COBALT: Study of Obeticholic Acid in Primary Biliary Cirrhosis
Research type
Research Study
Full title
A Phase 3b, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Effect of Obeticholic Acid on Clinical Outcomes in Subjects with Primary Biliary Cirrhosis.
IRAS ID
184648
Contact name
Gideon Hirschfield
Contact email
Sponsor organisation
Intercept Pharmaceuticals Inc.
Eudract number
2014-005012-42
Clinicaltrials.gov Identifier
Duration of Study in the UK
7 years, 4 months, 1 days
Research summary
Research Summary
Primary Biliary Cirrhosis (PBC) is a rare disease caused when the body's own immune system damages the bile ducts in the liver. Without treatment, PBC frequently progresses to liver fibrosis and eventual severe scarring of the liver (cirrhosis), requiring liver transplantation or resulting in death.
The drug being tested in this Phase 3 study is Obeticholic Acid (OCA). OCA is a modified (manmade) version of a compound made in the liver called a bile acid. Bile acids are used by the body to help with digestion and have additional effects on liver function.
The only drug currently approved to treat PBC is ursodeoxycholic acid (URSO®, UDCA). However, up to 50% of patients fail to see any improvement when treated with UDCA. The purpose of this study, therefore, is to find out how effective OCA, when given with or without standard of care (URSO®, UDCA) may be in preventing or delaying specific medical conditions or health related issues that can occur in patients with PBC.
A total of about 350 people are expected to participate in this study globally, at approximately 170 trial sites who are experienced in treating patients with PBC.
The study includes a screening period of up to 8 weeks. Eligible patients will be randomly allocated to treatment with either OCA 5mg or matching placebo tablets (dummy drug) taken orally, once daily.
Patients will visit the clinic approximately every 3 months and will provide blood and urine samples and complete questionnaires about their disease. Patients will also have a scan of their liver every 12 months and a scan of their bones ever 12 months.
It is estimated that patients will be in the study for a minimum of approximately 6 years. Prospective patients will be identified primarily from the hospital but may self-refer to a study doctor.
The study is sponsored by Intercept Pharmaceuticals Inc.Summary of Results
Participants in Study 747-302 reflected an advanced disease population. While baseline demographics including duration of primary biliary cholangitis were similar to previous primary biliary cholangitis studies, participants in Study 747-302 had higher baseline alkaline phosphatase, total bilirubin, model of end stage liver disease, and Rotterdam criteria. Of the 334 participants in Study 747-302, 55% were contraindicated per revised United States Prescribing Information and 21% were decompensated at enrolment. The estimated effect of treatment from the intent-to-treat population was under-powered and potentially biased resulting in difficulties in the interpretation of the tests of hypotheses for the primary and key secondary endpoints. − No treatment difference was observed between obeticholic acid and placebo for either the original composite endpoint (EMA primary) or expanded composite endpoint (FDA primary), in the intent-to-treat population. Drawing definitive efficacy conclusions from Study 747-302 was challenging given the potential bias, particularly in the placebo arm. − Due to inadequate enrolment and retention, the study was under-powered for the primary EMA composite endpoint and the FDA composite endpoint. The safety profile remained consistent with the known safety profile of obeticholic acid in participants with primary biliary cholangitis.
REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
15/WM/0363
Date of REC Opinion
30 Oct 2015
REC opinion
Further Information Favourable Opinion