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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis C

Treatments: Drug: BMS-791325; Drug: Ribavirin; Drug: BMS-650032; Drug: BMS-790052

Study type: Interventional

Funder types: Industry

Identifiers

NCT01455090

2011-002788-11 (EudraCT Number)

AI443-014

Details and patient eligibility

About

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

Full description

IND numbers: 79,599; 101,943

Enrollment: 320 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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320 participants in 13 patient groups

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

Experimental group

Description:

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

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: BMS-791325

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

Experimental group

Description:

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

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: BMS-791325

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

Experimental group

Description:

\* 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

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: BMS-791325

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

Experimental group

Description:

\* 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

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: BMS-791325

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

Experimental group

Description:

\* 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

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: BMS-791325

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

Experimental group

Description:

\* 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

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: BMS-791325

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

Experimental group

Description:

\* 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

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: BMS-791325

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

Experimental group

Description:

\* 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

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: BMS-791325

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

Experimental group

Description:

\* 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

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: BMS-791325

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

Experimental group

Description:

\* 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

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: BMS-791325

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

Experimental group

Description:

\* 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

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: BMS-791325

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

Experimental group

Description:

\* 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

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: BMS-791325

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

Experimental group

Description:

\* 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 \[if subject is \< 75 kg: 1000 mg per day orally (2 x 200 mg tablets in AM and 3 x 200 mg tablets in PM), or if ≥ 75 kg: 1200 mg per day orally (3 x 200 mg tablets in AM and 3 x 200 mg tablets in PM\]

Treatment:

Drug: BMS-790052

Drug: BMS-650032

Drug: Ribavirin

Drug: BMS-791325