Primary Biliary Cirrhosis
Conditions
Brief summary
The study is aimed to compare the efficacy and tolerability of a combination therapy with ursodeoxycholic acid (12-16 mg/kg body weight (BW)/d) plus budesonide (9 mg/d) vs. ursodeoxycholic acid (12-16 mg/kg BW/d) plus placebo in the treatment of PBC. Depending on ALT values 6 mg/d budesonide are allowed. The study population will be patients with PBC at risk for disease progression. It is assumed that the combination therapy will result in a decrease of treatment failures after 3 years of treatment.
Interventions
DRUGbudesonide
One budesonide 3 mg capsule TD or one budesonide 3 mg capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d for 3 years
DRUGbudesonide placebo
One placebo capsule TD or One placebo capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d for 3 years
Sponsors
Dr. Falk Pharma GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent 2. Age ≥ 18 years 3. UDCA treatment for at least 6 months prior to inclusion 4. Liver biopsy compatible with PBC 5. Liver biopsy performed within the last 6 months prior to inclusion 6. PBC patients at risk of disease progression based on one or more of the following criteria: * Serum alkaline phosphatase ≥ 3 times the upper limit of normal at any time since diagnosis of PBC and ALT ≥ 2 times upper limit of normal or * Total Bilirubin ≥ 1.0 mg/dl (≥ 17 µmol/L) or * Moderate to severe periportal or periseptal lymphocytic interface hepatitis or * Periportal and portal fibrosis with numerous septa (Ludwig stage III) without cirrhosis 7. Type 2 anti-mitochondrial antibodies \> 1:40 by direct immunofluorescence 8. Women of child-bearing potential have to apply appropriate contraceptive methods, e.g., hormonal contraception, intrauterine device (IUD), double-barrier method of contraception (e.g., use of a condom and spermicide), partner has undergone vasectomy and subject is in monogamous relationship. The investigator is responsible for determining whether the subject has adequate birth control for study participation
Exclusion criteria
1. Histologically proven cirrhosis 2. Positive Hepatitis B or C serology 3. Positive HIV serology 4. Primary Sclerosing Cholangitis 5. Wilson's-Disease 6. Celiac Disease (blood tests and/or oesophago-gastro-duodenoscopy with histological examination to be performed) 7. α1-anti-Trypsin-deficiency 8. Haemochromatosis 9. Autoimmune-Hepatitis (AIH; defined by an Alvarez score \> 15 without treatment or ≥ 17 with treatment); Note: PBC/AIH overlap disease, treated insufficiently with UDCA monotherapy may be enrolled 10. Treatment with any of the following drugs within the last 3 months prior to inclusion: colchicine, corticosteroids, azathioprine or other immunosuppressive drugs (e.g. cyclosporine, methotrexate), chlorambucil, D-penicillamine, fibrates, or antihyperlipidemic drugs 11. Treatment with ketoconazole or other CYP3A inhibitors within the last 4 weeks before baseline; rifampicin (up to 600 mg/d) is allowed to treat pruritus until baseline 12. Sonographic or endoscopic signs of portal hypertension 13. Ascites or history of ascites 14. Hepatic encephalopathy or history of hepatic encephalopathy 15. Total bilirubin \> 3.0 mg/dl (\> 50 µmol/L) 16. Albumin \< 36 g/L 17. Prothrombin ratio \< 70% 18. Platelet count \< 135.000/mm3 19. Osteoporosis proven by bone densitometry 20. Diabetes mellitus, defined as B-Glucose \> 125 mg/dl on an empty stomach (even when controlled) 21. Hypertension, defined as persistent raised blood pressure \> 140/90 mmHg 22. Suspected non-compliance of the patient (suspected difficulties to comply with the study period of 36 months) 23. Severe co-morbidity substantially reducing life expectancy 24. Known intolerance/hypersensitivity/resistance to study drugs or drugs of similar chemical structure or pharmacological profile 25. Existing or intended pregnancy or breast-feeding 26. Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rate of patients without treatment failure after 3 years of treatment | 3 years, LOCF |
Secondary
| Measure | Time frame |
|---|---|
| bone mineral density | 3 years, LOCF |
| course of pruritus | 3 years, LOCF |
| course of fatigue | 3 years, LOCF |
| course of Mayo Risk score | 3 years, LOCF |
Countries
France, Germany
Outcome results
None listed