Nonalcoholic steatohepatitis MedDRA version: 25.0 Level: PT Classification code 10029530 Term: Non-alcoholic fatty liver System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Trade Name: Ocaliva
Product Name: Obeticholic Acid
Product Code: INT-747, OCA,
Pharmaceutical Form: Tablet
INN or Proposed INN: Obeticholic Acid
CAS Number: 459789-99-2
Current Sponsor code: 6-ECDCA
Sponsors
Intercept Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologic evidence of NASH upon central read of a liver biopsy obtained no more than 6 months before Day 1 defined by presence of all 3 key histological features of NASH with a score of at least 1 for each and a combined score of 4 or greater out of a possible 8 points according to NASH CRN criteria. 2. Histologic evidence of fibrosis stage 2 or stage 3 as defined by the NASH CRN scoring of fibrosis, or histologic evidence of fibrosis stage 1a or stage 1b if accompanied by =1 of the following risk factors: obesity (BMI =30 kg/m2 ), type 2 diabetes diagnosed per 2013 American Diabetes Association criteria, or ALT >1.5× upper limit of normal (ULN). 3. For subjects with a historical biopsy, is either not taking or is on stable doses of TZDs/glitazones or vitamin E for 6 months before Day 1. 4. Stable body weight. 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 2170 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria: 1. Model for End-stage Liver Disease (MELD) score >12 2. ALT =10x ULN 3. HbA1c >9.5% 4. Total bilirubin >1.5 mg/dL 5. Evidence of other known forms of known chronic liver disease such as alcoholic liver disease, hepatitis B, hepatitis C, PBC, PSC, autoimmune hepatitis, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, drug-induced liver injury, known or suspected hepatocellular carcinoma (HCC) 6. History of liver transplant, or current placement on a liver transplant list 7. Current or history of significant alcohol consumption 8. Prior or planned ileal resection, or prior or planned bariatric surgery 9. Histological presence of cirrhosis. 10. History of biliary diversion 11. Known positivity for human immunodeficiency virus infection. 12. Acute cholecystitis or acute biliary obstruction. 13. BMI>45 kg/m².
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective assessed at the Months 18 Interim Analysis: 1. Evaluate the effect of OCA compared to placebo on liver histology in non-cirrhotic NASH subjects with stage 2 or 3 fibrosis by assessing the following endpoints: a. The proportion of OCA treated patients relative to placebo achieving at least one stage of liver fibrosis improvement with no worsening of NASH OR b. The proportion of OCA treated patients relative to placebo achieving NASH resolution with no worsening of liver fibrosis Primary objective assessed at the end of trial: 1.Evaluate the effect of OCA compared to placebo on all-cause mortality and liver-related clinical outcomes as measured by the time of first occurrence of any adjudicated events (clinical outcomes composite endpoint) ;Secondary Objective: Secondary objectives at the Month 18 Interim Analysis: 1. Evaluate the effect of OCA compared to placebo on histological improvement in NASH by assessing endpoints using NASH CRN scoring criteria 2. Evaluate the effect of OCA compared to placebo on liver biochemistry and markers of liver function Secondary objectives at end of study: 1. Evaluate the effect of OCA compared to placebo on histological improvement in NASH by assessing endpoints using NASH CRN scoring criteria 2. Evaluate the effect of OCA compared to placebo on liver biochemistry and markers of liver function ;Primary end point(s): At 18 months: a. Improvement in fibrosis with no worsening of NASH OR b. Resolution of NASH with no worsening of fibrosis At the end of study: a. Clinical outcomes composite endpoint ;Timepoint(s) of evaluation of this end point: 18 months and 10 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints at the Month 18 Interim Analysis: • Improvement of fibrosis by at lease 1 stage AND/OR resolution of NASH, without worsening of either • No worsening of fibrosis AND no worsening of NASH • Improvement in each histological feature of NASH by at least 1 point • Improvement of fibrosis by at least 2 stages • Improvement in NAS by at least 2 points with no worsening of fibrosis • Improvement of fibrosis and resolution of NASH as a composite endpoint and as defined by both endpoints being met in the same subject • Resolution of fibrosis • Histological progression to cirrhosis Secondary efficacy endpoints at EOS: • Improvement in fibrosis by at least 1 stage with no worsening of NASH • NASH resolution with no worsening of fibrosis • Improvement of fibrosis by at lease 1 stage AND/OR resolution of NASH, without worsening of either • No worsening of fibrosis AND no worsening of NASH • Improvement in each histological feature of NASH by at least 1 point • Improvement of fibrosis by at least 2 stages • Improvement in NAS by at least 2 points with no worsening of fibrosis • Improvement of fibrosis and resolution of NASH as a composite endpoint and as defined by both endpoints being met in the same subject • Resolution of fibrosis ;Timepoint(s) of evaluation of this end point: 18 months and 10 years | — |
Countries
Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Hungary, Israel, Italy, New Zealand, Poland, Portugal, Serbia, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactGlobal Regulatory Submissions
Fortrea Development Ltd
Outcome results
None listed