Study of BMS-650032 With Peginterferon Alfa-2a Plus Ribavirin

A Phase 2a/2b Study of BMS-650032 in Combination With Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment-Naive Subjects With Genotypes 1 and 4 Chronic Hepatitis C Infection

The purpose of this study is to identify one or more doses of BMS-650032 that, when used in combination with pegylated-interferon alpha and ribavirin are safe and demonstrate sufficient activity against hepatitis C virus (Genotypes 1 and 4).

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus
• Intervention / Treatment: Drug: BMS-650032; Drug: BMS-650032; Drug: Peginterferon Alfa-2a; Drug: Peginterferon Alfa-2a; Drug: Ribavirin; Drug: Ribavirin; Drug: Placebo; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 285
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1181
    • Local Institution
  • Buenos Aires
    • Ciudad De Buenos Aires, Buenos Aires, Argentina, C1121ABE
      • Local Institution
    • Prov. Buenos Aires, Buenos Aires, Argentina, 1629
      • Local Institution
  • Santa Fe
    • Prov De Santa Fe, Santa Fe, Argentina, 2000
      • Local Institution
• France
  • Creteil Cedex, France, 94010
    • Local Institution
  • Marseille Cedex 08, France, 13285
    • Local Institution
  • Montpellier Cedex 5, France, 34295
    • Local Instituition
  • Paris Cedex 13, France, 75651
    • Local Institution
  • Paris Cedex 14, France, 75679
    • Local Institution
  • Vandoeuvre Les Nancy, France, 54511
    • Local Institution
• Germany
  • Frankfurt, Germany, 60590
    • Local Institution
  • Heidelberg, Germany, 69120
    • Local Institution
  • Mainz, Germany, 55131
    • Local Institution
  • Wurzburg, Germany, 97080
    • Local Institution
• Ireland
  • Dublin, Ireland, DUBLIN 7
    • Local Institution
• Italy
  • Torino, Italy, 10126
    • Local Institution
• Spain
  • Alicante, Spain, 03010
    • Local Institution
  • Barcelona, Spain, 08035
    • Local Institution
  • Madrid, Spain, 28222
    • Local Institution
  • Malaga, Spain, 29010
    • Local Institution
  • Valencia, Spain, 46010
    • Local Institution
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SE5 9RS
      • Local Institution
    • London, Greater London, United Kingdom, W2 1NY
      • Local Institution
    • London, Greater London, United Kingdom, E1 2AT
      • 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
    • Birmingham, Alabama, United States, 35294-0006
      • University of Alabama at Birmingham
    • Montgomery, Alabama, United States, 36116
      • Alabama Liver & Digestive Specialists (Alds)
  • Florida
    • Orlando, Florida, United States, 32804
      • Florida Hospital Transplant Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
  • Massachusetts
    • Springfield, Massachusetts, United States, 01105
      • The Research Institute
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center
  • New York
    • Bronx, New York, United States, 10468
      • James J Peters VAMC
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina, Chapel Hill
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135-2920
      • Healthcare Research Consultants
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Science Univ
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
  • 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 to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects chronically infected with HCV genotype 1 (Phase 2a and Phase 2b)
• Subjects chronically infected with HCV genotype 4 (Phase 2b only)
• HCV RNA viral load of ≥ 10*5* IU/mL at screening
• BMI of 18 - 35 kg/m² at screening

Exclusion Criteria:

• Cirrhosis (Phase 2a only)
• Decompensated cirrhosis (Phase 2b)
• Co-infection with HBV or HIV
• Hepatocellular carcinoma
• Prior treatment with anti-HCV drugs

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2a: Arm 1	Drug: BMS-650032; Tablets, Oral, 200 mg, Twice Daily, 48 weeks; Drug: BMS-650032; Tablets, Oral, 200 mg, Twice Daily, 12 or 24 weeks, depending on response; Drug: Peginterferon Alfa-2a; Syringe, Subcutaneous injection, 180 mcg / 0.5 mL, Weekly, 48 weeks; Other Names: Pegasys; Drug: Peginterferon Alfa-2a; Syringe, Subcutaneous injection, 180 mcg / 0.5 mL, Weekly, 24 or 48 weeks, depending on response; Other Names: Pegasys; Drug: Ribavirin; Tablet, Oral, 500 or 600 mg based on weight, Twice Daily, 48 weeks; Other Names: Copegus; Drug: Ribavirin; Tablet, Oral, 500 or 600 mg based on weight, Twice Daily, 24 or 48 weeks depending on response; Other Names: Pegasys
Placebo Comparator: Phase 2a: Arm 2	Drug: Peginterferon Alfa-2a; Syringe, Subcutaneous injection, 180 mcg / 0.5 mL, Weekly, 48 weeks; Other Names: Pegasys; Drug: Peginterferon Alfa-2a; Syringe, Subcutaneous injection, 180 mcg / 0.5 mL, Weekly, 24 or 48 weeks, depending on response; Other Names: Pegasys; Drug: Ribavirin; Tablet, Oral, 500 or 600 mg based on weight, Twice Daily, 48 weeks; Other Names: Copegus; Drug: Ribavirin; Tablet, Oral, 500 or 600 mg based on weight, Twice Daily, 24 or 48 weeks depending on response; Other Names: Pegasys; Drug: Placebo; Tablets, Oral, 0 mg, twice daily, 48 weeks; Other Names: Pegasys; Drug: Placebo; Tablets, Oral, 0 mg, twice daily, 0 or 12 weeks (depending on response) beginning at Week 12; Drug: Placebo; Tablets, Oral, 0 mg, twice daily 24 weeks
Experimental: Phase 2b: Arm 1	Drug: BMS-650032; Tablets, Oral, 200 mg, Twice Daily, 48 weeks; Drug: BMS-650032; Tablets, Oral, 200 mg, Twice Daily, 12 or 24 weeks, depending on response; Drug: Peginterferon Alfa-2a; Syringe, Subcutaneous injection, 180 mcg / 0.5 mL, Weekly, 48 weeks; Other Names: Pegasys; Drug: Peginterferon Alfa-2a; Syringe, Subcutaneous injection, 180 mcg / 0.5 mL, Weekly, 24 or 48 weeks, depending on response; Other Names: Pegasys; Drug: Ribavirin; Tablet, Oral, 500 or 600 mg based on weight, Twice Daily, 48 weeks; Other Names: Copegus; Drug: Ribavirin; Tablet, Oral, 500 or 600 mg based on weight, Twice Daily, 24 or 48 weeks depending on response; Other Names: Pegasys; Drug: Placebo; Tablets, Oral, 0 mg, twice daily, 48 weeks; Other Names: Pegasys; Drug: Placebo; Tablets, Oral, 0 mg, twice daily, 0 or 12 weeks (depending on response) beginning at Week 12; Drug: Placebo; Tablets, Oral, 0 mg, twice daily 24 weeks
Placebo Comparator: Phase 2b: Arm 2	Drug: Peginterferon Alfa-2a; Syringe, Subcutaneous injection, 180 mcg / 0.5 mL, Weekly, 48 weeks; Other Names: Pegasys; Drug: Peginterferon Alfa-2a; Syringe, Subcutaneous injection, 180 mcg / 0.5 mL, Weekly, 24 or 48 weeks, depending on response; Other Names: Pegasys; Drug: Ribavirin; Tablet, Oral, 500 or 600 mg based on weight, Twice Daily, 48 weeks; Other Names: Copegus; Drug: Ribavirin; Tablet, Oral, 500 or 600 mg based on weight, Twice Daily, 24 or 48 weeks depending on response; Other Names: Pegasys; Drug: Placebo; Tablets, Oral, 0 mg, twice daily, 48 weeks; Other Names: Pegasys; Drug: Placebo; Tablets, Oral, 0 mg, twice daily, 0 or 12 weeks (depending on response) beginning at Week 12; Drug: Placebo; Tablets, Oral, 0 mg, twice daily 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 2a and Phase 2b: Safety, as measured by the frequency of SAEs and discontinuations due to AEs	12 weeks after first dose
Antiviral activity as determined by proportion of HCV genotype 1 subjects with extended rapid virologic response (eRVR), defined as undetectable HCV RNA	Week 4
Antiviral activity as determined by proportion of HCV genotype 1 subjects with extended rapid virologic response (eRVR), defined as undetectable HCV RNA	Week 12
Phase 2b only: Antiviral activity, as determined by the proportion of HCV genotype 1 subjects with 24-week sustained virologic response (SVR24), defined as undetectable HCV RNA	at follow-up Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of HCV genotype 1 subjects with rapid virologic response (RVR), defined as undetectable HCV RNA at Week 4	Week 4
Proportion of HCV genotype 1 subjects with complete early rapid virologic response (eEVR), defined as undetectable HCV RNA at Week 12 (Stage 2 only)	at Week 12 (Stage 2 only)
Proportion of HCV genotype 1 subjects with early virologic response (EVR) defined as ≥2 log10 decrease in HCV RNA from baseline at Week 12 (Stage 1 only)	Week 12 (Stage 1 only)
Proportion of HCV genotype 1 subjects with 12-week sustained virologic response (SVR12), defined as undetectable HCV RNA at follow-up Week 12	follow-up Week 12
Proportion of HCV genotype 1 subjects with 24-week sustained virologic response (SVR24) defined as undetectable HCV RNA at follow-up Week 24 (Stage 1 only)	follow-up Week 24 (Stage 1 only)
Resistant variants associated with virologic failure	48 weeks after last dose

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Bronowicki JP, Ratziu V, Gadano A, Thuluvath PJ, Bessone F, Martorell CT, Pol S, Terg R, Younes Z, He B, Eley T, Cohen D, Yu F, Hernandez D, McPhee F, Mendez P, Hughes E. Randomized trial of asunaprevir plus peginterferon alfa and ribavirin for previously untreated genotype 1 or 4 chronic hepatitis C. J Hepatol. 2014 Dec;61(6):1220-7. doi: 10.1016/j.jhep.2014.07.011. Epub 2014 Jul 16.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: December 10, 2009
• First Submitted That Met QC Criteria: December 10, 2009
• First Posted (Estimate): December 11, 2009

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; Hepatitis; Hepatitis C; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites; Immunologic Factors; Protease Inhibitors; Interferon-alpha; Ribavirin; Peginterferon alfa-2a; Asunaprevir
• Other Study ID Numbers: AI447-016; 2009-013652-69 (Registry Identifier: EUDRACT)