Study of Daclatasvir and TMC435 for Subjects With Genotype 1 Chronic Hepatitis C

This study has been completed.
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01628692
First received: June 25, 2012
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to assess the safety and efficacy of Daclatasvir and TMC435 with and without Ribavirin for genotype 1 chronic hepatitis C in subjects who are treatment-naive or null responders to previous Peginterferon/Ribavirin therapy.


Condition Intervention Phase
Hepatitis C Virus
Drug: Daclatasvir (DCV)
Drug: TMC435
Drug: Ribavirin
Biological: pegIFNα-2a
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label Study of Daclatasvir (BMS-790052) and TMC435 in Combination With or Without Ribavirin (RBV) For Treatment-Naive Subjects or Null Responders to Prior Peginterferon Alfa (PegIFN)/RBV Therapy With Genotype 1 Chronic Hepatitis C

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Antiviral activity, as determined by the proportion of subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for each cohort defined by the previous response status, HCV genotype, initial treatment regimen and treatment duration [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • On-treatment safety, as measured by the frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) [ Time Frame: Up to 24 weeks plus 7 days ] [ Designated as safety issue: Yes ]
  • Proportion of subjects with Sustained virologic response12 (SVR12) (HCV RNA < LOQ at post-treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28B gene for each treatment arm [ Time Frame: Post treatment week 12 ] [ Designated as safety issue: No ]
  • Proportion of subjects with Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Limit of quantitation (LOQ) [ Time Frame: Weeks 1, 2, 4, 6, and 8 (and 12); EOT (End of treatment) (up to 24 weeks), post-treatment Week 24 (SVR24) for each treatment arm, and post-treatment Week 36 (genotype 1b) for subjects in the 12 week treatment arms ] [ Designated as safety issue: No ]
  • Proportion of subjects with HCV RNA undetectable [ Time Frame: Weeks 1, 2, 4, 6, and 8 (and 12); EOT (up to 24 weeks), post-treatment Week 12 and post-treatment Week 24 for each treatment arm, and post-treatment Week 36 (genotype 1b) for subjects in the 12 week treatment arms ] [ Designated as safety issue: No ]

Enrollment: 168
Study Start Date: July 2012
Study Completion Date: November 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 Genotype 1b: DCV + TMC435

Potential additional treatment if criteria met with Peginterferon Alfa-2a, (pegIFNα-2a) and Ribavirin (RBV)

12 weeks. Subjects who complete Week 12 will undergo a second randomization (1:1 allocation) to stop treatment and enter a 36 week post treatment phase or to continue treatment through Week 24 and enter a 24 week post treatment phase

There is a potential for additional treatment for an additional 24 weeks during subjects treatment phase depending on criteria

Drug: Daclatasvir (DCV)
Tablets, Oral, 30 mg, once daily (QD), 12 or 24 weeks
Other Name: BMS-790052
Drug: TMC435
Capsule, Oral, 150 mg, QD, 12 or 24 weeks
Drug: Ribavirin
Tablets, Oral, 500-600 mg, twice daily, 24 weeks
Biological: pegIFNα-2a
Solution, Injection, 180 μg, Once a week, 24 weeks
Experimental: Cohort 2 Genotype 1b: DCV + TMC435 + RBV

Potential additional treatment if criteria met: Peginterferon Alfa-2a. (pegIFNα-2a)

12 weeks. Subjects who complete Week 12 will undergo a second randomization (1:1 allocation) to stop treatment and enter a 36 week post treatment phase or to continue treatment through Week 24 and enter a 24 week post treatment phase

There is a potential for additional treatment for an additional 24 weeks during subjects treatment phase depending on criteria

Drug: Daclatasvir (DCV)
Tablets, Oral, 30 mg, once daily (QD), 12 or 24 weeks
Other Name: BMS-790052
Drug: TMC435
Capsule, Oral, 150 mg, QD, 12 or 24 weeks
Drug: Ribavirin
Tablets, Oral, 500-600 mg, twice daily, 12 or 24 weeks
Biological: pegIFNα-2a
Solution, Injection, 180 μg, Once a week, 24 weeks
Experimental: Cohort 3 Genotype 1a: DCV + TMC435 + RBV

Potential additional treatment if criteria met: Peginterferon Alfa-2a, (pegIFNα-2a)

24 weeks. Subjects after 24 weeks will enter a 24 week post treatment phase

There is a potential for additional treatment for an additional 24 weeks during subjects treatment phase depending on criteria

Drug: Daclatasvir (DCV)
Tablets, Oral, 30 mg, QD, 24 weeks
Other Name: BMS-790052
Drug: TMC435
Capsule, Oral, 150 mg, QD, 24 weeks
Drug: Ribavirin
Tablets, Oral, 500-600 mg, twice daily, 24 weeks
Biological: pegIFNα-2a
Solution, Injection, 180 μg, Once a week, 24 weeks
Experimental: Cohort 4 Genotype 1a: DCV+TMC435+RBV

Potential additional treatment if criteria met: Peginterferon Alfa-2a, (pegIFNα-2a)

12 weeks. Subjects after 12 weeks will enter a 24 week post treatment phase.

There is a potential for additional treatment for an additional 24 weeks during subjects treatment phase depending on criteria

Drug: Daclatasvir (DCV)
Tablets, Oral, 30 mg, once daily (QD), 12 weeks
Other Name: BMS-790052
Drug: TMC435
Capsule, Oral, 150 mg, QD, 12 weeks
Drug: Ribavirin
Tablets, Oral, 500-600 mg, twice daily, 12 weeks
Biological: pegIFNα-2a
Solution, Injection, 180 μg, Once a week, 24 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HCV Genotype 1a or 1b
  • Males and females, ≥ 18 years of age
  • HCV RNA ≥ 10,000 IU/mL
  • Subjects with compensated cirrhosis are permitted

    • Advanced fibrosis (F3/F4) is capped at approximately 35% of the total treated population with a minimum of 20% F4 subjects
    • If no cirrhosis, a liver biopsy within 3 years prior to enrollment is required
    • If cirrhosis is present, any prior liver biopsy is sufficient

Exclusion Criteria:

Target Disease Exceptions

  • Liver or any other transplant (other than cornea and hair)
  • Evidence of a medical condition contributing to chronic liver disease other than HCV
  • Current or known history of cancer, (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment
  • Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
  • Subjects infected with Human immunodeficiency virus (HIV) or Hepatitis B virus (HBV)
  • Gastrointestinal disease impacting absorption of study drug
  • Uncontrolled diabetes or hypertension

Medication related

  • Prior exposure to an HCV direct acting agent (DAA)
  • Any criteria that would exclude the subject from receiving Ribavirin (RBV)

Exclusion Laboratory results

  • Absolute neutrophil count (ANC) < 1.5 x 1,000,000,000 cells/L (<1.2 x 1,000,000,000 cells/L for Black/African-Americans)
  • Platelets < 90 x 1,000,000,000 cells/L
  • Hemoglobin < 12 g/dL for females or < 13 g/dL for males
  • Alanine aminotransferase (ALT) ≥ 5 x Upper limit of normal (ULN)
  • In subjects without cirrhosis, total bilirubin ≥ 34 μmol/L (or ≥ 2 mg/dL) unless subject has a documented history of Gilbert's disease
  • In subjects with cirrhosis, total bilirubin ≥ 26 μmol/L (or ≥ 1.5 mg/dL)
  • International normalized ratio (INR) ≥ 1.7
  • QTcF or QTcB > 500 mSec
  • Creatinine Clearance (CrCl) ≤ 50 mL/min
  • Alpha Fetoprotein (AFP) > 100 ng/mL OR
  • AFP ≥ 50 ng/mL and ≤ 100 ng/mL requires a liver ultrasound [Hepatocellular carcinoma (HCC) are excluded]
  • Albumin < 3.5 g/dL (35 g/L)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01628692

Locations
United States, California
Kaiser Permanente Med Ctr
San Francisco, California, United States, 94118
San Francisco General Hospital
San Francisco, California, United States, 94110
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins University
Lutherville, Maryland, United States, 21093
United States, Tennessee
Nashville Medical Research Institute
Nashville, Tennessee, United States, 37205
United States, Texas
Texas Clinical Research Institute, Llc
Arlington, Texas, United States, 76012
United States, Virginia
Metropolitan Research
Fairfax, Virginia, United States, 22031
Argentina
Local Institution
Buenos Aires, Argentina, 1119
Local Institution
Buenos Aires, Argentina, C1181ACH
France
Local Institution
Creteil Cedex, France, 94010
Local Institution
Limoges, France, 87042
Local Institution
Marseille Cedex 08, France, 13285
Local Institution
Paris Cedex 13, France, 75651
Local Institution
Paris Cedex 14, France, 75679
Local Institution
Pessac, France, 33600
Local Institution
Vandoeuvre Les Nancy, France, 54511
Germany
Local Institution
Berlin, Germany, 10969
Local Institution
Frankfurt, Germany, 60590
Local Institution
Hamburg, Germany, 20099
Local Institution
Koeln, Germany, 50937
Hungary
Local Institution
Budapest, Hungary, 1097
Local Institution
Budapest, Hungary, 1126
Local Institution
Gyula, Hungary, 5700
Spain
Local Institution
Barcelona, Spain, 08035
Local Institution
Madrid, Spain, 28046
Local Institution
Valencia, Spain, 46010
Sponsors and Collaborators
Bristol-Myers Squibb
Janssen Research & Development, LLC
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01628692     History of Changes
Other Study ID Numbers: AI444-062, 2012-000070-28
Study First Received: June 25, 2012
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Russia: FSI Scientific Center of Expertise of Medical Application
Hungary: National Institute of Pharmacy
Chile: Instituto de Salud Pública de Chile
Germany: Federal Institute for Drugs and Medical Devices
Germany: Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Spanish Agency of Medicines
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014