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

NCT01455090 | Completed Phase 2

• 2 other identifiers: AI443-0142011-002788-11
• Study Type: interventional
• Target: 320
• Locations: 3 countries
• Sites: 32

Brief 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

Conditions

Chronic Hepatitis C

Outcome Measures

Primary Outcomes (1)

• Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12)

  12 weeks post-treatment

Secondary Outcomes (12)

• 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

• 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

• Proportion of subjects who experience viral breakthrough

  Formal analysis at SVR12, Week 48 of follow up period (or upon occurrence)

• 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)

• Maximum observed plasma concentration (Cmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712

  Day 1 and Day 14

Study Arms (13)

Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)

EXPERIMENTAL

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; Drug: BMS-790052; Drug: BMS-791325

Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)

EXPERIMENTAL

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; Drug: BMS-790052; Drug: BMS-791325

Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)

EXPERIMENTAL

\* 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; Drug: BMS-790052; Drug: BMS-791325

Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)

EXPERIMENTAL

\* 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; Drug: BMS-790052; Drug: BMS-791325

Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)

EXPERIMENTAL

\* 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; Drug: BMS-790052; Drug: BMS-791325

Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)

EXPERIMENTAL

\* 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; Drug: BMS-790052; Drug: BMS-791325

Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)

EXPERIMENTAL

\* 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; Drug: BMS-790052; Drug: BMS-791325

Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)

EXPERIMENTAL

\* 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; Drug: BMS-790052; Drug: BMS-791325

Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)

EXPERIMENTAL

\* 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; Drug: BMS-790052; Drug: BMS-791325

Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)

EXPERIMENTAL

\* 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; Drug: BMS-790052; Drug: BMS-791325

Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)

EXPERIMENTAL

\* 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; Drug: BMS-790052; Drug: BMS-791325

Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)

EXPERIMENTAL

\* 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; Drug: BMS-790052; Drug: BMS-791325

Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBV

EXPERIMENTAL

\* 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; Drug: BMS-790052; Drug: BMS-791325; Drug: Ribavirin

Interventions

BMS-650032 DRUG

Also known as: Asunaprevir (ASV)

Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg); Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg); Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg); Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg); Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg); Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg); Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg); Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg); Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg); Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg); Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg); Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg); Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBV

BMS-790052 DRUG

Also known as: Daclatasvir (DCV)

Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg); Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg); Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg); Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg); Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg); Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg); Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg); Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg); Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg); Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg); Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg); Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg); Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBV

BMS-791325 DRUG

Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg); Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg); Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg); Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg); Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg); Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg); Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg); Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg); Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg); Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg); Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg); Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg); Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBV

Ribavirin DRUG

Also known as: Copegus®

Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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:
• Documented Fibrotest score of ≤0.72 and aspartate transferase (transminase) to platelet ratio index (APRI) ≤2; OR
• Documented liver biopsy within 36 months preceding Day 1 showing absence of cirrhosis OR
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (32)

The Kirklin Clinic

Birmingham, Alabama, 35294, United States

Location

Southern California Research Center

Coronado, California, 92118, United States

Location

Peter J Ruane Md Inc

Los Angeles, California, 90036, United States

Location

Va Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

Research And Education, Inc.

San Diego, California, 92105, United States

Location

Precision Research Institute, Llc

San Diego, California, 92114, United States

Location

Medical Associates Research Group

San Diego, California, 92123, United States

Location

University Of Colorado Denver And Hospital

Aurora, Colorado, 80045, United States

Location

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Miami Research Associates

South Miami, Florida, 33143, United States

Location

Atlanta Gastroenterology Associates, Llc

Atlanta, Georgia, 30308, United States

Location

Mercy Medical Center, Inc.

Baltimore, Maryland, 21202, United States

Location

Johns Hopkins University

Lutherville, Maryland, 21093, United States

Location

Id Care

Hillsborough, New Jersey, 08844, United States

Location

Southwest Care Center

Santa Fe, New Mexico, 87505, United States

Location

James J Peters Vamc

The Bronx, New York, 10468, United States

Location

Options Health Research, Llc

Tulsa, Oklahoma, 74104, United States

Location

Healthcare Research Consultants

Tulsa, Oklahoma, 74135, United States

Location

Texas Clinical Research Institute

Arlington, Texas, 76012, United States

Location

Research Specialists Of Texas

Houston, Texas, 77030, United States

Location

Alamo Medical Research

San Antonio, Texas, 78215, United States

Location

Lifetree Clinical Research

Salt Lake City, Utah, 84106, United States

Location

Metropolitan Research

Fairfax, Virginia, 22031, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Dean Clinic

Madison, Wisconsin, 53715, United States

Location

Local Institution

Clichy, 92118, France

Location

Local Institution

Créteil, 9410, France

Location

Local Institution

Limoges, 87042, France

Location

Local Institution

Marseille, 13285, France

Location

Local Institution

Paris, 75679, France

Location

Fundacion De Investigacion De Diego

San Juan, 00927, Puerto Rico

Location

Related Publications (2)

• Everson GT, Sims KD, Thuluvath PJ, Lawitz E, Hassanein T, Rodriguez-Torres M, Desta T, Hawkins T, Levin JM, Hinestrosa F, Rustgi V, Schwartz H, Younossi Z, Webster L, Gitlin N, Eley T, Huang SP, McPhee F, Grasela DM, Gardiner DF. Daclatasvir + asunaprevir + beclabuvir +/- ribavirin for chronic HCV genotype 1-infected treatment-naive patients. Liver Int. 2016 Feb;36(2):189-97. doi: 10.1111/liv.12964. Epub 2015 Dec 6.

  PMID: 26473667 DERIVED

• Everson GT, Sims KD, Rodriguez-Torres M, Hezode C, Lawitz E, Bourliere M, Loustaud-Ratti V, Rustgi V, Schwartz H, Tatum H, Marcellin P, Pol S, Thuluvath PJ, Eley T, Wang X, Huang SP, McPhee F, Wind-Rotolo M, Chung E, Pasquinelli C, Grasela DM, Gardiner DF. Efficacy of an interferon- and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1 infection. Gastroenterology. 2014 Feb;146(2):420-9. doi: 10.1053/j.gastro.2013.10.057. Epub 2013 Oct 30.

  PMID: 24184132 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

asunaprevir; daclatasvir; 8-cyclohexyl-N-((dimethylamino)sulfonyl)-1,1a,2,12b-tetrahydro-11-methoxy-1a-((3-methyl-3,8-diazabicyclo(3.2.1)oct-8-yl)carbonyl)cycloprop(d)indolo(2,1-a)(2)benzazepine-5-carboxamide; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2011
• First Posted: October 19, 2011
• Study Start: November 30, 2011
• Primary Completion: March 31, 2014
• Study Completion: July 31, 2015
• Last Updated: April 27, 2017

Record last verified: 2017-04

Locations

US (26); FR (5); PR (1)