Safety and Efficacy of Daclatasvir (BMS-790052) Plus Standard of Care (Pegylated-interferon Alpha and Ribavirin)

A Phase 2a Study of BMS-790052 in Combination With Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Treatment Naive Subjects With Chronic Hepatitis C Virus Genotype 1

The purpose of this study is to identify 1 or more doses of daclatasvir, which when used in combination with pegylated interferon alpha and ribavirin, are safe and demonstrate sufficient anti-hepatitis C virus activity.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Infection
• Intervention / Treatment: Drug: Daclatasvir; Drug: Daclatasvir; Drug: Daclatasvir; Drug: Peginterferon alpha-2a; Drug: ribavirin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94010
    • Local Institution
  • Paris Cedex 14, France, 75679
    • Local Institution
  • Vandoeuvre Les Nancy, France, 54511
    • Local Institution
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36116
      • Alabama Liver & Digestive Specialists (Alds)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University Of Colorado Denver & Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Llc Dba The Research Institute
  • New York
    • Bronx, New York, United States, 10468
      • Veterans Affairs Medical Center
  • North Carolina
    • Statesville, North Carolina, United States, 28677
      • Carolinas Center For Liver Disease
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Options Health Research, LLC
    • Tulsa, Oklahoma, United States, 74135
      • Healthcare Research Consultants
  • Texas
    • Arlington, Texas, United States, 76012
      • North Texas Research Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Metropolitan 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:

• Patients chronically infected with hepatitis C virus (HCV) genotype 1
• HCV RNA viral load of ≥10*5* IU/mL (100,000 IU/mL) at screening
• Treatment naive

Key Exclusion Criteria:

• Women of child-bearing potential
• Cirrhosis
• Coinfection with HIV or hepatitis B virus

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: Daclatasvir, plus Peginterferon alpha-2a, ribavirin (A); Active Comparator	Drug: Daclatasvir; Tablets, oral, 3 mg, Daily, 48 weeks; Drug: Daclatasvir; Tablets, oral, 10 mg, Daily, 48 weeks; Drug: Daclatasvir; Tablets, oral, 60 mg, Daily, 48 weeks; Drug: Peginterferon alpha-2a; Syringe, subcutaneous, 180 µg, Weekly, 48 weeks; Other Names: Pegasys; Drug: ribavirin; Tablet, oral, 1000 or 1200 mg, based on weight, Daily, 48 weeks; Other Names: Copegus
Experimental: Daclatasvir, Peginterferon alpha-2a, ribavirin (B); Active Comparator	Drug: Daclatasvir; Tablets, oral, 3 mg, Daily, 48 weeks; Drug: Daclatasvir; Tablets, oral, 10 mg, Daily, 48 weeks; Drug: Daclatasvir; Tablets, oral, 60 mg, Daily, 48 weeks; Drug: Peginterferon alpha-2a; Syringe, subcutaneous, 180 µg, Weekly, 48 weeks; Other Names: Pegasys; Drug: ribavirin; Tablet, oral, 1000 or 1200 mg, based on weight, Daily, 48 weeks; Other Names: Copegus
Experimental: Daclatasvir, Peginterferon alpha-2a, ribavirin (C); Active Comparator	Drug: Daclatasvir; Tablets, oral, 3 mg, Daily, 48 weeks; Drug: Daclatasvir; Tablets, oral, 10 mg, Daily, 48 weeks; Drug: Daclatasvir; Tablets, oral, 60 mg, Daily, 48 weeks; Drug: Peginterferon alpha-2a; Syringe, subcutaneous, 180 µg, Weekly, 48 weeks; Other Names: Pegasys; Drug: ribavirin; Tablet, oral, 1000 or 1200 mg, based on weight, Daily, 48 weeks; Other Names: Copegus
Active Comparator: Placebo, Peginterferon alpha-2a, ribavirin (D)	Drug: Peginterferon alpha-2a; Syringe, subcutaneous, 180 µg, Weekly, 48 weeks; Other Names: Pegasys; Drug: ribavirin; Tablet, oral, 1000 or 1200 mg, based on weight, Daily, 48 weeks; Other Names: Copegus; Drug: Placebo; Tablet, oral, 0 mg, Daily 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Extended Rapid Virologic Response (eRVR) at Weeks 4 and 12	eRVR was defined as undetectable hepatitis C virus RNA less than the lower limit of detection (10 IU/mL) at Weeks 4 and 12.	A Weeks 4 and 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Rapid Virologic Response (RVR) at Week 4	RVR was defined as undetectable hepatitis C virus (HCV) RNA ie, HCV RNA less than the lower limit of detection (10 IU/mL) at Week 4.	At Week 4
Percentage of Participants With Early Virologic Response (EVR) at Week 12	EVR was defined as a ≥2 log10 decrease in hepatitis C virus (HCV) RNA from baseline at Week 12 , or HCV RNA <10 IU/mL for participants with baseline HCV RNA <1000 IU/mL.	At Week 12
Percentage of Participants With a Complete Early Virologic Response (cEVR) at Week 12	cEVR was defined as hepatitis C virus RNA <10 IU/mL at Week 12	At Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Treatment-related AEs and Who Died in Treatment Phase	An AE was defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a patient or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this 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.	SAE: From Day 1 up to 30 days after last dose of study drug, AE: From Day 1 to 7 days after last dose of study drug
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Treatment-related AEs and Who Died in Follow-up Period	An AE was defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a patient or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this 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.	From Day 31 up to Week 24 of post treatment follow-up
Number of Participants With Grade 3 to 4 Abnormalities on Laboratory Test Results	Clinically significant change in marked laboratory abnormalities (Grade 3 to 4 ) included: Alanine aminotransferase (ALT)- Grade 3 as >5.0 to 10.0* Upper Limit of Normal (ULN), Grade 4 as >10.0*ULN; Aspartate aminotransferase (AST)- Grade 3 as >5.0 to 10.0*ULN, Grade 4 as >10.0*ULN; Hemoglobin- Grade 3 as 7.0 to 8.9 g/dL, Grade 4 as <7.0 g/dL; Neutrophils- Grade 3 as 0.5 to 0.749*10^9/L, Grade 4 as <0.5*10^9/L; Lymphocytes- Grade 3 as 0.35 to 0.499*10^9/L, Grade 4 as <0.35*10^9/L; Total Bilirubin- Grade 3 as 2.6-5.0*ULN, Grade 4 as >5.0*ULN; Platelets- Grade 3 as 25000 to 49999*10^9/L, Grade 4 as <25000 10^9/L and white blood cells (WBC) - Grade 3 as 1000 to 1499*10^9/L, Grade 4 as <1000*10^9/L.	From screening up to Week 12 (treatment period)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Pol S, Ghalib RH, Rustgi VK, Martorell C, Everson GT, Tatum HA, Hezode C, Lim JK, Bronowicki JP, Abrams GA, Brau N, Morris DW, Thuluvath PJ, Reindollar RW, Yin PD, Diva U, Hindes R, McPhee F, Hernandez D, Wind-Rotolo M, Hughes EA, Schnittman S. Daclatasvir for previously untreated chronic hepatitis C genotype-1 infection: a randomised, parallel-group, double-blind, placebo-controlled, dose-finding, phase 2a trial. Lancet Infect Dis. 2012 Sep;12(9):671-7. doi: 10.1016/S1473-3099(12)70138-X. Epub 2012 Jun 18.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: April 2, 2009
• First Submitted That Met QC Criteria: April 2, 2009
• First Posted (Estimate): April 3, 2009

Study Record Updates

• Last Update Posted (Estimate): October 23, 2015
• Last Update Submitted That Met QC Criteria: September 23, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Antivirals
• 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2a
• Other Study ID Numbers: AI444-014; EUDRACT# 2009-010149-29