Chronic Hepatitis C
Conditions
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
Detailed description
IND numbers: 79,599; 101,943
Interventions
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12) | 12 weeks post-treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | viral breakthrough defined as: * Any increase in HCV RNA ≥ 1 log10 from nadir or * Any quantifiable HCV RNA ≥ 25 IU/mL (\> LOQ) on or after Week 8 |
| 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 | — |
| Observed plasma concentration at 12 hours (C12) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 | Day 1 and Day 14 | — |
| 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 | — |
| Trough observed plasma concentration (Ctrough) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 | Day 1 and Day 14 | — |
| Time of maximum observed plasma concentration (Tmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 | Day 1 and Day 14 | — |
| Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 | Day 1 and Day 14 | — |
| HCV genomic substitutions associated with exposure of BMS-650032, BMS-790052, and BMS-791325 | At the time of viral breakthrough or relapse | — |
| Frequency of deaths, serious adverse events (SAEs), discontinuations due to adverse events (AEs), severity Grade 3/4 AEs, and severity Grade 3/4 laboratory abnormalities | Formal analysis at week 48 of follow up period (or upon occurrence) | — |
| Observed plasma concentration at 24 hours (C24) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 | Day 1 and Day 14 | — |
Countries
France, Puerto Rico, United States
Outcome results
None listed