chronic hepatitis C
Conditions
Interventions
MK-7009 (Study Parts 1 and 2):
All doses of MK-7009 will be administered orally in an open-label fashion using
the Phase II formulation, which is a liquid filled capsule formulation (known
as nLFC3)
Sponsors
Merck Sharp & Dohme (MSD)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Patient is a male or female between 18 to 65 years of age. • Patient has a Body Mass Index (BMI) >=18.5 kg/m2 and levels >= 10,000 IU/mL) in peripheral blood. • The patient does not have cirrhosis as confirmed by FibroSure*/FibroTest® and/or local country procedure (e.g. transient elastography/Fibroscan). • Patient is treatment-naive, or treatment-experienced, with regard to prior treatment for chronic HCV infection, defined as: Patient has previously been treated with and has tolerated at least 12 weeks of continuous licensed interferon (including pegylated interferon) and ribavirin combination therapy for HCV (patients previously treated with licensed NS3/4A protease inhibitors are not eligible for inclusion) with at least a partial response (>=2-log10 drop in HCV RNA at week 12) and/or patient has previously been treated with investigational products and/or vaccines for chronic HCV infection, other than NS3/4A protease inhibitors, either alone or in combination with other licensed therapies for chronic HCV infection. • Patient is able to avoid use of anticoagulants, nonsteroidal anti-inflammatory agents and aspirin for at least seven (7) days preceding the initial liver biopsy and continuing throughout the entire study.
Exclusion criteria
Exclusion criteria: • Patient is under the age of legal consent, is mentally or legally incapacitated • Patient has a history of stroke, chronic seizures, or major neurological disorder. • Patient did not achieve a viral response to prior treatment with licensed interferon-based therapy (i.e., is a *null responder*). Viral response is defined by a >=2-log10 decline in HCV viral RNA within the first 12 weeks of therapy. • Patient has previously been treated with an NS3/4A protease inhibitor (investigational or licensed) for chronic HCV infection. • Evidence of high grade bridging fibrosis (e.g., METAVIR score >3, Ishak score >4 or Scheuer score >3) from prior liver biopsy within 3 years of study entry and/or non biopsy procedure (e.g. Fibroscan) as per local guidelines. • Patient has evidence or history of chronic hepatitis not caused by HCV infection including but not limited to non-HCV viral hepatitis, nonalcoholic steatohepatitis (NASH), drug-induced hepatitis or autoimmune hepatitis. • Patient has clinical or laboratory evidence of cirrhosis or other advanced liver disease. • Patient has a history of clinically significant uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases. • Patient has a history of clinically significant neoplastic disease (including leukemia, lymphoma, malignant melanoma), or myeloproliferative disease, regardless of the time since treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| MK-7009 Hepatic and Plasma PK Measurements: Hepatic tissue samples from FNA will be obtained at 3, 12 and 24-hours post-dose to assess hepatic concentrations of MK-7009 (CH,3hr, CH,12hr and CH,24hr, respectively), to calculate an apparent terminal half life (tH,1/2) in the liver for MK-7009, and an area under the liver concentration versus time curve (population AUCH,0-12hr), as appropriate. Samples will also be obtained (48 and 72 hours post-dose) to characterize the elimination phase in the liver. Plasma samples will be obtained throughout the dosing period (refer to the study flow chart for time-points) to assess the plasma PK of MK-7009 (e.g., population area under the plasma concentration versus time curve over 12 hours [AUC0-12hr], maximum concentration of drug in the plasma [Cmax], trough concentration of drug in the plasma [Ctrough], time to reach Cmax [Tmax], and apparent terminal half life [t1/2], as appropriate). Plasma sample may be analyzed for protein binding for MK-7009. The actual date and time of all PK samples, the actual date and time for the dose prior to each PK sample, and the actual date and time of the first MK-7009, Peg-IFN and RBV dose should be collected and recorded. Viral Resistance Measurements: Blood will be drawn from each patient prior to and after dosing on Day 7 to assess viral resistance mutations at the time-points as indicated in the Study Flow Chart. Efficacy Measurements: Blood will be drawn from patients to assess plasma HCV RNA levels at the time points as outlined in the study flow chart. Results from screening visit blood draws will be used to determine eligibility. Blood draws from time 0 through dosing and post-dosing will be used for efficacy analyses. RNA Profiling: RNA levels will be measured from blood samples for validation of blood specific gene expression for estimation of liver and blood content in the FNA samples. Refer to the study flow chart for collection times. | — |
Countries
Netherlands
Outcome results
None listed