Taribavirin Phase 2 Dose Finding Study for the Treatment of Hepatitis C Virus (HCV)
Condition: Chronic Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Taribavirin; Taribavirin; Taribavirin; Ribavirin
Intervention description: Oral (200 mg) Tablet: 20mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection. Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.; Oral (200 mg) Tablet: 25mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection. Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.; Oral (200mg)Tablet: 30mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection. Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.; Oral (200mg)Tablet: 800 mg/day, 1000 mg/day, 1200 mg/day, or 1400 mg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection. Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.
Intervention MeSH terms: Ribavirin; Taribavirin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 278.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Phase 2b Dose-Ranging Study

Summary:

      The objective of the study is to select an optimal dose of taribavirin by comparing the
      efficacy and safety of 3 taribavirin dose levels, 20, 25, and 30 mg/kg/day, versus ribavirin
      800 to 1400 mg/day based on body weight, both administered in combination with peginterferon
      alfa-2b to therapy-naive patients with chronic Hepatitis C Virus (HCV) genotype 1 infection.
    

Eligibility criteria:

        Subject Inclusion Criteria

        To be eligible for enrollment, patients must meet all of the following criteria:

          1. At least 18 years of age

          2. Diagnosed with compensated chronic HCV genotype 1 infection that has not been treated
             with interferon, peginterferon, ribavirin or any experimental therapy for >28 days

        2a Serum HCV RNA >2000 copies/mL (780 IU/mL) 2b Liver biopsy performed within 3 years prior
        to screening consistent with chronic HCV infection 2c Criteria for compensated HCV
        infection, including normal prothrombin time, serum albumin and bilirubin levels (unless
        due to non-hepatitis factors) and no history or evidence of bleeding esophageal varices,
        ascites, or hepatic encephalopathy

        3 History of alanine aminotransferase (ALT) elevation either within 6 months prior to
        screening, at screening, or on retest 2 weeks after a negative screening test, or
        histologic evidence of HCV infection and a detectable viral load

        4 Platelet count ≥90,000/mm3

        5 Absolute neutrophil count ≥1200/mm3

        6 Hemoglobin ≥12.0 g/dL for females or ≥13.0 g/dL for males

        7 Antinuclear antibody (ANA) titer ≤1:320

        8 Serum creatinine <1.5 mg/dL

        9 HbA1c ≤8.5% for diabetic patients

        10 Normal or adequately controlled TSH on prescription medication

        11 Alpha fetoprotein (AFP) <20 ng/mL or hepatocellular carcinoma ruled out (ultrasound, CT
        or MRI scan) within 6 months prior to the study (Patients with an AFP >20 ng/mL must have
        ongoing hepatocellular carcinoma screening during study as part of the patient's routine
        medical care)

        12 All other clinical laboratory values within normal limits, unless judged not clinically
        significant by the investigator

        13 Sterile or infertile (defined as vasectomy, tubal ligation, postmenopausal, or
        hysterectomy), or willing to use an approved method of double-barrier contraception
        (hormonal plus barrier or barrier plus barrier, eg, diaphragm plus condom) from the time of
        first dose administration until 6 months after the last dose

        14 Capable of understanding instructions, adhering to study schedules and requirements, and
        willing to provided informed consent

        Subject Exclusion Criteria

        Patients who have any of the following during the screening or Day 1 visit are not eligible
        for enrollment in this study:

          1. Positive HIV or HbsAg serology

          2. Severe psychiatric or neuropsychiatric disorders including severe depression, history
             of suicidal ideations or suicide attempt(s). (This would include patients with a
             history of suicidal ideations or suicide attempt(s) that occurred when the patient was
             a minor or many years ago; if the event occurred while under the influence of alcohol
             or drugs; if the suicidal ideations or suicide attempt(s) were connected to a
             traumatic event; if the patient was not hospitalized or treated; if the patient has
             obtained psychiatric clearance for treatment)

          3. History or clinical manifestations of significant metabolic, hematological, pulmonary,
             ischemic or unstable heart disease, gastrointestinal, neurological, renal, urological,
             endocrine, ophthalmologic (including severe retinopathy), or immune mediated disease

          4. History of thalassemia or other hemoglobinopathies (even if the hemoglobin is normal)

          5. Chronic hepatic disease other than hepatitis C

          6. Organ or bone marrow transplant

          7. Chronic (greater than 30 days) use of immunosuppressive medications including steroids
             in doses equivalent to 10 mg of prednisone or higher, 30 days prior to and anytime
             during the course of the study

          8. Female patients who are breast-feeding or have a positive pregnancy test at any time
             during the study

          9. Males whose female partners are pregnant

         10. Patients who have had a malignancy diagnosed and/or treated within the past 5 years,
             except for localized squamous or basal cell cancers treated by local excision

         11. Patients who have participated in a clinical trial and have received an
             investigational drug within 30 days prior to screening

         12. History of alcoholism or drug addiction 1 year prior to screening

         13. The use of methadone, buprenorphine or any similar drug, regardless of the prescribed
             indication or the length of time the patient has been on the drug

         14. Chronic (>4 weeks duration) diarrhea, including irritable bowel disease

         15. Fibrosis score F4 (cirrhosis) based on Metavir or equivalent index

         16. Weight >128 kg or <40 kg

         17. Patients infected with mixed HCV genotypes