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

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

Sponsors

Lead sponsor: Bristol-Myers Squibb

Source 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.

Overall Status Completed
Start Date December 2013
Completion Date November 2014
Primary Completion Date August 2014
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Proportion of treated subjects in each of the naive arms with sustained virologic response (SVR12) Post treatment 12 week
Secondary 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
Enrollment 202
Condition
Intervention

Intervention type: Drug

Intervention name: Daclatasvir

Other name: BMS-790052

Intervention type: Drug

Intervention name: Asunaprevir

Other name: BMS-650032

Intervention type: Drug

Intervention name: BMS-791325

Intervention type: Drug

Intervention name: Ribavirin

Other name: Ribasphere®

Intervention type: Drug

Intervention name: Placebo matching Ribavirin

Eligibility

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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

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

Australia

Canada

France

United States

Verification Date

September 2015

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Arm group label: A1: DCV/ASV/BMS-791325+Placebo matching RBV (naive)

Arm group type: Experimental

Description: 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

Arm group label: A2: DCV/ASV/BMS-791325 + RBV (naive)

Arm group type: Experimental

Description: 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

Arm group label: A3: DCV/ASV/BMS-791325+Placebo matching RBV (experienced)

Arm group type: Experimental

Description: 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

Arm group label: A4: DCV/ASV/BMS-791325 + RBV (experienced)

Arm group type: Experimental

Description: 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

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov