Trial Search Results

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

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.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Intercept Pharmaceuticals

Stanford Investigator(s):

Intervention(s):

  • Drug: Obeticholic Acid (OCA)
  • Drug: Placebo

Phase:

Phase 4

Eligibility


Inclusion Criteria:

   1. 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 prior to
      Day 0

      - 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

   2. A mean total bilirubin >ULN and ≤5x ULN and/or a mean ALP >3x ULN

   3. Age ≥18 years

   4. 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

   5. Contraception: Female subjects of childbearing potential must use ≥1 effective method
   of contraception during the trial and until 30 days following the last dose of
   investigational product. Effective methods of contraception are considered to be:

      - Hormonal (e.g. contraceptive pill, patch, intramuscular implant or injection; or

      - Double barrier method, i.e. (a) condom (male or female) or (b) diaphragm, with
      spermicide; or

      - Intrauterine device (IUD); or

      - Vasectomy (partner); or

      - Abstinence, if in line with the preferred and usual lifestyle of the subject

   6. Must provide written informed consent and agree to comply with the study protocol

Exclusion Criteria:

   1. 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

   2. 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 μmol/L)

   3. Mean total bilirubin >5x ULN

   4. Subjects who have undergone gastric bypass procedures (gastric lap band is acceptable)
   or ileal resection or plan to undergo either of these procedures

   5. Other medical conditions that may diminish life expectancy, including known cancers
   (except carcinomas in situ or other stable, relatively benign conditions such as
   chronic lymphocytic leukemia)

   6. If female: plans to become pregnant, known pregnancy or a positive urine pregnancy
   test (confirmed by a positive serum pregnancy test), or lactating

   7. Known history of human immunodeficiency virus infection

   8. Medical conditions that may cause nonhepatic increases in ALP (eg, Paget's disease or
   fractures within 3 months prior to Day 0)

   9. Other clinically significant medical conditions that are not well controlled or for
   which medication needs are anticipated to change during the study

10. History of alcohol abuse or other substance abuse within 1 year prior to Day 0

11. 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

12. Mental instability or incompetence, such that the validity of informed consent or
   ability to be compliant with the study is uncertain

13. History of known or suspected clinically significant hypersensitivity to OCA or any of
   its components

14. UDCA naïve (unless contraindicated)

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Pranali Suryavanshi
650-721-4288
Recruiting