A Prospective Study of Combination of Peginterferon Alfa-2b (40kD, Y-shape) and GM-CSF in Chronic Hepatitis B

A Prospective Phase 2 Clinical Trial to Assess the Efficacy and Safety of Combination of Peginterferon Alfa-2b (40kD, Y-shape) and GM-CSF in Chronic Hepatitis Patients.

This study is a multi-center, randomized, prospective open-label study to assess the efficacy and safety of combination of peginterferon alfa-2b (40kD, Y-shape) and GM-CSF in interferon-naïve chronic hepatitis B patients with HBeAg positive. Patients were randomized to one of the 2 groups to receive different antiviral treatment.

Inclusion Criteria:

• 18yrs≤age≤65yrs.
• 17≤BMI(body mass index)≤28.
• HBsAg positive≥6 months.
• Serum HBV DNA≥20,000IU/ml, HBsAg positive and HBeAg positive at screening.
• 2ULN≤ALT≤10ULN(ULN=upper limit of normal) at screening.
• Pregnancy test must be negative for female patients of childbearing potential. All patients take effective birth control measures during treatment and 6 months after the treatment.
• Agree to participate in the study and sign the informed consent.

Exclusion Criteria:

• Pregnant or lactating females
• Interferon treatment history, or using nucleos(t)ide analogues for chronic hepatitis B treatment within the previous 6 months, or any evidence of nucleosi(t)ide analogues resistance .
• Receiving strong immunomodulatory agents (e.g., steroids, thymosin) for more than two weeks 6 months prior to screening.
• Receiving hepatotoxicity agents (e.g., aczone, erythromycin, fluconazole, ketoconazole, rifampicin) for more than two weeks 6 months prior to screening.
• Co-infected with active hepatitis A, hepatitis C, hepatitis D, and/or human immunodeficiency virus (HIV).
• History or evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., autoimmune hepatitis, alcoholic liver disease, toxin exposures.
• Suffering from any other acute or chronic infectious disease.
• Mental disorder or physical disability, or family history of neurological and psychiatric disorders.
• Neutrophil count <1500 cells/mm3, or platelet count <90000 cells/mm3 at screening.
• Child-Pugh≥B, or other evidence of liver decompensation (e.g. serum albumin<35g/L , prothrombin time>3 seconds prolonged, serum bilirubin>2ULN, prothrombin activity <60%, history of liver decompensation).
• Serum creatinine level >ULN in screening period.
• Serum creatine kinase level >2ULN except for physiological factors (e.g., exercise).
• AFP>100ng/L. If 50ng/L<AFP<100ng/L at screening, retest 2 weeks later, and if AFP <50ng/L can enrolled, vs, excluded.
• Hepatocarcinoma or suffering from any other malignant tumor.
• Autoimmune disease(e.g., psoriasis, systemic lupus erythematosus).
• Moderate or severe hypertension, or mild hypertension without well controlled.
• With not well- controlled endocrine disease (e.g., thyroid dysfunction, diabetes mellitus).
• Drug abusing, or alcoholism.
• HBeAb positive or HBsAb positive at screening.
• Allergic to interferon, or GM-CSF, or any fragment of the study drug.
• Other conditions which in the opinion of the investigator precluding enrollment into the study(e.g., low compliance).