Pegylated Interferon(Peg-IFN) in Reducing Relapse Rate in Patients After Discontinuation of NUC Therapy

October 27, 2022 updated by: Jiming Zhang, Huashan Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

180

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China
        • Huashan Hospital affiliated to Fudan University
      • Shanghai, China
        • Changhai Hospital affiliated to Second Military Medical University
      • Shanghai, China
        • Ruijin Hospital Affiliate to Shanghai Jiao Tong University School of Medicine
      • Shanghai, China
        • Shanghai Public Health Clinical Center
      • Shanghai, China
        • Shanghai Third People's Hospital
      • Shanghai, China
        • Shuguang Hospital Affiliate to Shanghai University of Traditional Chinese Medicine
      • Shanghai, China
        • The Infectious Disease Hospital of Shanghai Huangpu Distric
    • Hubei
      • Wuhan, Hubei, China
        • Wuhan Seventh People's Hospital
    • Jiangsu
      • Changzhou, Jiangsu, China
        • Changzhou Third People's Hospital
      • Hangzhou, Jiangsu, China
        • First affiliated Hospital of Zhejiang University
      • Nanjing, Jiangsu, China
        • People's hospital of Jiangsu Province
      • Nantong, Jiangsu, China
        • Nantong Third People's Hospital
      • Suzhou, Jiangsu, China
        • The First Affiliated Hospital of Soochow University
      • Suzhou, Jiangsu, China
        • Suzhou Fifth People's Hospital
      • Taicang, Jiangsu, China
        • Taicang People's Hospital
      • Wuxi, Jiangsu, China
        • Wuxi Infectious Disease Hospital
      • Xuzhou, Jiangsu, China
        • Affiliated hospital of Xuzhou medical college
    • Shandong
      • Jinan, Shandong, China
        • Shandong Provincial Hospital
    • Zhejiang
      • Wenzhou, Zhejiang, China
        • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  1. HBeAg-Negative Chronic Hepatitis B Patients：HBsAg-Positive,HBsAb-Negative,HBeAg-Negative,HBeAb-Positive during screening period and before NA treatment
  2. 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
  3. Willing to stop the drug, and signed a written informed consent

Exclusion Criteria:

  1. HBsAb positive in screening period
  2. 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
  3. Hypersensitivity to interferon(IFN) or its active substance, and ineligible to IFN
  4. A history of immunoregulation drug therapy within one year before entry including IFN and so on.
  5. 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
  6. Autoimmune disease including Autoimmune hepatitis and Psoriasis and so on.
  7. 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
  8. A neutrophil count of less than 1500 per cubic millimeter or a platelet count of less than 90,000 per cubic millimeter
  9. A serum creatinine level that was more than 1.5 times the upper limit of the normal range
  10. With other malignant tumors(exclude the cured ones)
  11. Severe organ dysfunction
  12. With severe psychiatric condition or nervous disease such as epilepsy, depression, mania, epilepsy, schizophrenia and so on
  13. Uncontrolled diabetes, hypertension or thyroid disease
  14. Pregnant women and lactating women or patients with pregnancy plans and not willing to use contraception during the study period
  15. Participate in other clinical studies at the same time
  16. Patients unsuitable for the research

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Controlled Group
Discontinue the NA treatment and follow up for 96 weeks
Experimental: Pegasys 48 weeks
Discontinue the NA treatment ,PegIFN alfa-2a 180 μg by week for 48 weeks and follow up for 48 weeks
Drug: PegIFN alfa-2a
180 μg/ 0.5 ml ,hypodermic injection once a week
Other Names:
  • Pegasys

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who relapse
Time Frame: 96 weeks
The total number of relapse (HBV DNA>2000 IU/ml on 2 separate occasions 1 months apart) during the research period.
96 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who relapse
Time Frame: 48 weeks
The total number of relapse (HBV DNA>2000 IU/ml on 2 separate occasions 1 months apart) during the research period.
48 weeks
Number of participants who achieve HBsAg seroconversion
Time Frame: At the point of discontinuation of PegIFN therapy
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
At the point of discontinuation of PegIFN therapy
Number of participants who achieve HBsAg seroconversion
Time Frame: 24,48,72 weeks post-discontinuation of PegIFN therapy
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
24,48,72 weeks post-discontinuation of PegIFN therapy
HBsAg changes from Baseline
Time Frame: 12,24 and 48 weeks
Pegasys 24 weeks Group:12,24 weeks and Pegasys 48 weeks Group:12,24,48 weeks
12,24 and 48 weeks
Predictive value of other markers for recurrence after NUC withdrawal
Time Frame: 48 weeks and 96 weeks
To investigate whether the other markers including HBcAb quantification and so on can predict the recurrence of hepatitis B.
48 weeks and 96 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Huashan Hospital

Investigators

  • Principal Investigator: Jiming Zhang, M.D., Huashan Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2015

Primary Completion (Actual)

September 1, 2022

Study Completion (Actual)

September 1, 2022

Study Registration Dates

First Submitted

October 11, 2015

First Submitted That Met QC Criteria

October 30, 2015

First Posted (Estimate)

November 3, 2015

Study Record Updates

Last Update Posted (Actual)

October 31, 2022

Last Update Submitted That Met QC Criteria

October 27, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CEASE

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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