Study of pegInterferon Alfa-2a, Ribavirin, and Daclatasvir (BMS-790052) With or Without BMS-650032 for Participants in Some Hepatitis C Virus Trials

An Open-Label Re-Treatment Study With PegInterferon Alfa-2a, Ribavirin and BMS-790052 With or Without BMS-650032 for Subjects With Chronic Hepatitis C

The purpose of this study is to provide anti-hepatitis C virus drugs to patients who received placebo + peginterferon alfa-2a + ribavirin in prior Bristol-Myers Squibb (BMS) studies and determine whether addition of these drugs results in higher cure rates in patients who previously failed therapy. Approximately 100 genotype 1b patients who received placebo in BMS study NCT01428063 (AI447-028) will receive active drugs in this study.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus Infection
• Intervention / Treatment: Drug: Ribavirin; Drug: Daclatasvir; Drug: Asunaprevir; Drug: Pegylated interferon alfa-2a

Detailed Description

• Intervention Model:

  • Parallel: for all patients entering the trial
  • Cross-over: for genotype 1b patients rolling over from NCT01428063 (AI447-028) who require rescue therapy after initial treatment in this study
• Peginterferon alfa-2a
• Ribavirin
• Daclatasvir
• Asunaprevir

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1119
    • Local Institution
  • Buenos Aires
    • Ciudad De Buenos Aires, Buenos Aires, Argentina, C1121ABE
      • Local Institution
    • Ciudad De Buenos Aires, Buenos Aires, Argentina, C1181ACH
      • Local Institution
    • Prov. Buenos Aires, Buenos Aires, Argentina, 1629
      • Local Institution
  • Santa Fe
    • Prov De Santa Fe, Santa Fe, Argentina, 2000
      • Local Institution
• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Local Institution
    • Kogarah, New South Wales, Australia, 2218
      • Local Institution
    • Westmead Nsw, New South Wales, Australia, 2145
      • Local Institution
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution
  • Victoria
    • Clayton Vic, Victoria, Australia, 3168
      • Local Institution
    • Fitzroy, Victoria, Australia, 3065 VIC
      • Local Institution
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution
    • Melbourne, Victoria, Australia, 3004
      • Local Institution
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Local Institution
    • Perth, Western Australia, Australia, 6001
      • Local Institution
• Austria
  • Graz, Austria, 8036
    • Local Institution
  • Wien, Austria, 1090
    • Local Institution
• Canada
  • Quebec, Canada, G3K 2P8
    • Local Institution
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Local Institution
    • Victoria, British Columbia, Canada, V8V 3P9
      • Local Institution
  • Ontario
    • Toronto, Ontario, Canada, M6H 3M1
      • Local Institution
    • Toronto, Ontario, Canada, M5G 2N2
      • Local Institution
    • Toronto, Ontario, Canada, M5T 2S8
      • Local Institution
    • Vaughan, Ontario, Canada, L4L 4Y7
      • Local Institution
  • Quebec
    • Montreal, Quebec, Canada, H2L 4P9
      • Local Institution
    • Montreal, Quebec, Canada, H3T 1E2
      • Local Institution
• Denmark
  • Hvidovre, Denmark, 2650
    • Local Institution
• France
  • Bondy Cedex, France, 93143
    • Local Institution
  • Clichy Cedex, France, 92118
    • Local Institution
  • Creteil, France, 94000
    • Local Institution
  • Creteil, France, 94010
    • Local Institution
  • Lille, France, 59037
    • Local Institution
  • Lyon Cedex 02, France, 69288
    • Local Institution
  • Marseille Cedex 08, France, 13285
    • Local Institution
  • Montpellier Cedex 5, France, 34295
    • Local Institution
  • Nice Cedex 03, France, 06202
    • Local Institution
  • Paris Cedex 12, France, 75571
    • Local Institution
  • Paris Cedex 13, France, 75651
    • Local Institution
  • Paris Cedex 14, France, 75679
    • Local Institution
  • Toulouse, France, 31059
    • Local Institution
  • Toulouse Cedex 09, France, 31059
    • Local Institution
  • Vandoeuvre Cedex, France, 54511
    • Local Institution
  • Villejuif Cedex, France, 94804
    • Local Institution
• Germany
  • Berlin, Germany, 13353
    • Local Institution
  • Berlin, Germany, 12157
    • Local Institution
  • Bonn, Germany, 53105
    • Local Institution
  • Frankfurt, Germany, 60590
    • Local Institution
  • Hamburg, Germany, 20246
    • Local Institution
  • Hannover, Germany, 30625
    • Local Institution
  • Heidelberg, Germany, 69120
    • Local Institution
• Greece
  • Thesaloniki, Greece, 54639
    • Local Institution
• Ireland
  • Dublin, Ireland, DUBLIN 7
    • Local Institution
  • Dublin
    • Dublin 8, Dublin, Ireland
      • Local Institution
• Italy
  • Brescia, Italy, 25123
    • Local Institution
  • Cisanello (pisa), Italy, 56124
    • Local Institution
  • Messina, Italy, 98124
    • Local Institution
  • Milano, Italy, 20121
    • Local Institution
  • Pavia, Italy, 27100
    • Local Institution
  • Roma, Italy, 00161
    • Local Institution
  • Roma, Italy, 00149
    • Local Institution
  • Torino, Italy, 10126
    • Local Institution
  • Viale Del Policlinico, 155, Italy, 00161
    • Local Institution
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Local Institution
  • Busan, Korea, Republic of, 614-735
    • Local Institution
  • Busan, Korea, Republic of, 602-715
    • Local Institution
  • Daegu, Korea, Republic of, 700-721
    • Local Institution
  • Daegu, Korea, Republic of, 705-703
    • Local Institution
  • Gyeonggi-do, Korea, Republic of, 420-767
    • Local Institution
  • Seoul, Korea, Republic of, 120-752
    • Local Institution
  • Seoul, Korea, Republic of, 138-736
    • Local Institution
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • Local Institution
• New Zealand
  • Auckland, New Zealand, 92024
    • Local Institution
• Poland
  • Bialystok, Poland, 15-540
    • Local Institution
  • Wroclaw, Poland, 50-349
    • Local Institution
• Spain
  • Barcelona, Spain, 08036
    • Local Institution
• Sweden
  • Gothenburg, Sweden, SE-416 85
    • Local Institution
  • Stockholm, Sweden, 141 86
    • Local Institution
• Taiwan
  • Taichung, Taiwan, 40447
    • Local Institution
  • Taichung, Taiwan, 402
    • Local Institution
  • Taipei, Taiwan, 100
    • Local Institution
  • Taipei, Taiwan, 112
    • Local Institution
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SE5 9RS
      • Local Institution
    • London, Greater London, United Kingdom, SW17 0QT
      • Local Institution
    • London, Greater London, United Kingdom, NW3 2QG,
      • Local Institution
    • London, Greater London, United Kingdom, W2 1NY
      • Local Institution
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M8 5RB
      • Local Institution
  • Lanarkshire
    • Glasgow, Lanarkshire, United Kingdom, G12 0YN
      • Local Institution
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36116
      • Baptist Medical Center South
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • Los Angeles, California, United States, 90027
      • Scpmg/ Kaiser Permanente Los Angeles Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver and Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Hepatology Research at CTRB
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
    • Catonsville, Maryland, United States, 21228
      • Digestive Disease Associates, P.A.
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Manhasset, New York, United States, 11030
      • North Shore Long Island Jewish Health System
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Options Health Research, LLC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Nashville Medical Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Metropolitan Research
  • 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

Key Inclusion Criteria:

• Prior participation in any BMS-790052, BMS-650032, or BMS-791325 trial and assigned to control arm (pegIFNα-2a/ribavirin + placebo) during the trial
• Hepatitis C virus (HCV) genotype 1, 2, 3, or 4 (mixed genotypes are not permitted)
• HCV RNA viral load detectable

Key Exclusion Criteria:

• Discontinuation from a prior BMS HCV clinical trial due to a pegIFNα-2a/ribavirin-related event
• Any anti-HCV therapy following initial treatment with BMS-650032, BMS-790052, or BMS-791325
• Positive for hepatitis B infection (hepatitis B surface antigen) or HIV-1 or HIV-2 antibody at screening
• Evidence of medical condition associated with chronic liver disease other than HCV infection
• Evidence of decompensated cirrhosis based on radiologic criteria or biopsy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daclatasvir + Asunaprevir + PegIFNα-2a + Ribavirin; Patients received daclatasvir, 60-mg tablet, by mouth once daily + asunaprevir, 100-mg capsule or 200-mg tablet, by mouth twice daily + pegIFNα-2a, 180-μg solution, subcutaneously weekly + ribavirin, weight-based dosing (<75 kg=1000 mg once daily; >=75 kg=1200 mg once daily) for 24 weeks	Drug: Ribavirin; Other Names: Copegus®; Drug: Daclatasvir; Other Names: BMS-790052; Drug: Asunaprevir; Other Names: BMS-650032; Drug: Pegylated interferon alfa-2a; Other Names: pegIFNα-2a, Pegasys®
Experimental: Daclatasvir + PegIFNα-2a + Ribavirin; Patients received daclatasvir, (two 30-mg tablets or one 60-mg tablet, by mouth once daily) + pegIFNα-2a, 180-μg solution, subcutaneously weekly + ribavirin, weight-based dosing (<75 kg=1000 mg once daily; >=75 kg=1200 mg once daily) for 24 weeks	Drug: Ribavirin; Other Names: Copegus®; Drug: Daclatasvir; Other Names: BMS-790052; Drug: Pegylated interferon alfa-2a; Other Names: pegIFNα-2a, Pegasys®
Experimental: Daclatasvir + Asunaprevir; Patients received daclatasvir, 60-mg tablet, by mouth once daily + asunaprevir, 100-mg capsule, by mouth twice daily for 24 weeks	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
Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) for All Nonresponders With Genotype 1 Hepatitis C Virus (HCV)	SVR12 defined as HCV RNA<limit of quantitation at follow-up Week 12. Nonresponder (NR)=prior NR to pegIFN-2a or ribavirin.	Week 12 (Follow-up period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Other Than Genotype 1 With Sustained Virologic Response at Post Treatment Week 12 (SVR12)	SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected at follow-up Week 12.	Week 12 (Follow-up period)
Percentage of Participants With Rapid Virologic Response (RVR) at Post Treatment Week 4	RVR was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target not detected at Week 4.	Week 4
Percentage of Participants With Extended Rapid Virologic Response (eRVR)	eRVR was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target not detected at both weeks 4 and 12.	Week 4 and 12
Percentage of Participants With Complete Early Virologic Response (cEVR)	cEVR was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target not detected at week 12.	Week 12
Percentage of Participants With End of the Treatment Response (EOTR)	EOTR was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target not detected at end of treatment.	End of the study (Week 24)
Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24)	SVR24 was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected at follow-up week 24.	Week 24 (Follow-up)
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Who Died During the Study	AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization.	For AEs: Day 1 until last visit. For SAEs: Day 1 until 30 days post discontinuation of dosing or participation

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: September 1, 2011
• First Submitted That Met QC Criteria: September 1, 2011
• First Posted (Estimate): September 2, 2011

Study Record Updates

• Last Update Posted (Estimate): May 27, 2016
• Last Update Submitted That Met QC Criteria: April 21, 2016
• Last Verified: April 1, 2016

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; Hepatitis A; Hepatitis C; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Protease Inhibitors; Interferons; Interferon-alpha; Ribavirin; Peginterferon alfa-2a; Interferon alpha-2; Asunaprevir
• Other Study ID Numbers: AI444-026; 2011-000836-27 (EudraCT Number)