Safety and Efficacy of Daclatasvir (BMS-790052) Plus Standard of Care (Pegylated-interferon Alpha-2b and Ribavirin) in Japanese Patients

A Phase 2a Study of BMS-790052 in Combination With Peginterferon Alfa-2b (PegIntron®) and Ribavirin (Rebetol®) in Japanese Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

The purpose of this study is to identify at least 1 dose of daclatasvir that is safe, well tolerated, and efficacious when combined with peginterferon-alfa and ribavirin for the treatment of hepatitis C virus genotype 1 in chronically infected patients who are treatment-naïve and nonresponsive to the standard of care

Study Overview

• Status: Completed
• Conditions: Hepatitis C Infection
• Intervention / Treatment: Drug: Placebo; Drug: BMS-790052; Drug: BMS-790052; Drug: Peginterferon alfa-2b; Drug: Ribavirin

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Hiroshima
    • Hiroshima City, Hiroshima, Japan, 734-0037
      • Local Institution
  • Hokkaido
    • Sapporo-Shi, Hokkaido, Japan, 060-0033
      • Local Institution
  • Kanagawa
    • Kawasaki-Shi, Kanagawa, Japan, 2138587
      • Local Institution
  • Osaka
    • Suita-Shi, Osaka, Japan, 5650871
      • Local Institution
  • Saitama
    • Iruma-Gun, Saitama, Japan, 3500495
      • Local Institution
  • Tokyo
    • Minato-Ku, Tokyo, Japan, 105-0001
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 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 ≥10*5* IU/mL at screening
• Naïve or nonresponsive to the current standard of care

Key Exclusion Criteria:

• Cirrhosis
• Hepatocellular carcinoma
• Coinfection with hepatitis B virus, HIV-1 or HIV-2

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (BMS-790052, plus Peginterferon alfa-2b, Ribavirin); Treatment Naive	Drug: BMS-790052; Tablets, Oral, 10 mg, daily, 24-48 weeks; Drug: BMS-790052; Tablets, Oral, 60 mg, daily, 24-48 weeks; Drug: Peginterferon alfa-2b; Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks; Other Names: PegIntron®; Drug: Ribavirin; Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks; Other Names: Rebetol®
Experimental: Arm B (BMS-790052, plus Peginterferon alfa-2b, Ribavirin); Treatment Naive	Drug: BMS-790052; Tablets, Oral, 10 mg, daily, 24-48 weeks; Drug: BMS-790052; Tablets, Oral, 60 mg, daily, 24-48 weeks; Drug: Peginterferon alfa-2b; Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks; Other Names: PegIntron®; Drug: Ribavirin; Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks; Other Names: Rebetol®
Placebo Comparator: Arm C (Placebo, plus Peginterferon alfa-2b, Ribavirin); Treatment Naive	Drug: Placebo; Tablets, Oral, 0 mg, daily, 48 weeks; Drug: Peginterferon alfa-2b; Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks; Other Names: PegIntron®; Drug: Ribavirin; Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks; Other Names: Rebetol®
Experimental: Arm D (BMS-790052, plus peginterferon alfa-2b, Ribavirin); Non-Responder	Drug: BMS-790052; Tablets, Oral, 10 mg, daily, 24-48 weeks; Drug: BMS-790052; Tablets, Oral, 60 mg, daily, 24-48 weeks; Drug: Peginterferon alfa-2b; Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks; Other Names: PegIntron®; Drug: Ribavirin; Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks; Other Names: Rebetol®
Experimental: Arm E (BMS-790052, plus Peginterferon alfa-2b, Ribavirin); Non-Responder	Drug: BMS-790052; Tablets, Oral, 10 mg, daily, 24-48 weeks; Drug: BMS-790052; Tablets, Oral, 60 mg, daily, 24-48 weeks; Drug: Peginterferon alfa-2b; Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks; Other Names: PegIntron®; Drug: Ribavirin; Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks; Other Names: Rebetol®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Extended Rapid Virologic Response (eRVR)	eRVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at both Weeks 4 and 12. HCV RNA levels were measured by Tobas TaqMan HCV Auto from the central laboratory.	At Weeks 4 and 12 on treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Rapid Virologic Response (RVR)	RVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at Week 4. HCV RNA levels were measured by CobasTaqMan HCV Auto from the central laboratory .	At Week 4 on treatment
Percentage of Participants With Complete Early Virologic Response (cEVR)	cEVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at Week 12 on treatment. HCV RNA levels were measured by Cobas TaqMan HCV Auto from the central laboratory	At Week 12 on treatment
Percentage of Participants With a Sustained Virologic Response (SVR) at Weeks 4, 12, and 24	SVR at follow-up Week 4 (SVR4), follow-up Week 12 (SVR12), and follow-up Week 24 (SVR24) is defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at each of these timepoints. HCV RNA levels were measured by Cobas TaqMan HCV Auto from the central laboratory .	Follow-up Weeks 4, 12, and 24
Percentage of Participants With Virologic Failure	Virologic failure is defined by the following 6 categories: 1.Virologic breakthrough, defined as confirmed >1 log10 increase in hepatitis C virus (HCV) RNA over nadir or confirmed HCV RNA ≥limit of quantitation (LOQ) after confirmed undetectable HCV RNA while on treatment. 2. <1 log10 decrease in HCV RNA from baseline at Week 4 of treatment. 3. Failure to achieve early virologic response, defined as <2 log10 decrease in HCV RNA from baseline at Week 12 of treatment. 4. Detectable HCV RNA at Week 12, and HCV RNA ≥LOQ at Week 24 of treatment. 5. Detectable HCV RNA at end of treatment (including early discontinuation). 6 Relapse, defined as detectable HCV RNA during follow-up after undetectable HCV RNA levels at end of treatment.	From on-treatment Week 1 to Follow-up Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Treatment-related AEs, and Death as Outcome	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.	From baseline to 30 days after last dose of study drug
Number of Participants With Grade 3 to 4 Abnormalities on Laboratory Test Results	Clinically significant marked abnormalities in laboratory test results graded by the Division of AIDS grading table, 2004. Hemoglobin: Grade 3= <7.0 to 8.9 g/dL, Grade 4= <7.0 g/dL. Lymphocytes: Grade 3= 350-499 cells/mm^3, Grade 4= <350 cells/mm^3. Neutrophils: Grade 3= 500-999 cells/mm^3, Grade 4= <500 cells/mm^3. White blood cells (WBC): Grade 3= 1000-1499 cells/mm^3, Grade 4= <1000 cells/mm^3. Alanine aminotransferase (ALT): Grade 3= 5.1-10*upper limit of normal (ULN), Grade 4= >10.0*ULN. Aspartate aminotransferase (AST): Grade 3= 5.1-10*ULN, Grade 4= >10.0*ULN. Total bilirubin: Grade 3= 2.6-5*ULN, Grade 4= >5.0*ULN.	From baseline to 30 days after last dose of study drug

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Murakami E, Imamura M, Hayes CN, Abe H, Hiraga N, Honda Y, Ono A, Kosaka K, Kawaoka T, Tsuge M, Aikata H, Takahashi S, Miki D, Ochi H, Matsui H, Kanai A, Inaba T, McPhee F, Chayama K. Ultradeep sequencing study of chronic hepatitis C virus genotype 1 infection in patients treated with daclatasvir, peginterferon, and ribavirin. Antimicrob Agents Chemother. 2014;58(4):2105-12. doi: 10.1128/AAC.02068-13. Epub 2014 Jan 27.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: November 19, 2009
• First Submitted That Met QC Criteria: November 19, 2009
• First Posted (Estimate): November 20, 2009

Study Record Updates

• Last Update Posted (Estimate): October 12, 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; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Infections; Hepatitis; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2b
• Other Study ID Numbers: AI444-021