Combination Therapy With Interferon Plus Interleukin 2 and Hepatitis B Vaccine in Chronic Hepatitis B Patients
Combination Therapy of Interferon Alfa-2b Plus Interleukin 2 and Hepatitis B Vaccine in Entecavir-experienced Chronic Hepatitis B Patients With HBeAg Seroclearance: a Prospective, Randomized Open-label Trial (Endeavor Study, a Pilot Study)
1 other identifier
interventional
94
1 country
12
Brief Summary
This study is a multi-center, randomized, prospective, open-label Phase IV Clinical trial to evaluate efficacy and safety of interferon alfa-2b therapy combinated with interleukin 2 and hepatitis B therapeutic vaccine versus interferon alfa-2b alone in chronic hepatitis B patients with entecavir achieving HBeAg seroclearance. Patients were randomized to one of 3 groups to receive different antiviral treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4
Started Jun 2013
Longer than P75 for phase_4
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2013
CompletedFirst Submitted
Initial submission to the registry
February 2, 2015
CompletedFirst Posted
Study publicly available on registry
February 10, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2017
CompletedMay 9, 2018
October 1, 2017
3.5 years
February 2, 2015
May 8, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of HBsAg loss at week 48
Change from baseline in Percentage of HBsAg loss at week 48
week 48
Secondary Outcomes (2)
decline from baseline in HBsAg quantification at week 48
week 48
Change from baseline in HBsAg seroconversion at week 48
week 48
Other Outcomes (4)
Percentage of HBeAg seroconversion at week 48
week 48
Percentage of HBV DNA normalization
week 48
Percentage of sustained virology response at week 72
week 72
- +1 more other outcomes
Study Arms (3)
1, conventional control group
ACTIVE COMPARATOREntecavir 0.5 mg po daily for 72 weeks
2, combination and sequential group
EXPERIMENTALInterferon alfa-2b 600wIU qod iH for 48 weeks plus Entecavir 0.5mg qd po for 8 weeks
3, multitarget group
EXPERIMENTALInterferon alfa-2b 600wIU qod iH for 48 weeks plus Entecavir 0.5mg qd po for 8 weeks plus interleukin 2 25 wIU qod iH for 12 weeks plus Hepatitis B Vaccine 60ug qm im for 48 weeks
Interventions
In arm 1, Entecavir is used for 48 weeks and the follow up 24 weeks as conventional control, In arm 2 and 3, Entecavir is used for 8 weeks.
In arm 2 and 3, interferon alfa-2b is used for 48 weeks
In arm 3, Interleukin 2 is used for 12 weeks
Eligibility Criteria
You may qualify if:
- Male and female patients from 18 to 65 years of age;
- Undergoing treatment with entecavir for at least 1 year ;
- HBsAg(+), HBeAg(+), HBV DNA≥ 100000 copies/ml，ALT≥2 ULN and ≤10 ULN before receiving entecavir treatment;
- HBV DNA ≤1000 copies/mL;
- HBeAg (-);
- HBsAg (+);
- 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;
- Liver biopsy confirmed without cirrhosis (optional);
- Agree to participate in the study and sign the patient informed consent.
You may not qualify if:
- Patients who had NAs resistance;
- Other antiviral, anti-neoplastic or immunomodulatory treatment (including supra physiologic doses of steroids and radiation) 6 months prior to the first dose of randomized treatment (except for 7 days of acyclovir for herpetic lesions more than 1 month prior to first administration of randomized treatment). Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation are also excluded;
- Women with ongoing pregnancy or breast-feeding;
- Co-infection with active hepatitis A, hepatitis C, hepatitis D(Those hospitals which have the ability to do the test will do) and/or human immunodeficiency virus (HIV);
- ALT \>10 ULN;
- Evidence of decompensated liver disease (Child-Pugh score \> 5 ). Child-Pugh \> 5 means, if one of the following 6 conditions are met, the patient has to be excluded: a. Serum albumin \< 3.5 g/L; b. Prothrombin time \> 3 seconds prolonged; c. Serum bilirubin \> 34 μ mol/L; d. History of encephalopathy; e. History of variceal bleeding; f. Ascites;
- History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures, thalassemia);
- Signs or symptoms of hepatocellular carcinoma, patients with a value of alpha-fetoprotein \> 100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months. Patients with values \< 20 ng/mL but \> 100 ng/mL may be enrolled, if hepatic neoplasia has been excluded by liver imaging;
- Neutrophil count \< 1500 cells/mm3 or platelet count \<90,000 cells/mm3 at screening;
- Hemoglobin \< 11.5 g/dL for females and \<12.5 g/dL for men;
- Serum creatinine level \> 1.5 ULN in screening period.
- Phosphorus \< 0.65 mmol/L;
- ANA \> 1:100;
- History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at herapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease;
- History of a severe seizure disorder or current anticonvulsant use;
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Tongji Hospitallead
- Beijing Kawin Technology Share-Holding Co., Ltd.collaborator
- Fujian Cosunter Pharmaceutical Co. Ltdcollaborator
Study Sites (12)
Anhui Provincial Hospital
Hefei, Anhui, China
BeiJing YouAn Hospital, Capital Medical University
Beijing, Beijing Municipality, China
First Hospital, Beijing University
Beijing, Beijing Municipality, China
People'S Hospital Under Beijing University
Beijing, Beijing Municipality, China
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, China
Department of infectious disease, Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, China
Tongji Hospital
Wuhan, Hubei, 430030, China
Departmen of infectious disease, Xiangya Hospital, Central-south Universit
Changsha, Hunan, China
ShengJing Hospital of China Medical University
Shenyang, Liaoning, China
Shanghai Ruijin Hospital, Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, China
The First Affiliated Hospital of College of Medicine, Zhejiang University
Hangzhou, Zhejiang, China
The first affiliated hospital of Wenzhou medical universtiy
Wenzhou, Zhejiang, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Qin Ning, Ph.D. M.D.
Department of Infectious Diseases, Tongji Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director and Chair of Department of Infectious Diseases
Study Record Dates
First Submitted
February 2, 2015
First Posted
February 10, 2015
Study Start
June 1, 2013
Primary Completion
December 1, 2016
Study Completion
April 1, 2017
Last Updated
May 9, 2018
Record last verified: 2017-10