Study of Lenacapavir, Teropavimab, and Zinlirvimab Versus Cabotegravir and Rilpivirine in Virologically Suppressed Adults With HIV-1 on Oral Daily Antiretroviral Therapy

Brief Summary
The goal of this clinical study is to compare how effective a long-acting injectable treatment of lenacapavir (LEN), teropavimab (TAB), and zinlirvimab (ZAB) versus (CAB) and rilpivirine (RPV) injections given every 8 weeks in adults with HIV-1 whose virus is well controlled on daily oral treatment, after 1 year (52 weeks) of the treatment.

The primary objective of this study are to evaluate the efficacy of switching to the regimen of LEN, TAB, and ZAB versus switching to CAB and RPV in virologically suppressed people with HIV-1 (PWH) as determined by the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 52.
Brief Title
Study of Lenacapavir, Teropavimab, and Zinlirvimab Versus Cabotegravir and Rilpivirine in Virologically Suppressed Adults With HIV-1 on Oral Daily Antiretroviral Therapy
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-833-445-3230 (GILEAD-0)
Central Contact Email
GileadClinicalTrials@gilead.com
Completion Date
Completion Date Type
Estimated
Conditions
HIV INFECTIONS
Eligibility Criteria
Key Inclusion Criteria:

* Human immunodeficiency virus type 1 (HIV-1) susceptibility results from screening meeting specific criteria:

1\) Proviral phenotypic susceptibility to both TAB and ZAB by the investigational protocol-defined assay at screening.
* At least 1 documented HIV-1 RNA level measured between 6 months and 12 months (+2 months) prior to screening. This and any other HIV-1 RNA measurements documented in this period must be \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). A single virologic elevation of ≥ 50 copies/mL and \< 400 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable if the subsequent plasma HIV-1 RNA level is \< 50 copies/mL.
* A plasma HIV-1 RNA test \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) within the last 6 months prior to screening.

1\) If \> 1 plasma HIV-1 RNA measurements in the last 6 months prior to screening are available, all must be \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL).
* On a stable oral ARV therapy (ART) for ≥ 6 months prior to screening.

1. A change in ART regimen ≥ 3 months prior to the screening visit for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed; individuals with a change in ART regimen ≥ 3 months prior to screening must have been on the regimen for ≥ 3 months prior to screening, and all HIV-1 RNA measurements in that period must be \< 50 copies/mL. There are no permitted changes to ART regimens between screening and Day 1.

Key Exclusion Criteria:

* History of an opportunistic infection or illness indicative of Stage 3 HIV disease.
* History of treatment failure.
* Known or suspected resistance to either CAB or RPV.

1. Resistance to CAB defined as the following mutations: G118R, Q148K, Q148R, T66K+L74M, E92Q+N155H, E138A+Q148R, E138K+Q148K/R, G140C+Q148R, G140S+Q148H/K/R, Y143H+N155H, and Q148R+N155H.
2. Resistance to RPV defined as the following mutations: K101E and P; E138A, G, K, R, and Q; V179L; Y181C, I, and V; Y188L; H221Y; F227C; M230I and L, and the combination of L100I/K103N.
* Individuals with a dermatologic condition or implanted prothesis overlying the gluteal injection site for CAB + RPV.
* Known hypersensitivity to the study intervention, its metabolites, or formulation excipients.
* Active, serious infections (other than HIV-1) requiring therapy \< 30 days prior to randomization.
* Active tuberculosis infection.
* Acute hepatitis of any cause \< 30 days before randomization.
* History of, or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding) or severe hepatic impairment (Child-Pugh Class C).
* Active malignancy requiring acute systemic therapy.
* Have poor venous access that would limit phlebotomy or intravenous (IV) infusion of study drugs.
* Prior use of, or exposure to, LEN or a broadly neutralizing antibody (bNAb) for HIV-1.
* Prior use of, or exposure to, long-acting (LA) injectable CAB or LA injectable RPV.
* Prior use of, or exposure to, ibalizumab, fostemsavir, or maraviroc.
* Baseline regimen consisting of monotherapy with any single antiretroviral (ARV).
* Treatment with immunosuppressant therapies (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) within 4 weeks of screening (with the exception of a single short course of corticosteroids lasting ≤ 7 days) or have a comorbid condition with an anticipated need ongoing immunosuppressive treatment during the study.
* Hepatitis C virus (HCV) antibody positive and HCV RNA detectable.
* Chronic hepatitis B virus (HBV) infection, as determined by either:

1. Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit.
2. Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit.
* Severe renal impairment-estimated glomerular filtration rate \< 30 mL/min according to the Cockcroft-Gault formula.
* Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant, as determined by the investigator.
* Any of the following laboratory values at screening:

1. Alanine aminotransferase \> 5 x upper limit of normal (ULN).
2. Direct bilirubin \> 1.5 x ULN.
3. Platelets \< 50,000/mm\^3.
4. Hemoglobin \< 8.0 g/dL.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:

* Human immunodeficiency virus type 1 (HIV-1) susceptibility results from screening meeting specific criteria:

1\) Proviral phenotypic susceptibility to both TAB and ZAB by the investigational protocol-defined assay at screening.
* At least 1 documented HIV-1 RNA level measured between 6 months and 12 months (+2 months) prior to screening. This and any other HIV-1 RNA measurements documented in this period must be \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). A single virologic elevation of ≥ 50 copies/mL and \< 400 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable if the subsequent plasma HIV-1 RNA level is \< 50 copies/mL.
* A plasma HIV-1 RNA test \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) within the last 6 months prior to screening.

1\) If \> 1 plasma HIV-1 RNA measurements in the last 6 months prior to screening are available, all must be \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL).
* On a stable oral ARV therapy (ART) for ≥ 6 months prior to screening.

1. A change in ART regimen ≥ 3 months prior to the screening visit for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed; individuals with a change in ART regimen ≥ 3 months prior to screening must have been on the regimen for ≥ 3 months prior to screening, and all HIV-1 RNA measurements in that period must be \< 50 copies/mL. There are no permitted changes to ART regimens between screening and Day 1.

Inclusion/
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07682961
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-536-5938
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 3, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Switching to Long-acting Antiretroviral Therapy of Broadly Neutralizing Antibodies Teropavimab and Zinlirvimab in Combination With the Capsid Inhibitor Lenacapavir Twice-Yearly Versus Cabotegravir and Rilpivirine Every 8 Weeks in Virologically Suppressed Adults With HIV-1 on Oral Daily Antiretroviral Therapy
Primary Outcomes
Outcome Measure
Proportion of Participants With HIV-1 ribonucleic acid (RNA) ≥ 50 Copies/mL at Week 52 as Defined by the United States (US) Food and Drug Administration (FDA) Snapshot Algorithm.
Outcome Time Frame
Week 52
Secondary Ids
Secondary Id
2025-524335-39
Secondary Id
2025
Secondary Outcomes
Outcome Time Frame
Week 92
Outcome Measure
Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 92 as Defined by the US FDA Snapshot Algorithm.
Outcome Time Frame
Week 52
Outcome Measure
Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA Snapshot Algorithm
Outcome Time Frame
Week 92
Outcome Measure
Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 92 as Determined by the US FDA Snapshot Algorithm.
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change From Baseline in clusters of differentiation 4 (CD4) (CD4)+ T-cell Counts at Week 52
Outcome Time Frame
Baseline, Week 92
Outcome Measure
Change From Baseline in CD4+ T-cell Counts at Week 92
Outcome Time Frame
Up to Week 92
Outcome Measure
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs)
Outcome Time Frame
Up to Week 92
Outcome Measure
Percentages of Participants Prematurely Discontinuing Their Study Treatment due to an AE
Outcome Time Frame
Week 26
Outcome Measure
Trough Concentrations for LEN, TAB, and ZAB at Week 26
Outcome Time Frame
Week 52
Outcome Measure
Trough Concentrations for LEN, TAB, and ZAB at Week 52
Outcome Time Frame
Week 104
Outcome Measure
Trough Concentrations for LEN, TAB, and ZAB at Week 104
Outcome Time Frame
Up to 92 Weeks
Outcome Measure
Percentages of Participants With Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) of TAB
Outcome Time Frame
Up to 92 Weeks
Outcome Measure
Percentages of Participants With of ADAs and NAbs of ZAB
Start Date
Start Date Type
Actual
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Robert Grossberg
Investigator Email
rgrossbe@montefiore.org
Investigator Phone
718-920-5276
Investigator Department
Medicine
Investigator Division
Infectious Diseases
Investigator Sponsor Organization
Montefiore
Study Department
Medicine
Study Division
Infectious Diseases
Categories Mesh Debug
HIV/AIDS --- HIV INFECTIONS
Infectious Disease --- HIV INFECTIONS
Blood Disorders --- BLOOD-BORNE INFECTIONS
HIV/AIDS --- BLOOD-BORNE INFECTIONS
Infectious Disease --- BLOOD-BORNE INFECTIONS
Hepatitis --- COMMUNICABLE DISEASES
HIV/AIDS --- COMMUNICABLE DISEASES
Infectious Disease --- COMMUNICABLE DISEASES
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
HIV/AIDS --- SEXUALLY TRANSMITTED DISEASES, VIRAL
Infectious Disease --- SEXUALLY TRANSMITTED DISEASES, VIRAL
HIV/AIDS --- SEXUALLY TRANSMITTED DISEASES
Infectious Disease --- SEXUALLY TRANSMITTED DISEASES
Infectious Disease --- LENTIVIRUS INFECTIONS
Infectious Disease --- RETROVIRIDAE INFECTIONS
COVID-19 --- RNA VIRUS INFECTIONS
Infectious Disease --- RNA VIRUS INFECTIONS
COVID-19 --- VIRUS DISEASES
Hepatitis --- VIRUS DISEASES
Infectious Disease --- VIRUS DISEASES
Immune System --- IMMUNE SYSTEM DISEASES
MeSH Terms
HIV INFECTIONS
BLOOD-BORNE INFECTIONS
COMMUNICABLE DISEASES
INFECTIONS
SEXUALLY TRANSMITTED DISEASES, VIRAL
SEXUALLY TRANSMITTED DISEASES
LENTIVIRUS INFECTIONS
RETROVIRIDAE INFECTIONS
RNA VIRUS INFECTIONS
VIRUS DISEASES
GENITAL DISEASES
UROGENITAL DISEASES
IMMUNOLOGIC DEFICIENCY SYNDROMES
IMMUNE SYSTEM DISEASES
LENACAPAVIR
CABOTEGRAVIR
RILPIVIRINE
NITRILES
ORGANIC CHEMICALS
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS