Study in Genotype 2 or 3 Patients With Chronic Hepatitis Virus Infection

A Phase 2B Pilot Study of Short-Term Treatment of BMS-790052 in Combination With Peg-Interferon Alfa-2a and Ribavirin in Treatment Naive Subjects With Chronic Hepatitis C Genotype 2 or 3 Infection

To identify a shorter duration of antiviral therapy (12 or 16 weeks) for the combination of daclatasvir with pegylated interferon alfa-2a and ribavirin.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia, NSW 2050
    • Local Institution
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • 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
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Local Institution
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Local Institution
    • Edmonton, Alberta, Canada, T6G 2B7
      • Local Institution
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Local Institution
    • Victoria, British Columbia, Canada, V8V 3P9
      • Local Institution
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
      • Local Institution
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Local Institution
• Denmark
  • Hvidovre, Denmark, 2650
    • Local Institution
• France
  • Creteil, France, 94000
    • Local Institution
  • Lille Cedex, France, 59037
    • Local Institution
  • Montpellier Cedex 5, France, 34295
    • Local Institution
  • Nice Cedex 03, France, 06202
    • Local Institution
  • Paris Cedex 14, France, 75679
    • Local Institution
  • Pessac, France, 33604
    • Local Institution
• Italy
  • Brescia, Italy, 25123
    • Local Institution
  • Cisanello (pisa), Italy, 56124
    • Local Institution
  • Viale Del Policlinico, 155, Italy, 00161
    • Local Institution
• United States
  • California
    • Los Angeles, California, United States, 90048
      • California Liver Institute
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Digestive Disease Associates, P.A.
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Options Health Research, LLC
  • Texas
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research

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

Key Inclusion Criteria:

• Participants chronically infected with hepatitis C virus (HCV) genotype 2 or 3
• No previous exposure to an interferon formulation (ie, interferon alfa, pegylated interferon alfa-2a ) or ribavirin
• Body mass index (BMI) of 18 to 35 kg/m^2, inclusive. BMI=weight (kg)/height (m)^2
• Males and females, 18 - 70 years of age

Key Exclusion Criteria:

• Liver transplant recipients
• Documented or suspected hepatocellular carcinoma
• Evidence of decompensated cirrhosis
• History of chronic hepatitis B virus (HBV). Patients with resolved HBV infection may participate
• Current or known history of cancer
• Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug
• Inability to tolerate oral medication
• Poor venous access
• Severe psychiatric disease
• History of chronic pulmonary disease
• History of cardiomyopathy, coronary artery disease (including angina), interventive procedure for coronary artery disease (including angioplasty, stent procedure, or cardiac bypass surgery), ventricular arrhythmia,, or other clinically significant cardiac disease
• History of or current electrocardiogram findings indicative of cardiovascular instability
• Preexisting ophthalmologic disorders considered clinically significant on eye
• History of uncontrolled diabetes mellitus
• Any known contraindication to pegylated interferon alfa-2a or ribavirin not otherwise specified.
• Positive hepatitis B virus surface antigen, HIV-1 or HIV-2 Ab
• Prior exposure to any HCV direct antiviral agent (eg, HCV protease, polymerase, previous nonstructural protein 5A inhibitors)
• Exposure to any investigational drug or placebo

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Placebo + Pegylated interferon alfa-2a + Ribavirin	Drug: Placebo; Tablets, oral, 0 mg, once daily, for 24 weeks; Drug: Pegylated interferon alfa-2a; Solution for injection, subcutaneous injection, 180 µg/0.5 mL, once weekly, for 12, 16, or 24 weeks; Other Names: Pegasys®; Drug: Ribavirin; Tablets, oral, 800 mg, twice daily, for 12, 16, or 24 weeks; Other Names: Copegus®
Experimental: 12 Week Cohort; Daclatasvir + Pegylated interferon alfa-2a + Ribavirin	Drug: Pegylated interferon alfa-2a; Solution for injection, subcutaneous injection, 180 µg/0.5 mL, once weekly, for 12, 16, or 24 weeks; Other Names: Pegasys®; Drug: Ribavirin; Tablets, oral, 800 mg, twice daily, for 12, 16, or 24 weeks; Other Names: Copegus®; Drug: Daclatasvir; Tablets, oral, 60 mg, once daily, for 12, 16, or 24 weeks; Other Names: BMS-790052
Experimental: 16 Week Cohort; Daclatasvir + Pegylated interferon alfa-2a + Ribavirin	Drug: Pegylated interferon alfa-2a; Solution for injection, subcutaneous injection, 180 µg/0.5 mL, once weekly, for 12, 16, or 24 weeks; Other Names: Pegasys®; Drug: Ribavirin; Tablets, oral, 800 mg, twice daily, for 12, 16, or 24 weeks; Other Names: Copegus®; Drug: Daclatasvir; Tablets, oral, 60 mg, once daily, for 12, 16, or 24 weeks; Other Names: BMS-790052

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 2	SVR24 was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at follow-up Week 24. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.	Follow-up Week 24
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 3	SVR24 was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at follow-up Week 24. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.	Follow-up Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 2	RVR was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at Week 4. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.	Week 4
Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 3	RVR was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at Week 4. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.	Week 4
Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 2	cEVR was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at Week 12. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.	Week 12
Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 3	cEVR was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at Week 12. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.	Week 12
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 2	SVR12 was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at follow-up Week 12. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.	Follow-up Week 12
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 3	SVR12 was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at follow-up Week 12. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.	Follow-up Week 12
Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2	Virologic failure was defined as: Virologic breakthrough: confirmed >1 log10 increase in HCV RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA <LLOQ, target not detected (TND) while on treatment; <1 log10 decrease in HCV RNA from baseline at Week 4 of treatment; Failure to achieve early virologic response: <2 log10 decrease in HCV RNA from baseline and HCV RNA ≥LLOQ at Week 12 of treatment; HCV RNA ≥LLOQ or <LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation); Relapse, defined as HCV RNA ≥LLOQ or <LLOQ, TD during follow-up, after HCV RNA <LLOQ, TND at EOT. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.	Baseline up to Week 48
Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3	Virologic failure was defined as: Virologic breakthrough: confirmed >1 log10 increase in HCV RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA <LLOQ, target not detected (TND) while on treatment; <1 log10 decrease in HCV RNA from baseline at Week 4 of treatment; Failure to achieve early virologic response: <2 log10 decrease in HCV RNA from baseline and HCV RNA ≥LLOQ at Week 12 of treatment; HCV RNA ≥LLOQ or <LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation); Relapse, defined as HCV RNA ≥LLOQ or <LLOQ, TD during follow-up, after HCV RNA <LLOQ, TND at EOT. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.	Baseline up to Week 48
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period	AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has 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. Treatment-related AE was defined as an AE that had certain, probable, possible, or unknown relationship to study drug. Mild (Grade 1): awareness of event but easily tolerated; Moderate (Grade 2): discomfort enough to cause some interference with usual activity; Severe (Grade 3): inability to carry out usual activity; Very severe (Grade 4): debilitating, significantly incapacitates participant despite symptomatic therapy. Only Grade 2-4 treatment-related AEs were reported.	Baseline (Day 1) up to 24 weeks (treatment period)
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period	AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has 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.	From end of treatment period up to Week 48 (follow-up period)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Dore GJ, Lawitz E, Hezode C, Shafran SD, Ramji A, Tatum HA, Taliani G, Tran A, Brunetto MR, Zaltron S, Strasser SI, Weis N, Ghesquiere W, Lee SS, Larrey D, Pol S, Harley H, George J, Fung SK, de Ledinghen V, Hagens P, McPhee F, Hernandez D, Cohen D, Cooney E, Noviello S, Hughes EA. Daclatasvir plus peginterferon and ribavirin is noninferior to peginterferon and ribavirin alone, and reduces the duration of treatment for HCV genotype 2 or 3 infection. Gastroenterology. 2015 Feb;148(2):355-366.e1. doi: 10.1053/j.gastro.2014.10.007. Epub 2014 Oct 13.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: December 1, 2010
• First Submitted That Met QC Criteria: December 8, 2010
• First Posted (Estimate): December 9, 2010

Study Record Updates

• Last Update Posted (Estimate): December 14, 2015
• Last Update Submitted That Met QC Criteria: November 10, 2015
• Last Verified: November 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; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Ribavirin; Peginterferon alfa-2a; Interferon alpha-2
• Other Study ID Numbers: AI444-031; 2010-022408-28 (EudraCT Number)