Study to Determine the Effectiveness and Safety of a Three Drug Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) Infected Patients Not Previously Treated With Currently Available Medications

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01455090
First received: October 18, 2011
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to estimate the rate of sustained virologic response (SVR) SVR12, where SVR12 is defined as HCV RNA < LOQ (detectable or undetectable) 12 weeks post-treatment in Genotype 1 & Genotype 4 treatment naive patients, and Genotype (GT1) infected patients who are prior null responders to pegIFN/ribavirin


Condition Intervention Phase
Chronic Hepatitis C
Drug: BMS-650032
Drug: BMS-790052
Drug: BMS-791325
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: Open-Label, Multiple-Dose, Dose Escalation Study to Evaluate the Pharmacodynamics, Pharmacokinetics, and Safety of Coadministration of BMS-650032, BMS-790052, and BMS-791325 When Administered for 24 or 12 Weeks in Treatment-Naïve Subjects Infected With Hepatitis C Virus Genotype 1

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12) [ Time Frame: 12 weeks post-treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects with HCV ribonucleic acid (RNA) < limit of quantification (LOQ) (detectable and undetectable) [ Time Frame: Weeks 1, 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22 and 24 weeks of therapy; at end of treatment (EOT) (following 12 or 24 weeks of treatment, by Group); and Weeks 4, 12, 24, 36, and 48 weeks post-treatment ] [ Designated as safety issue: No ]
  • Proportion of subjects with HCV ribonucleic acid (RNA) undetectable [ Time Frame: Weeks 1, 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22 and 24 weeks of therapy; at end of treatment (EOT) (following 12 or 24 weeks of treatment, by Group); and Weeks 4, 12, 24, 36, and 48 weeks post-treatment ] [ Designated as safety issue: No ]
  • Proportion of subjects who experience viral breakthrough [ Time Frame: Formal analysis at SVR12, Week 48 of follow up period (or upon occurrence) ] [ Designated as safety issue: No ]

    viral breakthrough defined as:

    • Any increase in HCV RNA ≥ 1 log10 from nadir or
    • Any quantifiable HCV RNA ≥ 25 IU/mL (> LOQ) on or after Week 8

  • Proportion of subjects who experience viral relapse defined as confirmed quantifiable HCV RNA ≥ 25 IU/mL (>LOQ) in a subject with HCV RNA < LOQ or undetectable at End of treatment (EOT) [ Time Frame: End of treatment (Maximum up to 24 Weeks) ] [ Designated as safety issue: No ]
  • Maximum observed plasma concentration (Cmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
  • Observed plasma concentration at 12 hours (C12) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
  • Observed plasma concentration at 24 hours (C24) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
  • Trough observed plasma concentration (Ctrough) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
  • Time of maximum observed plasma concentration (Tmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
  • HCV genomic substitutions associated with exposure of BMS-650032, BMS-790052, and BMS-791325 [ Time Frame: At the time of viral breakthrough or relapse ] [ Designated as safety issue: No ]
  • Frequency of deaths, serious adverse events (SAEs), discontinuations due to adverse events (AEs), severity Grade 3/4 AEs, and severity Grade 3/4 laboratory abnormalities [ Time Frame: Formal analysis at week 48 of follow up period (or upon occurrence) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 316
Study Start Date: November 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)

BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks

BMS-790052 60 mg tablet by mouth once daily for 24 Weeks

BMS 791325 75 mg table by mouth twice daily for 24 Weeks

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325
Experimental: Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)

BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

BMS-790052 60 mg tablet by mouth once daily for 12 Weeks

BMS 791325 75 mg table by mouth twice daily for 12 Weeks

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325
Experimental: Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)

* Contingent upon review of safety data from all available treated subjects from Groups 1 and 2

BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks

BMS-790052 60 mg tablet by mouth once daily for 24 Weeks

BMS 791325 150 mg table by mouth twice daily for 24 Weeks

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325
Experimental: Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)

* Contingent upon review of safety data from all available treated subjects from Groups 1 and 2

BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

BMS-790052 60 mg tablet by mouth once daily for 12 Weeks

BMS 791325 150 mg table by mouth twice daily for 12 Weeks

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325
Experimental: Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)

* Genotype 1 treatment-naive subjects

BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks

BMS 791325 75 mg table by mouth twice daily for 12 Weeks

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325
Experimental: Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)

* Genotype 1 treatment-naive subjects

BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks

BMS 791325 150 mg table by mouth twice daily for 12 Weeks

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325
Experimental: Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)

* Genotype 4 treatment-naive subjects

BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks

BMS 791325 75 mg table by mouth twice daily for 12 Weeks

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325
Experimental: Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)

* Genotype 4 treatment-naive subjects

BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks

BMS 791325 150 mg table by mouth twice daily for 12 Weeks

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325
Experimental: Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)

* Genotype 1 treatment-null/non-responder subjects

BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks

BMS 791325 75 mg table by mouth twice daily for 12 Weeks

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325
Experimental: Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)

* Genotype 1 treatment-null/non-responder subjects

BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks

BMS 791325 150 mg table by mouth twice daily for 12 Weeks

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325
Experimental: Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)

* Genotype 1 treatment-null/non-responder subjects

BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks

BMS-790052 30 mg tablet by mouth twice daily for 24 Weeks

BMS 791325 75 mg table by mouth twice daily for 24 Weeks

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325
Experimental: Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)

* Genotype 1 treatment-null/non-responder subjects

BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks

BMS-790052 30 mg tablet by mouth twice daily for 24 Weeks

BMS 791325 150 mg table by mouth twice daily for 24 Weeks

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325
Experimental: Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBV

* Genotype 1 treatment-naive subjects

BMS-650032 200 mg tablets orally twice daily 12 weeks

BMS-790052 30 mg tablets orally twice daily 12 weeks

BMS-791325 75 mg tablets orally twice daily 12 weeks

Ribavirin (RBV) tablets orally weight based dosing daily 12 weeks [if subject is < 75 kg: 1000 mg per day orally (2 x 200 mg tablets in AM and 3 x 200 mg tablets in PM), or if ≥ 75 kg: 1200 mg per day orally (3 x 200 mg tablets in AM and 3 x 200 mg tablets in PM]

Drug: BMS-650032
Other Name: Asunaprevir (ASV)
Drug: BMS-790052
Other Name: Daclatasvir (DCV)
Drug: BMS-791325 Drug: Ribavirin
Other Name: Copegus®

Detailed Description:

IND numbers: 79,599; 101,943

  Eligibility

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

Inclusion Criteria:

  • Men and women, ages ≥18 years of age
  • Subjects who are naive to HCV treatment, defined as no previous exposure to an Interferon (IFN), Ribavirin (RBV); or any HCV-specific direct acting antiviral or experimental therapy or subjects who are null responders to previous pegylated Interferon alfa (pegIFNα) plus Ribavirin (RBV) treatment
  • Subjects should have chronic hepatitis C (CHC) as documented by:

    1. Positive for anti-HCV antibody, HCV RNA, or a positive HCV genotype test at least 6 months prior to screening, and positive for HCV RNA and Anti-HCV antibody at the time of screening, or
    2. Positive for anti-HCV antibody and HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed prior to enrollment with evidence of CHC disease, such as the presence of fibrosis)
  • HCV genotype 1a, 1b or 4 only
  • HCV RNA viral load of ≥10,000 IU/mL at screening
  • Have one of the following:

    1. Documented Fibrotest score of ≤0.72 and aspartate transferase (transminase) to platelet ratio index (APRI) ≤2; OR
    2. Documented liver biopsy within 36 months preceding Day 1 showing absence of cirrhosis OR
    3. Documented Fibroscan® ultrasound (where approved) within 12 months of screening showing absence of cirrhosis
  • Body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive
  • Subjects with compensated Child-Pugh A cirrhosis as documented by history of cirrhosis with any prior liver biopsy or Fibroscan® ultrasound (where approved) within 12 months prior to screening

Exclusion Criteria:

  • Evidence of a medical condition associated with chronic liver disease other than HCV (such as but not limited to: hemochromatosis, autoimmune hepatitis,metabolic liver disease, alcoholic liver disease, toxin exposures)
  • History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis
  • 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
  • Documented or suspected hepatocellular carcinoma (HCC)
  • Positive for hepatitis B surface antigen (HBsAg)
  • Positive for Human Immunodeficiency Virus-1 (HIV-1) and/or Human Immunodeficiency Virus-2 (HIV-2) antibodies
  • Alanine transferase (transminase) (ALT) >5x upper limit of normal (ULN)
  • Total Bilirubin ≥2 mg/dL
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01455090

  Show 33 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01455090     History of Changes
Other Study ID Numbers: AI443-014, 2011-002788-11
Study First Received: October 18, 2011
Last Updated: November 22, 2013
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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 April 17, 2014