
measure: Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 52
measure: Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 26
measure: Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 52
measure: Change from Baseline in Clusters of Differentiation 4 (CD4)+ T-cell Counts at Week 26
timeFrame: Baseline, Week 26
measure: Change from Baseline in Clusters of Differentiation 4 (CD4)+ T-cell Counts at Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: First dose date up to end of study (Up to approximately 6 years)
measure: Trough Concentration at Week 26 for GS-5423, GS-2872, and LEN
timeFrame: Week 26
measure: Trough Concentration at Week 52 for GS-5423, GS-2872, and LEN
timeFrame: Week 52
measure: Pharmacokinetic (PK) Parameter: AUC0-t for GS-5423, GS-2872, and LEN
timeFrame: First dose date up to end of study (Up to approximately 6 years)
measure: PK Parameter: AUClast for GS-5423, GS-2872, and LEN
timeFrame: First dose date up to end of study (Up to approximately 6 years)
measure: PK Parameter: t1/2 for GS-5423, GS-2872, and LEN
timeFrame: First dose date up to end of study (Up to approximately 6 years)
measure: PK Parameter: Cmax for GS-5423, GS-2872, and LEN
timeFrame: First dose date up to end of study (Up to approximately 6 years)
measure: PK Parameter: Tmax for GS-5423, GS-2872, and LEN
timeFrame: First dose date up to end of study (Up to approximately 6 years)
measure: Proportion of Participants with Treatment-emergent Anti-GS-5423 Antibodies
timeFrame: Up to end of study (Up to approximately 6 years)
measure: Proportion of Participants with Treatment-emergent Anti-GS-2872 Antibodies
timeFrame: Up to end of study (Up to approximately 6 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group, Inc.
state: California
city: Los Angeles
country: United States
facility: Mills Clinical Research
state: California
city: San Diego
country: United States
facility: UC San Diego (UCSD) AntiViral Research Center (AVRC)
state: California
city: San Francisco
country: United States
facility: Optimus Medical Group
state: California
city: Aurora
country: United States
facility: University of Colorado Clinical and Translational Research Center
state: Colorado
city: New Haven
country: United States
facility: Yale University; School of Medicine; AIDS Program
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: DeLand
country: United States
facility: Midland Florida Clinical Research Center, LLC
state: Florida
city: Fort Lauderdale
country: United States
facility: Can Community Health Care
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A.
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown Infectious Disease Clinic
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Saint Louis
country: United States
facility: Southhampton Healthcare, Inc
state: Missouri
city: Albuquerque
country: United States
facility: AXCES Research Group, LLC
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Chapel Hill
country: United States
facility: NC TraCS Institute - CTRC; University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Health Center
state: North Carolina
city: Greensboro
country: United States
facility: Regional Center for Infectious Disease Research
state: North Carolina
city: Greenville
country: United States
facility: The Brody School of Medicine at East Carolina University
state: North Carolina
city: Huntersville
country: United States
facility: Rosedale Health and Wellness
state: North Carolina
city: Columbia
country: United States
facility: Prisma Health - Clinical Research Unit
state: South Carolina
city: Memphis
country: United States
facility: St Jude Children's Research Hospital
state: Tennessee
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: AIDS Arms, Inc. DBA Prism Health North Texas
state: Texas
city: El Paso
country: United States
facility: AXCES Research Group, LLC
state: Texas
city: Houston
country: United States
facility: The Crofoot Research Center, INC
state: Texas
city: Annandale
country: United States
facility: Clinical Alliance for Research & Education, Infectious Diseases LLC (CARE-ID)
state: Virginia
city: Darlinghurst
country: Australia
facility: East Sydney Doctors
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Toronto
country: Canada
facility: Maple Leaf Research/Maple Leaf Medical Clinic
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: