Overview

This trial is active, not recruiting.

Condition primary biliary cirrhosis
Treatments obeticholic acid (oca), placebo
Phase phase 3
Sponsor Intercept Pharmaceuticals
Start date January 2012
End date January 2018
Trial size 217 participants
Trial identifier NCT01473524, 747-301

Summary

The investigational drug, Obeticholic Acid (OCA) is a modified bile acid. Bile acids are used by the body to help with digestion. It is hypothesized that regular treatment with OCA will improve liver function in persons with Primary Biliary Cirrhosis (PBC).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
OCA 5 mg for 6 months and then titrating up to 10 mg for remainder of double blind period. After completion of the 1 year double-blind period period subjects will be offered the opportunity to enter an open label long term safety extension for up to 5 years beginning at 5 mg OCA. Doses up to 25 mg daily will be evaluated.
obeticholic acid (oca) 6α-ethyl chenodeoxycholic acid (6-ECDCA)
5 or 10 mg tablets once daily for 12 months during double-blind phase. 5 - 25 mg once daily (higher doses may be approved by medical monitor) for up to 5 years during long term safety evaluation phase.
(Experimental)
OCA 10 mg for double-blind period After completion of the 1 year double-blind period period subjects will be offered the opportunity to enter an open label long term safety extension for up to 5 years beginning at 5 mg OCA. Doses up to 25 mg daily will be evaluated.
obeticholic acid (oca) 6α-ethyl chenodeoxycholic acid (6-ECDCA)
5 or 10 mg tablets once daily for 12 months during double-blind phase. 5 - 25 mg once daily (higher doses may be approved by medical monitor) for up to 5 years during long term safety evaluation phase.
(Placebo Comparator)
After completion of the 1 year double-blind period period subjects will be offered the opportunity to enter an open label long term safety extension for up to 5 years beginning at 5 mg OCA. Doses up to 25 mg daily will be evaluated.
placebo
One tablet daily for 12 months.

Primary Outcomes

Measure
Composite endpoint Alkaline Phosphatase and total bilirubin
time frame: 6 months and 12 months

Secondary Outcomes

Measure
Alkaline phosphatase
time frame: 12 months
Alkaline phosphatase/aspartate aminotransferase/bilirubin
time frame: 12 months
Alkaline phosphatase/aspartate aminotransferase/bilirubin
time frame: 12 months
Bilirubin and albumin
time frame: 12 months
Gamma-glutamyl transferase (GGT)
time frame: 12 months
Alanine aminotransferase (ALT)
time frame: 12 monhts
Aspartate aminotransferase (AST)
time frame: 12 months
Bilirubin (total and conjugated)
time frame: 12 months
Albumin
time frame: 12 months
Prothrombin Time
time frame: 12 Months
International Normalization Ratio (INR)
time frame: 12 Months
Liver Biopsy
time frame: 3 years
Quality of Life
time frame: 12 Months
Pruritus
time frame: 12 months
Enhanced Liver Fibrosis (ELF) test
time frame: 12 Months
Transient Elastography (TE)
time frame: 12 Months
Biomarkers of Liver Fibrosis
time frame: 12 Months
Bile acids and conjugates
time frame: 12 Month

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Definite or probable PBC diagnosis (consistent with American Association for the Study of Liver Disease [AASLD] and European Association for 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 antibodies (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. At least 1 of the following qualifying biochemistry values: - ALP ≥ 1.67x upper limit of normal (ULN) - Total bilirubin > ULN but < 2x ULN 3. Age ≥ 18 years 4. Taking ursodeoxycholic acid (UDCA) for at least 12 months (stable dose for ≥ 3 months) prior to Day 0, or unable to tolerate UDCA (no UDCA for ≥ 3 months) prior to Day 0. 5. Contraception: Female patients must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use ≥ 1 effective (≤ 1% failure rate) method of contraception during the trial and until the end of treatment (EOT) visit. 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) 6. Must provide written informed consent and agree to comply with the trial protocol. Exclusion Criteria: 1. History or presence of other concomitant liver diseases including: - Hepatitis B or C virus (HCV, HBV) infection - Primary sclerosing cholangitis (PSC) - Alcoholic liver disease - Definite autoimmune liver disease or overlap hepatitis - Nonalcoholic steatohepatitis (NASH) - Gilbert's Syndrome (due to interpretability of bilirubin levels) 2. Presence of clinical complications of PBC or clinically significant hepatic decompensation, including: - History of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥ 15 - Portal hypertension and complications, including: known esophageal varices, poorly controlled or diuretic resistant ascites, history of variceal bleeds or related interventions (e.g., insertion of variceal bands or transjugular intrahepatic portosystemic shunts [TIPS]), hepatic encephalopathy - Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN - Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 μmol/L) 3. Patients with a history of severe pruritus requiring current or prior systemic treatment (e.g., with bile acid sequestrant [BAS] or rifampicin) 4. Administration of the following medications is prohibited as specified below: - Prohibited 6 months prior to Day 0 and throughout the trial (i.e., to last dose to last dose and/or EOT): azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline; fenofibrate or other fibrates; budesonide and other systemic corticosteroids; potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin) - Prohibited 12 months prior to Day 0 and throughout the trial (i.e., to last dose to last dose and/or EOT): antibodies or immunotherapy directed against interleukins or other cytokines or chemokines 5. Patients who have previously participated in a clinical trial of OCA will not be allowed to participate 6. History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pretreatment) QT or QTc interval of > 500 msec 7. If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating 8. Known history of human immunodeficiency virus (HIV) infection 9. History or presence of any other disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs including bile salt metabolism in the intestine (e.g., inflammatory bowel disease or gastric bypass procedures; [gastric lap band is acceptable]) 10. Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease) or which may diminish life expectancy to < 2 years, including known cancers (except carcinomas in situ or other stable, relatively benign conditions such as chronic lymphatic leukemia) 11. Other clinically significant medical conditions that are not well controlled or for which medication needs are anticipated to change during the trial 12. Anticipated changes to current concomitant medications during the course of the trial 13. History of alcohol abuse, defined as consumption of more than 210 mL of alcohol per week (i.e., the equivalent of 14 4-ounce (125 mL) glasses of wine or 14 12 ounce cans/bottles of beer), or other substance abuse within 1 year prior to Day 0 14. Participation in another investigational drug, biologic, or medical device trial within 30 days prior to Screening 15. History of noncompliance with medical regimens, or patients who are considered to be potentially unreliable 16. Blood or plasma donation within 30 days prior to Day 0 17. Mental instability or incompetence, such that the validity of informed consent or compliance with the trial is uncertain

Additional Information

Official title A Phase 3, Double Blind, Placebo Controlled Trial and Long Term Safety Extension of Obeticholic Acid in Patients With Primary Biliary Cirrhosis
Principal investigator David Shapiro, MD
Trial information was received from ClinicalTrials.gov and was last updated in December 2014.
Information provided to ClinicalTrials.gov by Intercept Pharmaceuticals.