Clinical trial NCT06900166: Pegylated Interferon Alfa-2b in Reducing Relapse Rates After Nucleos(t)ide Analogue Withdrawal in HBeAg-negative CHB Patients with Low Level HBsAg
Official title: A Prospective, Open-Label, Randomized, Controlled, Multicenter Clinical Study of Pegylated Interferon Alfa-2b in Reducing Relapse Rates After Nucleos(t)ide Analogue Withdrawal in HBeAg-Negative Chronic Hepatitis B Patients with Low-Level HBsAg
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Chronic Hepatitis B
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2025-03-28
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: All enrolled patients must meet the European Guidelines for the Prevention and Treatment of Chronic Hepatitis B (EASL, 2017) recommended discontinuation criteria, that is, HBeAg-negative chronic hepatitis B patients without fibrosis or cirrhosis who have undetectable HBV DNA for more than 3 years after receiving NUC treatment can attempt to discontinue the drug. At the same time, the patient's HBsAg level will not be higher than 1000 IU/mL. The study will set up three groups, group A directly stopped nucleoside analogues, follow-up to 96 weeks; Group B received PegIFNα-2b monotherapy for 48 weeks, group C received PegIFNα-2b combined with NUC treatment for 48 weeks, group B and group C stopped all antiviral drugs after completing 48 weeks of treatment, and then followed up for 96 weeks, a total of 144 weeks of follow-up. This study aims to further optimize the design on the basis of previous clinical studies to observe whether sequential interferon or combined with NUC therapy can reduce the virological relapse rate of HBeAg-negative chronic hepatitis B patients with low HBsAg level after 96 weeks of discontinuation, and to observe the impact on the functional cure rate.


Eligibility criteria: Inclusion Criteria:

1. Aged between 18 and 65 (inclusive), regardless of gender;
2. Fibroscan ≤ 7.4kpa;
3. HBeAg-negative CHB patients: HBsAg positive, HBeAg negative, HBsAb negative and HBeAb positive before receiving NUC treatment and during screening in this study;
4. HBeAg-negative chronic hepatitis B patients without liver cirrhosis who have been viral-negative for more than 3 years after receiving NUC treatment, and they meet the 2017 EASL guideline discontinuation standard (HBV DNA is lower than the lower limit of detection, that is, \<20 IU/ml);
5. HBsAg≤1000 IU/ml;
6. Have the intention to stop taking the drug, and sign a written informed consent.

Exclusion Criteria:

1. HBsAb positive during screening;
2. Patients with hepatitis B cirrhosis in the compensatory and decompensated stage: patients with a clear history of cirrhosis (imaging or histological evidence) or Child-Pugh score ≥5 before NUC treatment, or complications of cirrhosis in the decompensated stage such as ascites, hepatic encephalopathy, esophageal variceal hemorrhage, etc.;
3. Patients who are allergic to alpha interferon and its drug ingredients, and the researchers judge that alpha interferon is not suitable for patients;
4. Received immunomodulators (including interferon, etc.) within 1 year before screening;
5. Combined with HAV, HCV, HDV, HEV, HIV infection, alcoholic liver disease, genetic metabolic liver disease, drug liver disease, non-alcoholic fatty liver disease and other chronic liver diseases;
6. Combined with autoimmune diseases, including autoimmune liver disease, psoriasis, etc.
7. Patients with primary liver cancer or screening with AFP greater than 100 ng/ml and imaging findings indicating the possibility of malignant liver occupation; Or AFP greater than 100 ng/ml for 3 months;
8. Neutrophil count \< 1.5 x 109 cells /L or platelet count \< 90 x 109 cells /L;
9. Creatinine is 1.5 times higher than the upper limit of normal;
10. Patients with other malignant tumors (excluding cured patients);
11. Patients with serious diseases of heart, lung, kidney, brain, blood and other important organs;
12. Patients with severe neurological and psychiatric disorders (such as epilepsy, depression, mania, seizures, schizophrenia, etc.);
13. Control unstable diabetes, hypertension, thyroid disease, etc.;
14. Pregnant and lactating women or patients who had pregnancy plans during the study period and did not want to use contraception;
15. Participate in other clinical investigators;
16. Patients who were not considered suitable for participation in this study by the investigators.

Primary outcomes:
measure: Number of participants who relapse
timeFrame: 96 weeks after stopping NAs
Secondary outcomes:
measure: Number of participants who relapse
timeFrame: 72 weeks after stopping all antivirals
measure: Number of participants who relapse Clinically
timeFrame: 72 weeks and 96 weeks after stopping all antivirals
measure: Number of participants who achieve HBsAg clearance and HBsAg seroconversion
timeFrame: 96 weeks after stopping all antivirals
measure: Number of participants who restart treatment
timeFrame: 96 weeks after stopping all antivirals
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
state: Shanghai
Study officials:
affiliation: Huashan Hospital
name: Principal Investigator Jiming Zhang, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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