Back to resultsPegylated Interferon(Peg-IFN) in Reducing Relapse Rate in Patients After Discontinuation of NUC Therapy
Primary Purpose
Chronic Hepatitis B
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
PegIFN alfa-2a
Sponsored by
About this trial
This is an interventional prevention trial for Chronic Hepatitis B
Eligibility Criteria
Inclusion Criteria:
- HBeAg-Negative Chronic Hepatitis B Patients：HBsAg-Positive,HBsAb-Negative,HBeAg-Negative,HBeAb-Positive during screening period and before NA treatment
- NUC monotherapy (including adefovir and entecavir) for more than 2.5 years,and reached stopping rule in 《Chinese chronic hepatitis B prevention and treatment guidelines》(2010):the patients who achieved undetectable HBV DNA (<300 copies/mL) with normal alanine aminotransferase (ALT) and the consolidation therapy reached 1.5 years ,total course of the treatment reached 2.5 years can stop NUC therapy
- Willing to stop the drug, and signed a written informed consent
Exclusion Criteria:
- HBsAb positive in screening period
- Compensated or Decompensated liver cirrhosis:with history of cirrhosis before NUC treatment or Child-Pugh score ≥ 5 or Complications of liver cirrhosis such as ascites, hepatic encephalopathy, esophageal gastric varices bleeding
- Hypersensitivity to interferon(IFN) or its active substance, and ineligible to IFN
- A history of immunoregulation drug therapy within one year before entry including IFN and so on.
- Coinfection with HAV、HCV、HDV、HEV 、HIV or with Other chronic liver diseases such as Alcoholic Liver Disease,Inherited Metabolic Liver Disease,Drug induced Liver Disease and nonalcoholic fatty liver
- Autoimmune disease including Autoimmune hepatitis and Psoriasis and so on.
- Hepatocellular carcinoma(HCC) or alpha feto protein(AFP) levels more than 100 ng/ml and Hepatic malignant potential of Imaging examination or AFP levels more than 100 ng/ml for 3 months
- A neutrophil count of less than 1500 per cubic millimeter or a platelet count of less than 90,000 per cubic millimeter
- A serum creatinine level that was more than 1.5 times the upper limit of the normal range
- With other malignant tumors(exclude the cured ones)
- Severe organ dysfunction
- With severe psychiatric condition or nervous disease such as epilepsy, depression, mania, epilepsy, schizophrenia and so on
- Uncontrolled diabetes, hypertension or thyroid disease
- Pregnant women and lactating women or patients with pregnancy plans and not willing to use contraception during the study period
- Participate in other clinical studies at the same time
- Patients unsuitable for the research
Sites / Locations
- Wuhan Seventh People's Hospital
- Changzhou Third People's Hospital
- First Affiliated Hospital of Zhejiang University
- People's Hospital of Jiangsu Province
- Nantong Third People's Hospital
- Suzhou Fifth People's Hospital
- The First Affiliated Hospital of Soochow University
- Taicang People's Hospital
- Wuxi Infectious Disease Hospital
- Affiliated Hospital of Xuzhou Medical College
- Shandong Provincial Hospital
- The First Affiliated Hospital of Wenzhou Medical University
- Changhai Hospital Affiliated to Second Military Medical University
- Huashan Hospital Affiliated to Fudan University
- Ruijin Hospital Affiliate to Shanghai Jiao Tong University School of Medicine
- Shanghai Public Health Clinical Center
- Shanghai Third People's Hospital
- Shuguang Hospital Affiliate to Shanghai University of Traditional Chinese Medicine
- The Infectious Disease Hospital of Shanghai Huangpu Distric
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Controlled Group
Pegasys 48 weeks
Arm Description
Discontinue the NA treatment and follow up for 96 weeks
Discontinue the NA treatment ,PegIFN alfa-2a 180 μg by week for 48 weeks and follow up for 48 weeks
Outcomes
Primary Outcome Measures
Number of participants who relapse
The total number of relapse (HBV DNA>2000 IU/ml on 2 separate occasions 1 months apart) during the research period.
Secondary Outcome Measures
Number of participants who relapse
The total number of relapse (HBV DNA>2000 IU/ml on 2 separate occasions 1 months apart) during the research period.
Number of participants who achieve HBsAg seroconversion
To investigate whether Peg-IFN alfa-2a can improve the HBsAg seroconversion in CHB patients at the point of discontinuation of PegIFN therapy compared to the control group ,which will be measured by the number of participants who achieve HBsAg seroconversion. Pegasys 24 weeks Group:24 weeks and Pegasys 48 weeks Group:48 weeks
Number of participants who achieve HBsAg seroconversion
To investigate whether Peg-IFN alfa-2a can improve the HBsAg seroconversion in CHB patients at 24,48 or 72 weeks post-discontinuation of PegIFN therapy compared to the control group ,which will be measured by the number of participants who achieve HBsAg seroconversion. Pegasys 24 weeks Group:48,72,96 weeks and Pegasys 48 weeks Group:72,96 weeks
HBsAg changes from Baseline
Pegasys 24 weeks Group:12,24 weeks and Pegasys 48 weeks Group:12,24,48 weeks
Predictive value of other markers for recurrence after NUC withdrawal
To investigate whether the other markers including HBcAb quantification and so on can predict the recurrence of hepatitis B.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02594293
Brief Title
Pegylated Interferon(Peg-IFN) in Reducing Relapse Rate in Patients After Discontinuation of NUC Therapy
Official Title
A Prospective, Randomized, Controlled Clinical Trial to Evaluate the Role of Peg-IFN Alfa-2a in Reducing RelapSe Rate in Patients With Hepatitis B e Antigen(HBeAg)-nEgative Chronic Hepatitis B After Discontinuation of NUC Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
October 2015 (Actual)
Primary Completion Date
September 2022 (Actual)
Study Completion Date
September 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Huashan Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study evaluates whether Peg-IFN alfa-2a can reduce the recurrence rate of hepatitis B in 96 weeks after nucleoside analogue (NUC) withdrawal.
The HBV HBeAg-Negative patients who received NUC anti-virus treatment for 2.5 years and reached stopping rule in 《Chinese chronic hepatitis B prevention and treatment guidelines》(2010) were randomly assigned into three groups: One group discontinue the NUC treatment and follow up for 96 weeks,One discontinue the NUC treatment ,receive Peg-IFN alfa-2a 180 μg by week for 24 weeks and follow up for 72 weeks,The other discontinue the NUC treatment ,receive Peg-IFN alfa-2a 180 μg by week for 48 weeks and follow up for 48 weeks.
Detailed Description
NUC is a potent inhibitor of hepatitis B viral(HBV) replication, but long-term therapy may be required. Therefore, NUC resistance is an important clinical risk resulting from long-term therapy in chronic hepatitis B (CHB) management. Discontinuation of NUC is a feasible strategy to reduce resistance. However, the high rate of relapse after cessation of NUC treatment in CHB patients remains a big problem. NUC treatment of how to safely stop drug needs to be solved.
Peg-IFN can clear HBV by direct anti-viral and immune regulation mechanisms including enhancing natural killer cell response, increased cluster of differentiation 8(CD8 +) T lymphocytes and other mechanisms to restore and enhance the immune response in patients with CHB. Response to PEG-IFN is frequently sustained after a finite treatment course due to its immune modulating capacity.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
180 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Controlled Group
Arm Type
No Intervention
Arm Description
Discontinue the NA treatment and follow up for 96 weeks
Arm Title
Pegasys 48 weeks
Arm Type
Experimental
Arm Description
Discontinue the NA treatment ,PegIFN alfa-2a 180 μg by week for 48 weeks and follow up for 48 weeks
Intervention Type
Drug
Intervention Name(s)
PegIFN alfa-2a
Other Intervention Name(s)
Pegasys
Intervention Description
180 μg/ 0.5 ml ,hypodermic injection once a week
Primary Outcome Measure Information:
Title
Number of participants who relapse
Description
The total number of relapse (HBV DNA>2000 IU/ml on 2 separate occasions 1 months apart) during the research period.
Time Frame
96 weeks
Secondary Outcome Measure Information:
Title
Number of participants who relapse
Description
The total number of relapse (HBV DNA>2000 IU/ml on 2 separate occasions 1 months apart) during the research period.
Time Frame
48 weeks
Title
Number of participants who achieve HBsAg seroconversion
Description
To investigate whether Peg-IFN alfa-2a can improve the HBsAg seroconversion in CHB patients at the point of discontinuation of PegIFN therapy compared to the control group ,which will be measured by the number of participants who achieve HBsAg seroconversion. Pegasys 24 weeks Group:24 weeks and Pegasys 48 weeks Group:48 weeks
Time Frame
At the point of discontinuation of PegIFN therapy
Title
Number of participants who achieve HBsAg seroconversion
Description
To investigate whether Peg-IFN alfa-2a can improve the HBsAg seroconversion in CHB patients at 24,48 or 72 weeks post-discontinuation of PegIFN therapy compared to the control group ,which will be measured by the number of participants who achieve HBsAg seroconversion. Pegasys 24 weeks Group:48,72,96 weeks and Pegasys 48 weeks Group:72,96 weeks
Time Frame
24,48,72 weeks post-discontinuation of PegIFN therapy
Title
HBsAg changes from Baseline
Description
Pegasys 24 weeks Group:12,24 weeks and Pegasys 48 weeks Group:12,24,48 weeks
Time Frame
12,24 and 48 weeks
Title
Predictive value of other markers for recurrence after NUC withdrawal
Description
To investigate whether the other markers including HBcAb quantification and so on can predict the recurrence of hepatitis B.
Time Frame
48 weeks and 96 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
HBeAg-Negative Chronic Hepatitis B Patients：HBsAg-Positive,HBsAb-Negative,HBeAg-Negative,HBeAb-Positive during screening period and before NA treatment
NUC monotherapy (including adefovir and entecavir) for more than 2.5 years,and reached stopping rule in 《Chinese chronic hepatitis B prevention and treatment guidelines》(2010):the patients who achieved undetectable HBV DNA (<300 copies/mL) with normal alanine aminotransferase (ALT) and the consolidation therapy reached 1.5 years ,total course of the treatment reached 2.5 years can stop NUC therapy
Willing to stop the drug, and signed a written informed consent
Exclusion Criteria:
HBsAb positive in screening period
Compensated or Decompensated liver cirrhosis:with history of cirrhosis before NUC treatment or Child-Pugh score ≥ 5 or Complications of liver cirrhosis such as ascites, hepatic encephalopathy, esophageal gastric varices bleeding
Hypersensitivity to interferon(IFN) or its active substance, and ineligible to IFN
A history of immunoregulation drug therapy within one year before entry including IFN and so on.
Coinfection with HAV、HCV、HDV、HEV 、HIV or with Other chronic liver diseases such as Alcoholic Liver Disease,Inherited Metabolic Liver Disease,Drug induced Liver Disease and nonalcoholic fatty liver
Autoimmune disease including Autoimmune hepatitis and Psoriasis and so on.
Hepatocellular carcinoma(HCC) or alpha feto protein(AFP) levels more than 100 ng/ml and Hepatic malignant potential of Imaging examination or AFP levels more than 100 ng/ml for 3 months
A neutrophil count of less than 1500 per cubic millimeter or a platelet count of less than 90,000 per cubic millimeter
A serum creatinine level that was more than 1.5 times the upper limit of the normal range
With other malignant tumors(exclude the cured ones)
Severe organ dysfunction
With severe psychiatric condition or nervous disease such as epilepsy, depression, mania, epilepsy, schizophrenia and so on
Uncontrolled diabetes, hypertension or thyroid disease
Pregnant women and lactating women or patients with pregnancy plans and not willing to use contraception during the study period
Participate in other clinical studies at the same time
Patients unsuitable for the research
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jiming Zhang, M.D.
Organizational Affiliation
Huashan Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wuhan Seventh People's Hospital
City
Wuhan
State/Province
Hubei
Country
China
Facility Name
Changzhou Third People's Hospital
City
Changzhou
State/Province
Jiangsu
Country
China
Facility Name
First Affiliated Hospital of Zhejiang University
City
Hangzhou
State/Province
Jiangsu
Country
China
Facility Name
People's Hospital of Jiangsu Province
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
Nantong Third People's Hospital
City
Nantong
State/Province
Jiangsu
Country
China
Facility Name
Suzhou Fifth People's Hospital
City
Suzhou
State/Province
Jiangsu
Country
China
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
Country
China
Facility Name
Taicang People's Hospital
City
Taicang
State/Province
Jiangsu
Country
China
Facility Name
Wuxi Infectious Disease Hospital
City
Wuxi
State/Province
Jiangsu
Country
China
Facility Name
Affiliated Hospital of Xuzhou Medical College
City
Xuzhou
State/Province
Jiangsu
Country
China
Facility Name
Shandong Provincial Hospital
City
Jinan
State/Province
Shandong
Country
China
Facility Name
The First Affiliated Hospital of Wenzhou Medical University
City
Wenzhou
State/Province
Zhejiang
Country
China
Facility Name
Changhai Hospital Affiliated to Second Military Medical University
City
Shanghai
Country
China
Facility Name
Huashan Hospital Affiliated to Fudan University
City
Shanghai
Country
China
Facility Name
Ruijin Hospital Affiliate to Shanghai Jiao Tong University School of Medicine
City
Shanghai
Country
China
Facility Name
Shanghai Public Health Clinical Center
City
Shanghai
Country
China
Facility Name
Shanghai Third People's Hospital
City
Shanghai
Country
China
Facility Name
Shuguang Hospital Affiliate to Shanghai University of Traditional Chinese Medicine
City
Shanghai
Country
China
Facility Name
The Infectious Disease Hospital of Shanghai Huangpu Distric
City
Shanghai
Country
China
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Pegylated Interferon(Peg-IFN) in Reducing Relapse Rate in Patients After Discontinuation of NUC Therapy
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