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

• Register: ClinicalTrials.gov
• Last refreshed on: 10 August 2021
• Main ID: NCT03633227
• Date of registration: 08/04/2018
• Prospective Registration: Yes
• Primary sponsor: Intercept Pharmaceuticals
• Public title: Study of OCA Evaluating Pharmacokinetics and Safety in Patients With PBC and Hepatic Impairment
• Scientific title: A Phase 4, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Pharmacokinetics and Safety of Obeticholic Acid in Patients With Primary Biliary Cholangitis and Moderate to Severe Hepatic Impairment
• Date of first enrolment: June 22, 2018
• Target sample size: 22
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03633227
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 4

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Estonia, Germany, Hungary, Italy, Lithuania, Spain, United States

Contacts

• Name: George Harb, M.D.
• Affiliation: Intercept Pharmaceuticals

Key inclusion & exclusion 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



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

Health Condition(s) or Problem(s) studied

Liver Cirrhosis, Biliary

Intervention(s)

Drug: Placebo

Drug: Obeticholic Acid (OCA)

Primary Outcome(s)

Evaluate area under the concentration curve versus time curve from 0 to 24 hours (AUC 0-24) of OCA, its conjugates and total OCA [Time Frame: 24 hours at Day 1, and Weeks 12, 18, 24, 30, 36, and 48]

Evaluate maximum concentration (Cmax) of OCA, its conjugates and total OCA (sum of OCA and its conjugates) [Time Frame: Weeks 12, 18, 24, 30 and 48: 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours at]

Evaluate safety and tolerability as assessed by the incidence of treatment emergent adverse events and serious treatment emergent adverse events comparing OCA to placebo [Time Frame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, 48, and every 3 months thereafter through approximately 3 years]

Secondary Outcome(s)

Evaluate the effect of OCA treatment compared to placebo on platelets (109/L) [Time Frame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, 48, and every 3 months thereafter through approximately 3 years]

Evaluate the effect of OCA treatment compared to placebo on the model of end-stage liver disease (MELD) and its components [Time Frame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, 48, and every 3 months thereafter through approximately 3 years]

Evaluate the effect of OCA treatment compared to placebo on plasma bile acids (µmol/L) [Time Frame: Weeks 3, 6, 12, 18, 24, 30, 36, 42, 48, and every 3 months thereafter through approximately 3 years]

Evaluate the effect of OCA treatment compared to placebo on alkaline phosphatase (U/L), alanine aminotransferase (U/L), aspartate transaminase (U/L), and gamma glutamyl transaminase (U/L) [Time Frame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, 48, and every 3 months thereafter through approximately 3 years]

Evaluate the effect of OCA treatment compared to placebo on Child-Pugh score and its components [Time Frame: At Day 1, and Weeks 6, 12, 18, 24, 30, 36, and 48]

. Evaluate the effect of OCA treatment compared to placebo on 7a hydroxy-4-cholesten-3-one (ng/mL) [Time Frame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, 48, and every 3 months thereafter through approximately 3 years]

Evaluate the effect of OCA treatment compared to placebo on fibroblast growth factor-19 (pg/mL) [Time Frame: Baseline, Screening, Day 1, Weeks 3, 6, 12, 18, 24, 30, 36, 42, 48, and every 3 months thereafter through approximately 3 years]

Evaluate the effect of OCA treatment compared to placebo on total bilirubin (mg/dL) and direct bilirubin (mg/dL) [Time Frame: Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, 48, and every 3 months thereafter through approximately 3 years]

Secondary ID(s)

747-401

Source(s) of Monetary Support

Please refer to primary and secondary sponsors