Clinical trial NCT04811040: Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1 Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2021-03-23
Enrollment: 32
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 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).


Eligibility 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.

Primary outcomes:
measure: Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 26
Secondary outcomes:
measure: Primary Cohort: Percentage of Participants With Human Immunodeficiency Virus- 1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 26 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm
timeFrame: Week 26
measure: Primary Cohort: Percentage 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: Primary Cohort: Percentage of Participants With Positive Anti-Teropavimab Antibodies
timeFrame: Week 26
measure: Primary Cohort: Percentage of Participants With Positive Anti-zinlirvimab Antibodies
timeFrame: Week 26
measure: Primary Cohort: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 26
timeFrame: Baseline; Week 26
measure: Primary Cohort: Number of Participants Who Develop Treatment-Emergent Resistance to LEN, Teropavimab, and Zinlirvimab
timeFrame: Day 1 up to Week 26
measure: Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to Week 26
measure: Primary Cohort: Pharmacokinetic (PK) Parameter: AUC0-26 of Teropavimab
timeFrame: Predose and at End of Infusion (EOI) of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26
measure: Primary Cohort: PK Parameter: AUC0-26 of Zinlirvimab
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26
measure: Primary Cohort: PK Parameter: AUClast of Teropavimab
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
measure: Primary Cohort: PK Parameter: AUClast of Zinlirvimab
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
measure: Primary Cohort: PK Parameter: T1/2 of LEN
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
measure: Primary Cohort: PK Parameter: T1/2 of Teropavimab
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
measure: Primary Cohort: PK Parameter: T1/2 of Zinlirvimab
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
measure: Primary Cohort: PK Parameter: Cmax of Teropavimab
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
measure: Primary Cohort: PK Parameter: Cmax of Zinlirvimab
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
measure: Primary Cohort: PK Parameter: Tmax of Teropavimab
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
measure: Primary Cohort: PK Parameter: Tmax of Zinlirvimab
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
measure: Primary Cohort: PK Parameter: Tlast of LEN
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
measure: Primary Cohort: PK Parameter: Tlast of Teropavimab
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
measure: Primary Cohort: PK Parameter: Tlast of Zinlirvimab
timeFrame: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
measure: Primary Cohort: PK Parameter: C26week of LEN
timeFrame: Week 26
measure: Primary Cohort: PK Parameter: C26week of Teropavimab
timeFrame: Week 26
measure: Primary Cohort: PK Parameter: C26week of Zinlirvimab
timeFrame: Week 26
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: Sacramento
country: United States
facility: One Community Health
state: California
city: San Diego
country: United States
facility: UCSD AntViral Research Center (AVRC)
state: California
city: New Haven
country: United States
facility: Yale University; School of Medicine; AIDS Program
state: Connecticut
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine Schiff Center for Liver Disease
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: Macon
country: United States
facility: Mercer University, Department of Internal Medicine
state: Georgia
city: Indianapolis
country: United States
facility: Indiana CTSI Clinical Research Center
state: Indiana
city: Bethesda
country: United States
facility: National Institutes of Health/Clinical Center
state: Maryland
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Santa Fe
country: United States
facility: AXCES Research Group
state: New Mexico
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai-Clinical and Translational Research 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: Greenville
country: United States
facility: The Brody School of Medicine at East Carolina University, ECU Adult Specialty Care
state: North Carolina
city: Huntersville
country: United States
facility: Rosedale Health & Wellness
state: North Carolina
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania
state: Pennsylvania
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: Houston
country: United States
facility: The Crofoot Research, INC.
state: Texas
city: Seattle
country: United States
facility: Peter Shalit, M.D.
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Eron JJ, Cook PP, Mehrotra ML, Huang H, Caskey M, Crofoot GE, DeJesus E, Gorgos L, VanderVeen LA, Osiyemi OO, Brinson C, Collins SE. Lenacapavir Plus bNAbs for People with HIV and Susceptibility to Either Teropavimab or Zinlirvimab [Oral]. Conference on Retroviruses and Opportunistic Infections (CROI); 2024 3-6 March, Denver, CO.
citation: Eron JJ, Little SJ, Crofoot G, Cook P, Ruane PJ, Jayaweera D, VanderVeen LA, DeJesus E, Zheng Y, Mills A, Huang H, Waldman SE, Ramgopal M, Gorgos L, Collins SE, Baeten JM, Caskey M. Safety of teropavimab and zinlirvimab with lenacapavir once every 6 months for HIV treatment: a phase 1b, randomised, proof-of-concept study. Lancet HIV. 2024 Mar;11(3):e146-e155. doi: 10.1016/S2352-3018(23)00293-X. Epub 2024 Jan 30.
citation: Eron J, Little SJ, Crofoot G, Cook P, Ruane PJ, Jayaweera D, DeJesus E, Walkman SE, Mehrotra ML, VanderVeen L, Huang H, Collins S, Baeten J, Caskey M. Lenacapavir with bNAbs Teropavimab (GS-5423) and Zinlirvimab (GS-2872) Dosed Every 6 Months in People with HIV [Oral 193]. Conference on Retroviruses and Opportunistic Infections (CROI); 2023 19-22 February, Seattle, WA
citation: Selzer L, VanderVeen LA, Parvangada A, Martin R, Collins SE, Mehrotra M, Callebaut C. Susceptibility Screening to bNAbs Teropavimab (GS-5423) and Zinlirvimab (GS-2872) in ART-Suppressed Participants [Poster]. Conference on Retroviruses and Opportunistic Infections (CROI); 2023 19-22 February; Seattle, WA
citation: Lisa Selzer, Sally Demirdjian, Ross Martin, Brie Falkard, Sean E. Collins, Joseph Eron, Laurie A. VanderVeen, Christian Callebaut. Resistance analyses during treatment of lenacapavir with broadly neutralizing antibodies in people with HIV (Poster WEPEB146) AIDS 2024; Munich, Germany
citation: Selzer L, VanderVeen LA, Parvangada A, Martin R, Collins SE, Mehrotra M, Callebaut C. Susceptibility Screening of HIV-1 Viruses to Broadly Neutralizing Antibodies, Teropavimab and Zinlirvimab, in People With HIV-1 Suppressed by Antiretroviral Therapy. J Acquir Immune Defic Syndr. 2025 Jan 1;98(1):64-71. doi: 10.1097/QAI.0000000000003528.