Chronic Hepatitis B. Clinical Trial
— STOPOfficial title:
Determinants of Sustained Virological Response After Discontinuation of Long-term Nucleoside Analogue Therapy in Chronic Hepatitis B Patients
Evaluation of the rate of sustained virological response among HBeAg-negativechronic
hepatitis B patients who discontinue long-term NA therapy.
During this study participants will cease their prescribed medications, this will occur with
immediate effect once enrolled into the study. The duration of cessation will be indefinite,
unless clinically indicated for NA therapy re-start. Participants will be monitored as per
protocol following cessation, monitoring will be by clinic visit and through blood test to
monitor virological response. Clinical visits will be at the intervals of week 2, week, 4,
week 8, week 12, week 18, following this they will be every 3 months out to 2 years when the
participant will have completed the trial. Once the participant has completed the trial they
will not commence again, the aim is for an indefinite cessation of NA therapy.
| Status | Recruiting |
| Enrollment | 200 |
| Est. completion date | May 2018 |
| Est. primary completion date | May 2018 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Male or Female, age >18 years - Subjects must be able to understand and agree to comply with the prescribed intervention (NA cessation), visits and reliably communicate with study personal about adverse events - Able to provide informed consent. - Chronic Hepatitis B virus infection - HBeAg negative at time if initiation of NA therapy - Meet current APASL guidelines for consideration of antiviral cessation: - uninterrupted NA treatment for >2 years and - undetectable serum HBV DNA on three separate occasions >= 6 months apart (undetectable defined by a value < lower limit of detection using a sensitive commercial PCR assay) - Normal serum ALT levels (according to the uppers limit of normal of the local laboratory) - Minimal to moderate liver fibrosis defined as: - METAVIR liver fibrosis stage F0-F3 inclusive prior to initial NA therapy and/or - Transient liver elastogram (TLE) (Fibroscan) < /= 9.6 kPa at screening Exclusion Criteria: - HBeAg positive chronic hepatitis B at the time of NA initiation - HBV associated extra hepatic manifestations - Documented or suspected hepatocellular carcinoma (HCC) - History of decompensated liver disease - Compensated cirrhosis defined as: - METAVIR liver fibrosis stage 4 on pre-treatment biopsy; OR - TLE > 9.6 kPa at screening - Co-infection with HIV,HCV or HDV - Latrogenic or disease related immunosuppression (e.g. treatment with systemic glucocorticoids, TNFa-antibodies, and other immunosuppressive drugs) - Significant alcohol consumption (> 30 g/day for women and > 50 g/day for men) - Current known history of cancer within 5 years of screening - Pregnant or breast feeding - Other known significant liver disease (including but not limited to haemochromatosis, autoimmune hepatitis, alcoholic liver disease) - Participation in any other interventional trial - Poor Venous access - Suspected lack of compliance - Any medical or social reason which in the opinion of the investigator would make the subject inappropriate for the study |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Australia | St Vincent's Hospital | Melbourne | Victoria |
| Lead Sponsor | Collaborator |
|---|---|
| St Vincent's Hospital Melbourne | National Health and Medical Research Council, Australia |
Australia,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | The primary aim of this study is to evaluate the rate of sustained virological response among HBeAg-negative chronic hepatitis B patients who discontinue long-term NA therapy. The outcome is to be assessed by serum assay. | Patients will be closely followed for 2 years prospectively, at the following time points; 2 weeks post cessation, 4 weeks, 8 weeks, 12 weeks, 18 weeks, then from 6 months the visits will be 3 monthly out to two years, to observe for virological changes. | Yes | |
| Secondary | To identify novel immunological determinants of SVR, the assessment will be by serum assay. | Patients will be closely followed for 2 years prospectively, at the following time points; 2 weeks post cessation, 4 weeks, 8 weeks, 12 weeks, 18 weeks, then from 6 months the visits will be 3 monthly out to two years. | Yes |