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: August 11, 2014
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
Primary Completion Date: March 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
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: 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: August 11, 2014
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
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2014