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

A Phase 3 Evaluation of a Daclatasvir/Asunaprevir/BMS-791325 Fixed Dose Combination in Subjects With Genotype 1 Chronic Hepatitis C and Compensated Cirrhosis

To demonstrate the effectiveness of DCV 3DAA fixed dose combination with or without Ribavirin in treatment naive cirrhotic subjects.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: BMS-791325; Drug: Ribavirin; Drug: Daclatasvir; Drug: Asunaprevir; Drug: Placebo matching Ribavirin

Detailed Description

Masking is Double blind for RBV: two or more parties are unaware of the intervention assignment.

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Local Institution
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Local Institution
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution
    • Fitzroy, Victoria, Australia, 3065
      • Local Institution
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Local Institution
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Local Institution
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1H2
      • Local Institution
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • Local Institution
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Local Institution
    • Victoria, British Columbia, Canada, V8V 3P9
      • Local Institution
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Local Institution
    • Toronto, Ontario, Canada, M6H 3M1
      • Local Institution
  • Quebec
    • Montreal, Quebec, Canada, H2L 4P9
      • Local Institution
    • Montreal, Quebec, Canada, H2X 2P4
      • Local Institution
    • Montreal, Quebec, Canada, H3A 1T1
      • Local Institution
• France
  • Creteil, France, 94010
    • Local Institution
  • Marseille Cedex 08, France, 13285
    • Local Institution
  • Montpellier, France, 34000
    • Local Institution
  • Nice Cedex 03, France, 06202
    • Local Institution
  • Paris Cedex, France, 75013
    • Local Institution
  • Paris Cedex 12, France, 75571
    • Local Institution
• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • San Diego, California, United States, 92123
      • Medical Associates Research Group
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University Of Colorado Denver & Hospital
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Borland-Groover Clinic
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Kansas City Care Clinic
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute
  • New York
    • Binghamton, New York, United States, 13903
      • Binghamton Gastroenterology Associates
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates, PA
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Statesville, North Carolina, United States, 28677
      • Carolinas Center For Liver Disease
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18102
      • Lehigh Valley Health Network
  • Tennessee
    • Nashville, Tennessee, United States, 37211
      • Quality Medical Research PLLC
  • Texas
    • Houston, Texas, United States, 77030
      • Advanced Liver Therapies
    • San Antonio, Texas, United States, 78215
      • Texas Liver Institute
  • Virginia
    • Alexandria, Virginia, United States, 22306
      • Mt Vernon Endoscopy Center
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • Dean Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A1: DCV/ASV/BMS-791325+Placebo matching RBV (naive); 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	Drug: BMS-791325; Drug: Daclatasvir; Other Names: BMS-790052; Drug: Asunaprevir; Other Names: BMS-650032; Drug: Placebo matching Ribavirin
Experimental: A2: DCV/ASV/BMS-791325 + RBV (naive); 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	Drug: BMS-791325; Drug: Ribavirin; Other Names: Ribasphere®; Drug: Daclatasvir; Other Names: BMS-790052; Drug: Asunaprevir; Other Names: BMS-650032
Experimental: A3: DCV/ASV/BMS-791325+Placebo matching RBV (experienced); 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	Drug: BMS-791325; Drug: Daclatasvir; Other Names: BMS-790052; Drug: Asunaprevir; Other Names: BMS-650032; Drug: Placebo matching Ribavirin
Experimental: A4: DCV/ASV/BMS-791325 + RBV (experienced); 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	Drug: BMS-791325; Drug: Ribavirin; Other Names: Ribasphere®; Drug: Daclatasvir; Other Names: BMS-790052; Drug: Asunaprevir; Other Names: BMS-650032

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of treated subjects in each of the naive arms with sustained virologic response (SVR12)	SVR12 is defined as Hepatitis C virus ribonucleic acid (HCV RNA) < Limit of Quantification (LOQ) target detected or target not detected (LOQ TD/TND)	Post treatment 12 week

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of treated subjects in each of the experienced arms with SVR12	Post treatment 12 Week
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)
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 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
Differences in rates of selected Grade 3 - 4 laboratory test result abnormalities	Up to end of treatment (week 12) + 7 days
Proportion of subjects achieving SVR12 associated with HCV geno subtype 1a vs 1b	Post treatment 12 Week
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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Muir AJ, Poordad F, Lalezari J, Everson G, Dore GJ, Herring R, Sheikh A, Kwo P, Hezode C, Pockros PJ, Tran A, Yozviak J, Reau N, Ramji A, Stuart K, Thompson AJ, Vierling J, Freilich B, Cooper J, Ghesquiere W, Yang R, McPhee F, Hughes EA, Swenson ES, Yin PD. Daclatasvir in combination with asunaprevir and beclabuvir for hepatitis C virus genotype 1 infection with compensated cirrhosis. JAMA. 2015 May 5;313(17):1736-44. doi: 10.1001/jama.2015.3868.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: October 25, 2013
• First Submitted That Met QC Criteria: October 30, 2013
• First Posted (Estimate): October 31, 2013

Study Record Updates

• Last Update Posted (Estimate): October 9, 2015
• Last Update Submitted That Met QC Criteria: September 23, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Ribavirin; Asunaprevir
• Other Study ID Numbers: AI443-113; 2013-002458-66 (EudraCT Number)