Phase 4 Study of Obeticholic Acid Evaluating Clinical Outcomes in Patients With Primary Biliary Cholangitis

  • STATUS
    Recruiting
  • End date
    Apr 14, 2025
  • participants needed
    428
  • sponsor
    Intercept Pharmaceuticals
Updated on 14 October 2020
Investigator
Liz Glynn
Primary Contact
Royal Prince Alfred Hospital (7.5 mi away) Contact
+322 other location
investigational drug
liver disease
liver transplant
cirrhosis
chenodeoxycholic acid
bile acid
ursodiol
obeticholic acid
antimitochondrial antibody

Summary

Primary Biliary Cholangitis (PBC) is a serious, life-threatening, bile acid related liver disease of unknown cause. Without treatment, it frequently progresses to liver fibrosis and eventual cirrhosis requiring liver transplantation or resulting in death. The investigational drug, Obeticholic Acid (OCA) is a modified bile acid and FXR agonist that is derived from the primary human bile acid chenodeoxycholic acid. The key mechanisms of action of OCA, including its choleretic, anti-inflammatory, and anti-fibrotic properties, underlie its hepatoprotective effects and result in attenuation of injury and improved liver function in a cholestatic liver disease such as PBC. The study will assess the effect of OCA compared to placebo, combined with stable standard care, on clinical outcomes in PBC patients.

Description

This Phase 4, double-blind, randomized, placebo-controlled, multicenter study is being undertaken at up to 170 sites internationally to evaluate the effect of OCA on clinical outcomes in 428 subjects with PBC. The study will include a screening period of up to 8 weeks, requiring two clinic visits. Eligible participants will be randomly allocated (1:1) to treatment with either OCA 5 mg or matching placebo tablets, taken orally once daily for the majority of subjects; dose and frequency will be modified for subjects with cirrhosis and classified as Child-Pugh B or C. Randomization will be stratified by standard treatment with UDCA (yes/no) and baseline liver function. The treatment period involves clinic visits approximately every 3 months. At the 3 month visit or any study visit thereafter, if study treatment is tolerated, participants' dose should be titrated per protocol in a blinded manner eg for participants who are non-cirrhotic or classified as Child-Pugh A and randomized to OCA, they should receive the maximum daily dose of 10 mg OCA, those on placebo continue to receive placebo. Subsequently, daily dosage may return to 5 mg if necessary for these participants who are non-cirrhotic or classified as Child-Pugh A, but should be increased to 10 mg if possible, based on tolerability and clinical judgment. Safety and tolerability will be assessed by monitoring adverse events and vital signs, and blood and urine testing. The study is event driven and total duration will be determined by the time required to accrue approximately 127 primary endpoint events, estimated to be approximately 10 years. Subjects are expected to have a minimum follow-up time of approximately 6 years.

Details
Treatment Placebo, Obeticholic Acid (OCA)
Clinical Study IdentifierNCT02308111
SponsorIntercept Pharmaceuticals
Last Modified on14 October 2020

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Eligibility

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Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Primary biliary cirrhosis or Primary Biliary Cholangitis?
Definite or probable PBC diagnosis (consistent with American Association for the Study of Liver Diseases [AASLD] and the European Association for the Study of the Liver [EASL] practice guidelines; Lindor 2009; EASL 2009), as demonstrated by the presence of 2 of the following 3 diagnostic factors
History of elevated Alkaline phosphatase levels for at least 6 months
Positive antimitochondrial antibody (AMA) titer or if AMA negative or in 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
A mean total bilirubin >ULN and 5x ULN and/or a mean ALP >3x ULN
Either is not taking UDCA (no UDCA dose in the past 3 months) or has been taking UDCA for at least 12 months with a stable dose for 3 months prior to Day 0

Exclusion Criteria

History or presence of other concomitant liver diseases including
Hepatitis C virus infection
Active Hepatitis B infection; however, subjects 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 (PSC)
Alcoholic liver disease
Definite autoimmune liver disease or overlap hepatitis
Nonalcoholic steatohepatitis (NASH)
Gilbert's Syndrome
Presence of clinical complications of PBC or clinically significant hepatic decompensation, including
History of liver transplant, current placement on a liver transplant list, or current Model of End Stage Liver Disease (MELD) score >12\. Subjects who are placed on a transplant list despite a relatively early disease stage (for example per regional guidelines) may be eligible as long as they do not meet any of the other exclusion criteria
Cirrhosis with complications, including history (within the past 12 months) or presence of
Variceal bleed
Uncontrolled ascites
Encephalopathy
Spontaneous bacterial peritonitis
Known or suspected HCC
Prior transjugular intrahepatic portosystemic shunt procedure
Hepatorenal syndrome (type I or II) or screening (Visit 1 or 2) serum creatinine >2 mg/dL (178 mol/L)
Mean total bilirubin >5x ULN
Subjects who have undergone gastric bypass procedures (gastric lap band is acceptable) or ileal resection or plan to undergo either of these procedures
Other medical conditions that may diminish life expectancy, including known cancers (except carcinomas in situ or other stable, relatively benign conditions)
If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
Known history of human immunodeficiency virus infection
Medical conditions that may cause nonhepatic increases in ALP (eg, Paget's disease or fractures within 3 months)
Other clinically significant medical conditions that are not well controlled or for which medication needs are anticipated to change during the study
History of alcohol abuse or other substance abuse within 1 year prior to Day 0
Participation in another investigational product, biologic, or medical device study within 30 days prior to Screening. Participation in a previous study of OCA is allowed with 3 months washout prior to enrollment in this study
Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain
History of known or suspected clinically significant hypersensitivity to OCA or any of its components
UDCA nave (unless contraindicated)
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