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. april 2017 oppdatert av: 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
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
IND numbers: 79,599; 101,943
Studietype
Intervensjonell
Registrering (Faktiske)
320
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Alabama
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Birmingham, Alabama, Forente stater, 35294
- The Kirklin Clinic
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California
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Coronado, California, Forente stater, 92118
- Southern California Research Center
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Los Angeles, California, Forente stater, 90073
- VA Greater Los Angeles Healthcare System
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Los Angeles, California, Forente stater, 90036
- Peter J Ruane Md Inc
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San Diego, California, Forente stater, 92105
- Research and Education, Inc.
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San Diego, California, Forente stater, 92123
- Medical Associates Research Group
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San Diego, California, Forente stater, 92114
- Precision Research Institute, LLC
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Colorado
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Aurora, Colorado, Forente stater, 80045
- University of Colorado Denver and Hospital
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District of Columbia
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Washington, D.C., District of Columbia, Forente stater, 20007
- MedStar Georgetown University Hospital
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Florida
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Orlando, Florida, Forente stater, 32803
- Orlando Immunology Center
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South Miami, Florida, Forente stater, 33143
- Miami Research Associates
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Georgia
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Atlanta, Georgia, Forente stater, 30308
- Atlanta Gastroenterology Associates, LLC
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Maryland
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Baltimore, Maryland, Forente stater, 21202
- Mercy Medical Center, Inc.
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Lutherville, Maryland, Forente stater, 21093
- Johns Hopkins University
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New Jersey
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Hillsborough, New Jersey, Forente stater, 08844
- ID care
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New Mexico
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Santa Fe, New Mexico, Forente stater, 87505
- Southwest CARE Center
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New York
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The Bronx, New York, Forente stater, 10468
- James J Peters VAMC
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Oklahoma
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Tulsa, Oklahoma, Forente stater, 74104
- Options Health Research, LLC
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Tulsa, Oklahoma, Forente stater, 74135
- Healthcare Research Consultants
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Texas
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Arlington, Texas, Forente stater, 76012
- Texas Clinical Research Institute
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Houston, Texas, Forente stater, 77030
- Research Specialists of Texas
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San Antonio, Texas, Forente stater, 78215
- Alamo Medical Research
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Utah
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Salt Lake City, Utah, Forente stater, 84106
- Lifetree Clinical Research
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Virginia
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Fairfax, Virginia, Forente stater, 22031
- Metropolitan Research
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Falls Church, Virginia, Forente stater, 22042
- Inova Fairfax Hospital
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Wisconsin
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Madison, Wisconsin, Forente stater, 53715
- Dean Clinic
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Clichy Cedex, Frankrike, 92118
- Local Institution
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Creteil Cedex, Frankrike, 9410
- Local Institution
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Limoges, Frankrike, 87042
- Local Institution
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Marseille Cedex 08, Frankrike, 13285
- Local Institution
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Paris Cedex 14, Frankrike, 75679
- Local Institution
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San Juan, Puerto Rico, 00927
- Fundacion De Investigacion de Diego
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: 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 |
Andre navn:
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Eksperimentell: 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 |
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Eksperimentell: 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 |
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Eksperimentell: 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 |
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Eksperimentell: 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 |
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Eksperimentell: 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 |
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Eksperimentell: 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 |
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Eksperimentell: 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 |
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Eksperimentell: 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 |
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Eksperimentell: 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 |
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Eksperimentell: 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 |
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Eksperimentell: 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 |
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Eksperimentell: 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] |
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
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Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12)
Tidsramme: 12 weeks post-treatment
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12 weeks post-treatment
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Proportion of subjects with HCV ribonucleic acid (RNA) < limit of quantification (LOQ) (detectable and undetectable)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
Hjelpsomme linker
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
30. november 2011
Primær fullføring (Faktiske)
31. mars 2014
Studiet fullført (Faktiske)
31. juli 2015
Datoer for studieregistrering
Først innsendt
18. oktober 2011
Først innsendt som oppfylte QC-kriteriene
18. oktober 2011
Først lagt ut (Anslag)
19. oktober 2011
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
27. april 2017
Siste oppdatering sendt inn som oppfylte QC-kriteriene
26. april 2017
Sist bekreftet
1. april 2017
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Sykdommer i fordøyelsessystemet
- RNA-virusinfeksjoner
- Virussykdommer
- Infeksjoner
- Blodbårne infeksjoner
- Smittsomme sykdommer
- Leversykdommer
- Flaviviridae-infeksjoner
- Hepatitt, viral, menneskelig
- Enterovirusinfeksjoner
- Picornaviridae-infeksjoner
- Hepatitt, kronisk
- Hepatitt
- Hepatitt A-virus
- Hepatitt C
- Hepatitt C, kronisk
- Molekylære mekanismer for farmakologisk virkning
- Anti-infeksjonsmidler
- Antivirale midler
- Enzymhemmere
- Antimetabolitter
- Proteasehemmere
- Ribavirin
- Asunaprevir
Andre studie-ID-numre
- AI443-014
- 2011-002788-11 (EudraCT-nummer)
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .