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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05729568
• Other study ID #: GS-US-536-5939
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 15, 2023
• Est. completion date: December 2029

Study information

• Verified date: June 2024
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 83
• Est. completion date: December 2029
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• Infections

Intervention

Drug:
• Teropavimab
Administered intravenously
• Zinlirvimab
Administered intravenously
• Lenacapavir Tablet
Administered orally
• Lenacapavir Injection
Administered subcutaneously
• Antiretroviral Therapy
Antiretroviral therapy, administered orally may include regimens such as: bictegravir/emtricitabine/tenofovir alafenamide, darunavir/cobicistat/emtricitabine/tenofovir alafenamide, dolutegravir/abacavir lamivudine, and rilpivirine/emtricitabine/tenofovir alafenamide.

Locations

Country	Name	City	State
Australia	East Sydney Doctors	Darlinghurst	New South Wales
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Holdsworth House Medical Practice	Sydney	New South Wales
Canada	Maple Leaf Research/Maple Leaf Medical Clinic	Toronto
Puerto Rico	Clinical Research Puerto Rico	San Juan
United States	AXCES Research Group, LLC	Albuquerque	New Mexico
United States	Clinical Alliance for Research & Education, Infectious Diseases LLC (CARE-ID)	Annandale	Virginia
United States	Emory University Hospital Midtown Infectious Disease Clinic	Atlanta	Georgia
United States	University of Colorado Clinical and Translational Research Center	Aurora	Colorado
United States	Central Texas Clinical Research	Austin	Texas
United States	Montefiore Medical Center	Bronx	New York
United States	NC TraCS Institute - CTRC; University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Prisma Health - Clinical Research Unit	Columbia	South Carolina
United States	AIDS Arms, Inc. DBA Prism Health North Texas	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Midland Florida Clinical Research Center, LLC	DeLand	Florida
United States	Duke University Health Center	Durham	North Carolina
United States	AXCES Research Group, LLC	El Paso	Texas
United States	Can Community Health Care	Fort Lauderdale	Florida
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	Regional Center for Infectious Disease Research	Greensboro	North Carolina
United States	The Brody School of Medicine at East Carolina University	Greenville	North Carolina
United States	The Crofoot Research Center, INC	Houston	Texas
United States	Rosedale Health and Wellness	Huntersville	North Carolina
United States	Mills Clinical Research	Los Angeles	California
United States	Ruane Clinical Research Group, Inc.	Los Angeles	California
United States	St Jude Children's Research Hospital	Memphis	Tennessee
United States	Yale University; School of Medicine; AIDS Program	New Haven	Connecticut
United States	Orlando Immunology Center	Orlando	Florida
United States	Southhampton Healthcare, Inc	Saint Louis	Missouri
United States	UC San Diego (UCSD) AntiViral Research Center (AVRC)	San Diego	California
United States	Optimus Medical Group	San Francisco	California
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Triple O Research Institute, P.A.	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Week 26
Secondary	Proportion of Participants with HIV-1 RNA = 50 copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm		Week 52
Secondary	Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm		Week 26
Secondary	Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm		Week 52
Secondary	Change from Baseline in Clusters of Differentiation 4 (CD4)+ T-cell Counts at Week 26		Baseline, Week 26
Secondary	Change from Baseline in Clusters of Differentiation 4 (CD4)+ T-cell Counts at Week 52		Baseline, Week 52
Secondary	Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)		First dose date up to end of study (Up to approximately 6 years)
Secondary	Trough Concentration at Week 26 for GS-5423, GS-2872, and LEN	Trough Concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.	Week 26
Secondary	Trough Concentration at Week 52 for GS-5423, GS-2872, and LEN	Trough Concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.	Week 52
Secondary	Pharmacokinetic (PK) Parameter: AUC0-t for GS-5423, GS-2872, and LEN	AUC0-t is defined as the partial area under the concentration versus time curve from time "0" to time "t".	First dose date up to end of study (Up to approximately 6 years)
Secondary	PK Parameter: AUClast for GS-5423, GS-2872, and LEN	AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.	First dose date up to end of study (Up to approximately 6 years)
Secondary	PK Parameter: t1/2 for GS-5423, GS-2872, and LEN	t1/2 is defined as the terminal elimination half-life.	First dose date up to end of study (Up to approximately 6 years)
Secondary	PK Parameter: Cmax for GS-5423, GS-2872, and LEN	Cmax is defined as the maximum observed concentration of drug.	First dose date up to end of study (Up to approximately 6 years)
Secondary	PK Parameter: Tmax for GS-5423, GS-2872, and LEN	Tmax is defined as the time (observed time point) of Cmax.	First dose date up to end of study (Up to approximately 6 years)
Secondary	Proportion of Participants with Treatment-emergent Anti-GS-5423 Antibodies		Up to end of study (Up to approximately 6 years)
Secondary	Proportion of Participants with Treatment-emergent Anti-GS-2872 Antibodies		Up to end of study (Up to approximately 6 years)

External Links

•   Gilead Clinical Trials Website