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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01973049
First received: October 25, 2013
Last updated: September 23, 2015
Last verified: September 2015
  Purpose
To demonstrate the effectiveness of DCV 3DAA fixed dose combination with or without Ribavirin in treatment naive cirrhotic subjects.

Condition Intervention Phase
Hepatitis C
Drug: Daclatasvir
Drug: Asunaprevir
Drug: BMS-791325
Drug: Ribavirin
Drug: Placebo matching Ribavirin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3 Evaluation of a Daclatasvir/Asunaprevir/BMS-791325 Fixed Dose Combination in Subjects With Genotype 1 Chronic Hepatitis C and Compensated Cirrhosis

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Proportion of treated subjects in each of the naive arms with sustained virologic response (SVR12) [ Time Frame: Post treatment 12 week ] [ Designated as safety issue: No ]
    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:
  • Proportion of treated subjects in each of the experienced arms with SVR12 [ Time Frame: Post treatment 12 Week ] [ Designated as safety issue: No ]
  • Proportion of subjects in each arm who achieve HCV RNA < LOQ TD/TND [ Time Frame: Weeks: 1, 2, 4, 6, 8, and 12; Post treatment Weeks 4 (SVR4), 8 (SVR8) and 24 (SVR24) ] [ Designated as safety issue: No ]
  • Proportion of subjects in each arm who achieve HCV RNA < LOQ TND [ Time Frame: Weeks: 1, 2, 4, 6, 8, and 12; Post treatment Weeks 4 (SVR4), 8 (SVR8), 12 (SVR12) and 24 (SVR24) ] [ Designated as safety issue: No ]
  • Safety as measured by frequency of Serious Adverse Events(SAEs)and discontinuations due to Adverse Events(AEs) [ Time Frame: Up to end of treatment (week 12) + 7 days ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: Up to end of treatment (week 12) + 7 days ] [ Designated as safety issue: Yes ]
  • Differences in rates of selected Grade 3 - 4 laboratory test result abnormalities [ Time Frame: Up to end of treatment (week 12) + 7 days ] [ Designated as safety issue: Yes ]
  • Proportion of subjects achieving SVR12 associated with HCV geno subtype 1a vs 1b [ Time Frame: Post treatment 12 Week ] [ Designated as safety issue: No ]
  • Proportion of subjects in each arm achieving SVR12 associated with IL28B rs12979860 single nucleotide polymorphism(SNP) status (CC genotype or non-CC genotype) [ Time Frame: Post treatment 12 Week ] [ Designated as safety issue: No ]

Enrollment: 202
Study Start Date: December 2013
Study Completion Date: November 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Daclatasvir
Other Name: BMS-790052
Drug: Asunaprevir
Other Name: BMS-650032
Drug: BMS-791325 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: Daclatasvir
Other Name: BMS-790052
Drug: Asunaprevir
Other Name: BMS-650032
Drug: BMS-791325 Drug: Ribavirin
Other Name: Ribasphere®
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: Daclatasvir
Other Name: BMS-790052
Drug: Asunaprevir
Other Name: BMS-650032
Drug: BMS-791325 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: Daclatasvir
Other Name: BMS-790052
Drug: Asunaprevir
Other Name: BMS-650032
Drug: BMS-791325 Drug: Ribavirin
Other Name: Ribasphere®

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01973049

  Show 49 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01973049     History of Changes
Other Study ID Numbers: AI443-113  2013-002458-66 
Study First Received: October 25, 2013
Last Updated: September 23, 2015
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: National Health and Medical Research Council
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United States: Institutional Review Board

Additional relevant MeSH terms:
Hepatitis, Chronic
Hepatitis C
Fibrosis
Hepatitis
Hepatitis A
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Pathologic Processes
Enterovirus Infections
Picornaviridae Infections
Ribavirin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 28, 2016