Phase III Hallmark DUAL: ASV+DCV (Nulls/Partials, Intolerants/Ineligibles. Naives)
- Conditions
- Hepatitis C Virus
- Interventions
- Drug: Asunaprevir (ASV)Drug: Daclatasvir (DCV)Drug: Pegylated-interferon alfa 2a (PegIFN)Drug: Ribavirin (RBV)
- Registration Number
- NCT01581203
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to estimate efficacy, as determined by the proportion of subjects with Sustained virologic response at post-treatment Week 12 (SVR12), defined as Hepatitis C virus (HCV) Ribonucleic acid (RNA) \< Limit of quantitation (LOQ) at post-treatment Week 12, for subjects who are prior null or partial responders to P/R or who are treatment-naive.
- Detailed Description
Allocation: Treatment naive cohort: Randomized Controlled Trial, Null/partial responder and intolerant/ineligible cohorts: N/A (Single arm study)
Masking: Treatment naive cohort: Double Blind, Null/partial responder and intolerant/ineligible cohorts: Open
Intervention Model: Treatment naive cohort: Parallel, Null/partial responder and intolerant/ineligible cohorts: Single group
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 748
- Males and females, ≥ 18 years of age
- HCV Genotype 1b who previously failed treatment with peginterferon alfa and ribavirin, classified as previous null or partial responders based on previous therapy, OR intolerant or ineligible to P/R due to neutropenia, anemia, depression or thrombocytopenia with fibrosis/cirrhosis, OR treatment naive
- HCV RNA ≥ 10,000 IU/mL
- Seronegative for Human immunodeficiency virus (HIV) and Hepatitis B surface antigen (HBsAg)
- Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 25% of treated population)
- Prior treatment of HCV with HCV direct acting antiviral (DAA)
- Evidence of a medical condition contributing to chronic liver disease other than HCV
- Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
- Diagnosed or suspected hepatocellular carcinoma or other malignancies
- Uncontrolled diabetes or hypertension
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 4: Null or Partial Responder to P/R (ASV + DCV) 24/48 week Asunaprevir (ASV) Subjects meeting prespecified rescue criteria in the null or partial responder cohort or active arm of the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks Ribavirin 1000 mg / 1200 mg (total daily dose) Tablet by mouth, for 24 or 48 weeks Arm 4: Null or Partial Responder to P/R (ASV + DCV) 24/48 week Daclatasvir (DCV) Subjects meeting prespecified rescue criteria in the null or partial responder cohort or active arm of the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks Ribavirin 1000 mg / 1200 mg (total daily dose) Tablet by mouth, for 24 or 48 weeks Arm 3: Treatment naive (ASV + DCV) Daclatasvir (DCV) \[Subjects will receive ASV + DCV for 24 weeks\] followed by ASV + DCV for 24 weeks in protocol AI444026\] Subjects meeting prespecified rescue criteria in the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks Ribavirin 1000 mg/1200 mg (total daily dose) tablet by mouth for 24 or 48 weeks Arm 1: Null or Partial Responder to P/R (ASV + DCV) Asunaprevir (ASV) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks Arm 2: Intolerant to or Ineligible for P/R (ASV + DCV) Daclatasvir (DCV) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks Arm 1: Null or Partial Responder to P/R (ASV + DCV) Daclatasvir (DCV) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks Arm 2: Intolerant to or Ineligible for P/R (ASV + DCV) Asunaprevir (ASV) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks Arm 3: Treatment naive (ASV + DCV) Pegylated-interferon alfa 2a (PegIFN) \[Subjects will receive ASV + DCV for 24 weeks\] followed by ASV + DCV for 24 weeks in protocol AI444026\] Subjects meeting prespecified rescue criteria in the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks Ribavirin 1000 mg/1200 mg (total daily dose) tablet by mouth for 24 or 48 weeks Arm 3: Treatment naive (ASV + DCV) Ribavirin (RBV) \[Subjects will receive ASV + DCV for 24 weeks\] followed by ASV + DCV for 24 weeks in protocol AI444026\] Subjects meeting prespecified rescue criteria in the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks Ribavirin 1000 mg/1200 mg (total daily dose) tablet by mouth for 24 or 48 weeks Arm 4: Null or Partial Responder to P/R (ASV + DCV) 24/48 week Ribavirin (RBV) Subjects meeting prespecified rescue criteria in the null or partial responder cohort or active arm of the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks Ribavirin 1000 mg / 1200 mg (total daily dose) Tablet by mouth, for 24 or 48 weeks Arm 3: Treatment naive (ASV + DCV) Asunaprevir (ASV) \[Subjects will receive ASV + DCV for 24 weeks\] followed by ASV + DCV for 24 weeks in protocol AI444026\] Subjects meeting prespecified rescue criteria in the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks Ribavirin 1000 mg/1200 mg (total daily dose) tablet by mouth for 24 or 48 weeks Arm 4: Null or Partial Responder to P/R (ASV + DCV) 24/48 week Pegylated-interferon alfa 2a (PegIFN) Subjects meeting prespecified rescue criteria in the null or partial responder cohort or active arm of the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks Ribavirin 1000 mg / 1200 mg (total daily dose) Tablet by mouth, for 24 or 48 weeks
- Primary Outcome Measures
Name Time Method Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post treatment Week 12, for subjects who are prior null or partial responders to P/R or are treatment-naive At 12 weeks post-treatment
- Secondary Outcome Measures
Name Time Method On treatment safety, as measured by frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) End of Treatment (up to 48 weeks) plus 7 days Differences in rates of selected grade 3-4 laboratory abnormalities during the first 12 weeks between treatments (ASV + DCV vs PBO) for naive subjects Up to first 12 weeks Proportion of subjects with anemia At 12 weeks post-treatment Proportion of genotype 1b subjects with HCV RNA undetectable At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up to 24 weeks), post-treatment Week 12, or post-treatment Week 24 for each cohort eRVR = Extended rapid virologic response, EOT = End of treatment
Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for subjects who are intolerant or ineligible to P/R Post-treatment Week 12 Proportion of genotype 1b subjects with SVR12 (HCV RNA < LOQ at post treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28B gene for each cohort Post-treatment Week 12 Proportion of subjects with rash At 12 weeks post-treatment Proportion of genotypes 1b subjects with HCV RNA < LOQ At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [VR(4&12)]; EOT (up to 24 weeks), post-treatment Week 24 (SVR24) for each cohort
Trial Locations
- Locations (27)
The Health Care Authority For Baptist Health
🇺🇸Montgomery, Alabama, United States
Scpmg/ Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
University Of Colorado Denver And Hospital
🇺🇸Aurora, Colorado, United States
Uf Hepatology Research At Ctrb
🇺🇸Gainesville, Florida, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
North Shore-Long Island Jewish Health System
🇺🇸Manhasset, New York, United States
Johns Hopkins Medical Institutions
🇺🇸Lutherville, Maryland, United States
University Of North Carolina At Chapel Hill School Of Med
🇺🇸Chapel Hill, North Carolina, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Baylor College Of Medicine
🇺🇸Houston, Texas, United States
Dean Clinic
🇺🇸Madison, Wisconsin, United States
Alamo Medical Research
🇺🇸San Antonio, Texas, United States
Local Institution
🇬🇧Glasgow, Lanarkshire, United Kingdom
Gastrointestinal Research Institute (G.I.R.I.)
🇨🇦Vancouver, British Columbia, Canada
Percuro Clinical Research Ltd
🇨🇦Victoria, British Columbia, Canada
Toronto General Hospital-University Health Network
🇨🇦Toronto, Ontario, Canada
Toronto Liver Centre
🇨🇦Toronto, Ontario, Canada
Toronto Digestive Disease Associates, Inc.
🇨🇦Vaughan, Ontario, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Clinique Medicale Lactuel
🇨🇦Montreal, Quebec, Canada
Alpha-Recherche Clinique
🇨🇦Quebec, Canada
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Scripps Clinic
🇺🇸La Jolla, California, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Vamc
🇺🇸Houston, Texas, United States