Chronic Hepatitis C Virus
Conditions
Keywords
HCV, Hepatitis C, chronic hepatitis C, antiviral
Brief summary
Parts A and B of this study are designed to evaluate the safety, tolerability, efficacy and pharmacokinetic profiles of samatasvir and simeprevir when administered in combination with ribavirin (RBV) for 12 weeks in treatment-naïve, Genotype (GT) 1b, 4 and 6 hepatitic C virus (HCV)-infected participants. Part C of this study is designed to evaluate the safety, tolerability, efficacy and pharmacokinetic profiles of samatasvir, simeprevir, TMC647055 and ritonavir (RTV) when administered in combination with or without RBV for 12 weeks in treatment-naïve or interferon/RBV-treatment relapsed, GT 1a and 1b HCV-infected participants.
Detailed description
Part A of this study is randomized and double-blind. Parts B and C are randomized and open-label.
Interventions
DRUGSamatasvir
Samatasvir (IDX719) will be supplied as 25 mg and 50 mg oral tablets.
DRUGSimeprevir
Simeprevir will be supplied as 75 and 150 mg oral capsules.
DRUGRibavirin (RBV)
Ribavirin will be supplied as 200 mg oral tablets. Participants in the RBV-free arms experiencing non-response or virologic breakthrough during the treatment period will be offered RBV dosed according to the product label as an add-on to the participant's randomized treatment assignment.
DRUGTMC647055
TMC647055 will be supplied as 150 mg oral capsules.
DRUGRitonavir (RTV)
Ritonavir will be supplied as 80 mg/mL oral solution.
BIOLOGICALPegylated interferon (Peg-IFN)
Participants experiencing non-response or virologic breakthrough during the treatment period will be offered Peg-IFN (subcutaneous injection) dosed according to the product label as an add-on to the participant's randomized treatment assignment.
OTHERSamatasvir matching placebo
Samatasvir matching placebo will be supplied for the 50 mg tablets used in Part A.
Sponsors
Janssen Research & Development, LLC
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Must have Genotype 1a, 1b, 4 or 6 HCV infection. * Documented clinical history compatible with chronic hepatitis C * HCV treatment-naïve or interferon/RBV-treatment relapsed (Part C) * Must agree to use an acceptable double method of birth control (one of which must be a barrier method) for at least 6 months after the last dose of study drugs.
Exclusion criteria
* Female participants who are pregnant or breastfeeding. * Body Mass Index (BMI) \> 36 kg/m2. * Co-infected with hepatitis B virus or human immunodeficiency virus (HIV). * History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC. * History or signs of decompensated liver disease: ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of portal hypertension or hepatic insufficiency. * Has one or more known primary or secondary causes of liver disease, other than hepatitis C * History of, or active, acute or chronic, liver or biliary injury due to drugs, toxins, non-HCV viral hepatitis, gallstones or other etiologies * Donated blood or had significant blood loss 30 days prior to dosing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of participants who experienced an adverse event (AE) | Up to approximately 95 weeks |
| Percentage of participants who experienced a serious adverse event (SAE) | Up to approximately 95 weeks |
| Percentage of participants who experienced a Grade 1-4 laboratory abnormality | Up to 66 weeks |
| Percentage of participants who experienced sustained virologic response 4 weeks after the end of treatment (SVR4) | Up to 16 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of participants who experienced sustained virologic response 24 weeks after the end of treatment (SVR24) | Up to 36 weeks |
| Pharmacokinetic Parameter:Area under the concentration-time curve from time zero to t | Days 1, 4, 7, 10, 14, 21, 28, 42, 56 and 84 |
| Percentage of participants who experienced rapid virologic response (RVR) | Week 4 |
| Pharmacokinetic Parameter: Trough drug concentration (Ctrough) | Days 1, 4, 7, 10, 14, 21, 28, 42, 56 and 84 |
| Pharmacokinetic Parameter: Maximum observed drug concentration (Cmax) | Days 1, 4, 7, 10, 14, 21, 28, 42, 56 and 84 |
| Percentage of participants who experienced early virologic response (EVR) | Week 12 |
| Percentage of participants who experienced sustained virologic response 8 weeks after the end of treatment (SVR8) | Up to 20 weeks |
| Percentage of participants who experienced sustained virologic response 12 weeks after the end of treatment (SVR12) | Up to 24 weeks |
Outcome results
None listed