Study Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (REVERSE)

Intercept Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Compensated Cirrhosis; Nonalcoholic Steatohepatitis

Treatments: Drug: Obeticholic acid (10 mg to 25 mg); Drug: Obeticholic acid (10 mg); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03439254

747-304

Details and patient eligibility

About

The primary objective of this study is to evaluate whether obeticholic acid (OCA; INT-747) can lead to histological improvement in fibrosis with no worsening of NASH in adults with compensated cirrhosis due to NASH.

Enrollment: 919 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key inclusion criteria:

1. Subjects with a confirmed diagnosis of NASH and a fibrosis score of 4 based upon the NASH CRN scoring system determined by central reading

Key exclusion criteria:

1. Current or past history of a clinically evident hepatic decompensation event, such as ascites, hepatic encephalopathy (HE), or variceal bleeding
2. Current or past history of CP score ≥7 points
3. Model for End-stage Liver Disease (MELD) score > 12
4. ALT ≥ 5 X ULN
5. Calculated creatinine clearance <60mL/min using Cockcroft-Gault method
6. Hemoglobin A1c (HbA1c) ≥ 9.5 %
7. Evidence of other known forms of 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)
8. History of liver transplant, or current placement on a liver transplant list

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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919 participants in 3 patient groups, including a placebo group

Obeticholic Acid (OCA) 10 mg

Experimental group

Description:

10 mg OCA for up to 18 months

Treatment:

Drug: Obeticholic acid (10 mg)

Obeticholic Acid (OCA) 10 mg to 25 mg

Experimental group

Description:

10 mg OCA for the first 3 months and then may titrate up to 25 mg OCA for the remaining 15 months of the study

Treatment:

Drug: Obeticholic acid (10 mg to 25 mg)

Placebo

Placebo Comparator group

Description:

Placebo for up to 18 months

Treatment:

Drug: Placebo