Clinical trial NCT02594293: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hepatitis B
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2015-11-03
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants who relapse
timeFrame: 96 weeks
Secondary outcomes:
measure: Number of participants who relapse
timeFrame: 48 weeks
measure: Number of participants who achieve HBsAg seroconversion
timeFrame: At the point of discontinuation of PegIFN therapy
measure: Number of participants who achieve HBsAg seroconversion
timeFrame: 24,48,72 weeks post-discontinuation of PegIFN therapy
measure: HBsAg changes from Baseline
timeFrame: 12,24 and 48 weeks
measure: Predictive value of other markers for recurrence after NUC withdrawal
timeFrame: 48 weeks and 96 weeks
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Wuhan Seventh People's Hospital
state: Hubei
city: Changzhou
country: China
facility: Changzhou Third People's Hospital
state: Jiangsu
city: Hangzhou
country: China
facility: First Affiliated Hospital of Zhejiang University
state: Jiangsu
city: Nanjing
country: China
facility: People's Hospital of Jiangsu Province
state: Jiangsu
city: Nantong
country: China
facility: Nantong Third People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: Suzhou Fifth People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Taicang
country: China
facility: Taicang People's Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi Infectious Disease Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Affiliated Hospital of Xuzhou Medical College
state: Jiangsu
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Shanghai
country: China
facility: Changhai Hospital Affiliated to Second Military Medical University
city: Shanghai
country: China
facility: Huashan Hospital Affiliated to Fudan University
city: Shanghai
country: China
facility: Ruijin Hospital Affiliate to Shanghai Jiao Tong University School of Medicine
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
city: Shanghai
country: China
facility: Shanghai Third People's Hospital
city: Shanghai
country: China
facility: Shuguang Hospital Affiliate to Shanghai University of Traditional Chinese Medicine
city: Shanghai
country: China
facility: The Infectious Disease Hospital of Shanghai Huangpu Distric
Study officials:
affiliation: Huashan Hospital
name: Jiming Zhang, M.D.
role: PRINCIPAL_INVESTIGATOR
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