The purpose of this study is to determine if combination therapy with Pegylated Interferon Lambda (BMS-914143) plus Ribavirin (RBV) with a single direct antiviral agent (BMS-790052 or BMS-650032) for 24 weeks is effective and safe for treatment of Chronic Hepatitis C (CHC) compared to current standard therapy with Pegylated Interferon Alpha-2a plus RBV for 48 weeks.
Study Classification: Pharmacokinetics/ Pharmacodynamics
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
165
Solution, Subcutaneous, 180 μg/mL, Once weekly, 24 or 48 weeks depending on response
Tablets, Oral, 60 mg, Once daily, 24 weeks
Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 48 weeks
Safety and tolerability (as measured by the frequency of serious adverse events (SAEs), dose reductions and discontinuations due to adverse events (AEs)
Time frame: Up to end of treatment ( maximum of 48 weeks) plus 30 days
Antiviral activity as determined by the proportion of Hepatitis C virus (HCV) genotype 1 subjects with 24-week sustained virologic response (SVR24)
Time frame: At end of treatment (maximum of 48 weeks)
Antiviral activity as determined by the proportion of Hepatitis C virus (HCV) genotype 1 subjects with 24-week sustained virologic response (SVR24)
Time frame: Post-treatment Week 24
Proportion of HCV genotype 1 subjects with Protocol definition of virologic response (PDR) for Part A and Part B
* Part A PDR is defined as HCV RNA at Week 4 \< LLOQ and Week 12 undetectable * Part B PDR is defined as HCV RNA at Week 2 ≥ 2 log10 decrease (or \< Lower limit of quantitation (LLOQ) if baseline HCV RNA \< 2400 IU/mL), Week 4 \< LLOQ and Week 12 undetectable
Time frame: Weeks 4, Weeks 12 and post-treatment Weeks 24
Proportion of subjects with either a 2-log or greater decrease in Hepatitis C virus (HCV) Ribonucleic acid (RNA) levels from baseline or undetectable levels of HCV RNA
Time frame: Weeks 2, Weeks 4 and Weeks 12
Proportion of subjects with viral breakthrough, defined as confirmed > 1 log10 increase in HCV RNA over nadir or confirmed HCV RNA ≥ Lower limit of quantitation (LLOQ) after confirmed undetectable HCV RNA while on treatment
Time frame: Post-treatment Week 48
Proportion of subjects with undetectable HCV RNA at the end of treatment that develop detectable levels of HCV RNA in the post-treatment follow-up period
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Tablets, Oral, 200 mg, Twice daily, 24 weeks
Solution, Subcutaneous, 180 μg/mL, Once weekly, 48 weeks
Solution, Subcutaneous, 180 μg/mL, Once weekly, 24 weeks
Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 24 weeks
Solution, Subcutaneous, 180 μg/mL, Once weekly, 16 weeks
Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 16 weeks
Tablets, Oral, 60 mg, Once daily, 16 weeks
Tablets, Oral, 200 mg, Twice daily, 16 weeks
Tablets, Oral, 0 mg, Twice daily, 24 weeks
Tablets, Oral, 0 mg, Once daily, 24 weeks
Tablets, Oral, 0 mg, Twice daily, 24 weeks
Tablets, Oral, 0 mg, Twice daily, 16 weeks
Mayo Clinic Hospital
Phoenix, Arizona, United States
Desert Medical Group Inc.
Palm Springs, California, United States
University Of Colorado Denver And Hospital
Aurora, Colorado, United States
Yale University School Of Medicine
New Haven, Connecticut, United States
Johns Hopkins University
Lutherville, Maryland, United States
Henry Ford Health System
Detroit, Michigan, United States
Bristol-Myers Squibb/David E. Bernstein, Md
Manhasset, New York, United States
Carolinas Medical Center
Charlotte, North Carolina, United States
Carolinas Center For Liver Disease
Statesville, North Carolina, United States
St. Luke'S Episcopal Hospital - Baylor College Of Medicine
Houston, Texas, United States
...and 30 more locations
Time frame: Post-treatment Week 48
Serum HCV Ribonucleic acid (RNA) levels over time
Time frame: Days 1, 3, Weeks 1, 2, 4, 6, 8, 12, 16, 20, and end of treatment (Week 16, 24 or 48 depending on treatment assignment)
Proportion of subjects with undetectable HCV RNA over time
Time frame: Days 1, 3, Weeks 1, 2, 4, 6, 8, 12, 16, 20, and end of treatment (Week 16, 24 or 48 depending on treatment assignment)
Time to viral clearance, defined as an absence of detectable HCV RNA
Time frame: Day 1, 3, Week 1, 2, 4, 6, 8, 12, 24, 36, end of treatment (Week 48), Post-Treatment at Week 4, 12, 24, 36, 48, and 56
Serum levels of pegIFNλ and pegIFNα-2a and plasma levels of BMS-790052 and BMS-650032: In PK sub-study group Maximum observed serum/plasma concentration (Cmax)
Time frame: Cmax will be determined at Dose 5 (Study Visit Week 4: 0 - 12 h for BMS-650032, 0 - 24 h for BMS-790052, and 0 - 168 h for pegIFNλ and pegIFNα-2a)
Serum levels of pegIFNλ and pegIFNα-2a and plasma levels of BMS-790052 and BMS-650032: In PK sub-study group Time to maximum concentration (Tmax)
Time frame: Tmax will be determined at Dose 5 (Study Visit Week 4: 0 - 12 h for BMS-650032, 0 - 24 h for BMS-790052, and 0 - 168 h for pegIFNλ and pegIFNα-2a)
Serum levels of pegIFNλ and pegIFNα-2a and plasma levels of BMS-790052 and BMS-650032: In PK sub-study group Minimal observed serum/plasma concentration (Cmin)
Time frame: Cmin will be determined at Dose 5 (Study Visit Week 4: 0 - 12 h for BMS-650032, 0 - 24 h for BMS-790052, and 0 - 168 h for pegIFNλ and pegIFNα-2a)
Serum levels of pegIFNλ and pegIFNα-2a and plasma levels of BMS-790052 and BMS-650032: In PK sub-study group Area under the serum/plasma concentration-time curve during one dose interval AUC(TAU)
Time frame: AUC(TAU) will be determined at Dose 5 (Study Visit Week 4: 0 - 12 h for BMS-650032, 0 - 24 h for BMS-790052, and 0 - 168 h for pegIFNλ and pegIFNα-2a)
Serum levels of pegIFNλ and pegIFNα-2a and plasma levels of BMS-790052 and BMS-650032: In all subjects, trough concentrations will be assessed (Ctrough)
Time frame: Troughs at baseline (week 0), weeks 2, 4, 8, 12, 16, and 24
Proportion of subjects with 12-week sustained virologic response (SVR12), defined as undetectable HCV RNA
Time frame: At end of treatment (maximum of 48 weeks) and follow-up Week 12
Proportion of subjects with 4-week sustained virologic response (SVR4), defined as undetectable HCV RNA
Time frame: At end of treatment (maximum of 48 weeks) and follow-up Week 4