Hepatitis C
Conditions
Brief summary
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.
Detailed description
Study Classification: Pharmacokinetics/ Pharmacodynamics
Interventions
BIOLOGICALPegylated Interferon Lambda (pegIFNλ)
Solution, Subcutaneous, 180 μg/mL, Once weekly, 24 or 48 weeks depending on response
DRUGBMS-790052 (NS5A Inhibitor)
Tablets, Oral, 60 mg, Once daily, 24 weeks
DRUGRibavirin (RBV)
Tablets, Oral, 1000 or 1200 mg based on weight, Twice daily, 48 weeks
DRUGBMS-650032 (NS3 Protease Inhibitor)
Tablets, Oral, 200 mg, Twice daily, 24 weeks
Solution, Subcutaneous, 180 μg/mL, Once weekly, 48 weeks
DRUGPlacebo (PBO) for BMS-650032 (Placebo for NS3 Protease Inhibitor)
Tablets, Oral, 0 mg, Twice daily, 24 weeks
DRUGPlacebo (PBO) for BMS-790052 (Placebo for NS5A Inhibitor)
Tablets, Oral, 0 mg, Once daily, 24 weeks
DRUGPlacebo for Ribavirin (RBV)
Tablets, Oral, 0 mg, Twice daily, 24 weeks
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: * Chronic Hepatitis C, Genotype 1 * HCV RNA \>100,000 IU/mL at screening; * Seronegative for Human immunodeficiency virus (HIV) and Hepatitis B surface antigen (HBsAg); * Liver biopsy within prior 2 years; subjects with compensated cirrhosis can enroll and will be capped at approximately 10%
Exclusion criteria
* Any evidence of liver disease other than HCV; * Co-infection with HIV; * Diagnosed or suspected hepatocellular carcinoma; * Medical history or laboratory value abnormalities that would prohibit the use of Pegylated Interferon Alpha-2a or Ribavirin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability (as measured by the frequency of serious adverse events (SAEs), dose reductions and discontinuations due to adverse events (AEs) | 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) | At end of treatment (maximum of 48 weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | Post-treatment Week 48 | — |
| Serum HCV Ribonucleic acid (RNA) levels over time | 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 | 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 | 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) | 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) | — |
| Proportion of HCV genotype 1 subjects with Protocol definition of virologic response (PDR) for Part A and Part B | Weeks 4, Weeks 12 and post-treatment Weeks 24 | * 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 |
| 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) | 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) | 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) | 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 | 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 | At end of treatment (maximum of 48 weeks) and follow-up Week 4 | — |
| 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) | 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) | — |
| 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 | Weeks 2, Weeks 4 and Weeks 12 | — |
Countries
Australia, France, Germany, Italy, Japan, New Zealand, Puerto Rico, Spain, United States
Outcome results
None listed