Randomized Global Phase 3 Study to Evaluate the Impact on NASH With Fibrosis of Obeticholic Acid Treatment

• Register: ClinicalTrials.gov
• Last refreshed on: 23 October 2023
• Main ID: NCT02548351
• Date of registration: 01/09/2015
• Prospective Registration: Yes
• Primary sponsor: Intercept Pharmaceuticals
• Public title: Randomized Global Phase 3 Study to Evaluate the Impact on NASH With Fibrosis of Obeticholic Acid Treatment REGENERATE
• Scientific title: A Phase 3, Double-Blind, Randomized, Long-Term, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of Obeticholic Acid in Subjects With Nonalcoholic Steatohepatitis
• Date of first enrolment: September 22, 2015
• Target sample size: 2480
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT02548351
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Netherlands, New Zealand, Poland, Portugal, Puerto Rico, Serbia, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Sangeeta Sawhney, MD
• Affiliation: Intercept Pharmaceuticals

Key inclusion & exclusion 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
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

- 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.

Exclusion Criteria:

1. Model for End-stage Liver Disease (MELD) score >12

2. ALT =10× 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



Age minimum: 18 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Non Alcoholic Steatohepatitis (NASH)

Intervention(s)

Drug: Obeticholic Acid

Drug: Placebo

Primary Outcome(s)

To evaluate the effect of Obeticholic Acid compared to placebo on all-cause mortality and liver-related clinical outcomes as measured by the time to first occurrence of any of the listed adjudicated events (clinical outcomes composite endpoint) [Time Frame: Time to accrue a pre-specified number of adjudicated events, End of Study, estimated to be 7 years]

To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in non-cirrhotic nonalcoholic steatohepatitis (NASH) subjects with stage 2 or 3 fibrosis by assessing the following primary endpoints [Time Frame: Measurements at Baseline and 18 months]

Secondary Outcome(s)

To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in NASH [Time Frame: 18 month Interim Analysis]

To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in NASH [Time Frame: End of Study, estimated to be 7 years]

To evaluate the effect of Obeticholic Acid compared to placebo on liver biochemistry and markers of liver function [Time Frame: 18 months and End of Study, estimated to be 7 years]

Secondary ID(s)

747-303

Source(s) of Monetary Support

Please refer to primary and secondary sponsors