Patients with chronic hepatitis B infection and a relevant grade of fibrosis (histological >= F2) MedDRA version: 15.0 Level: LLT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Baraclude
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ENTECAVIR
CAS Number: 142217-69-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number:
Sponsors
Universitätsklinikum Aachen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Patients aged 18 to 75 years at the time of inclusion in the study •Written informed consent of the patient •Chronic hepatitis B infection (cHBV) with detectable HBV-DNA at study start •Availability of results from a recent liver biopsy. The date of the liver biopsy may not be more than six months before the day of the screen-ing visit. •Evidence for relevant liver fibrosis in the liver histology after percutane-ous or laparoscopic puncture (histologically >= F2) according to the as-sessment of an experienced pathologist and sufficient evaluability of the biopsy material (as a rule, evaluation of at least eight portal fields) or clinical evidence of a liver cirrhosis (on the basis of unequivocal endo-scopic or sonographic indications). The number of patients included with clinical evidence for a liver cirrhosis may not exceed 40%. After in-clusion of 40 patients (= 40%) with clinical evidence for a liver cirrhosis all study centres will be notified not to include more patients from this subgroup •Therapy indication according to the current guidelines for the cHBV infection (i.e. every virus replication in patients with liver cirrhosis or de-tection of an HBV-DNA >= 2000 IU/ml and/or liver histology with inflam-mation >= degree 2/ fibrosis >= stage 2 and ALT 40mlU/ml) ?-6 weeks after operative sterilisation by bilateral tubal ligation or bi-lateral ovarectomy with or without hysterectomy ?-Correct use of two methods for reliable contraception. This includes any combination of a hormonal contraceptive (pill, intra-uterine spi-ral, depot injection, hormone implant, hormone patch or vaginal ring) or an intra-uterine device with spermicidal barrier contracep-tive agent (diaphragm, cervical cap, lea contraceptivum, femidom or condom) or a spermacide ?-Sexual abstinence from two weeks before the first administration of the investigational medicinal product (IMP), during the entire dura-tion of the study, and 30 days following the study, covering the elimination of the IMP -Patients with only female sexual partners -Male partner of a patient who is sterile before inclusion of the fe-male patient in the study and is the only sexual partner of the fe-male patient 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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: •Anamnestically known hypersensitivity to Baraclude® or its components or to medication with a similar chemical structure •Participation of the patient in another clinical study within the last four weeks before inclusion or simultaneous participation in another clinical study •Anamnestically known addictive or other disorders, which do not allow the person to assess the nature, impact and possible consequences of the clinical study •Indications that the patient will probably not comply with the study pro-tocol (e.g. lack of willingness to co-operate) •Anamnestically known co-infection with hepatitis C, hepatitis D or HIV •Evidence for a hepatocellular carcinoma •Severe chronic disease with an estimated survival prognosis of less than three years •Any previous therapy with lamivudine or telbivudine or previous therapy within the last six months before inclusion in the clinical study with an-other active anti-viral drug •Contra-indications for taking entecavir •Creatinine clearance 15 points and/ or evidence for ascites
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Prospective evaluation of fibrosis regression for therapy with entecavir (Baraclude®) in patients with cHBV infection by means of non-invasive markers (FibroScan®, hyaluronic acid value) after 12 months ;Secondary Objective: -Prospective evaluation of fibrosis regression by means of procollagen III N peptide, TIMP-1 and YKL-40 after 12 months -Investigation of diagnostic accuracy (on the basis of sensitivity and speci-ficity) of the non-invasive markers (FibroScan®, serum parameters) with liver biopsy as gold standard -Evaluation of the proportional decrease in liver fibrosis after 6, 18, 24, and 36 months therapy with entecavir by means of FibroScan® and serum pa-rameters -Assessment of the anti-viral efficacy and safety of three years therapy with entecavir for fibrosis regression -Investigation of the relationship between fibrosis regression and the effi-cacy and kinetics of viral suppression with entecavir (Baraclude®) therapy ;Primary end point(s): Co-primary endpoints: Change in the liver stiffness measurement (LSM) value measured with the FibroScan® and the hyaluronic acid value after 12 months therapy with entecavir (Baraclude®) ;Timepoint(s) of evaluation of this end point: 12 month | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change in the serum parameters procollagen III N peptide, TIMP-1 and YKL-40 after 12 months 2. Sensitivity and specificity of the FibroScan and the serum parameters compared with baseline with the result of the liver biopsy as gold standard 3. Change in the LSM value (from the FibroScan®) and the serum pa-rameters after 6, 18, 24 and 36 months 4. Reduction of HBV-DNA and the fraction of patients with non-detectable HBV-DNA at the different study visits (6, 12, 18, 24 and 36 months) 5. Fraction of patients with ALT normalisation at the different study vis-its (6, 12, 18, 24 and 36 months) 6. Fraction of patients with HBeAg loss, anti-HBe sero-conversion, HBsAg loss and anti-HBs sero-conversion at the different study visits 6, 12, 18, 24 and 36 months) ;Timepoint(s) of evaluation of this end point: 1. 12 month 2. 12 month 3. 6, 18, 24 and 36 months 4.-6. 6, 12, 18, 24 and 36 months | — |
Countries
Germany
Contacts
Public ContactProf. Dr. med. Christian Trautwein
Universitätsklinikum Aachen
Outcome results
None listed