Hepatitis C Treatment Naive Genotype 1 Consensus Interferon Trial

• Status: Completed
• Trial end date: 2009-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Minneapolis Veterans Affairs Medical Center
• Collaborators: Center for Veterans Research and Education; InterMune; Kadmon Pharmaceuticals; Minnesota Veterans Medical Research and Education Foundation; San Diego Veterans Healthcare System; US Department of Veterans Affairs; VA Office of Research and Development
• Treatments: Interferon alfacon-1; Interferon-alpha; Interferons; Ribavirin

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.