A Study of BMS-824393 in Combination With Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment Naive Subjects With Chronic Hepatitis C Virus Genotype I

A Randomized, Placebo-controlled, Phase 2a Study of BMS-824393 in Combination With Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment Naive Subjects With Chronic Hepatitis C Virus Genotype I

Based on 12-week on-treatment data, at least 1 dose of BMS-824393 can be identified which is safe, well tolerated, and has sufficient antiviral activity to progress to late stage clinical trials when combined with pegIFNα/RBV for treatment of chronically infected hepatitis C virus genotype 1 treatment-naive subjects.

Study Overview

• Status: Withdrawn
• Conditions: Chronic Hepatitis C Virus Genotype 1
• Intervention / Treatment: Drug: BMS-824393; Drug: BMS-824393; Drug: BMS-824393; Drug: Peginterferon Alpha-2a; Drug: Ribavirin; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Coronado, California, United States, 92118
      • Local Institution
    • San Diego, California, United States, 92105
      • Research and Education, Inc.
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Bradenton, Florida, United States, 34209
      • Bach and Godofsky Infectious Diseases
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Tamarac, Florida, United States, 33319
      • Vita Medical Center & Research Solutions, Inc.
  • Georgia
    • Mareitta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia PC
  • Maryland
    • Laurel, Maryland, United States, 20707
      • Maryland Digestive Disease Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Local Institution
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Liver Institute of Virginia Bon Secours Health System

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:

• Treatment-naive subjects with genotype 1 chronic HCV
• HCV RNA ≥ 100,000 IU/mL at screening
• Seronegative for HIV and HBsAg
• Liver biopsy within prior 2 years demonstrating no cirrhosis

Exclusion Criteria:

• Any evidence of liver disease other than hepatitis C
• Diagnosed or suspected hepatocellular carcinoma
• Laboratory values: neutrophil count < 1500 cells/μL, platelet count < 90,000/μL; Hemoglobin ≤ 12 g/dL (120g/L) for women and ≤ 13 g/dL (130 g/L) for men
• Cirrhosis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMS-824393 (10mg); Plus Peginterferon Alfa-2a and Ribavirin Day 1 - Week 12	Drug: BMS-824393; Capsule, Oral, 10 mg, once daily; Drug: BMS-824393; Capsule, Oral, 30 mg, once daily; Drug: BMS-824393; Capsule, Oral, 100 mg, once daily; Drug: Peginterferon Alpha-2a; Syringe, subcutaneous 180 mcg/0.5 mL, weekly; Other Names: Pegasys; Drug: Ribavirin; Tablet, Oral, 400 or 600 mg based on weight (am) and 600 mg (pm), twice daily; Other Names: Copegus
Experimental: BMS-824393 (30 mg); Plus Peginterferon Alfa-2a and Ribavirin Day 1 - Week 12	Drug: BMS-824393; Capsule, Oral, 10 mg, once daily; Drug: BMS-824393; Capsule, Oral, 30 mg, once daily; Drug: BMS-824393; Capsule, Oral, 100 mg, once daily; Drug: Peginterferon Alpha-2a; Syringe, subcutaneous 180 mcg/0.5 mL, weekly; Other Names: Pegasys; Drug: Ribavirin; Tablet, Oral, 400 or 600 mg based on weight (am) and 600 mg (pm), twice daily; Other Names: Copegus
Experimental: BMS-824393 (100 mg); Plus Peginterferon Alfa-2a and Ribavirin Day 1 - Week 12	Drug: BMS-824393; Capsule, Oral, 10 mg, once daily; Drug: BMS-824393; Capsule, Oral, 30 mg, once daily; Drug: BMS-824393; Capsule, Oral, 100 mg, once daily; Drug: Peginterferon Alpha-2a; Syringe, subcutaneous 180 mcg/0.5 mL, weekly; Other Names: Pegasys; Drug: Ribavirin; Tablet, Oral, 400 or 600 mg based on weight (am) and 600 mg (pm), twice daily; Other Names: Copegus
Placebo Comparator: Placebo; Plus Peginterferon Alfa-2a and Ribavirin Day 1 - Week 12	Drug: Peginterferon Alpha-2a; Syringe, subcutaneous 180 mcg/0.5 mL, weekly; Other Names: Pegasys; Drug: Ribavirin; Tablet, Oral, 400 or 600 mg based on weight (am) and 600 mg (pm), twice daily; Other Names: Copegus; Drug: Placebo; Capsule, Oral, 0 mg, once daily
Other: Peginterferon alfa-2a plus Ribavirin; Weeks 13 - 48	Drug: Peginterferon Alpha-2a; Syringe, subcutaneous 180 mcg/0.5 mL, weekly; Other Names: Pegasys; Drug: Ribavirin; Tablet, Oral, 400 or 600 mg based on weight (am) and 600 mg (pm), twice daily; Other Names: Copegus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety as measured by the frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs)	Week 4
Safety as measured by the frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs)	Week 12
Safety as measured by the frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs)	Week 24
Safety as measured by the frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs)	Week 48
Antiviral activity as determined by the proportion of subjects with extended rapid virologic response (eRVR) defined as undetectable HCV RNA	Week 4
Antiviral activity as determined by the proportion of subjects with extended rapid virologic response (eRVR) defined as undetectable HCV RNA	Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with rapid virologic response (RVR), defined as undetectable RNA	Week 4
Proportion of subjects with complete early virologic response (cEVR), defined as undetectable HCV RNA	Week 12
Proportion of subjects with a sustained virologic response (SVR), defined as HCV RNA undetectable	Week 12 (SVR12)
Proportion of subjects with a sustained virologic response (SVR), defined as HCV RNA undetectable	Week 24 (SVR24)
Resistant variants associated with virologic failure	Week 4
Resistant variants associated with virologic failure	Week 12
Resistant variants associated with virologic failure	Follow up Week 12
Resistant variants associated with virologic failure	Week 24

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Anticipated): December 1, 2010
• Study Completion (Anticipated): December 1, 2010

Study Registration Dates

• First Submitted: June 3, 2010
• First Submitted That Met QC Criteria: June 10, 2010
• First Posted (Estimate): June 11, 2010

Study Record Updates

• Last Update Posted (Estimate): March 15, 2011
• Last Update Submitted That Met QC Criteria: March 14, 2011
• Last Verified: March 1, 2011

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; Hepatitis, Chronic; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2a
• Other Study ID Numbers: AI451-004; 2010-018702-36 (EudraCT Number)