autoimmune liver disease Primary Biliary Cirrhosis
Conditions
Interventions
In the DB phase, first of three group of patients will receive orally placebo
once daily for 12 months, patients in the second group will receive orally 10
mg of OCA once daily for 12 months, and th
Sponsors
Intercept Pharmaceuticals Inc.
Eligibility
Age
18 Years to 99 Years
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 =18 years;4. Taking UDCA for at least 12 months (stable dose for >= 3 months) prior to Day 0, or unable to tolerate UDCA (no UDCA for >= 3 months) prior to Day 0;5. Contraception: Female patients of childbearing potential must use >= 1 effective (
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 bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN;-Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 µmol/L) ;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 |
|---|---|
| Primary Endpoint (evaluated as a responder analysis): ALP = 15% (to exclude clinically insignificant ALP changes) | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Netherlands
Outcome results
None listed