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

Chronic Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01455090
• Other study ID #: AI443-014
• Secondary ID: 2011-002788-11
• Status: Completed
• Phase: Phase 2
• First received: October 18, 2011
• Last updated: April 26, 2017
• Start date: November 30, 2011
• Est. completion date: July 31, 2015

Study information

• Verified date: April 2017
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

IND numbers: 79,599; 101,943

Recruitment information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: July 31, 2015
• Est. primary completion date: March 31, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (pegIFNa) 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

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• BMS-650032

• BMS-790052

• BMS-791325

• Ribavirin

Locations

Country	Name	City	State
France	Local Institution	Clichy Cedex
France	Local Institution	Creteil Cedex
France	Local Institution	Limoges
France	Local Institution	Marseille Cedex 08
France	Local Institution	Paris Cedex 14
Puerto Rico	Fundacion De Investigacion De Diego	San Juan
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Atlanta Gastroenterology Associates, Llc	Atlanta	Georgia
United States	University Of Colorado Denver And Hospital	Aurora	Colorado
United States	Mercy Medical Center, Inc.	Baltimore	Maryland
United States	The Kirklin Clinic	Birmingham	Alabama
United States	Southern California Research Center	Coronado	California
United States	Metropolitan Research	Fairfax	Virginia
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Id Care	Hillsborough	New Jersey
United States	Research Specialists Of Texas	Houston	Texas
United States	Peter J Ruane Md Inc	Los Angeles	California
United States	Va Greater Los Angeles Healthcare System	Los Angeles	California
United States	Johns Hopkins University	Lutherville	Maryland
United States	Dean Clinic	Madison	Wisconsin
United States	Orlando Immunology Center	Orlando	Florida
United States	Lifetree Clinical Research	Salt Lake City	Utah
United States	Alamo Medical Research	San Antonio	Texas
United States	Medical Associates Research Group	San Diego	California
United States	Precision Research Institute, Llc	San Diego	California
United States	Research And Education, Inc.	San Diego	California
United States	Southwest Care Center	Santa Fe	New Mexico
United States	Miami Research Associates	South Miami	Florida
United States	James J Peters Vamc	The Bronx	New York
United States	Healthcare Research Consultants	Tulsa	Oklahoma
United States	Options Health Research, Llc	Tulsa	Oklahoma
United States	Medstar Georgetown University Hospital	Washington, D.C.	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  France,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12)		12 weeks post-treatment
Secondary	Proportion of subjects with HCV ribonucleic acid (RNA) < limit of quantification (LOQ) (detectable and undetectable)		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
Secondary	Proportion of subjects with HCV ribonucleic acid (RNA) undetectable		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
Secondary	Proportion of subjects who experience viral breakthrough	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	Formal analysis at SVR12, Week 48 of follow up period (or upon occurrence)
Secondary	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)		End of treatment (Maximum up to 24 Weeks)
Secondary	Maximum observed plasma concentration (Cmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712		Day 1 and Day 14
Secondary	Observed plasma concentration at 12 hours (C12) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712		Day 1 and Day 14
Secondary	Observed plasma concentration at 24 hours (C24) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712		Day 1 and Day 14
Secondary	Trough observed plasma concentration (Ctrough) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712		Day 1 and Day 14
Secondary	Time of maximum observed plasma concentration (Tmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712		Day 1 and Day 14
Secondary	Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-650032, BMS-790052, BMS 791325, and BMS-794712		Day 1 and Day 14
Secondary	HCV genomic substitutions associated with exposure of BMS-650032, BMS-790052, and BMS-791325		At the time of viral breakthrough or relapse
Secondary	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		Formal analysis at week 48 of follow up period (or upon occurrence)

External Links

•   BMS Clinical Trial Information
•   FDA Safety Alerts and Recalls