Primary Biliary Cholangitis MedDRA version: 21.0 Level: LLT Classification code 10036680 Term: Primary biliary cirrhosis System Organ Class: 100000004871
Conditions
Interventions
Trade Name: Ocaliva
Product Name: Obeticholic acid
Product Code: OCA, INT-747
Pharmaceutical Form: Tablet
INN or Proposed INN: Obeticholic Acid
CAS Number: 459789-99-2
Current Sponsor code: 6-ECDCA
O
Sponsors
Intercept Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Definite or probable PBC diagnosis (consistent with American Association for the Study of Liver Diseases [AASLD] and the European Association for the Study of the Liver [EASL] practice guidelines; Lindor 2009; EASL 2009), as demonstrated by the presence of =2 of the following 3 diagnostic factors: a. History of elevated Alkaline phosphatase levels for at least 6 months. b. Positive antimitochondrial antibody (AMA) titer or if AMA negative or in low titer (ULN and =5x ULN and/or a mean ALP >3xULN. 3. Either is not taking UDCA (no UDCA dose in the past =3 months) or has been taking UDCA for at least 12 months with a stable dose for =3 months prior to Day 0. 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 278 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: 1. History or presence of other concomitant liver diseases including: a. Hepatitis C virus infection b. Active hepatitis B infection; however, subjects who have seroconverted (hepatitis B surface antigen and hepatitis B e antigen negative) may be included in this study after consultation with the medical monitor c. Primary sclerosing cholangitis d. Alcoholic liver disease e. Definite autoimmune liver disease or overlap hepatitis f. Nonalcoholic steatohepatitis g. Gilbert’s Syndrome 2. Presence of clinical complications of PBC or clinically significant hepatic decompensation, including: a. History of liver transplant, current placement on a liver transplant list, or current MELD score >12. Subjects who are placed on a transplant list despite a relatively early disease stage (for example per regional guidelines) may be eligible as long as they do not meet any of the other exclusion criteria b. Cirrhosis with complications, including history (within the past 12 months) or presence of: i. Variceal bleeding ii. Uncontrolled ascites iii. Encephalopathy iv. Spontaneous bacterial peritonitis c. Known or suspected hepatocellular carcinoma d. Prior transjugular intrahepatic portosystemic shunt procedure e. Hepatorenal syndrome (type I or II) or Screening (visit 1 or 2) serum creatinine >2 mg/dL (178 µmol/L) 3. Mean total bilirubin >5× ULN 4. Subjects who have undergone gastric bypass procedures (gastric lap band is acceptable) or ileal resection or plan to undergo either of these procedures 5. Other medical conditions that may diminish life expectancy, including known cancers (except carcinomas in situ or other stable, relatively benign conditions) 6. If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating 7. Known history of human immunodeficiency virus infection 8. Medical conditions that may cause nonhepatic increases in ALP (eg, Paget's disease or fractures within 3 months prior do Day 0) 9. Other clinically significant medical conditions that are not well controlled or for which medication needs are anticipated to change during the study 10. History of alcohol abuse or other substance abuse within 1 year prior to Day 0 11. Participation in another investigational product, biologic, or medical device study within 30 days prior to Screening. Participation in a previous study of OCA is allowed with 3 months washout prior to enrollment in this study 12. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain 13. History of known or suspected clinically significant hypersensitivity to OCA or any of its components 14. UDCA naive unless contraindicated
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess the effect of OCA compared to placebo, in conjunction with established local standard of care, on clinical outcomes in subjects with PBC as measured by time to first occurrence of any of the following adjudicated events, derived as a composite event endpoint: a. Death (all-cause) b. Liver transplant c. Model of end stage liver disease (MELD) score =15 d. Hospitalization (as defined by a stay of 24 hours or greater) for new onset or recurrence of: i. Variceal bleed ii. Hepatic Encephalopathy (as defined by a West Haven score of =2) iii. Spontaneous bacterial peritonitis (confirmed by diagnostic paracentesis) e.Uncontrolled ascites (diuretic resistant ascites requiring therapeutic paracentesis at a frequency of at least twice in a month);Secondary Objective: To assess the effect of OCA compared to placebo on time to first occurrence of each individual component of the primary endpoint as listed above. To assess the effect of OCA compared to placebo on time to occurrence of liver-related death. To assess the effect of OCA compared to placebo on progression to cirrhosis. To assess the effect of OCA compared to placebo on time to occurrence of HCC. To assess the effect of OCA compared to placebo on disease progression via the following: • Liver biochemistry • Markers of inflammation and fibrosis To assess the effect of OCA compared to historical controls on liver related clinical outcomes. To characterize the PK of OCA and its conjugates in a subset of subjects. To assess health outcomes and pharmacoeconomics including costeffectiveness, resource utilization, and quality of life measures in subjects treated with OCA compared to placebo. To assess the safety and tolerability in subjects treated with OCA compared to placebo.;Primary end point(s): The primary efficacy endpoint will be the time to first occurrence of one of the following post randomization: a. Death (all | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Analyses The key secondary efficacy endpoints are as follows: a. Time to first occurrence of MELD score =15 b. Time to liver transplant or death (all-cause) c. Change from Baseline in total bilirubin at end of study d. Change from Baseline in ALP at end of study Other Efficacy Analyses The following time to event secondary efficacy analyses will compare OCA versus placebo using the ITT population: • Time to each component of the primary efficacy endpoint (except MELD score =15 which is captured above) • Time to development of varix/varices • Progression to cirrhosis • Time to occurrence of HCC • Time to liver-related death • Time to liver-related death or liver transplant • Time to liver-related death, liver transplant, or MELD score =15 Safety Analysis Safety data, including AEs, AEs of special interest including pruritus and hepatic safety, vitals, electrocardiogram, and clinical laboratory results will be summarized by treatment group for Health outcomes and pharmacokinetic analyses;Timepoint(s) of evaluation of this end point: 10 years | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Denmark, Estonia, Finland, France, Germany, Hong Kong, Hungary, Israel, Italy, Korea, Republic of, Lithuania, Mexico, Netherlands, New Zealand, Poland, Portugal, Serbia, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactProject management
Syneos Health UK Limited
Outcome results
None listed