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 avril 2017 mis à jour par: 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
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
IND numbers: 79,599; 101,943
Type d'étude
Interventionnel
Inscription (Réel)
320
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Clichy Cedex, France, 92118
- Local Institution
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Creteil Cedex, France, 9410
- Local Institution
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Limoges, France, 87042
- Local Institution
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Marseille Cedex 08, France, 13285
- Local Institution
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Paris Cedex 14, France, 75679
- Local Institution
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San Juan, Porto Rico, 00927
- Fundacion De Investigacion de Diego
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Alabama
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Birmingham, Alabama, États-Unis, 35294
- The Kirklin Clinic
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California
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Coronado, California, États-Unis, 92118
- Southern California Research Center
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Los Angeles, California, États-Unis, 90073
- VA Greater Los Angeles Healthcare System
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Los Angeles, California, États-Unis, 90036
- Peter J Ruane Md Inc
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San Diego, California, États-Unis, 92105
- Research and Education, Inc.
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San Diego, California, États-Unis, 92123
- Medical Associates Research Group
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San Diego, California, États-Unis, 92114
- Precision Research Institute, LLC
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Colorado
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Aurora, Colorado, États-Unis, 80045
- University of Colorado Denver and Hospital
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District of Columbia
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Washington, D.C., District of Columbia, États-Unis, 20007
- MedStar Georgetown University Hospital
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Florida
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Orlando, Florida, États-Unis, 32803
- Orlando Immunology Center
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South Miami, Florida, États-Unis, 33143
- Miami Research Associates
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Georgia
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Atlanta, Georgia, États-Unis, 30308
- Atlanta Gastroenterology Associates, LLC
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Maryland
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Baltimore, Maryland, États-Unis, 21202
- Mercy Medical Center, Inc.
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Lutherville, Maryland, États-Unis, 21093
- Johns Hopkins University
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New Jersey
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Hillsborough, New Jersey, États-Unis, 08844
- ID care
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New Mexico
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Santa Fe, New Mexico, États-Unis, 87505
- Southwest CARE Center
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New York
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The Bronx, New York, États-Unis, 10468
- James J Peters VAMC
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Oklahoma
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Tulsa, Oklahoma, États-Unis, 74104
- Options Health Research, LLC
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Tulsa, Oklahoma, États-Unis, 74135
- Healthcare Research Consultants
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Texas
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Arlington, Texas, États-Unis, 76012
- Texas Clinical Research Institute
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Houston, Texas, États-Unis, 77030
- Research Specialists of Texas
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San Antonio, Texas, États-Unis, 78215
- Alamo Medical Research
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Utah
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Salt Lake City, Utah, États-Unis, 84106
- Lifetree Clinical Research
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Virginia
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Fairfax, Virginia, États-Unis, 22031
- Metropolitan Research
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Falls Church, Virginia, États-Unis, 22042
- INOVA Fairfax Hospital
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Wisconsin
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Madison, Wisconsin, États-Unis, 53715
- Dean Clinic
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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 |
Autres noms:
Autres noms:
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|
Expérimental: 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 |
Autres noms:
Autres noms:
|
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Expérimental: 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 |
Autres noms:
Autres noms:
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Expérimental: 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 |
Autres noms:
Autres noms:
|
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Expérimental: 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 |
Autres noms:
Autres noms:
|
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Expérimental: 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 |
Autres noms:
Autres noms:
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Expérimental: 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 |
Autres noms:
Autres noms:
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Expérimental: 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 |
Autres noms:
Autres noms:
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Expérimental: 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 |
Autres noms:
Autres noms:
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Expérimental: 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 |
Autres noms:
Autres noms:
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Expérimental: 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 |
Autres noms:
Autres noms:
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Expérimental: 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 |
Autres noms:
Autres noms:
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Expérimental: 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] |
Autres noms:
Autres noms:
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
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Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12)
Délai: 12 weeks post-treatment
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12 weeks post-treatment
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Proportion of subjects with HCV ribonucleic acid (RNA) < limit of quantification (LOQ) (detectable and undetectable)
Délai: 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
Délai: 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
Délai: 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)
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- 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.
Liens utiles
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
30 novembre 2011
Achèvement primaire (Réel)
31 mars 2014
Achèvement de l'étude (Réel)
31 juillet 2015
Dates d'inscription aux études
Première soumission
18 octobre 2011
Première soumission répondant aux critères de contrôle qualité
18 octobre 2011
Première publication (Estimation)
19 octobre 2011
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
27 avril 2017
Dernière mise à jour soumise répondant aux critères de contrôle qualité
26 avril 2017
Dernière vérification
1 avril 2017
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système digestif
- Infections par virus à ARN
- Maladies virales
- Infections
- Infections transmissibles par le sang
- Maladies transmissibles
- Maladies du foie
- Infections à Flaviviridae
- Hépatite, virale, humaine
- Infections à entérovirus
- Infections à Picornaviridae
- Hépatite chronique
- Hépatite
- Hépatite A
- Hépatite C
- Hépatite C chronique
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Inhibiteurs d'enzymes
- Antimétabolites
- Inhibiteurs de protéase
- Ribavirine
- Asunaprévir
Autres numéros d'identification d'étude
- AI443-014
- 2011-002788-11 (Numéro EudraCT)
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .