A Phase 3 Evaluation of Daclatasvir and Asunaprevir in Treatment-naive Subjects With Chronic Hepatitis C Genotype 1b Infection

The purpose of this study is to determine whether a regimen consisting of daclatasvir and asunaprevir is effective in treatment-naive patients with chronic hepatitis genotype 1b infection.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Daclatasvir; Drug: Asunaprevir

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100039
    • Local Institution
  • Beijing
    • Beijing, Beijing, China, 100034
      • Local Institution
    • Beijing, Beijing, China, 100050
      • Local Institution
    • Beijing, Beijing, China, 100054
      • Local Institution
    • Beijing, Beijing, China, 100015
      • Local Institution
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Local Institution
    • Guangzhou, Guangdong, China, 510060
      • Local Institution
  • Hebei
    • Shi Jia Zhuang, Hebei, China, 050051
      • Local Institution
  • Hunan
    • Changsha, Hunan, China, 410008
      • Local Institution
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • Local Institution
    • Nanjing, Jiangsu, China, 210029
      • Local Institution
    • Nanjing, Jiangsu, China, 210003
      • Local Institution
    • Zhenjiang, Jiangsu, China, 212000
      • Local Institution
  • Jilin
    • Changchun, Jilin, China, 130021
      • Local Institution
  • Liaoning
    • Shenyang, Liaoning, China, 110006
      • Local Institution
    • Shenyang, Liaoning, China, 110002
      • Local Institution
  • Shandong
    • Qingdao, Shandong, China, 266011
      • Local Institution
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Local Institution
    • Shanghai, Shanghai, China, 200083
      • Local Institution
    • Shanghai, Shanghai, China, 200062
      • Local Institution
  • Shanxi
    • Xi'an, Shanxi, China, 710061
      • Local Institution
    • Xi'an, Shanxi, China, 710038
      • Local Institution
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Local Institution
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Local Institution
  • Seoul, Korea, Republic of, 08308
    • Local Institution
  • Seoul, Korea, Republic of, 07061
    • Local Institution
• Russian Federation
  • Moscow, Russian Federation, 127015
    • Local Institution
  • St. Petersburg, Russian Federation, 191167
    • Local Institution
  • St.petersburg, Russian Federation, 190103
    • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Patients chronically infected with HCV Genotype 1b
• No previous exposure to any interferon formulation, Ribavirin (RBV), and HCV direct acting antiviral agent
• HCV RNA viral load ≥ 10,000 IU/mL at screening
• Seronegative for HIV and HBsAg
• BMI of 18-35 kg/m2, inclusive
• Patients with compensated cirrhosis are permitted

Exclusion Criteria:

• Infection with HCV other than genotype (GT) -1b
• Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
• Evidence of a medical condition contributing to chronic liver disease other than HCV
• Diagnosed or suspected hepatocellular carcinoma or other malignancies
• Uncontrolled diabetes or hypertension
• History of moderate to severe depression. Well-controlled mild depression is allowed
• Confirmed alanine aminotransferase (ALT) ≥ 5x Upper Limit of Normal (ULN)
• Confirmed platelet count < 50,000 cells/mm3
• Confirmed hemoglobin < 8.5 g/dL

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active dual arm; Daclatasvir in tablet form at the dose of 60 mg QD and Asunaprevir in soft capsule form at the dose of 100 mg BID from day 1 to 12 week Daclatasvir in tablet form at the dose of 60 mg QD and Asunaprevir in soft capsule form at the dose of 100 mg BID from 12 to 24 week and follow up to week 48	Drug: Daclatasvir; Daclatasvir tablet 60mg; Drug: Asunaprevir; Asunaprevir soft capsule 100 mg
Placebo Comparator: Placebo arm; Daclatasvir placebo in tablet form QD and Asunaprevir placebo in soft capsule form BID from day 1 to 12 week Daclatasvir in tablet form at the dose of 60 mg QD and Asunaprevir in soft capsule form at the dose of 100 mg BID from 12 to 36 week and follow up to week 60	Drug: Daclatasvir; Daclatasvir tablet 60mg; Drug: Asunaprevir; Asunaprevir soft capsule 100 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of treated subjects randomized to Active Dual therapy with Sustained Virologic Response (SVR12)	HCV RNA < Lower limit of quantitation (LLOQ) target detected (TD) or target not detected (TND) at follow-up Week 12	Post-treatment Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with anemia on active Dual therapy	Post-treatment Week 12
Proportion of subjects with neutropenia on active Dual therapy	Post-treatment Week 12
Proportion of subjects with thrombocytopenia on active Dual therapy	Post-treatment Week 12
On treatment safety, as measured by frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs)	Post-treatment week 12
Differences in rates of selected Grade 3-4 laboratory abnormalities for hematology between treatments (DCV + Asunaprevir (ASV) vs PBO)	first 12 weeks on treatment
Differences in rates of selected Grade 3-4 laboratory abnormalities for liver function between treatments (DCV + Asunaprevir (ASV) vs PBO)	first 12 weeks on treatment
Proportion of subjects with SVR12 by the rs12979860 single nucleotide polymorphism (SNP) in the interleukin (IL) -28B gene for each cohort	Post-treatment visit week 12
Proportion of subjects with hepatitis C virus (HCV) RNA < LLOQ-TD/TND in each arm at various intervals after the initiation of active Dual therapy	post-treatment visit Week 24
Proportion of subjects who achieve HCV RNA < LLOQ-TND at each arm at various intervals after the initiation of active Dual therapy	post-treatment visit Week 24
Proportion of treated subjects with SVR12 for subjects randomized to placebo	Post-treatment visit week 12

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: August 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: July 9, 2015
• First Submitted That Met QC Criteria: July 9, 2015
• First Posted (Estimate): July 14, 2015

Study Record Updates

• Last Update Posted (Actual): April 19, 2017
• Last Update Submitted That Met QC Criteria: April 17, 2017
• Last Verified: September 1, 2016

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, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Asunaprevir
• Other Study ID Numbers: AI447-114