Comparison of virological response during high and low-dose regimen with natural IFN a in combination with ribavirin in patients with genotype 1 chronic hepatitis C who have experienced an incomplete response after treatment with pegylated recombinant IFN a

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 102

Inclusion Criteria

Documentation of genotype 1 HCV infection (mixed genotype accepted) by licensed diagnostic tests (RIBA or HCV PCR, with genotyping assay).

Viral relapser or non-responder to a previous treatment with pegylated interferon and ribavirin of no less than 12 weeks, with an initial viral response characterized by a reduction of plasma HCV-RNA PCR from baseline by at least 1 log10 at any time during pegylated interferon treatment.

Ability and willingness to give written informed consent.

Male and female subjects, ages > 18 to 65 years, weight < 130 kg.

Chronic liver disease consistent with HCV infection on a liver biopsy in the previous 2 years. Judged by a local pathologist. Eligible subjects must have a total fibrosis score of > 0. Those subjects who have not had biopsies in the past 2 years will be required to have a biopsy prior to enrollment.

If hepatic cirrhosis is defined by liver biopsy (fibrosis score of 6) or by imaging study, then subjects must be no more than Child-Pugh class A and have a serum a-fetoprotein less than or equal to the ULN within 28 days prior to study entry.

Laboratory values that meet the following criteria within 28 days before study entry:
Absolute neutrophil count = 1.0x109/L. Platelet count =70x109/L. Hemoglobin =100 g/L. Serum creatinine =150 µmol/L. Thyroid-stimulating hormone (TSH) values within the normal range of the local institution laboratory. ALT level < 10 time ULN.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Previously treated with more than two courses of treatment with an IFN-a based regimen -including consensus IFN-a (i.e. a course of treatment is any treatment of more than 12 weeks of therapy).

Known HIV 1 or HIV 2 antibody positivity or Hepatitis B Surface Antigen (HBsAg) positivity at any time prior to entry.

Any past evidence of medical conditions associated with chronic liver disease other than HCV (e.g., genetic hemochromatosis, autoimmune hepatitis, alcoholic cirrhosis, toxin exposures).

Severe psychiatric disease, especially depression. Subjects with severe psychiatric disease, a previous suicidal attempt or hospitalization for a psychiatric episode within the previous 24 weeks.

History of hypersensitivity to ribavirin, IFN or other component of the study products.

History of uncontrolled seizure disorders.

Any past or current evidence of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis).

Evidence of chronic pulmonary disease associated with functional limitation (forced to stop periodically every few minutes or every 100 meters by dyspnea, or need for ambulatory oxygen supplementation).

Evidence of severe cardiac insufficiency (e.g., Patients with heart disease who are comfortable at rest but have symptoms with less than ordinary activity), myocardial infarction, or ventricular tachyarrhythmia requiring ongoing treatment or unstable angina within 24 weeks of entry.

Severe retinopathy due to diabetes, hypertension, or macular degeneration.

History of major organ transplantation with an existing functional graft.

History or other evidence of severe illness, malignancy or any other conditions that would make the subject, in the opinion of the investigator, unsuitable for the study, i.e., a history of a solid tumor or active bacterial infection, conditions that could potentially be exacerbated by the study drugs.

Any systemic antineoplastic or immunomodulatory treatment or radiation within 24 weeks of the study entry or the expectation that such treatment will be needed at any time during the study.

More than or equal to a 30-day use of supraphysiologic doses of corticosteroid (>10 mg of prednisone daily or equivalent) within the previous 90 days of study entry.

Active drug or alcohol abuse or dependence, which in the opinion of the investigator, would interfere with adherence to study requirements, or endanger the subject’s health while on the study. Subjects in methadone programs are eligible to participate.

Known hemoglobinopathy (e.g. thalassemia) or any other cause of or tendency to hemolysis.

Administration of investigational drug with potential activity against HCV within 6 weeks of study entry (e.g. IL-10, polymerase or protease inhibitor).

Presence of acute or active infection within 4 weeks of study entry.

Women who are pregnant or breast-feeding.

Women with a positive serum or urine pregnancy test within 28 days prior to study entry and at study entry.

All women of reproductive potential (defined for this study as sexually mature women who have not been postmenopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or have not undergone hysterectomy or oophorectomy) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL performed within 24 hours before