Lowering Viral Load With Nucleos(T)Ide Analogues Prior to Peginterferon Treatment to Ncrease Sustained Response in CHB (PEGON)
Primary Purpose
Chronic Hepatitis B
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
PegIFN alfa-2b
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Hepatitis B, sustained response, peginterferon, nucleos(t)ide analogues
Eligibility Criteria
Inclusion Criteria:
- Chronic hepatitis B (HBsAg positive > 6 months)
- HBeAg positive, anti-HBe negative within 4 weeks prior to initiation of peginterferon alfa-2b
- HBV DNA < 2000 IU/ml within one month prior to initiation of peginterferon alfa-2b after a minimum of 12 months treatment with either Entecavir (one of all 3 brands) or Tenofovir
- ALT < 5x ULN
- Compensated liver disease
- Age ≥ 18 years and ≤ 70 years
- Written informed consent
Exclusion Criteria:
- Treatment with any investigational drug within 30 days of entry to this protocol
- Treatment with Telbivudine
- Severe hepatitis activity as documented by ALT > 5 x ULN
- History of decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, bleeding gastric or esophageal varices or encephalopathy)
- Pre-existent neutropenia (neutrophils < 1,500/mm3) or thrombocytopenia (platelets < 90,000/mm3)
- Co-infection with hepatitis C virus or human immunodeficiency virus (HIV)
- Other acquired or inherited causes of liver disease: alcoholic liver disease, obesity induced liver disease, drug related liver disease, auto-immune hepatitis, hemochromatosis, Wilson's disease or alpha-1 antitrypsin deficiency
- Alpha fetoprotein > 50 ng/ml
- Hyper- or hypothyroidism (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/exclusion criteria are met)
- Immune suppressive treatment within the previous 6 months
- Contra-indications for alfa-interferon therapy like suspected hypersensitivity to interferon or Peginterferon or any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study.
- Pregnancy, breast-feeding
- Other significant medical illness that might interfere with this study: significant pulmonary dysfunction in the previous 6 months, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g. HIV positivity, auto-immune diseases, organ transplants other than cornea and hair transplant)
- Any medical condition requiring, or likely to require chronic systemic administration of steroids, during the course of the study
- Substance abuse, such as alcohol (> 80 g/day), I.V. drugs and inhaled drugs in the past 2 years.
- Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study
Sites / Locations
- Ruijin Hospital "Jiaolong University"
- Public Health Center "Fu Dan University"
- Zhong Shan Hospital "Fu Dan University"
- Erasmus MC, University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
PegIFN alfa-2b + nucleos(t)ide analogue
Nucleos(t)ide analogue
Arm Description
Peginterferon alfa-2b 1.5 μg/kg per week s.c. for 48 weeks in addition to standard nucleos(t)ide analogue treatment
Continuation of Nucleos(t)ide analogue mono-therapy
Outcomes
Primary Outcome Measures
Sustained response
Sustained response to therapy, defined as the combined presence of HBeAg seroconversion and HBV DNA < 200 IU/mL
Secondary Outcome Measures
Full Information
NCT ID
NCT01532843
First Posted
February 10, 2012
Last Updated
January 3, 2019
Sponsor
Foundation for Liver Research
1. Study Identification
Unique Protocol Identification Number
NCT01532843
Brief Title
Lowering Viral Load With Nucleos(T)Ide Analogues Prior to Peginterferon Treatment to Ncrease Sustained Response in CHB
Acronym
PEGON
Official Title
Lowering Viral Load With Nucleos(T)Ide Analogues Prior to Peginterferon Alfa-2b Treatment to Increase Sustained Response in HBeAg-positive Chronic Hepatitis B (PEGON-study)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Foundation for Liver Research
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Treatment with a nucleoside analogue and subsequent viral decline has shown to partially restore immune hyporesponsiveness in chronic hepatitis B patients. Recent pilot studies investigating whether the effect of lowering viral load with nucleoside analogue therapy prior to the initiation of peginterferon results in higher sustained off-treatment responses showed contradictory findings.
The aim of this study is to investigate sustained off-treatment response to peginterferon alfa-2b in chronic HBeAg-positive hepatitis B patients who are pretreated with nucleos(t)ide analogues, thereby lowering viral load
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
Hepatitis B, sustained response, peginterferon, nucleos(t)ide analogues
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
82 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PegIFN alfa-2b + nucleos(t)ide analogue
Arm Type
Active Comparator
Arm Description
Peginterferon alfa-2b 1.5 μg/kg per week s.c. for 48 weeks in addition to standard nucleos(t)ide analogue treatment
Arm Title
Nucleos(t)ide analogue
Arm Type
No Intervention
Arm Description
Continuation of Nucleos(t)ide analogue mono-therapy
Intervention Type
Drug
Intervention Name(s)
PegIFN alfa-2b
Other Intervention Name(s)
Pegintron
Intervention Description
Peginterferon alpha-2b 1.5 μg/kg per week s.c.for 48 weeks
Primary Outcome Measure Information:
Title
Sustained response
Description
Sustained response to therapy, defined as the combined presence of HBeAg seroconversion and HBV DNA < 200 IU/mL
Time Frame
at week 72
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Chronic hepatitis B (HBsAg positive > 6 months)
HBeAg positive, anti-HBe negative within 4 weeks prior to initiation of peginterferon alfa-2b
HBV DNA < 2000 IU/ml within one month prior to initiation of peginterferon alfa-2b after a minimum of 12 months treatment with either Entecavir (one of all 3 brands) or Tenofovir
ALT < 5x ULN
Compensated liver disease
Age ≥ 18 years and ≤ 70 years
Written informed consent
Exclusion Criteria:
Treatment with any investigational drug within 30 days of entry to this protocol
Treatment with Telbivudine
Severe hepatitis activity as documented by ALT > 5 x ULN
History of decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, bleeding gastric or esophageal varices or encephalopathy)
Pre-existent neutropenia (neutrophils < 1,500/mm3) or thrombocytopenia (platelets < 90,000/mm3)
Co-infection with hepatitis C virus or human immunodeficiency virus (HIV)
Other acquired or inherited causes of liver disease: alcoholic liver disease, obesity induced liver disease, drug related liver disease, auto-immune hepatitis, hemochromatosis, Wilson's disease or alpha-1 antitrypsin deficiency
Alpha fetoprotein > 50 ng/ml
Hyper- or hypothyroidism (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/exclusion criteria are met)
Immune suppressive treatment within the previous 6 months
Contra-indications for alfa-interferon therapy like suspected hypersensitivity to interferon or Peginterferon or any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study.
Pregnancy, breast-feeding
Other significant medical illness that might interfere with this study: significant pulmonary dysfunction in the previous 6 months, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g. HIV positivity, auto-immune diseases, organ transplants other than cornea and hair transplant)
Any medical condition requiring, or likely to require chronic systemic administration of steroids, during the course of the study
Substance abuse, such as alcohol (> 80 g/day), I.V. drugs and inhaled drugs in the past 2 years.
Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harry LA Janssen, MD PHD
Organizational Affiliation
Erasmus MC, University Medical Center Rotterdam
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ruijin Hospital "Jiaolong University"
City
Shanghai
ZIP/Postal Code
200025
Country
China
Facility Name
Public Health Center "Fu Dan University"
City
Shanghai
ZIP/Postal Code
200083
Country
China
Facility Name
Zhong Shan Hospital "Fu Dan University"
City
Shanghai
ZIP/Postal Code
200083
Country
China
Facility Name
Erasmus MC, University Medical Center
City
Rotterdam
Country
Netherlands
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30689258
Citation
Liem KS, van Campenhout MJH, Xie Q, Brouwer WP, Chi H, Qi X, Chen L, Tabak F, Hansen BE, Janssen HLA. Low hepatitis B surface antigen and HBV DNA levels predict response to the addition of pegylated interferon to entecavir in hepatitis B e antigen positive chronic hepatitis B. Aliment Pharmacol Ther. 2019 Feb;49(4):448-456. doi: 10.1111/apt.15098.
Results Reference
derived
PubMed Identifier
28329061
Citation
Chi H, Hansen BE, Guo S, Zhang NP, Qi X, Chen L, Guo Q, Arends P, Wang JY, Verhey E, de Knegt RJ, Xie Q, Janssen HLA. Pegylated Interferon Alfa-2b Add-on Treatment in Hepatitis B Virus Envelope Antigen-Positive Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogue: A Randomized, Controlled Trial (PEGON). J Infect Dis. 2017 Apr 1;215(7):1085-1093. doi: 10.1093/infdis/jix024.
Results Reference
derived
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Lowering Viral Load With Nucleos(T)Ide Analogues Prior to Peginterferon Treatment to Ncrease Sustained Response in CHB
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