A Phase 3, Comparative Study of Asunaprevir and Daclatasvir Combination Therapy Versus Telaprevir Therapy in Japanese HCV Subjects

A Phase 3, Comparative Study of Asunaprevir and Daclatasvir (DUAL) Combination Therapy Versus Telaprevir Therapy in Japanese Genotype 1b Chronic Hepatitis C IFN Eligible-naive Subjects With a Single Arm Assessment of DUAL Therapy in IFN-therapy Relapsers

The purpose of this study is to assess the anti-viral activity of BMS-790052 and BMS-650032 combination therapy in Japanese subject.

The purpose of this study is to compare the anti-viral activity of the co-administration of Asunaprevir (ASV) and Daclatasvir (DCV) to Telaprevir (TVR) included therapy in Japanese Hepatitis C virus (HCV) subjects

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus Infection
• Intervention / Treatment: Drug: Ribavirin; Drug: Daclatasvir; Drug: Asunaprevir; Drug: Telaprevir; Biological: pegIFNα-2b

Detailed Description

Intervention Model: Parallel in the Naive cohort and Single group in the Relapser cohort

• Study Type: Interventional
• Enrollment (Actual): 258
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukui, Japan, 9188503
    • Local Institution
  • Fukuoka, Japan, 8158555
    • Local Institution
  • Fukuoka, Japan, 8140180
    • Local Institution
  • Gifu, Japan, 5008513
    • Local Institution
  • Kumamoto, Japan, 8628655
    • Local Institution
  • Nagoya-shi, Japan, 4678602
    • Local Institution
  • Nishinomiya-shi, Japan, 6638501
    • Local Institution
  • Osaka, Japan, 5400006
    • Local Institution
  • Saitama, Japan, 3380001
    • Local Institution
  • Aichi
    • Nagoya-shi, Aichi, Japan, 4668560
      • Local Institution
    • Toyoake Shi, Aichi, Japan, 4701192
      • Local Institution
  • Chiba
    • Chiba-shi, Chiba, Japan, 2608677
      • Local Institution
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 8108563
      • Local Institution
    • Kurume, Fukuoka, Japan, 8300011
      • Local Institution
  • Gifu
    • Ogaki-shi, Gifu, Japan, 5038502
      • Local Institution
  • Gunma
    • Takasaki City, Gunma, Japan, 3700829
      • Local Institution
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan, 7340037
      • Local Institution
  • Hokkaido
    • Obihiro-shi, Hokkaido, Japan, 080-0016
      • Local Institution
    • Sapporo-shi, Hokkaido, Japan, 0600033
      • Local Institution
    • Sapporo-shi, Hokkaido, Japan, 0608648
      • Local Institution
  • Kagawa
    • Takamatsu-shi, Kagawa, Japan, 760-8557
      • Local Institution
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan, 8908520
      • Local Institution
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan, 2138587
      • Local Institution
    • Yokohama-shi, Kanagawa, Japan, 2360004
      • Local Institution
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan, 8608556
      • Local Institution
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 6028566
      • Local Institution
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 9808574
      • Local Institution
  • Nagano
    • Matsumoto, Nagano, Japan, 3908621
      • Local Institution
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan, 8528501
      • Local Institution
    • Omura, Nagasaki, Japan, 8568562
      • Local Institution
  • Nara
    • Kashihara, Nara, Japan, 6348522
      • Local Institution
  • Oita
    • Yufu, Oita, Japan, 8795593
      • Local Institution
  • Okayama
    • Okayama-shi, Okayama, Japan, 7008558
      • Local Institution
  • Osaka
    • Osaka-sayama-shi, Osaka, Japan, 5898511
      • Local Institution
    • Osaka-shi, Osaka, Japan, 5438555
      • Local Institution
    • Osaka-shi, Osaka, Japan, 5458586
      • Local Institution
    • Suita, Osaka, Japan, 5640013
      • Local Institution
    • Suita-shi, Osaka, Japan, 5650871
      • Local Institution
  • Saitama
    • Iruma-gun, Saitama, Japan, 3500495
      • Local Institution
  • Shizuoka
    • Izunokuni, Shizuoka, Japan, 4102295
      • Local Institution
  • Tochigi
    • Shimotsuke-shi, Tochigi, Japan, 3290498
      • Local Institution
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 1138655
      • Local Institution
    • Bunkyo-ku, Tokyo, Japan, 1138519
      • Local Institution
    • Minato-ku, Tokyo, Japan, 1058470
      • Local Institution
    • Musashino-shi, Tokyo, Japan, 1808610
      • Local Institution
    • Shinagawa-ku, Tokyo, Japan, 1428666
      • Local Institution
  • Yamagata
    • Yamagata-shi, Yamagata, Japan, 9909585
      • Local Institution
  • Yamanashi
    • Chuo-shi, Yamanashi, Japan, 4093898
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic HCV-1b infected patient
• HCV Ribonucleic acid (RNA) > 100,000 IU/mL at screening
• Ages 20 to 70 years (for the Naive cohort), ages 20 to 75 years (for the Relapser cohort)
• Treatment naive subjects to Interferon (IFN) based therapy
• Subjects who had undetectable HCV RNA at end of treatment with prior exposure to an IFN-containing regimen, but HCV RNA detectable within 24 weeks of treatment follow-up

Exclusion Criteria:

• Patients who have;

  • Hepatocellular carcinoma
  • Co-infection with Hepatitis B virus (HBV) or Human immunodeficiency virus (HIV)
  • Severe or uncontrollable complication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Daclatasvir + Asunaprevir; Daclatasvir 60 mg tablets by mouth once daily and Asunaprevir 200 mg capsules by mouth twice daily for 24 weeks - Naive cohort	Drug: Daclatasvir; Drug: Asunaprevir
Active Comparator: Arm 2: Telaprevir + pegIFNα-2b + Ribavirin; Telaprevir 750 mg tablets by mouth three times daily, pegIFNα-2b 1.5 μg/kg solution by Subcutaneous weekly & Ribavirin 600- 1000 mg Capsules by mouth twice daily for 24 Weeks - Naive cohort	Drug: Ribavirin; Drug: Telaprevir; Biological: pegIFNα-2b
Experimental: Arm 3: Daclatasvir + Asunaprevir; Daclatasvir 60 mg tablets by mouth once daily and Asunaprevir 200 mg capsules by mouth twice daily for 24 weeks - Relapser cohort	Drug: Daclatasvir; Drug: Asunaprevir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with SVR12, defined as HCV RNA target detected or target not detected below LLOQ in the naive cohort	SVR12 = Sustained virologic response at post-treatment Week 12; LLOQ = Lower Limit of quantitation	After 12 weeks of the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with hemoglobin < 10g/dL		First 12 weeks of treatment
Proportion of subjects with rash-related dermatologic events		First 12 weeks of treatment
Proportion of subjects with HCV RNA target detected or target not detected below LLOQ in the naive cohort	EOT = End of treatment	At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12; EOT (up to 24 weeks), post-treatment Week 4 and post-treatment Week 24
Proportion of subjects with HCV RNA target not detected in the naive cohort	eRVR = Extended rapid virologic response	At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up to 24 weeks), post-treatment Week 4, post-treatment Week 12 and post-treatment Week 24
Proportion of subjects with SVR12, defined as HCV RNA target detected or target not detected below LLOQ in the relapser cohort		At post-treatment Week 12
Proportion of subjects with HCV RNA target detected or target not detected below LLOQ in the relapser cohort		At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12; EOT (up to 24 weeks), post-treatment Week 4 and Week 24
Proportion of subjects with HCV RNA target not detected in the relapser cohort		At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up to 24 weeks), post-treatment Week 4, post-treatment Week 12 and post-treatment Week 24
On treatment safety, as measured by the frequency of Severe adverse events (SAEs), discontinuation and dose modification/interruption due to Adverse events (AEs), Grade 3-4 abnormalities observed from clinical laboratory tests for each treatment group		End of treatment (24 weeks) plus 7days

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: October 29, 2012
• First Submitted That Met QC Criteria: October 29, 2012
• First Posted (Estimate): October 31, 2012

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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Ribavirin; Asunaprevir
• Other Study ID Numbers: AI447-031