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

Intercept Pharmaceuticals

Status and phase: Terminated; Phase 3

Conditions: Non Alcoholic Steatohepatitis (NASH)

Treatments: Drug: Obeticholic Acid; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02548351

747-303

Details and patient eligibility

About

The primary objectives of this study are to evaluate the effect of Obeticholic Acid treatment compared to placebo on 1) histological improvement and 2) liver-related clinical outcomes in patients with non-cirrhotic nonalcoholic steatohepatitis (NASH) with liver fibrosis.

Enrollment: 2,477 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,477 participants in 3 patient groups, including a placebo group

10 mg Obeticholic Acid

Experimental group

Description:

10 mg Obeticholic Acid daily for the remainder of the study

Treatment:

Drug: Obeticholic Acid

25 mg Obeticholic Acid

Experimental group

Description:

25 mg Obeticholic Acid daily for the remainder of the study

Treatment:

Drug: Obeticholic Acid

Placebo

Placebo Comparator group

Description:

One tablet daily for the remainder of the study

Treatment:

Drug: Placebo