Clinical trial NCT02332473: A Prospective Study of Combination of Peginterferon Alfa-2b (40kD, Y-shape) and GM-CSF in Chronic Hepatitis B
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Lead sponsor: Xiamen Amoytop Biotech Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Peking University First Hospital
First posted: 2015-01-06
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Percentage of HBeAg seroconversion at the end of treatment
timeFrame: week 48
Secondary outcomes:
measure: Percentage of HBsAg undetectable and seroconversion at the end of treatment
timeFrame: week 48
measure: Percentage of HBeAg undetectable and seroconversion at week 12, 24, 36 and 48
timeFrame: week 12, 24, 36 and 48
measure: Change of HBsAg and HBeAg from baseline at week 12, 24, 36, and 48
timeFrame: week 12, 24, 36, and 48
measure: Change of HBV DNA from baseline and percentage of HBV DNA undetectable at week 12, 24, 36, and 48
timeFrame: treatment week 12, 24, 36, and 48
measure: Percentage of ALT normalization at week 24, 36 and 48
timeFrame: week 24 ,36 and 48
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hosopital
state: Beijing
city: Fuzhou
country: China
facility: Fuzhou Infectious Disease Hospital
state: Fujian
city: Xiamen
country: China
facility: Xiamen Hospital of T.C.M
state: Fujian
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital, Huazhong University of Science & Technology
state: Hubei
city: Changsha
country: China
facility: Xiangya Second Hospital, Central-south University
state: Hunan
city: Shenyang
country: China
facility: Shenyang Sixed People's Hospital
state: Liaoning
city: Shanghai
country: China
facility: Ruijing Hospital
state: Shanghai
city: Xi'an
country: China
facility: Xijing Hospital
state: Shanxi
city: Wenzhou
country: China
facility: First Affiliated Hospital of Wenzhou Medical College
state: Zhejiang
Study officials:
References: