Intrahepatic HCV RNA and Telaprevir Kinetics in Hepatitis C Virus (HCV)
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: Telaprevir; Peginterferon alfa-2a; Ribavirin
Intervention description: Fifteen subjects will receive the same treatment: 12 weeks of telaprevir (750 mg q8h) with Peg-IFN- alfa-2a (Pegasys(R)) (180 mcg SQ qwk) and RBV (1200 mg per day if >75 kg or 1000mg per day if < 75 kg).; Fifteen subjects will receive the same treatment: 12 weeks of telaprevir (750 mg q8h) with Peg-IFN- alfa-2a (Pegasys(R)) (180 mcg SQ qwk) and RBV (1200 mg per day if >75 kg or 1000mg per day if < 75 kg).; Fifteen subjects will receive the same treatment: 12 weeks of telaprevir (750 mg q8h) with Peg-IFN- alfa-2a (Pegasys(R)) (180 mcg SQ qwk) and RBV (1200 mg per day if >75 kg or 1000mg per day if < 75 kg).
Intervention MeSH terms: Ribavirin; Peginterferon alfa-2a
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: hepatitis C; FNA; intrahepatic

Summary:

      The purpose of this study is to determine the decline of virus in the blood and liver in
      patients treated with telaprevir, pegylated interferon and ribavirin.

      Fine Needle Aspiration (FNA) procedure will be used to repeatedly sample the liver to enhance
      the understanding of how the virus decays in the liver in response to treatment with
      anti-viral compounds and the measurement of the concentration of the drugs in the liver. FNA
      is an alternative procedure to core needle biopsy in its ability to repeatedly sample the
      liver with significantly reduced morbidity.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female subjects, 18-65 years of age, inclusive.

          2. Cases will be genotype 1 (confirmed by standard testing). Enrollment of controls will
             not be restricted by genotype.

          3. All patients must show evidence of chronic hepatitis C, confirmed by detectable plasma
             HCV RNA. Chronic disease status must be confirmed by at least one of the following
             standard criteria:

             History of a remote risk factor, or Abnormal ALT levels for >6 months prior to
             screening period (Note: elevated ALT is not an inclusion criteria, if one of the other
             criteria for "chronic" hepatitis C is met), or Detectable HCV RNA for at least 6
             months before the screening period

          4. Liver biopsy obtained within 24 months of study enrollment demonstrating absence of
             cirrhosis (stage 0-3) for cases. Enrollment of controls will not be restricted by
             stage of fibrosis.

          5. Judged to be in good health on the basis of medical history and physical examination
             (including vital signs and ECG), with any chronic medical conditions under stable
             medical control.

          6. Screening Visit laboratory values must be within the following:

               -  Laboratory variable: acceptable range

               -  Absolute neutrophil count: 1200/cmm³

               -  Platelet count: 90,000/cmm³

               -  Hemoglobin: within normal range

               -  HbsAg (screening visit only): seronegative

               -  HIV1 and 2 Ab (screening visit only): seronegative

             In addition, all other hematology and clinical chemistry must be within normal limits
             or show no clinically significant abnormalities.

          7. Subjects (or their female partners) must be not pregnant, planning to become pregnant
             within the next 72 weeks, or they must be permanently sterile or otherwise of non
             childbearing potential. They must also not be breastfeeding. If of child-bearing
             potential, subjects must agree to use 2 effective methods of contraception from
             screening through 6 months after the last dose of RBV. Male subjects who have a female
             partner of childbearing potential must agree to use 2 effective methods of
             contraception from Screening through 7 months after the last dose of RBV unless
             vasectomized.

          8. Female subjects must have a negative pregnancy test at all visits (screening and
             predose Day 1) before the first dose of study drugs.

          9. Willing to refrain from the concomitant use of any medications, substances or foods.

         10. Able to read and understand the Informed Consent Form (ICF) and willing to sign the
             ICF and abide by the study requirements and restrictions.

        Exclusion Criteria:

          1. Received more than 4 weeks of any approved or investigational drug or drug regimen for
             the treatment of hepatitis C.

          2. Any medical contraindications to Peg-IFN alpa-2a or RBV therapy, including any of the
             following:

               1. Abnormal thyroid stimulating hormone (TSH) levels or poorly controlled thyroid
                  function

               2. Evidence of clinically significant cardiac dysfunction;

               3. History of psychiatric disorders determined by the investigator to contraindicate
                  the use of IFN-based therapy;

               4. Antinuclear antibody (ANA) titer 1:320;

               5. History of hemoglobinopathies.

          3. Patients coinfected with either human immunodeficiency virus (HIV) or hepatitis B
             virus (HBV).

          4. Decompensated liver disease as indicated by a history of ascites, hepatic
             encephalopathy, or bleeding esophageal varices.

          5. Diagnosed or suspected hepatocellular carcinoma. Alfa-fetoprotein (AFP) during
             screening must be less than 100 ng/mL.

          6. For cases, histologic evidence of hepatic cirrhosis on any liver biopsy

             o Most recent liver biopsy must be within 2 years prior to study screening.

          7. Has taken any of the prohibited medications within 28 days of initiation of therapy.

          8. A history of any illness that, in the opinion of the investigator, might confound the
             results of the study or pose an additional risk in administering study drug to the
             subject. This may include but is not limited to a history of relevant drug or food
             allergies, history of cardiovascular or central nervous system disease, history or
             presence of clinically significant illness, or history of mental illness that may
             affect compliance with study requirements.

          9. Alcohol abuse or excessive use (in the opinion of the investigator, as judged by
             medical history) in the last 12 months.

         10. Participation in any investigational drug study within 90 days before drug
             administration or participation in more than 2 drug studies in the last 12 months
             (exclusive of the current study).

         11. For cases, hypersensitivity to tartrazine (known as yellow dye #5).

         12. Men whose female partners are pregnant