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
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Huashan Hospital
- Enrollment
- 180
- Locations
- 19
- Primary Endpoint
- Number of participants who relapse
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Pegasys 48 weeks
Discontinue the NA treatment ,PegIFN alfa-2a 180 μg by week for 48 weeks and follow up for 48 weeks
Intervention: PegIFN alfa-2a (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Number of participants who achieve HBsAg seroconversion(24,48,72 weeks post-discontinuation of PegIFN therapy)
- HBsAg changes from Baseline(12,24 and 48 weeks)
- Number of participants who relapse(48 weeks)
- Predictive value of other markers for recurrence after NUC withdrawal(48 weeks and 96 weeks)
Investigators
Jiming Zhang
chief physician,professor
Huashan Hospital