Study to Determine the Effectiveness of Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) Infected Patients Who Have Previously Failed Standard of Care

Sponsor

Bristol-Myers Squibb (Industry)

Overall Status

Completed

CT.gov ID

NCT01012895

Collaborator

(none)

215

Enrollment

Locations

Arms

Duration (Months)

11.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether BMS-650032 and BMS-790052 in combination alone, together with Ribavirin, or together with Interferon and Ribavirin are effective in the treatment of Hepatitis C in patients who have not responded to prior therapy.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: BMS-790052 Drug: BMS-650032 Drug: BMS-650032 Drug: BMS-650032 Drug: Pegylated-interferon alfa-2a Drug: Ribavirin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

215 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Parallel, Open-Label, Randomized, Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-790052 and BMS-650032 in Combination in Null Responders to Standard of Care Infected With Chronic Hepatitis C Virus Genotype 1

Study Start Date :

Dec 1, 2009

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: Sentinel A BMS-790052 (60mg) once daily + BMS-650032 (600 mg) twice daily	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 600 mg, twice daily, 24 weeks
Experimental: Arm 2: Sentinel B BMS-790052 (60mg) once daily + BMS-650032 (600mg) twice daily + Pegylated-interferon alfa-2a + Ribavirin	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 600 mg, twice daily, 24 weeks Drug: Pegylated-interferon alfa-2a Syringe, Subcutaneous Injection, 180 µg, once weekly Other Names: Pegasys Drug: Ribavirin Tablets, Oral For subjects weighing < 75 kg: 1000 mg; For subjects weighing ≥ 75 kg: 1200 mg Twice daily (< 75 kg: 400 mg in ante meridian (AM) and 600 mg in post meridian (PM); ≥ 75 kg: 600 mg in AM and PM), 24 weeks Other Names: Copegus
Experimental: Arm 3: Expansion A1 BMS-790052 (60mg) once daily + BMS-650032 (200mg) twice daily	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 200mg, twice daily, 24 weeks
Experimental: Arm 4: Expansion A2 BMS-790052 (60mg) once daily + BMS-650032 (200mg) once daily	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 200 mg, once daily, 24 weeks
Experimental: Arm 5: Expansion B1 BMS-790052 (60mg) once daily + BMS-650032 (200 mg) twice daily + Pegylated-interferon alfa-2a + Ribavirin	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 200mg, twice daily, 24 weeks Drug: Pegylated-interferon alfa-2a Syringe, Subcutaneous Injection, 180 µg, once weekly Other Names: Pegasys Drug: Ribavirin Tablets, Oral For subjects weighing < 75 kg: 1000 mg; For subjects weighing ≥ 75 kg: 1200 mg Twice daily (< 75 kg: 400 mg in ante meridian (AM) and 600 mg in post meridian (PM); ≥ 75 kg: 600 mg in AM and PM), 24 weeks Other Names: Copegus
Experimental: Arm 6: Expansion B2 BMS-790052 (60mg) once daily + BMS-650032 (200 mg) once daily + Pegylated-interferon alfa-2a + Ribavirin	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 200 mg, once daily, 24 weeks Drug: Pegylated-interferon alfa-2a Syringe, Subcutaneous Injection, 180 µg, once weekly Other Names: Pegasys Drug: Ribavirin Tablets, Oral For subjects weighing < 75 kg: 1000 mg; For subjects weighing ≥ 75 kg: 1200 mg Twice daily (< 75 kg: 400 mg in ante meridian (AM) and 600 mg in post meridian (PM); ≥ 75 kg: 600 mg in AM and PM), 24 weeks Other Names: Copegus
Experimental: Arm 7: Expansion B3 BMS-790052 (60 mg) once daily + BMS-650032 (200 mg) twice daily + Ribavirin	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 200mg, twice daily, 24 weeks Drug: Ribavirin Tablets, Oral For subjects weighing < 75 kg: 1000 mg; For subjects weighing ≥ 75 kg: 1200 mg Twice daily (< 75 kg: 400 mg in ante meridian (AM) and 600 mg in post meridian (PM); ≥ 75 kg: 600 mg in AM and PM), 24 weeks Other Names: Copegus

Outcome Measures

Primary Outcome Measures

Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in subjects' blood before, during and after treatment [12 weeks post treatment]

Secondary Outcome Measures

Safety assessments will be based on medical review of the frequency of SAEs and AEs, discontinuations due to AEs, and abnormalities observed from vital sign and ECG measurements, physical examinations and clinical laboratory results [12 weeks post-treatment]
Serious Adverse Events (SAEs), Adverse Events (AEs), Electrocardiogram (ECG)
Pharmacokinetic parameter maximum observed concentration [Cmax] will be derived from plasma concentration versus time. Trough concentration (Ctrough) and sparse Pharmacokinetics (PK) samples will also be collected. [Day 1 and Day 14]
Pharmacokinetic parameter trough observed concentration [Cmin] will be derived from plasma concentration versus time. Trough concentration (Ctrough) and sparse Pharmacokinetics (PK) samples will also be collected. [Days 1, Days 7, Days 14, Weeks 4, Weeks 8, Weeks 12, Weeks 16]
Pharmacokinetic parameter time of maximum observed concentration [Tmax] will be derived from plasma concentration versus time. Trough concentration (Ctrough) and sparse Pharmacokinetics (PK) samples will also be collected. [Day 1 and Day 14]
Pharmacokinetic parameter area under the concentration-time curve in one dosing interval [AUC(TAU)] will be derived from plasma concentration versus time. Trough concentration (Ctrough) and sparse Pharmacokinetics (PK) samples will also be collected. [Day 1 and Day 14]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female subjects ages 18 to 70 years
HCV-Infected Genotype 1 Null responders to current standard of care
Expansion Cohorts A1 and A2 are restricted to patients infected with HCV Genotype 1b only.

Exclusion Criteria:

Evidence of a medical condition associate with chronic liver disease other than HCV
History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis
History of Cancer within 5 years of enrollment
History of gastrointestinal disease or surgical procedure (except Cholecystectomy)
History of clinically significant cardiac disease
History of Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Documented cirrhosis within 12 months prior to dosing
Positive for Human Immunodeficiency Virus (HIV) or Hepatitis B Virus (HBV)
Pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Advanced Clinical Research Institute	Anaheim	California	United States	92801
2	Southern California Liver Centers	Coronado	California	United States	92118
3	San Jose Gastroenterology	San Jose	California	United States	95128
4	University Of Colorado Denver & Hospital	Aurora	Colorado	United States	80045
5	Mercy Medical Center	Baltimore	Maryland	United States	21202
6	University Of Michigan Health System	Ann Arbor	Michigan	United States	48109
7	Carolinas Center For Liver Disease	Statesville	North Carolina	United States	28677
8	Texas Clinical Research Institute, Llc	Arlington	Texas	United States	76012
9	Alamo Medical Research	San Antonio	Texas	United States	78215
10	Metropolitan Research	Fairfax	Virginia	United States	22031
11	Local Institution	Clichy Cedex		France	92118
12	Local Institution	Creteil Cedex		France	94010
13	Local Institution	Marseille Cedex 08		France	13285
14	Local Institution	Paris Cedex 12		France	75571
15	Local Institution	Paris Cedex 13		France	75651
16	Local Institution	Paris Cedex 14		France	75679
17	Local Institution	Pessac		France	33604
18	Local Institution	San Juan		Puerto Rico	00927