Study of Lenacapavir, Teropavimab, and Zinlirvimab Versus Cabotegravir and Rilpivirine in Virologically Suppressed Adults With HIV-1 on Oral Daily Antiretroviral Therapy
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
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.
Visão geral do estudo
Status
Condições
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 3
Contactos e Locais
Contato de estudo
- Nome: Gilead Clinical Study Information Center
- Número de telefone: 1-833-445-3230 (GILEAD-0)
- E-mail: GileadClinicalTrials@gilead.com
Locais de estudo
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New South Wales
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Surry Hills, New South Wales, Austrália, 2010
- Recrutamento
- Taylor Square Private Clinic
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Sydney, New South Wales, Austrália, 2010
- Recrutamento
- East Sydney Doctors
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California
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San Francisco, California, Estados Unidos, 94102
- Recrutamento
- Optimus Medical Group
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Florida
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DeLand, Florida, Estados Unidos, 32720
- Recrutamento
- Midland Florida Clinical Research Center, LLC
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Fort Lauderdale, Florida, Estados Unidos, 33316
- Recrutamento
- CAN Community Health Fort Lauderdale
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Ft. Pierce, Florida, Estados Unidos, 34982
- Recrutamento
- Midway Immunology and Research Center
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Miami Gardens, Florida, Estados Unidos, 33055
- Recrutamento
- CAN Community Health Miami Gardens
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Orlando, Florida, Estados Unidos, 32803
- Recrutamento
- BLISS Health Inc.
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Tampa, Florida, Estados Unidos, 33614
- Recrutamento
- MOORE Clinical Research, Inc d/b/a TrueBlue Clinical Research
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West Palm Beach, Florida, Estados Unidos, 33407
- Recrutamento
- Triple O Research Institute, P.A.
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West Palm Beach, Florida, Estados Unidos, 33409
- Recrutamento
- Atlantic Clinical Research Institute
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Georgia
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Atlanta, Georgia, Estados Unidos, 30309
- Recrutamento
- Atlanta ID Group, PC
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Savannah, Georgia, Estados Unidos, 31401
- Recrutamento
- Chatham County Health Department
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Michigan
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Berkley, Michigan, Estados Unidos, 48072
- Recrutamento
- Be Well Medical Center
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Missouri
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Kansas City, Missouri, Estados Unidos, 64111
- Recrutamento
- KC Care Health Center
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Texas
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Dallas, Texas, Estados Unidos, 75246
- Recrutamento
- North Texas Infectious Diseases Consultants, P.A.
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Virginia
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Annandale, Virginia, Estados Unidos, 22003
- Recrutamento
- Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)
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Washington
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Seattle, Washington, Estados Unidos, 98104
- Recrutamento
- TribalMed PLLC
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Osaka, Japão, 540-0006
- Recrutamento
- National Hospital Organization Osaka National Hospital
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
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.
- 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.
- 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.
- 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:
- Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit.
- 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:
- Alanine aminotransferase > 5 x upper limit of normal (ULN).
- Direct bilirubin > 1.5 x ULN.
- Platelets < 50,000/mm^3.
- Hemoglobin < 8.0 g/dL.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)
Participants will receive oral LEN 600 mg, subcutaneous (SC) LEN 927 mg, and intravenously (IV) infusions of TAB and ZAB on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. Every 26 weeks, participants will receive SC LEN and IV infusions of TAB and ZAB up to Week 92. After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the extension phase, until completion of the extension phase, permanently discontinuing the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first. |
Administrado por via oral
Outros nomes:
Administered subcutaneously
Outros nomes:
Administered intravenously (IV)
Outros nomes:
Administered IV
Outros nomes:
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Comparador Ativo: Treatment Group 2: Cabotegravir (CAB) + Rilpivirine (RPV)
Participants will discontinue their baseline oral antiretroviral therapy (ART) and will receive intramuscular (IM) CAB 600 mg + RPV 900 mg on Day 1, Week 4 and then every 8 weeks for up to 92 weeks. After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the extension phase, until completion of the extension phase, permanently discounting the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first. |
Administered intramuscular (IM)
Outros nomes:
Administered IM
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
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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.
Prazo: Week 52
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Week 52
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Medidas de resultados secundários
Medida de resultado |
Prazo |
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Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 92 as Defined by the US FDA Snapshot Algorithm.
Prazo: Week 92
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Week 92
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Trough Concentrations for LEN, TAB, and ZAB at Week 26
Prazo: Week 26
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Week 26
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Trough Concentrations for LEN, TAB, and ZAB at Week 52
Prazo: Week 52
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Week 52
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Trough Concentrations for LEN, TAB, and ZAB at Week 104
Prazo: Week 104
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Week 104
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Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA Snapshot Algorithm
Prazo: Week 52
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Week 52
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Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 92 as Determined by the US FDA Snapshot Algorithm.
Prazo: Week 92
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Week 92
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Change From Baseline in clusters of differentiation 4 (CD4) (CD4)+ T-cell Counts at Week 52
Prazo: Baseline, Week 52
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Baseline, Week 52
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Change From Baseline in CD4+ T-cell Counts at Week 92
Prazo: Baseline, Week 92
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Baseline, Week 92
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Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs)
Prazo: Up to Week 92
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Up to Week 92
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Percentages of Participants Prematurely Discontinuing Their Study Treatment due to an AE
Prazo: Up to Week 92
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Up to Week 92
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Percentages of Participants With Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) of TAB
Prazo: Up to 92 Weeks
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Up to 92 Weeks
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Percentages of Participants With of ADAs and NAbs of ZAB
Prazo: Up to 92 Weeks
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Up to 92 Weeks
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Gilead Study Director, Gilead Sciences
Publicações e links úteis
Links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Infecções transmitidas pelo sangue
- Doenças urogenitais
- Doenças Genitais
- Doenças do sistema imunológico
- Infecções
- Infecções por vírus de RNA
- Doenças Virais
- Doenças Transmissíveis
- Doenças Sexualmente Transmissíveis, Virais
- Doenças Sexualmente Transmissíveis
- Infecções por Lentivírus
- Infecções por Retroviridae
- Síndromes de Deficiência Imunológica
- Infecções por HIV
- Produtos químicos orgânicos
- Compostos heterocíclicos, 1 anel
- Compostos heterocíclicos
- Pirimidinas
- Nitrilos
- Rilpivirina
- Lenacapavir
- Cabotegravir
Outros números de identificação do estudo
- GS-US-536-5938
- 2025-524335-39 (Outro identificador: European Medicines Agency)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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