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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Ypeginterferon alfa-2b; Drug: Granulocyte-macrophage colony stimulating factor

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Peking University First Hospital
    • Beijing, Beijing, China
      • Peking University People's Hosopital
  • Fujian
    • Fuzhou, Fujian, China
      • Fuzhou Infectious Disease Hospital
    • Xiamen, Fujian, China
      • Xiamen Hospital of T.C.M
  • Guangdong
    • Guangzhou, Guangdong, China
      • Nanfang Hospital
  • Henan
    • Zhengzhou, Henan, China
      • Henan Provincial People's Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Tongji hospital, Huazhong University of Science & Technology
  • Hunan
    • Changsha, Hunan, China
      • Xiangya Second Hospital, Central-south University
  • Liaoning
    • Shenyang, Liaoning, China
      • Shenyang Sixed People's Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Ruijing Hospital
  • Shanxi
    • Xi'an, Shanxi, China
      • Xijing Hospital
  • Zhejiang
    • Wenzhou, Zhejiang, China
      • First Affiliated Hospital of Wenzhou Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; Ypeginterferon alfa-2b,sc. Qw. 48 weeks.	Drug: Ypeginterferon alfa-2b; Other Names: peginterferon alfa-2b
Experimental: Arm B; 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; Other Names: peginterferon alfa-2b; Drug: Granulocyte-macrophage colony stimulating factor; Other Names: GM-CSF

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Xiamen Amoytop Biotech Co., Ltd.
• Collaborators: Peking University First Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: January 4, 2015
• First Submitted That Met QC Criteria: January 4, 2015
• First Posted (Estimate): January 6, 2015

Study Record Updates

• Last Update Posted (Estimate): January 25, 2017
• Last Update Submitted That Met QC Criteria: January 23, 2017
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Peginterferon alfa-2b; Sargramostim; Molgramostim
• Other Study ID Numbers: TB1405IFN