A phase IV, 2x2 factorial, double blind study of 24 versus 48 weeks and 90 versus 180 mcg doses of pegylated interferon alfa 2a 40KD (PEG IFN, Ro 25-8310) in adult patients with HBeAg positive chronic hepatitis B. - NEPTUNE

• Conditions: In adult patients with HBeAg positive chronic hepatitis B.; MedDRA version: 9.1Level: LLTClassification code 10008910Term: Chronic hepatitis B

• Registration Number: EUCTR2006-000870-63-DE
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-02-20
• Last Update Posted: 17 December 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 524

Inclusion Criteria

•Age >= 18 years
•Positive HBsAg for more than 6 months, positive HBeAg, detectable HBV DNA (patients must have > 500,000 copies/ml (100,000 IU/ml) as measured by PCR) and anti HBs negative
•Elevated serum ALT > ULN but <= 10 x 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 <= 35 days prior to the first dose.
•A liver biopsy obtained within the past 2 years (and more than 6 months after the end of any previous therapy for hepatitis B) demonstrating liver disease consistent with chronic hepatitis B. Patients with cirrhosis or bridging fibrosis on liver biopsy must also have a liver imaging study to rule out hepatic carcinoma.
•Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and for 3 months after treatment completion.

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) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Patients must not have received antiviral therapy for their chronic hepatitis B within the previous 6 months. 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.
•Positive test at screening for HAV IgM Ab, HCV-RNA or HCVAb, HDV Ab or HIV Ab.
•Serum concentrations of ceruloplasmin or alfa1-antitrypsin consistent with an increased risk of metabolic liver disease.
•Any evidence of decompensated liver disease (Childs B-C, Appendix 2)
•History or other evidence of a medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures, thalassemia).
•Women with ongoing pregnancy or who are breast feeding.
•Neutrophil count < 1500 cells/mm3or platelet count < 90,000 cells/mm3.
•Serum creatinine level > 1.5 times the upper limit of normal at screening.
•Evidence of alcohol and/or drug abuse within one year of entry.
•History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as major depression or psychosis, suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease.
•History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis).
•History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease.
•History or other evidence of chronic pulmonary disease associated with functional limitation.
•History of 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).
•History of a severe seizure disorder or current anticonvulsant use.
•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 for hepatic malignancy on a screening imaging study will only be eligible if the likelihood of carcinoma is <=10% following an appropriate evaluation.
•History of having received any systemic anti-neoplastic (including radiation) or immunomodulatory treatment (including systemic corticosteroids) <= 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.
•History of major organ transplantation with an existing functional graft
•History of thyroid disease poorly controlled on prescribed medications. Patients with elevated thyroid stimulating hormone concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded.
•History or other evidence of severe retinopathy
•Inability or unwillingness to provide informed consent or abide by the requirements of the study.
•History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.
•Patients with a value of alpha-fetoprotein >100 ng/mL are excluded, unless sta

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy and safety of PEG-IFN given for both varied duration, either 24 or 48 weeks and at different doses, 90 or 180mcg weekly doses in the treatment of HBeAg positive patients with chronic hepatitis B virus infection, 24 weeks after the end of therapy;Secondary Objective: To compare the influence of varied duration and dose on the secondary endpoints and in the event of equivocal findings to explore potential subsets of patients who might benefit from particular treatment regimens.;Primary end point(s): HBeAg seroconversion (loss of HBeAg and presence of anti-HBe) at the end of the initial 24 week treatment free follow up.