Chronic Hepatitis C
Conditions
Brief summary
This study is divided into 2 segments, and proposes to qualify fine needle aspiration (FNA) as a platform to evaluate the hepatic pharmacokinetics of low and high oral doses of Grazoprevir (MK-5172) in non-cirrhotic participants chronically infected with hepatitis C virus (HCV). The first segment, is a procedural pilot conducted prior to the main study, that is aimed at ensuring optimal execution of the FNA procedure. During the procedural pilot, core needle biopsy (CNB) will be performed on participants as part of their standard of care, but no study drugs will be administered, nor will any procedures other than FNA be conducted. The second segment, the main study, is designed to evaluate the feasibility of measuring Grazoprevir by FNA. During the main study, drugs will be administered, and other additional procedures will be conducted.
Interventions
DRUGRibavirin
Ribavirin, 600-1400 mg administered orally, twice daily, over the entire course of the study.
DRUG800 mg Grazoprevir
800 mg Grazoprevir administered orally, once per day, for 7 consecutive days.
DRUG100 mg Grazoprevir
100 mg Grazoprevir administered orally, once per day, for 7 consecutive days.
PROCEDURELiver samples from CNB and FNA
Tissue samples from the liver are collected by CNB as part of standard of care, and also by FNA during a single visit.
DRUGPeg-Interferon
Polyethyleneglycolated Interferon alfa-2b at 1.5 ug/kg/week, administered subcutaneously, once a week, over the entire course of the study.
PROCEDURELiver Samples from FNA
Tissue samples are collected at 3 separate visits, with each collection consisting of 3-4 fine needle aspiration (FNA) passes through the liver, guided by ultrasound.
PROCEDURELiver Samples from CNB
Tissue samples are collected at 1 of six possible visits by core needle biopsy (CNB) of the liver.
PROCEDUREBlood Samples
Blood is collected from multiple blood draws, with the total volume for each participant not expected to exceed 500 ml.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Has chronic compensated HCV infection. * No contraindications to CNB or FNA procedures. * Pilot study only: All comers with chronic HCV already scheduled to undergo CNB for fibrosis staging. * Pilot study only: Requires a diagnostic liver biopsy to monitor progression of liver disease. * Pilot study only: Does not have cirrhosis. * Main study only: Males or non-pregnant and postmenopausal females willing to use medically acceptable contraception during, and for 6 months or longer after study. * Main study only: Body mass index of 18.5 - 32.0 kg/m\^2. * Main study only: Can avoid aspirin, anticoagulants, and non steroidal inflammatory agents. * Main study only: Has undergone prior treatment or is treatment naive for chronic HCV infection.
Exclusion criteria
for Main study only: * History of any of the following: stroke, chronic seizures, major neurological disorders, gastric bypass surgery or bowel resection. * No viral response to prior interferon based therapy. * Prior treatment for HCV with an NS3/4A protease inhibitor. * History of either clinically significant, uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities/diseases. * History of neoplastic or myeloproliferative disease. * Has any of the following : cirrhosis, decompensated liver disease, or other advanced liver disease, hepatocellular carcinoma, infection with human immunodeficiency virus (HIV), or hepatitis B. * Evidence of high grade bridging fibrosis from prior liver biopsy or chronic hepatitis not caused by HCV. * History of illicit drug use or alcohol abuse. * Had surgery, donated at least one unit of blood, or participated in any other investigational study within 4 weeks prior to screening visit. * History of multiple and/or severe allergies.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants from whom detectable concentrations of hepatic Grazoprevir are obtained by FNA. | Days 7-12. |
Outcome results
None listed