UNITY 2: A Study of an Investigational Treatment Regimen of DCV+ASV+BMS-791325 in a Fixed Dose Combination (the DCV 3DAA (Direct Acting Antiviral) Regimen) With or Without RBV for 12 Weeks for the Treatment of Chronic Hepatitis C Virus(HCV)Genotype 1 Infection in Subjects With Compensated Cirrhosis
- Conditions
- Hepatitis C
- Interventions
- Registration Number
- NCT01973049
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
To demonstrate the effectiveness of DCV 3DAA fixed dose combination with or without Ribavirin in treatment naive cirrhotic subjects.
- Detailed Description
Masking is Double blind for RBV: two or more parties are unaware of the intervention assignment.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 202
- Subjects chronically infected with HCV genotype 1
- Subjects with compensated cirrhosis
- HCV RNA ≥ 10,000 IU/mL at screening
- Treatment-naïve subjects with no previous exposure to an interferon formulation (ie, IFNα, pegIFNα), Ribavirin (RBV), or HCV Direct Acting Antivirals (DAA) (protease, polymerase inhibitor, etc.)
- Treatment-experienced subjects are eligible including exposure to anti-HCV agents of a mechanistic class other than those contained in the Daclatasvir (DCV) / Asunaprevir (ASV) /BMS-791325 triple regimen is permitted. Examples of permitted agents include, but are not limited to nucleoside/nucleotide inhibitors of nonstructural protein 5B (NS5B) polymerase, inhibitors of cyclophilin, or inhibitors of microRNA.
- Subjects without cirrhosis
- Liver or any other organ transplant
- Current or known history of cancer within 5 years prior to screening
- Documented or suspected hepatocellular carcinoma(HCC)
- Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A1: DCV/ASV/BMS-791325+Placebo matching RBV (naive) BMS-791325 Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Placebo matching Ribavirin 0mg tablet orally twice a day for 12 weeks A1: DCV/ASV/BMS-791325+Placebo matching RBV (naive) Placebo matching Ribavirin Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Placebo matching Ribavirin 0mg tablet orally twice a day for 12 weeks A3: DCV/ASV/BMS-791325+Placebo matching RBV (experienced) BMS-791325 Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Placebo matching Ribavirin 0 mg tablet orally twice a day for 12 weeks A2: DCV/ASV/BMS-791325 + RBV (naive) BMS-791325 Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Ribavirin 200mg tablet orally twice a day for 12 weeks A4: DCV/ASV/BMS-791325 + RBV (experienced) BMS-791325 Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Ribavirin 200 mg tablet orally twice a day for 12 weeks, Weight based dosing: If \< 75 kg, 1000 mg per day (two 200 mg tablets in AM and three 200 mg tablets in PM); if ≥ 75 kg, 1200 mg per day (three 200 mg tablets in AM and three 200 mg tablets in PM), AM=in the morning, PM=in the evening A3: DCV/ASV/BMS-791325+Placebo matching RBV (experienced) Placebo matching Ribavirin Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Placebo matching Ribavirin 0 mg tablet orally twice a day for 12 weeks A1: DCV/ASV/BMS-791325+Placebo matching RBV (naive) Daclatasvir Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Placebo matching Ribavirin 0mg tablet orally twice a day for 12 weeks A1: DCV/ASV/BMS-791325+Placebo matching RBV (naive) Asunaprevir Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Placebo matching Ribavirin 0mg tablet orally twice a day for 12 weeks A2: DCV/ASV/BMS-791325 + RBV (naive) Daclatasvir Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Ribavirin 200mg tablet orally twice a day for 12 weeks A3: DCV/ASV/BMS-791325+Placebo matching RBV (experienced) Asunaprevir Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Placebo matching Ribavirin 0 mg tablet orally twice a day for 12 weeks A2: DCV/ASV/BMS-791325 + RBV (naive) Asunaprevir Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Ribavirin 200mg tablet orally twice a day for 12 weeks A2: DCV/ASV/BMS-791325 + RBV (naive) Ribavirin Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Ribavirin 200mg tablet orally twice a day for 12 weeks A3: DCV/ASV/BMS-791325+Placebo matching RBV (experienced) Daclatasvir Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Placebo matching Ribavirin 0 mg tablet orally twice a day for 12 weeks A4: DCV/ASV/BMS-791325 + RBV (experienced) Daclatasvir Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Ribavirin 200 mg tablet orally twice a day for 12 weeks, Weight based dosing: If \< 75 kg, 1000 mg per day (two 200 mg tablets in AM and three 200 mg tablets in PM); if ≥ 75 kg, 1200 mg per day (three 200 mg tablets in AM and three 200 mg tablets in PM), AM=in the morning, PM=in the evening A4: DCV/ASV/BMS-791325 + RBV (experienced) Asunaprevir Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Ribavirin 200 mg tablet orally twice a day for 12 weeks, Weight based dosing: If \< 75 kg, 1000 mg per day (two 200 mg tablets in AM and three 200 mg tablets in PM); if ≥ 75 kg, 1200 mg per day (three 200 mg tablets in AM and three 200 mg tablets in PM), AM=in the morning, PM=in the evening A4: DCV/ASV/BMS-791325 + RBV (experienced) Ribavirin Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Ribavirin 200 mg tablet orally twice a day for 12 weeks, Weight based dosing: If \< 75 kg, 1000 mg per day (two 200 mg tablets in AM and three 200 mg tablets in PM); if ≥ 75 kg, 1200 mg per day (three 200 mg tablets in AM and three 200 mg tablets in PM), AM=in the morning, PM=in the evening
- Primary Outcome Measures
Name Time Method Proportion of treated subjects in each of the naive arms with sustained virologic response (SVR12) Post treatment 12 week SVR12 is defined as Hepatitis C virus ribonucleic acid (HCV RNA) \< Limit of Quantification (LOQ) target detected or target not detected (LOQ TD/TND)
- Secondary Outcome Measures
Name Time Method Safety as measured by frequency of Serious Adverse Events(SAEs)and discontinuations due to Adverse Events(AEs) Up to end of treatment (week 12) + 7 days Proportion of subjects in each arm who achieve HCV RNA < LOQ TD/TND Weeks: 1, 2, 4, 6, 8, and 12; Post treatment Weeks 4 (SVR4), 8 (SVR8) and 24 (SVR24) Proportion of subjects in each arm who achieve HCV RNA < LOQ TND Weeks: 1, 2, 4, 6, 8, and 12; Post treatment Weeks 4 (SVR4), 8 (SVR8), 12 (SVR12) and 24 (SVR24) Proportion of subjects achieving SVR12 associated with HCV geno subtype 1a vs 1b Post treatment 12 Week Differences in rates of selected Grade 3 - 4 laboratory test result abnormalities Up to end of treatment (week 12) + 7 days Proportion of treated subjects in each of the experienced arms with SVR12 Post treatment 12 Week Proportion of subjects with anemia defined as Hg < 10 g/dL on-treatment and Hg ≥ 10 g/dL at baseline in each arm within each cohort Up to end of treatment (week 12) + 7 days Proportion of subjects in each arm achieving SVR12 associated with IL28B rs12979860 single nucleotide polymorphism(SNP) status (CC genotype or non-CC genotype) Post treatment 12 Week
Trial Locations
- Locations (27)
Scripps Clinic
🇺🇸La Jolla, California, United States
Binghamton Gastroenterology Associates
🇺🇸Binghamton, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Mt Vernon Endoscopy Center
🇺🇸Alexandria, Virginia, United States
Borland-Groover Clinic
🇺🇸Jacksonville, Florida, United States
Miami Research Associates
🇺🇸South Miami, Florida, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Digestive And Liver Disease Specialists
🇺🇸Norfolk, Virginia, United States
Dean Clinic
🇺🇸Madison, Wisconsin, United States
Local Institution
🇫🇷Paris Cedex, France
Medical Associates Research Group
🇺🇸San Diego, California, United States
Quest Clinical Research
🇺🇸San Francisco, California, United States
University Of Colorado Denver & Hospital
🇺🇸Aurora, Colorado, United States
Gastrointestinal Specialists Of Georgia
🇺🇸Marietta, Georgia, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Indiana University Health
🇺🇸Indianapolis, Indiana, United States
Kansas City Care Clinic
🇺🇸Kansas City, Missouri, United States
Kansas City Research Institute
🇺🇸Kansas City, Missouri, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Carolinas Center For Liver Disease
🇺🇸Statesville, North Carolina, United States
University Of Chicago
🇺🇸Chicago, Illinois, United States
Quality Medical Research Pllc
🇺🇸Nashville, Tennessee, United States
Asheville Gastroenterology Associates, Pa
🇺🇸Asheville, North Carolina, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Texas Liver Institute
🇺🇸San Antonio, Texas, United States
Lehigh Valley Health Network
🇺🇸Allentown, Pennsylvania, United States
Advanced Liver Therapies
🇺🇸Houston, Texas, United States