Phase 2b Study of BMS-986094 and Daclatasvir, With or Without Ribavirin for the Treatment of Patients With Chronic Hepatitis C

Phase 2b Evaluation of PegIFNα Free Combinations of BMS-986094 (INX-08189) and Daclatasvir, With or Without Ribavirin, in Treatment Naive and Treatment Experienced Patients With Chronic Hepatitis C

The purpose of this study is to evaluate the effectiveness of BMS-986094 and Daclatasvir (DCV) when given in combination with or without Ribavirin

Study Overview

• Status: Withdrawn
• Conditions: Hepatitis C Virus
• Intervention / Treatment: Drug: Daclatasvir; Drug: Daclatasvir; Drug: BMS-986094; Drug: BMS-986094; Drug: BMS-986094; Drug: Placebo for BMS-986094; Drug: Ribavirin

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32804
      • 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

Inclusion Criteria:

• Males and females, ≥ 18 years of age
• Subjects chronically infected with Hepatitis C virus (HCV) genotype 1,2,3 or 4
• HCV RNA viral load ≥ 10,000 IU/mL
• Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 25% of treated population)
• Body Mass Index (BMI) of 18 to 35 kg/m2
• Seronegative for Hepatitis C virus (HIV) and Hepatitis B

Exclusion Criteria:

• Evidence of decompensated liver disease
• Evidence of medical condition contributing to chronic liver disease other than HCV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1: Daclasasvir + BMS-986094 (100 mg) + Placebo; Subjects will be re-randomized at Week 12 to complete therapy at this visit and enter post-treatment follow-up, or continue therapy for an additional 12 weeks (24 weeks of therapy) Re-Randomized Arm 1 to Arm 1a and 1b (additional 12 weeks treatment)	Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 12 or 24 weeks; Other Names: BMS-790052 (DCV); Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 24 weeks; Other Names: BMS-790052 (DCV); Drug: BMS-986094; Capsule, Oral, 100 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 24 Weeks; Drug: Placebo for BMS-986094; Capsule, Oral, 0 mg, Once daily, 12 or 24 weeks
EXPERIMENTAL: Arm 2: Daclasasvir + BMS-986094 (200 mg); Subjects will be re-randomized at Week 12 to complete therapy at this visit and enter post-treatment follow-up, or continue therapy for an additional 12 weeks (24 weeks of therapy) Re-Randomized Arm 2 to Arm 2a and 2b (additional 12 weeks treatment)	Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 12 or 24 weeks; Other Names: BMS-790052 (DCV); Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 24 weeks; Other Names: BMS-790052 (DCV); Drug: BMS-986094; Capsule, Oral, 100 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 24 Weeks
EXPERIMENTAL: Arm 3: Daclasasvir + BMS-986094 (100 mg) + Placebo + Ribavirin; Subjects will be re-randomized at Week 12 to complete therapy at this visit and enter post-treatment follow-up, or continue therapy for an additional 12 weeks (24 weeks of therapy) Re-Randomized Arm 3 to Arm 3a and 3b (additional 12 weeks treatment)	Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 12 or 24 weeks; Other Names: BMS-790052 (DCV); Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 24 weeks; Other Names: BMS-790052 (DCV); Drug: BMS-986094; Capsule, Oral, 100 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 24 Weeks; Drug: Placebo for BMS-986094; Capsule, Oral, 0 mg, Once daily, 12 or 24 weeks; Drug: Ribavirin; Film coated tablet, Oral, 1000 mg or 1200 mg based on weight, Twice daily, 12 or 24 weeks; Other Names: Copegus®
EXPERIMENTAL: Arm 4: Daclasasvir + BMS-986094 (200 mg) + Ribavirin; Subjects will be re-randomized at Week 12 to complete therapy at this visit and enter post-treatment follow-up, or continue therapy for an additional 12 weeks (24 weeks of therapy) Re-Randomized Arm 4 to Arm 4a and 4b (additional 12 weeks treatment)	Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 12 or 24 weeks; Other Names: BMS-790052 (DCV); Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 24 weeks; Other Names: BMS-790052 (DCV); Drug: BMS-986094; Capsule, Oral, 100 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 24 Weeks; Drug: Ribavirin; Film coated tablet, Oral, 1000 mg or 1200 mg based on weight, Twice daily, 12 or 24 weeks; Other Names: Copegus®
EXPERIMENTAL: Arm 5: Daclasasvir + BMS-986094 (200 mg); Genotype 1 PI-failure subjects	Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 12 or 24 weeks; Other Names: BMS-790052 (DCV); Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 24 weeks; Other Names: BMS-790052 (DCV); Drug: BMS-986094; Capsule, Oral, 100 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 24 Weeks
EXPERIMENTAL: Arm 6: Daclasasvir + BMS-986094 (200 mg); Genotype 4 naive subjects	Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 12 or 24 weeks; Other Names: BMS-790052 (DCV); Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 24 weeks; Other Names: BMS-790052 (DCV); Drug: BMS-986094; Capsule, Oral, 100 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 24 Weeks
EXPERIMENTAL: Arm 7: Daclasasvir + BMS-986094 (200 mg); Genotype 2/3 NR/relapse Subjects	Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 12 or 24 weeks; Other Names: BMS-790052 (DCV); Drug: Daclatasvir; Film coated tablet, Oral, 60 mg, Once daily, 24 weeks; Other Names: BMS-790052 (DCV); Drug: BMS-986094; Capsule, Oral, 100 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 12 or 24 weeks; Drug: BMS-986094; Capsule, Oral, 200 mg, Once daily, 24 Weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with SVR4 defined as HCV RNA < LOQ (25 IU/mL; detectable or undetectable) at 4 weeks post treatment to be evaluated in GT1 (naive and NR) subjects randomized to the 12-week treatment arm (arms 1a, 2a, 3a, 4a)	SVR = Sustained virologic response; HCV = Hepatitis C virus; RNA = Ribonucleic acid; LOQ = Limit of quantitation	Follow up Week 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of treated subjects with SVR4 in genotype (GT) 1 naive and non-responder (NR) subjects randomized to the 24-week treatment arms (arms 1b, 2b, 3b, 4b)	Follow up Week 4 (SVR4)
Proportion of treated subjects with SVR4 in genotype 1 protease inhibitor (PI)failures, genotype 4 naive, and genotype 2/3 NR/relapse subjects (arms 5, 6, 7)	Follow up Week 4 (SVR4)
Proportion of treated subjects in each study population (GT1 naive, GT1 NR, or GT1 PI-failure, GT4 naive, GT2/3 NR/relapse), for each regimen and duration, who achieve HCV RNA < LOQ at post-treatment	Post-treatment Week 2 (SVR2), Week 8 (SVR8), Week 12 (SVR12), Week 24 (SVR24), and Week 36 (SVR36, for the 12 week arms)
Proportion of treated subjects in each study population, by regimen, who achieve HCV RNA < LOQ (detectable/undetectable)	Weeks 1, 2, 4, 6, 8, 12 and End of Treatment (Week 12 or 24)
Proportion of subjects in each study population, be regimen, who achieve HCV RNA undetectable	Weeks 1, 2, 4, 6, 8, 12 and End of Treatment (Week 12 or 24)
Safety and tolerability of BMS-986094 and DCV ± RBV as measured by the frequency of deaths, serious adverse events (SAEs), discontinuations due to Adverse Events (AEs), and severity Grade 3/4 laboratory abnormalities	Up to post treatment Week 36

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: March 1, 2013
• Primary Completion (ANTICIPATED): February 1, 2014
• Study Completion (ANTICIPATED): June 1, 2014

Study Registration Dates

• First Submitted: June 26, 2012
• First Submitted That Met QC Criteria: June 26, 2012
• First Posted (ESTIMATE): June 28, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): May 9, 2014
• Last Update Submitted That Met QC Criteria: May 8, 2014
• Last Verified: May 1, 2014

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; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin
• Other Study ID Numbers: AI472-007; 2012-002519-24 (EUDRACT_NUMBER)