Primary Sclerosing Cholangitis MedDRA version: 20.1 Level: LLT Classification code 10036732 Term: Primary sclerosing cholangitis System Organ Class: 100000004871
Conditions
Interventions
Trade Name: LEVOVANOX
Product Name: LEVOVANOX
Product Code: [LEVOVANOX]
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: VANCOMICINA CLORIDRATO
Current Sponsor code: VANCOMICINA
Concentration u
Sponsors
UNIVERSITÀ DEGLI STUDI MILANO BICOCCA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to give informed consent prior to any study specific procedure being performed; 2. Male and non-pregnant, non-lactating female subjects, including women of child bearing potential (WOCBP), between 15-70 years of age at the time of informed consent; 3. Diagnosis of large-duct PSC based on cholangiogram (at MRCP, Endoscopic retrograde cholangiopancreatography [ERCP], percutaneous transhepatic cholangiography [PTC]) according to the most recent published guidelines (EASL); 4. Baseline ALP =1.5 times upper limit normal at screening; 5. Absence of biliary obstruction and/or malignancy within 6-12 months of entry into the study; 6. If a patient is on ursodeoxycholic acid (UDCA) or 5-aminosalicylic acid he or she is expected to remain on the same daily dose during the study period; 7. Patients who received antibiotics or probiotics may participate if they had a washout period of at least 3-month prior to study entry; 8. If a patient has been on obeticholic acid or other experimental therapies (e.g. cilofexor and norUDCA) for PSC, they must complete a 3-month washout period before study entry; 9. PSC with or without IBD. IBD diagnosis should be documented and with a minimum disease duration of 6 months, as determined by endoscopic and histopathology assessment. IBD should be in clinical remission or mildly active according to CDAI and partial Mayo score for CD and UC, respectively (i.e. patients with CDAI score =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Receiving an antibiotic or probiotic within 3 months prior to the study; 2. Expected to receive antibiotics within the weeks leading up to enrollment (such as patients with recurrent cholangitis, ongoing infectious illnesses, etc.) ; 3. Allergy to vancomycin or teicoplanin; 4. Biliary intervention within 3 months prior to study enrollment or planned; 5. Alcohol abuse (defined as greater than 14 standard drinks units per week in men; greater than 7 standard drinks units per week); 6. Pregnancy and lactation; 7. Advanced renal disease (glomerular filtration rate [GFR ]4 mg/dL) ; 12. On active transplantation list; 13. IBD with uncontrolled moderate to severe activity; 14. Treatment with any immunosuppressive medication for controlling IBD (i.e. azathioprine, 6-mercaptopurine, tacrolimus, methotrexate, infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, tofacitinib, ozanimod). Treatment with corticosteroids (including budesonide, budesonide MMX and beclomethasone) in the previous four weeks; 15. Treatment with rifampicin; 16. Dose change within last 3 months prior to baseline of concomitant treatment with vitamin D or fibrates; 17. Treatment with any experimental drug within the previous three months; 18. Any known relevant infectious disease (e.g. active tuberculosis, AIDS defining disease); 19. Any active malignant disease; 20. Well found doubt about patient’s cooperation, e.g. addiction to alcohol or drugs; 21. Imprisoned person, person admitted to nursing homes, persons under legal guardianship, and persons not able to express their consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effect of OV at different doses versus placebo on alkaline phosphatase (ALP) at 6 months.;Secondary Objective: - To determine the safety and tolerability of OV in each treatment arm; - To evaluate the effect of OV at different doses versus placebo at 6 months on the following: •liver fibrosis assessed by liver stiffness measurements (LSM) using transient elastography (TE) •magnetic resonance cholangiopancreatography (MRCP) traditional semiquantitative scoring (Amsterdam criteria/Anali criteria) and continuous scoring using MRCP+ & Liver multiscan technology (Perspectum Diagnostics Ltd) •non-invasive biomarkers of liver fibrosis (ELF, PRO-C3, PRO-C5; C3M, C4M and BGM), cell apoptosis and necrosis (CK18 M30 and M65), cytokines (TGF-ß, IL-4, IL-13, IL-10, etc.) peripheral blood mononuclear cells (Th1 and Th17 subsets), and biomarkers of farnesoid-X-receptor (FXR) activity (FGF-19, C4 and bile acid) •clinical, endoscopic and histologic activity of IBD •quality of life;Primary end point(s): ALP levels at 6 months;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - reduction of ALP levels =40% (for those of 15-17-year-old the liver isoenzyme will be evaluated); - safety and tolerability: adverse events, clinical hematology, clinical chemistry, urinalysis, single 12-lead electrocardiograms (ECGs), vital sign measurements including body weight, systolic and diastolic blood pressure (BP), body temperature and pulse rate. Rectal swab to exclude infection or colonisation with vancomycin-resistant enterococci (VRE); - reduction of serum gammaglutamyltransferase (GGT) levels; - reduction of serum aspartate-aminotransferase (AST) and Alanine-aminotransferase (ALT) levels; - normalization of serum bilirubin levels; - change in Amsterdam-Oxford prognostic score; - change in the Revised PSC Mayo Risk Score; - lack of progression in LSM at FibroScan (change in liver stiffness <= 1.3 kPa); - lack of progression in bile duct strictures and dilatation (evaluated at MCRP using traditional semiquantitative scoring such as Amsterdam criteria and Anali criteria); - changes in IBD activity indexes: Crohn's Disease Activity Index [CDAI] score and partial Mayo score [pMCS], for Crohn’s disease [CD] and UC respectively; changes in C-reactive protein (CRP) and fecal calprotectin levels; changes in Simple Endoscopic Score for Crohn’s Disease [SES-CD] and endoscopic Mayo score, for CD and UC respectively; changes in Nancy Histological Index for UC and Global Histologic Disease Activity Score [GHAS] for CD; - proportion of patients who are in clinical remission (defined as CDAI<150 for CD or partial Mayo Score <2 for UC) at baseline, week 4, 12 and 24. and week 12 of follow up; proportion of patients achieving endoscopic remission (defined as SES-CD = 2 for CD or endoscopic Mayo score <1 for UC) at baseline and week 24; proportion of patients achieving histologic healing (as defined as GHAS =4 for CD or Nancy Histological Index <1 for UC) at baseline and week 24; - changes in ultrasound activity indices (length of disease, | — |
Countries
Italy
Contacts
Public ContactUfficio BiCRO (Bicocca Clinical Res
Università Milano-Bicocca
Outcome results
None listed