Study to Determine the Effectiveness and Safety of a Three Drug Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) Infected Patients Not Previously Treated With Currently Available Medications
26 de abril de 2017 atualizado por: Bristol-Myers Squibb
Open-Label, Multiple-Dose, Dose Escalation Study to Evaluate the Pharmacodynamics, Pharmacokinetics, and Safety of Coadministration of BMS-650032, BMS-790052, and BMS-791325 When Administered for 24 or 12 Weeks in Treatment-Naïve Subjects Infected With Hepatitis C Virus Genotype 1
The purpose of this study is to estimate the rate of sustained virologic response (SVR) SVR12, where SVR12 is defined as HCV RNA < LOQ (detectable or undetectable) 12 weeks post-treatment in Genotype 1 & Genotype 4 treatment naive patients, and Genotype (GT1) infected patients who are prior null responders to pegIFN/ribavirin
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
IND numbers: 79,599; 101,943
Tipo de estudo
Intervencional
Inscrição (Real)
320
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Alabama
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Birmingham, Alabama, Estados Unidos, 35294
- The Kirklin Clinic
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California
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Coronado, California, Estados Unidos, 92118
- Southern California Research Center
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Los Angeles, California, Estados Unidos, 90073
- VA Greater Los Angeles Healthcare System
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Los Angeles, California, Estados Unidos, 90036
- Peter J Ruane Md Inc
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San Diego, California, Estados Unidos, 92105
- Research and Education, Inc.
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San Diego, California, Estados Unidos, 92123
- Medical Associates Research Group
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San Diego, California, Estados Unidos, 92114
- Precision Research Institute, LLC
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- University of Colorado Denver and Hospital
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District of Columbia
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Washington, D.C., District of Columbia, Estados Unidos, 20007
- MedStar Georgetown University Hospital
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Florida
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Orlando, Florida, Estados Unidos, 32803
- Orlando Immunology Center
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South Miami, Florida, Estados Unidos, 33143
- Miami Research Associates
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Georgia
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Atlanta, Georgia, Estados Unidos, 30308
- Atlanta Gastroenterology Associates, LLC
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Maryland
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Baltimore, Maryland, Estados Unidos, 21202
- Mercy Medical Center, Inc.
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Lutherville, Maryland, Estados Unidos, 21093
- Johns Hopkins University
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New Jersey
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Hillsborough, New Jersey, Estados Unidos, 08844
- ID care
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New Mexico
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Santa Fe, New Mexico, Estados Unidos, 87505
- Southwest CARE Center
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New York
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The Bronx, New York, Estados Unidos, 10468
- James J Peters VAMC
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Oklahoma
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Tulsa, Oklahoma, Estados Unidos, 74104
- Options Health Research, LLC
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Tulsa, Oklahoma, Estados Unidos, 74135
- Healthcare Research Consultants
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Texas
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Arlington, Texas, Estados Unidos, 76012
- Texas Clinical Research Institute
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Houston, Texas, Estados Unidos, 77030
- Research Specialists of Texas
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San Antonio, Texas, Estados Unidos, 78215
- Alamo Medical Research
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Utah
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Salt Lake City, Utah, Estados Unidos, 84106
- Lifetree Clinical Research
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Virginia
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Fairfax, Virginia, Estados Unidos, 22031
- Metropolitan Research
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Falls Church, Virginia, Estados Unidos, 22042
- Inova Fairfax Hospital
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Wisconsin
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Madison, Wisconsin, Estados Unidos, 53715
- Dean Clinic
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Clichy Cedex, França, 92118
- Local Institution
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Creteil Cedex, França, 9410
- Local Institution
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Limoges, França, 87042
- Local Institution
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Marseille Cedex 08, França, 13285
- Local Institution
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Paris Cedex 14, França, 75679
- Local Institution
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San Juan, Porto Rico, 00927
- Fundacion De Investigacion de Diego
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Men and women, ages ≥18 years of age
- Subjects who are naive to HCV treatment, defined as no previous exposure to an Interferon (IFN), Ribavirin (RBV); or any HCV-specific direct acting antiviral or experimental therapy or subjects who are null responders to previous pegylated Interferon alfa (pegIFNα) plus Ribavirin (RBV) treatment
Subjects should have chronic hepatitis C (CHC) as documented by:
- Positive for anti-HCV antibody, HCV RNA, or a positive HCV genotype test at least 6 months prior to screening, and positive for HCV RNA and Anti-HCV antibody at the time of screening, or
- Positive for anti-HCV antibody and HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed prior to enrollment with evidence of CHC disease, such as the presence of fibrosis)
- HCV genotype 1a, 1b or 4 only
- HCV RNA viral load of ≥10,000 IU/mL at screening
Have one of the following:
- Documented Fibrotest score of ≤0.72 and aspartate transferase (transminase) to platelet ratio index (APRI) ≤2; OR
- Documented liver biopsy within 36 months preceding Day 1 showing absence of cirrhosis OR
- Documented Fibroscan® ultrasound (where approved) within 12 months of screening showing absence of cirrhosis
- Body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive
- Subjects with compensated Child-Pugh A cirrhosis as documented by history of cirrhosis with any prior liver biopsy or Fibroscan® ultrasound (where approved) within 12 months prior to screening
Exclusion Criteria:
- Evidence of a medical condition associated with chronic liver disease other than HCV (such as but not limited to: hemochromatosis, autoimmune hepatitis,metabolic liver disease, alcoholic liver disease, toxin exposures)
- History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis
- Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment
- Documented or suspected hepatocellular carcinoma (HCC)
- Positive for hepatitis B surface antigen (HBsAg)
- Positive for Human Immunodeficiency Virus-1 (HIV-1) and/or Human Immunodeficiency Virus-2 (HIV-2) antibodies
- Alanine transferase (transminase) (ALT) >5x upper limit of normal (ULN)
- Total Bilirubin ≥2 mg/dL
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
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: Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)
BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks BMS-790052 60 mg tablet by mouth once daily for 24 Weeks BMS 791325 75 mg table by mouth twice daily for 24 Weeks |
Outros nomes:
Outros nomes:
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Experimental: Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)
BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks BMS-790052 60 mg tablet by mouth once daily for 12 Weeks BMS 791325 75 mg table by mouth twice daily for 12 Weeks |
Outros nomes:
Outros nomes:
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Experimental: Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)
* Contingent upon review of safety data from all available treated subjects from Groups 1 and 2 BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks BMS-790052 60 mg tablet by mouth once daily for 24 Weeks BMS 791325 150 mg table by mouth twice daily for 24 Weeks |
Outros nomes:
Outros nomes:
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Experimental: Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)
* Contingent upon review of safety data from all available treated subjects from Groups 1 and 2 BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks BMS-790052 60 mg tablet by mouth once daily for 12 Weeks BMS 791325 150 mg table by mouth twice daily for 12 Weeks |
Outros nomes:
Outros nomes:
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Experimental: Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 1 treatment-naive subjects BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks BMS 791325 75 mg table by mouth twice daily for 12 Weeks |
Outros nomes:
Outros nomes:
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Experimental: Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 1 treatment-naive subjects BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks BMS 791325 150 mg table by mouth twice daily for 12 Weeks |
Outros nomes:
Outros nomes:
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Experimental: Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 4 treatment-naive subjects BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks BMS 791325 75 mg table by mouth twice daily for 12 Weeks |
Outros nomes:
Outros nomes:
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Experimental: Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 4 treatment-naive subjects BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks BMS 791325 150 mg table by mouth twice daily for 12 Weeks |
Outros nomes:
Outros nomes:
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Experimental: Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 1 treatment-null/non-responder subjects BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks BMS 791325 75 mg table by mouth twice daily for 12 Weeks |
Outros nomes:
Outros nomes:
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Experimental: Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 1 treatment-null/non-responder subjects BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks BMS 791325 150 mg table by mouth twice daily for 12 Weeks |
Outros nomes:
Outros nomes:
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Experimental: Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)
* Genotype 1 treatment-null/non-responder subjects BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks BMS-790052 30 mg tablet by mouth twice daily for 24 Weeks BMS 791325 75 mg table by mouth twice daily for 24 Weeks |
Outros nomes:
Outros nomes:
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Experimental: Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)
* Genotype 1 treatment-null/non-responder subjects BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks BMS-790052 30 mg tablet by mouth twice daily for 24 Weeks BMS 791325 150 mg table by mouth twice daily for 24 Weeks |
Outros nomes:
Outros nomes:
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Experimental: Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBV
* Genotype 1 treatment-naive subjects BMS-650032 200 mg tablets orally twice daily 12 weeks BMS-790052 30 mg tablets orally twice daily 12 weeks BMS-791325 75 mg tablets orally twice daily 12 weeks Ribavirin (RBV) tablets orally weight based dosing daily 12 weeks [if subject is < 75 kg: 1000 mg per day orally (2 x 200 mg tablets in AM and 3 x 200 mg tablets in PM), or if ≥ 75 kg: 1200 mg per day orally (3 x 200 mg tablets in AM and 3 x 200 mg tablets in PM] |
Outros nomes:
Outros nomes:
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
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Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12)
Prazo: 12 weeks post-treatment
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12 weeks post-treatment
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Proportion of subjects with HCV ribonucleic acid (RNA) < limit of quantification (LOQ) (detectable and undetectable)
Prazo: Weeks 1, 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22 and 24 weeks of therapy; at end of treatment (EOT) (following 12 or 24 weeks of treatment, by Group); and Weeks 4, 12, 24, 36, and 48 weeks post-treatment
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Weeks 1, 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22 and 24 weeks of therapy; at end of treatment (EOT) (following 12 or 24 weeks of treatment, by Group); and Weeks 4, 12, 24, 36, and 48 weeks post-treatment
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Proportion of subjects with HCV ribonucleic acid (RNA) undetectable
Prazo: Weeks 1, 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22 and 24 weeks of therapy; at end of treatment (EOT) (following 12 or 24 weeks of treatment, by Group); and Weeks 4, 12, 24, 36, and 48 weeks post-treatment
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Weeks 1, 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22 and 24 weeks of therapy; at end of treatment (EOT) (following 12 or 24 weeks of treatment, by Group); and Weeks 4, 12, 24, 36, and 48 weeks post-treatment
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Proportion of subjects who experience viral breakthrough
Prazo: Formal analysis at SVR12, Week 48 of follow up period (or upon occurrence)
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viral breakthrough defined as:
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Formal analysis at SVR12, Week 48 of follow up period (or upon occurrence)
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Proportion of subjects who experience viral relapse defined as confirmed quantifiable HCV RNA ≥ 25 IU/mL (>LOQ) in a subject with HCV RNA < LOQ or undetectable at End of treatment (EOT)
Prazo: End of treatment (Maximum up to 24 Weeks)
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End of treatment (Maximum up to 24 Weeks)
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Maximum observed plasma concentration (Cmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712
Prazo: Day 1 and Day 14
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Day 1 and Day 14
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Observed plasma concentration at 12 hours (C12) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712
Prazo: Day 1 and Day 14
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Day 1 and Day 14
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Observed plasma concentration at 24 hours (C24) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712
Prazo: Day 1 and Day 14
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Day 1 and Day 14
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Trough observed plasma concentration (Ctrough) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712
Prazo: Day 1 and Day 14
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Day 1 and Day 14
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Time of maximum observed plasma concentration (Tmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712
Prazo: Day 1 and Day 14
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Day 1 and Day 14
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Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-650032, BMS-790052, BMS 791325, and BMS-794712
Prazo: Day 1 and Day 14
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Day 1 and Day 14
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HCV genomic substitutions associated with exposure of BMS-650032, BMS-790052, and BMS-791325
Prazo: At the time of viral breakthrough or relapse
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At the time of viral breakthrough or relapse
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Frequency of deaths, serious adverse events (SAEs), discontinuations due to adverse events (AEs), severity Grade 3/4 AEs, and severity Grade 3/4 laboratory abnormalities
Prazo: Formal analysis at week 48 of follow up period (or upon occurrence)
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Formal analysis at week 48 of follow up period (or upon occurrence)
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Publicações Gerais
- Everson GT, Sims KD, Thuluvath PJ, Lawitz E, Hassanein T, Rodriguez-Torres M, Desta T, Hawkins T, Levin JM, Hinestrosa F, Rustgi V, Schwartz H, Younossi Z, Webster L, Gitlin N, Eley T, Huang SP, McPhee F, Grasela DM, Gardiner DF. Daclatasvir + asunaprevir + beclabuvir +/- ribavirin for chronic HCV genotype 1-infected treatment-naive patients. Liver Int. 2016 Feb;36(2):189-97. doi: 10.1111/liv.12964. Epub 2015 Dec 6.
- Everson GT, Sims KD, Rodriguez-Torres M, Hezode C, Lawitz E, Bourliere M, Loustaud-Ratti V, Rustgi V, Schwartz H, Tatum H, Marcellin P, Pol S, Thuluvath PJ, Eley T, Wang X, Huang SP, McPhee F, Wind-Rotolo M, Chung E, Pasquinelli C, Grasela DM, Gardiner DF. Efficacy of an interferon- and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1 infection. Gastroenterology. 2014 Feb;146(2):420-9. doi: 10.1053/j.gastro.2013.10.057. Epub 2013 Oct 30.
Links úteis
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
30 de novembro de 2011
Conclusão Primária (Real)
31 de março de 2014
Conclusão do estudo (Real)
31 de julho de 2015
Datas de inscrição no estudo
Enviado pela primeira vez
18 de outubro de 2011
Enviado pela primeira vez que atendeu aos critérios de CQ
18 de outubro de 2011
Primeira postagem (Estimativa)
19 de outubro de 2011
Atualizações de registro de estudo
Última Atualização Postada (Real)
27 de abril de 2017
Última atualização enviada que atendeu aos critérios de controle de qualidade
26 de abril de 2017
Última verificação
1 de abril de 2017
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Doenças do aparelho digestivo
- Infecções por vírus de RNA
- Doenças Virais
- Infecções
- Infecções transmitidas pelo sangue
- Doenças Transmissíveis
- Doenças do Fígado
- Infecções por Flaviviridae
- Hepatite, Viral, Humana
- Infecções por Enterovírus
- Infecções por Picornaviridae
- Hepatite Crônica
- Hepatite
- Hepatite A
- Hepatite C
- Hepatite C Crônica
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Anti-Infecciosos
- Antivirais
- Inibidores Enzimáticos
- Antimetabólitos
- Inibidores de Protease
- Ribavirina
- Asunaprevir
Outros números de identificação do estudo
- AI443-014
- 2011-002788-11 (Número EudraCT)
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .