Study of OCA Evaluating Pharmacokinetics and Safety in Patients With PBC and Hepatic Impairment

• Status: Terminated
• Trial end date: 2021-07-09
• Target enrollment: 0
• Participant gender: All

Summary

This Phase 4, randomized, double-blind, placebo-controlled study will evaluate the PK and safety of OCA treatment in patients with primary biliary cholangitis (PBC) and moderate to severe hepatic impairment over a 48 week treatment period. Patients who have completed their 48-week double blind treatment period will continue double-blind treatment until all randomized patients have completed their 48-week treatment period and the database for that period is locked. An open-label extension study in which all patients receive OCA will be considered following review of blinded safety and PK data.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Intercept Pharmaceuticals
• Treatments: Chenodeoxycholic Acid

Criteria

Inclusion Criteria:

1. A definite or probable diagnosis of PBC (consistent with American Association for the Study of Liver Diseases [AASLD] and European Association for the Study of the Liver [EASL] Practice Guidelines [Lindor 2009, EASL 2009]), defined as having ≥2 of the following 3 diagnostic factors:

• History of elevated ALP levels for at least 6 months

• Positive antimitochondrial antibody (AMA) titer or if AMA negative or low titer (≤1:80), PBC specific antibodies (anti-GP210 and/or anti-SP100) and/or antibodies against the major M2 components (PDC-E2, 2-oxo-glutaric acid dehydrogenase complex)

• Liver biopsy consistent with PBC (collected at any time prior to Screening)

2. Evidence of cirrhosis including at least one of the following:

• Biopsy results consistent with PBC Stage 4

• Liver stiffness as assessed by Transient Elastography (TE) Median Value ≥16.9kPa

• Clinical evidence in the absence of acute liver failure consistent with cirrhosis including: gastroesophageal varices, ascites, radiological evidence of cirrhosis (nodular liver or enlargement of portal vein and splenomegaly)

• Combined low platelet count (<140 000/mm3) with

• persistent decrease in serum albumin, or

• elevation in prothrombin time /INR (not due to antithrombotic agent use), or

• elevated bilirubin (2× ULN)

3. Satisfy the criteria of the modified CP classification for hepatic impairment during Screening:

• Moderate: CP-B (Scores 7 to 9) or

• Severe: CP-C (Scores 10 to 12)

4. MELD score of 6 to 24 at Screening

5. Taking UDCA for at least 12 months (stable dose for ≥3 months) prior to Day 1, or unable to tolerate or unresponsive to UDCA (no UDCA for ≥3 months)

Exclusion Criteria:

1. Non-cirrhotic or cirrhotic CP-A (Mild; Score 5 to 6)

2. History of liver transplant or organ transplant

3. History of alcohol or drug abuse within 12 months prior to Screening

4. Hepatic encephalopathy (as defined by a West Haven score of ≥2 [AASLD, EASL 2014])

5. History or presence of other concomitant liver diseases including:

• Hepatitis C virus infection and RNA positive

• Active hepatitis B infection; however, patients 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

• Primary sclerosing cholangitis

• Alcoholic liver disease

• Definite autoimmune liver disease or overlap hepatitis

• Gilbert's Syndrome

6. In the opinion of the Investigator, fluctuating or rapidly deteriorating hepatic function prior to randomization