Primary biliary cirrhosis MedDRA version: 20.0 Level: SOC Classification code 10019805 Term: Hepatobiliary disorders System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Sponsors
Intercept Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Definite or probable PBC diagnosis (consistent with AASLD and EASL Practice Guidelines; [Lindor 2009; EASL 2009]), as demonstrated by the presence of = 2 of the following 3 diagnostic factors: -History of elevated ALP levels for at least 6 months -Positive AMA titer or PBC specific antibodies -Liver biopsy consistent with PBC 2. At least 1 of the following qualifying biochemistry values: - ALP=1.67x ULN -Total bilirubin > ULN but =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Patients will be excluded from the trial if they meet any of the following: 1. History or presence of other concomitant liver diseases including: -Hepatitis C virus (HCV) infection; patients with active hepatitis B (HBV) infection will be excluded, however, patients who have seroconverted (HbsAg and Hbe Ag negative) may be included after consultation with the medical monitor. -Primary sclerosing cholangitis (PSC) -Alcoholic liver disease -Definite autoimmune liver disease or overlap hepatitis -Nonalcoholic steatohepatitis (NASH) -Gilbert’s Syndrome (exclusion due to interpretability of bilirubin levels) 2. Presence of clinical complications of PBC or clinically significant hepatic decompensation, including: -History of liver transplantation, current placement on a liver transplant list or current MELD score = 15 -Portal hypertention with complications, including: known gastric or large esophageal varices, poorly controlled or diuretic resistant ascites, history of variceal bleeds or related therapeutic or prophylactic interventions (e.g., beta blockers, insertion of variceal bands or transjugular intrahepatic portosystemic shunt [TIPS]), or hepatic encephalopathy -Cirrhosis with complications, including history or presence of: spontaneous -Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 µmol/L) bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN 3. Patients with severe pruritus or those requiring systemic treatment for pruritus (e.g., with bile acid sequestrants [BAS] or rifampicin) within 2 months of Day 0 will be excluded. 4. Administration of the following medications is prohibited as specified below: -Prohibited 6 months prior to Day 0 and throughout the trial (i.e., to last dose and/or EOT): azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline; fenofibrate or other fibrates; budesonide and other systemic corticosteroids; potentially hepatotoxic drugs (including a-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin) -Prohibited 12 months prior to Day 0 and throughout the trial (i.e., to last dose and/or EOT): antibodies or immunotherapy directed against interleukins or other cytokines or chemokines 5. Patients who have previously participated in a clinical trial of OCA will not be allowed to participate. 6.History or presence of clinically concerning cardiac arrhythmias likely to affect survival during the trial, or prolongation of Screening (pretreatment) QT or QTc interval of > 500 milliseconds (msec). 7. If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effects of OCA in patients with PBC on: -Serum alkaline phosphatase (ALP) and total bilirubin, together as a composite endpoint -Safety;Secondary Objective: To assess the effects of OCA in patients with PBC on: -Hepatocellular injury and liver function, including histology (inflammatory, structural [portal, parenchymal] and fibrotic assessments) -Disease specific symptoms -Biomarkers and noninvasive assessments of liver fibrosis -Bile acids (BA) -Other exploratory evaluations;Primary end point(s): Primary Endpoint (evaluated as a responder analysis): ALP < 1.67x ULN and total bilirubin within normal limits (WNL), and ALP decrease of = 15% (to exclude clinically insignificant ALP changes);Timepoint(s) of evaluation of this end point: Time expected for all patients to be enrolled: Approximately 12 months Duration of individual patient participation: 12 months during the DB phase; Up to 5 years (60 months) in the LTSE Total duration of trial (excluding data collection and analysis): DB phase: 24 months (2 years) with open label LTSE phase: 84 months (7 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Analyses regarding secondary endpoints will be specified in the SAP and conducted for the following parameters. It is anticipated that additional disease prognostic algorithms will be published during the course of the trial. Where appropriate, secondary analyses will be conducted using such algorithms. At the blinded data review a determination will be made as to which algorithms will be evaluated statistically, as it is likely that there will be small numbers of patients for some algorithms and formal statistical analysis will not therefore be appropriate. • ALP response rates of 10%, 20% and 40% change • Disease Prognostic Risk (criteria in relevant patients): -ALP = 3x ULN and AST = 2x ULN and normal bilirubin - ALP = 1.5x ULN and AST = 1.5x ULN and bilirubin within normal limits - ALP = 1.67x ULN and normal bilirubin - Normal bilirubin and normal albumin • Clinical laboratory values: - GGT, ALT, AST, total and conjugated bilirubin - Albumin, prothrombin time and INR • Liver biopsy/histology: Inflammatory, structural (portal, parenchymal) and fibrotic assessments • Disease Specific Symptoms: - PBC-40 - 5-D Pruritus Questionnaire - Pruritus VAS • Biomarkers and non-invasive assessments of liver fibrosis - Fibrosis biomarkers (ELF) - TE (at selected trial sites) - Other analytes: TNF-a, TGF-ß, IL-6, CK-18 and lysophosphatidic acid • Bile acids - Plasma OCA, other bile acids and conjugate concentrations - Bile and feces concentrations (at selected trial sites) | — |
Countries
Australia, Austria, Belgium, Canada, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trials Info
Accelsiors CRO and Consultancy Services
Outcome results
None listed