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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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.

Conditions
-----------------
Chronic Hepatitis B

Intervention / Treatment
-----------------
* Drug: Ypeginterferon alfa-2b
* Drug: Granulocyte-macrophage colony stimulating factor


Participation Criteria
=================
Eligibility Criteria
-----------------
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).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Ypeginterferon alfa-2b,sc. Qw. 48 weeks. | Drug: Ypeginterferon alfa-2b<br> <br> * Other names: peginterferon alfa-2b;|
| Experimental: Arm B<br>Ypeginterferon alfa-2b,sc. Qw. 48 weeks. Granulocyte-macrophage colony stimulating factor,sc.qd, the first three day of every 28 days, starting from interferon treatment week 13. | Drug: Ypeginterferon alfa-2b<br> <br> * Other names: peginterferon alfa-2b;Drug: Granulocyte-macrophage colony stimulating factor<br> <br> * Other names: GM-CSF;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of HBeAg seroconversion at the end of treatment |  | week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of HBsAg undetectable and seroconversion at the end of treatment |  | week 48 | 
| Percentage of HBeAg undetectable and seroconversion at week 12, 24, 36 and 48 |  | week 12, 24, 36 and 48 | 
| Change of HBsAg and HBeAg from baseline at week 12, 24, 36, and 48 |  | week 12, 24, 36, and 48 | 
| Change of HBV DNA from baseline and percentage of HBV DNA undetectable at week 12, 24, 36, and 48 |  | treatment week 12, 24, 36, and 48 | 
| Percentage of ALT normalization at week 24, 36 and 48 |  | week 24 ,36 and 48 |