All patients will receive PEGASYS® 180 microgram, administered sc once per week for 48 weeks and stopped thereafter. The dose of ADF dipivoxil (HEPSERA®) will be 10 mg daily for 48 weeks and stopped thereafter.
Conditions
Interventions
During prescreening and at the end of treatment at 48 weeks each patient will undergo a liverbiopsy.
All patients will receive PEGASYS® 180 microgram, administered sc once per week for 48 weeks and s
Sponsors
Roche Pahrmaceuticals
Giliad UCB
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male and female patients > 18 years of age; 2. Positive HBsAg for more than 6 months; 3. a) For HBeAg positive patients: HBeAg positive, anti-HBe negative and HBV DNA > 100,000 cop/mL (> 17,000 IU/mL) as measured by PCR. b)For HBeAg negative patients: HBeAg negative for more than 6 months, and anti-HBeAg positive, HBV DNA (>100,000 cop/mL (> 17,000 IU/mL)) as measured by PCR; 4. Patients with CHB who are either naïve to HBV treatment, or have received and have not responded/relapsed to either conventional interferon (IFN) or Lamivudine (LAM) in the past; 5. If the patient has used LAM, the patient must have been on LAM for a period of at least 6 months; 6. Elevated serum ALAT > ULN but  10X ULN as determined by two abnormal values taken >14 days apart during the six months before the first dose of study drug with at least one of the determinations obtained during the screening period; 7. A liver biopsy obtained at a maximum of one year prior to study enrollment, demonstrating liver disease consistent with chronic hepatitis B and/or > fibrosis stage 2 (Ishak classification). Patients with cirrhosis or marked fibrosis on liver biopsy must also have a liver imaging study to rule out hepatic carcinoma.
Exclusion criteria
Exclusion criteria: 1. Patients co-infected with HCV, HDV, HIV or who have decompensated liver disease, hepato-cellular carcinoma, pre-existing severe depression or other psychiatric disease, significant cardiac disease, significant renal disease, seizure disorders or severe retinopathy will be excluded; 2. Patients who have received LAM therapy for their chronic hepatitis B within 6 weeks before enrollment or any other antiviral therapy for their chronic hepatitis B within 6 months before enrollment (e.g. INF); 3. Patients must not have received any other systemic anti-viral, anti-neoplastic or immuno-modulatory treatment (including supraphysiologic doses of steroids or radiation); 4. Positive test at screening for anti-HAV IgM, anti-HIV, anti-HCV, HCV RNA or anti-HDV; 5. Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded. Exception: patients who have had a limited (7 day) course of acyclovir for herpetic lesions more than 1 month prior to the first administration of test drug are not excluded; 6. Evidence of decompensated liver disease (Child B-C); 7. Serum total bilirubin > twice the upper limit of normal at screening; 8. History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease; 9. History or other evidence of a medical condition associated with chronic liver disease other than HBV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver diseases including Wilson’s disease and alfa1-antitrypsin deficiency, alcoholic liver disease, toxin exposures, thalassemia); 10. Women with ongoing pregnancy or who are breast feeding; 11. Neutrophil count 1.5 times the upper limit of normal at screening; 14. History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as major depression or psychosis, a period of treatment with an antidepressant medication or major tranquilizer at therapeutic doses for depression or psychosis for at least 3 months, a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease; 15. History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis); 16. History or other evidence of chronic pulmonary disease associated with functional limitation. Severe cardiac disease (e.g., NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases); 17. History of a severe seizure disorder or current anticonvulsant use; 18. Evidence of an active or suspected cancer or a history of malignancy where the risk of recurrence is 20% within 2 years. Patients with a lesion suspicious of hepatic malignancy on a screening imaging study will only be eligible if the likelihood of carcinoma is 10% following an appropriate evaluation; 19. History of having received any
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To establish the rate of response (HBV-DNA levels < 100,000 cop/mL (17,000 IU/mL)) at end of follow-up and to determine if markers at base line and early during treatment can predict response. | — |
Secondary
| Measure | Time frame |
|---|---|
| To establish rate of response at levels HBV-DNA <10,000 cop/mL (<1,700 IU/mL), <400 cop/mL (72 IU/mL) and at limit of detection (<300 cop/mL (54 IU/mL)) at end of follow-up. - To establish predictive markers for response of primary and secondary end points. - To establish the rate of HBeAg seroconversion at end of follow-up in HBeAg positive patients only. | — |
Contacts
Public ContactSecretary Patientclinic Hepatology
Academic Medical Center (AMC), Department of Gastroenterology and Hepatolgy, Room C2-331, P.O. Box 22660
Outcome results
None listed