Obeticholic Acid (OCA) in Primary Sclerosing Cholangitis (PSC) (AESOP)
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Clinical Trial Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects With Primary Sclerosing Cholangitis|
- Evaluate the effects of obeticholic acid (OCA) on serum alkaline phosphatase (ALP) in subjects with Primary Sclerosing Cholangitis (PSC) [ Time Frame: 24 weeks ]
- Evaluate the effects of OCA on safety in subjects with PSC [ Time Frame: 24 weeks ]
- Hepatic biochemistry and indices of function [ Time Frame: 24 weeks ]
- Hepatic Fibrosis [ Time Frame: 24 weeks ]
- Gastrointestinal inflammation and disease [ Time Frame: 24 weeks ]
- Farnesoid X receptor (FXR) activity [ Time Frame: 24 weeks ]
- Inflammatory bowel disease (IBD) [ Time Frame: 24 weeks ]
- Exposure response of total OCA (OCA and its conjugates) to biomarkers [ Time Frame: 24 weeks ]
- Long-term efficacy [ Time Frame: 24 months ]
- Long term safety [ Time Frame: 24 months ]
- Disease-specific symptoms [ Time Frame: 24 weeks ]
- Pharmacokinetics (PK) of OCA and other bile acids [ Time Frame: 24 Weeks ]
|Study Start Date:||December 2014|
|Estimated Study Completion Date:||June 2019|
|Estimated Primary Completion Date:||November 2018 (Final data collection date for primary outcome measure)|
Experimental: 1.5 mg OCA titrating to 3 mg OCA
Subjects randomized to 1.5 mg will take 1.5 mg OCA daily for 12 weeks followed by 3 mg OCA for an additional 12 weeks.
Experimental: 5 mg OCA titrating to 10 mg OCA
Subjects randomized to 5 mg will take 5 mg OCA daily for 12 weeks followed by 10 mg OCA for an additional 12 weeks.
Subjects randomized to placebo will take placebo for 24 weeks
This is a Phase 2, randomized, double-blind, placebo-controlled, dose-finding evaluation of the efficacy and safety of OCA in subjects with PSC. Approximately 75 subjects who provide written informed consent and meet all of the inclusion and none of the exclusion criteria will be randomized to 1 of 3 treatment groups as follows: 1.5 mg titrating to 3 mg OCA, 5 mg titrating to 10 mg OCA, or placebo, in a 1:1:1 ratio. Subjects will administer investigational product (IP) orally, once daily for 2 consecutive 12-week periods.
For the first 12 weeks, the subject's dose will be 1.5 mg OCA, 5 mg OCA, or placebo. After 12 weeks, the subject's dose will be titrated as follows, providing there are no limiting safety or tolerability concerns in the opinion of the investigator, while maintaining the trial blind: the 1.5 mg OCA treatment group will titrate to 3 mg, the 5 mg OCA treatment group will titrate to 10 mg OCA, and the placebo group will remain on placebo. Double-blind treatment will continue for a further 12 weeks at that dose.
Any subjects whose dose is not titrated, due to safety or tolerability concerns, will remain on their starting treatment (1.5 mg OCA, 5 mg OCA, or placebo) for the remainder of the double-blind phase to Week 24.
Randomization will be stratified by the presence or absence of concomitant ursodeoxycholic acid (UDCA) use and total bilirubin level (≤ 1.5x upper limit of normal [ULN] or > 1.5x ULN but < 2.5x ULN).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02177136
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|Study Director:||David Shapiro, MD||Intercept Pharmaceuticals|