Hepatitis C Treatment Naive Genotype 1 Consensus Interferon Trial
Condition: Chronic Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Intervention: consensus interferon (Interferon Alfacon-1) and ribavirin; Consensus Interferon alfa (CIFN) and ribavirin
Intervention description: CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B); CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B)
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alfacon-1
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Hepatitis C; interferon alfa; ribavirin; interferon alfacon-1; antiviral therapy

Summary:

      Data have suggested that consensus interferon (CIFN) has greater antiviral activity in vitro
      compared with interferon alfa-2a or alfa-2b. Several clinical studies also suggest that CIFN
      has greater antiviral activity in patients with genotype 1 hepatitis C infection,
      particularly if given as a daily injection. These data indicate that the use of a regimen of
      daily CIFN and ribavirin will lead to greater virologic response rates compared with
      pegylated interferon alfa-2b and ribavirin in patients with genotype 1 infection, with
      comparable adverse events. Emerging data indicate that HCV genotype 1 patients with a delayed
      virologic response to initial therapy may benefit from an extended duration of therapy.
      Therefore, the goals of this pilot study are to determine the tolerability and efficacy of
      daily CIFN plus ribavirin when given for 52 weeks or an extended duration of therapy. The
      target population will consist of "difficult-to-treat" patients, defined as having the
      following characteristics: genotype 1, a North American patient population, predominantly
      male gender, and no specific exclusions for pre-existing psychiatric or substance abuse
      co-morbidities.
    

Eligibility criteria:

        Inclusion Criteria:

        1. Chronic hepatitis C. This is defined as the documentation of the presence of circulating
        hepatitis C virus by a positive hepatitis C PCR test and a positive HCV genotype test for
        genotype 1, and a liver biopsy (within the previous 5 years) that is compatible with
        chronic hepatitis. In the case of patients that have refused liver biopsies a clinical
        diagnosis of chronic hepatitis C is required.

        2. Positive HCV RNA by PCR, Genotype 1, treatment naive 3. Age 18-65 years. 4. Patient must
        be able to give informed consent. 5. Eligible for interferon alfa and ribavirin-based
        antiviral treatment:

          1. Reconfirmation and documentation that sexually active female patients of childbearing
             potential are practicing adequate contraception. A urine pregnancy test obtained at
             entry prior to the initiation of treatment must be negative.

          2. Reconfirmation that sexually active male subjects are practicing acceptable methods of
             contraception during the treatment period and for six months following the last dose
             of study medication.

          3. For patients with cirrhosis or stage 4 fibrosis on liver biopsy, they must have an
             alpha fetoprotein (AFP) value < 80 ng/mL obtained within 3 months prior to entry.
             Cirrhotics with an alpha fetoprotein value >30 ng/mL but <80ng/mL may be enrolled
             after a normal ultrasound or triphasic CT scan within the previous 3 months.
             Cirrhotics with alpha fetoprotein levels up to 30 ng/ml must have an ultrasound or CT
             scan within 6 months of enrolling that is negative for hepatocellular cancer. Patients
             with an AFP > 80 ng/mL may not be enrolled.

        5) Compensated liver disease with the following laboratory results at entry:

          -  Hemoglobin >=to 12 gm/dL for females and >= 13gm/dl for males

          -  WBC >= 2,000/mm3

          -  Neutrophil >=1,500/mm3

          -  Platelets >=75,000/mm3

          -  Albumin > 3.0 g/dL

          -  Total bilirubin <2.0

          -  Serum creatinine < 1.4 mg/dL

          -  INR <1.8

          -  If diabetic, must have glycosylated Hgb test that demonstrates adequate control of
             diabetes in the opinion of the investigator

          -  TSH within normal limits

        Exclusion Criteria:

          1. Patient unable or unwilling to participate.

          2. Liver disease in addition to chronic hepatitis C (HBsAg positive, autoimmune liver
             disease, hemochromatosis, PBC, PSC, alpha-1 antitrypsin deficiency, Wilson's disease,
             etc.)

          3. Decompensated liver disease, with history of encephalopathy, variceal bleeding, or
             ascites or CHILD-PUGH class B or C.

          4. Baseline BDI > 19 or current suicidal or homicidal ideation. (Note: if baseline BDI is
             > 19 pt. will require a psychiatric evaluation and treatment; if deemed stable after
             this he may be considered according to site PI clinical judgment.)

          5. Current substance use disorder (Must be evaluated and demonstrate engagement and
             compliance with care before they will be eligible).

          6. Patients with active or uncontrolled psychiatric disease including patients who have
             had recent prior severe psychiatric disease (hospitalized) within the last 2 years.

          7. Accepted and reasonable exclusion criteria for interferon alfa and ribavirin based
             treatments:

        1) CNS trauma or active seizure disorders requiring medication. 2) Significant
        cardiovascular dysfunction within the past 12 months 3) Poorly controlled diabetes mellitus
        (in the opinion of the site PI). 4) Moderate or severe chronic pulmonary disease 5)
        Clinically significant immunologically mediated disease 6) Hemoglobinopathies (e.g.,
        Thalassemia) or any other cause of hemolytic anemia.

        7) Any medical condition requiring, or likely to require during the course of the study,
        chronic systemic administration of steroids.

        8) Hypersensitivity to interferon alfa or ribavirin 9) Known anti-HIV positive 10)
        Clinically significant retinopathy 11) Previous solid organ transplantation 12) Any
        condition that, in the opinion of the investigator, will prevent the patient from being
        compliant with study medications or appointments.