Chronic Hepatitis B Infection
Conditions
Interventions
Trade Name: Baraclude
Pharmaceutical Form: Tablet
INN or Proposed INN: ENTECAVIR
CAS Number: 142217-69-4
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 0.5-1
Trad
Sponsors
Antwerp University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Stop group: • = 18 year old and = 75 year old • Chronic hepatitis B, defined as HBsAg positive or HBV DNA positive =6 months • Start of treatment HBeAg negative • Under continuous NA treatment (Lamivudin, Adefovir, Tenofovir or Entecavir) • HBV DNA below the local limit of quantification for at least 36 months at cessation or =2log IU/mL for at least 48 months at cessation • ALT =2x Upper Limit Normal (ULN) on 2 sequential measurements at least 6 months apart (one of which is at screening) Control Group: • = 18 year old and = 75 year old • Chronic hepatitis B, defined as HBsAg positive or HBV DNA positive =6 months • Start of treatment HBeAg negative • Under continuous NA treatment (Lamivudin, Adefovir, Tenofovir or Entecavir) for at least 1 year • HBV DNA below the local limit of quantification for at least 6 months at inclusion • ALT =2xULN on 2 sequential measurements at least 6 months apart (one of which is at screening) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: Stop group: • INR >1.3xULN (unless caused by anticoagulation therapy or vitamin K deficiency) at any point prior to or at the time of screening • Total bilirubin >1.2xULN (unless there is documentation of a benign cause such as Gilbert’s disease) at any point prior to or at the time of screening • Fibrosis =F3 at pre-treatment start biopsy and/or ever a Fibroscan result >9 kPa and/or ever a ShearWave elastography (SWE) > 8.15 kPa (unless a recent (1.3xULN (unless caused by anticoagulation therapy or vitamin K deficiency) at any point prior to or at the time of screening • Total bilirubin >1.2xULN (unless there is documentation of a benign cause such as Gilbert’s disease) at any point prior to or at the time of screening • Fibrosis =F4 at pre-treatment start biopsy and/or ever a Fibroscan result =11.4 kPa and/or ever a SWE =11.5 kPa (unless a recent (<6 months old) liver biopsy shows Metavir fibrosis <F4). • Active confection: HCV RNA positive, HDV RNA positive, HIV Ag-Ab positive • Immunocompromised individuals, defined as (in line with the NHS criteria) o Patients undergoing any radiotherapy or chemotherapy <1 year before study start o Solid organ transplant recipients o Bone marrow or stem cell transplant recipients o Patients having multiple myeloma or genetic disorders affecting the immune system o Individuals receiving immunosuppressive or immunomodulating biological therapy <6 months before study start o Patients receiving protein kinase or PARP o Individuals treated with steroid sparing agents such as cyclophosphamide and mycophenolate mofetil o Individuals treated with or likely to be treated with systemic steroids for more than a month at a dose equivalent to prednisolone at 20 mg or more per day for adults o Patients with a history of haematological malignancy, including leukaemia, lymphom
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We will conduct the first prospective open-label clinical trial powered to examine the contribution of ethnicity to off-treatment viral outcomes, by controlled treatment interruption in an equal number of Caucasian and non-Caucasian patients with start of treatment HBeAg negative chronic hepatitis B infection. The off-treatment responses of the Caucasian participants will be compared versus the non-Caucasian participants. We hypothesize that compared to non-Caucasian patients, a substantially higher proportion of Caucasian patients who stop treatment will reach the primary study endpoint (i.e. off-treatment HBV DNA =2000 IU/mL and ALT =2xULN 72 weeks after treatment cessation). ;Secondary Objective: This study has two secondary objectives: first we will compare the occurrence of HBsAg-loss at week 72 after treatment stop and the time for reaching HBsAg-loss between the Caucasian patients and the non-Caucasian patients of the stop group. We hypothesize that compared to non-Caucasian patients a higher fraction of the Caucasian patients will reach the secondary endpoint (i.e. HBsAg-loss) and they will also do this more quickly. Another secondary objective is to estimate the cost-effectiveness of treatment cessation and long-term projections, based on data acquired during the clinical trial and in control patients who continue treatment as part of routine clinical practise. The HRQoL and health care expenditures of the stop group participants will be compared versus the control group participants. We hypothesize that treatment cessation will result in a reduction in health care expenditures and an increase in HRQoL.;Primary end point(s): The primary endpoint of this study is the occurrence of viral control defined as HBV DNA =2000 IU/mL and ALT =2xULN 72 weeks after treatment cessation. ;Timepoint(s) of evaluation of this end point: 72 weeks after treatment cessation. HBV DNA and ALT levels will be followed up every 2 to 6 weeks during the cli | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoint of this study is HBsAg loss at week 72 after treatment cessation. ;Timepoint(s) of evaluation of this end point: 72 weeks after treatment cessation. HBsAg status will be followed up every 2 to 6 weeks during the trial. | — |
Countries
Belgium
Contacts
Public ContactClinical Trial Center
Antwerp University Hospital
Outcome results
None listed