Hepatitis B, Chronic
Conditions
Brief summary
Multicenter, Prospective Open-label Single Arm Trial Chronic hepatitis B male and female adults on antiviral treatment for hepatitis B, without cirrhosis who are currently HBV DNA (-) and HBeAg (-) To evaluate the safety and efficacy of stopping long-term antiviral therapy in chronic hepatitis B patients without cirrhosis who are currently HBV DNA (-) and HBeAg (-)
Detailed description
This clinical trial is a multicenter, Prospective Open-label Single Arm Trial to evaluate the safety and efficacy of stopping long-term antiviral therapy in chronic hepatitis B patients without cirrhosis who are currently HBV DNA (-) and HBeAg (-). Approximately 140 subjects meeting eligibility criteria will be enrolled a Intervention Arm as below; \- Intervention Arm: 140 subjects, discontinue antiviral treatment (stop group) Participants are scheduled to be followed up to 48 weeks. Patients are retreated with nucleos(t)ide analogues that had been prescribed previously if they fulfill one of the following criteria: 1) HBV DNA \>2,000 IU/mL, 2) at the participant's request or at the treating investigator's discretion, 3) progression to liver cirrhosis, or 4) development of hepatocellular carcinoma.
Interventions
DRUGStop group
discontinue antiviral treatment
Sponsors
Asan Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide written informed consent prior to study entry 2. Age ≥19 years and ≤65 years at the time of screening 3. HBsAg titer \<3,000 IU/mL at the time of screening 4. Antiviral treatment continued at least 2 years and HBeAg (-) at the time of screening 5. Undetectable HBV DNA level at the time of screening 6. Serum ALT level \<80 IU/mL at the time of screening 7. Estimated creatinine clearance ≥30 ml/min (by calculation of creatinine clearance or using the CKD-EPI equation) 8. Ability to comply with all study requirements
Exclusion criteria
1. Confirmed known co-infection with HCV, HIV, or HDV 2. Evidence of liver cirrhosis defined as meeting any of the following criteria: 3. Current alcohol (60g/day) or substance abuse judged by the investigator that will potentially interfere with subject compliance (1) Splenomegaly (\>12 cm) assessed by ultrasound, CT, or MRI (2) Fibroscan ≥9.0 kPa (3) Platelet count \<150,000/mm3 However, if the above criteria were satisfied at the time of antiviral treatment initiation, subjects may be eligible if they have low possibility of having liver cirrhosis with improvement in liver function by long-term antiviral treatment, following the opinion of the investigator. 4. Any history of clinical hepatic decompensation (e.g., ascites, encephalopathy, variceal hemorrhage) within 12 months prior to the screening or Child-Pugh score of ≥7 at the time of screening 5. Currently on or have received therapy with Interferon or immunosuppressant (including systemic chemotherapy) within 12 months prior to the screening 6. Requirement for chronic use of systemic immunosuppressant including, but not limited to, corticosteroid (prednisone equivalent of \>40 mg/day for \>2 weeks), azathioprine, or monoclonal antibodies 7. Received solid organ or bone marrow transplant 8. Any other clinical conditions (cardiovascular, respiratory, neurologic, or renal conditions) or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements. 9. History or current evidence of hepatocellular carcinoma (HCC), or high α-fetoprotein (AFP) \> 20 ng/mL. (But, the patients with AFP \> 20 ng/mL can be enrolled and there is no evidence of HCC by dynamic CT or MRI perfomred within 4 months prior to the screening) 10. Malignancy other than hepatocellular carcinoma within the 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (within 2 years prior to screening with confirmation of no evidence of disease). Subjects under evaluation for possible malignancy are not eligible. 11. Concurrent enrollment in another clinical study for other type of antiviral treatment for CHB or immune modulatory drug within 3 months prior to Screening, participation to an observational (non-interventional) clinical studies or interventional studies not using anti-HBV or immune modulatory drugs, or during the follow-up period of an interventional study are not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| virological relapse | Change from baseline in HBV DNA result in 48 weeks | Proportion of virological relapse defined as HBV DNA ≥2,000 IU/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical relapse | From baseline, clinical events will be collected within 48 weeks | ALT ≥80 U/L with HBV DNA ≥2000 IU/mL |
| ALT flare | 48 weeks | ALT ≥200 U/L after documented virological relapse |
| Retreatment | 48 weeks | Retreatment |
| HBsAg seroclearance | 48 weeks | HBsAg seroclearance |
| Hepatic decompensation | 48 weeks | ascites, encephalopathy, variceal bleeding, or jaundice |
Countries
South Korea
Contacts
PRINCIPAL_INVESTIGATORYoung-Suk Lim, PhD
Asan Medical Center
Outcome results
None listed