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Study of Daclatasvir (BMS-790052) and Simeprevir (TMC435) in Patients With Genotype 1 Chronic Hepatitis C Virus

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: October 29, 2015
Last verified: October 2015
  Purpose
The purpose of this study is to assess the safety and efficacy of daclatasvir and simeprevir with and without ribavirin for genotype 1 chronic hepatitis C virus infection in patients who are treatment-naive or null responders to previous pegylated interferon/ribavirin therapy.

Condition Intervention Phase
Hepatitis C Virus
Drug: Daclatasvir
Drug: Simeprevir
Drug: Ribavirin
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:
  • Percentage of Participants With Sustained Virologic Response Rate at Post-treatment Week 12 (SVR12) [ Time Frame: Post Treatment Week 12 (Follow-up period) ] [ Designated as safety issue: No ]
    SVR12 rate was defined as hepatitis C virus (HCV) RNA levels to be <lower limit of quantitation, target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.


Secondary Outcome Measures:
  • Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    RVR was defined as hepatitis C virus (HCV) RNA levels to be <lower limit of quantitation, target not detected at Week 4. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

  • Percentage of Participants With Complete Early Virologic Response (cEVR) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    cEVR was defined as hepatitis C virus (HCV) RNA levels to be <lower limit of quantitation, target not detected at Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

  • Percentage of Participants With Extended Rapid Virologic Response (eRVR) [ Time Frame: Week 4 and Week 12 ] [ Designated as safety issue: No ]
    eRVR were defined as hepatitis C virus (HCV) RNA levels to be <lower limit of quantitation, target not detected at both Week 4 and Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

  • Percentage of Participants With End of Treatment Response (EOTR) [ Time Frame: End of treatment (Week 24) ] [ Designated as safety issue: No ]
    EOTR were defined as hepatitis C virus (HCV) RNA levels <lower limit of quantitation, target not detected at end of treatment. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

  • Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) by rs12979860 Single Nucleotide Polymorphisms in the IL-28B Gene Categories [ Time Frame: Baseline, post-treatment Week 12 (Follow-up period) ] [ Designated as safety issue: No ]
    Participants were categorized into 3 genotypes based on single nucleotide polymorphisms in the IL28B gene. SVR12 was defined as hepatitis C virus (HCV) RNA levels below lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

  • Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died [ Time Frame: From start of treatment (Day 1) up to 7 days post last dose of study treatment (Week 24) ] [ Designated as safety issue: Yes ]
    AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have 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. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.


Enrollment: 230
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) Daclatasvir + Simeprevir
Participants with hepatitis C virus genotype 1b received daclatasvir, 30 mg, once daily with or without food + simeprevir, 150 mg, once daily with a meal for 12 weeks
Drug: Daclatasvir
Tablets, oral, 30 mg, once daily
Other Name: BMS-790052
Drug: Simeprevir
Capsule, oral, 150 mg, once daily
Other Name: TMC435
Experimental: Cohort 2: (Genotype 1b) Daclatasvir + Simeprevir + Ribavirin
Participants with hepatitis C virus genotype 1b received daclatasvir, 30 mg, once daily with or without food + simeprivir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day) for 12 weeks.
Drug: Daclatasvir
Tablets, oral, 30 mg, once daily
Other Name: BMS-790052
Drug: Simeprevir
Capsule, oral, 150 mg, once daily
Other Name: TMC435
Experimental: Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin
Participants with hepatitis C virus genotype 1a received daclatasvir, 30 mg, once daily with or without food + simeprevir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day) for 12 weeks.
Drug: Daclatasvir
Tablets, oral, 30 mg, once daily
Other Name: BMS-790052
Drug: Simeprevir
Capsule, oral, 150 mg, once daily
Other Name: TMC435
Drug: Ribavirin
Tablets, oral, 500-600 mg, twice daily
Experimental: Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin
Participants with hepatitis C virus genotype 1a received daclatasvir, 30 mg, once daily with or without food + simeprivir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing <75 kg received a total ribavirin dose of 1000 mg per day; those weighing >=75 kg received 1200 mg per day.
Drug: Daclatasvir
Tablets, oral, 30 mg, once daily
Other Name: BMS-790052
Drug: Simeprevir
Capsule, oral, 150 mg, once daily
Other Name: TMC435
Drug: Ribavirin
Tablets, oral, 500-600 mg, twice daily

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Hepatitis C virus (HCV) genotype 1a or 1b
  • Males and females, ≥18 years of age
  • HCV RNA ≥10,000 IU/mL
  • Participants 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 patients
    • If no cirrhosis, a liver biopsy within 3 years prior to enrollment
    • If cirrhosis is present, any prior liver biopsy

Key Exclusion Criteria:

  • Liver or any other transplant (other than cornea and hair)
  • Evidence of a medical condition contributing to chronic liver disease other than HCV infection
  • 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
  • Patients infected with HIV or hepatitis B virus
  • Gastrointestinal disease impacting absorption of study drug
  • Uncontrolled diabetes or hypertension
  • Prior exposure to an HCV direct-acting agent
  • Any criteria that would exclude the patient from receiving ribavirin
  • Absolute neutrophil count <1.5*1,000,000,000 cells/L (<1.2*1,000,000,000 cells/L for Black/African Americans)
  • Platelets <90*1,000,000,000 cells/L
  • Hemoglobin <12 g/dL for females, <13 g/dL for males
  • Alanine aminotransferase ≥5*upper limit of normal
  • In patients without cirrhosis, total bilirubin ≥2 mg/dL unless patient has a documented history of Gilbert's disease
  • In patients with cirrhosis, total bilirubin o ≥1.5 mg/dL
  • International normalized ratio ≥1.7
  • QTcF or QTcB >500 mSec
  • Creatinine clearance ≤50 mL/min
  • Alpha fetoprotein (AFP) >100 ng/mL OR
  • AFP ≥50 ng/mL and ≤100 ng/mL requiring liver ultrasound
  • Albumin <3.5 g/dL
  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
San Francisco General Hospital
San Francisco, California, United States, 94110
Kaiser Permanente Med Ctr
San Francisco, California, United States, 94118
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:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Results First Received: August 13, 2015
Last Updated: October 29, 2015
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 C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Simeprevir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2016