Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir (GS-6207) in Virologically Suppressed Adults With HIV-1 Infection

HIV-1 Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04811040
• Other study ID #: GS-US-536-5816
• Status: Completed
• Phase: Phase 1
• Start date: April 8, 2021
• Est. completion date: October 17, 2023

Study information

• Verified date: October 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: October 17, 2023
• Est. primary completion date: April 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• HIV-1 Infection
• Infections

Intervention

Drug:
• Oral Lenacapavir
Tablets administered without regard to food
• Subcutaneous Lenacapavir
Administered in the abdomen via subcutaneous injections
• Teropavimab
Administered intravenously
• Zinlirvimab
Administered intravenously

Locations

Country	Name	City	State
United States	Central Texas Clinical Research	Austin	Texas
United States	Be Well Medical Center	Berkley	Michigan
United States	National Institutes of Health/Clinical Center	Bethesda	Maryland
United States	NC TraCS Institute-CTRC; University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	The Brody School of Medicine at East Carolina University, ECU Adult Specialty Care	Greenville	North Carolina
United States	The Crofoot Research, INC.	Houston	Texas
United States	Rosedale Health & Wellness	Huntersville	North Carolina
United States	Indiana CTSI Clinical Research Center	Indianapolis	Indiana
United States	Mills Clinical Research	Los Angeles	California
United States	Ruane Clinical Research Group Inc.	Los Angeles	California
United States	Mercer University, Department of Internal Medicine	Macon	Georgia
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	University of Miami Miller School of Medicine Schiff Center for Liver Disease	Miami	Florida
United States	Yale University; School of Medicine; AIDS Program	New Haven	Connecticut
United States	Icahn School of Medicine at Mount Sinai-Clinical and Translational Research Center	New York	New York
United States	Orlando Immunology Center	Orlando	Florida
United States	Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	One Community Health	Sacramento	California
United States	UCSD AntViral Research Center (AVRC)	San Diego	California
United States	AXCES Research Group	Santa Fe	New Mexico
United States	Peter Shalit, M.D.	Seattle	Washington
United States	Triple O Research Institute, P.A	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)		First dose date up to Week 26
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 26 as Determined by the US FDA-defined Snapshot Algorithm		Week 26
Secondary	Proportion of Participants With Positive Anti-Teropavimab Antibodies		Week 26
Secondary	Proportion of Participants With Positive Anti-zinlirvimab Antibodies		Week 26
Secondary	Change from Baseline in CD4+ Cell Count at Week 26		Baseline; Week 26
Secondary	Proportion of Participants Who Develop Treatment-Emergent Resistance to Lenacapvir (LEN), Teropavimab, and Zinlirvimab		Day 1 up to Week 26
Secondary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs)		First dose date up to Week 26
Secondary	Pharmacokinetic (PK) Parameter: AUC0-t of Teropavimab, and Zinlirvimab, and LEN	AUC0-t is defined as the concentration of drug over time from time zero to time "t".	Day 1 up to Week 52
Secondary	PK Parameter: AUClast of Teropavimab, and Zinlirvimab, and LEN	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Day 1 up to Week 52
Secondary	PK Parameter: T1/2 of Teropavimab, and Zinlirvimab, and LEN	T1/2 is defined as the estimate of the terminal elimination half-life of the drug.	Day 1 up to Week 52
Secondary	PK Parameter: Cmax of Teropavimab, and Zinlirvimab, and LEN	Cmax is defined as the maximum observed concentration of drug.	Day 1 up to Week 52
Secondary	PK Parameter: Tmax of Teropavimab, and Zinlirvimab, and LEN	Tmax is defined as the time (observed time point) of Cmax.	Day 1 up to Week 52
Secondary	PK Parameter: Tlast of Teropavimab, and Zinlirvimab, and LEN	Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).	Day 1 up to Week 52
Secondary	PK Parameter: Ct of Teropavimab, and Zinlirvimab, and LEN	Ct is the concentration at a particular time (t).	Day 1 up to Week 52

External Links

•   Gilead Clinical Trials Website