The researchers propose conducting a multi-center, randomized, placebo-controlled study to investigate the potential role of etrasimod for the primary and secondary prevention of pouchitis among high-risk patients submitted to total proctocolectomy (TPC) with ileal-pouch anal anastomosis (IPAA) for medically refractory disease. The trial will be conducted in compliance with this protocol, Good Clinical Practice guidelines, and Institutional Review Board requirements.
This is a multi-center, randomized, double-blind, placebo-controlled study to investigate the efficacy of etrasimod as primary and secondary prevention of pouchitis among high-risk ulcerative colitis (UC) patients who have undergone TPC + IPAA and have no evidence of pouchitis (i.e., are in remission) at time of enrollment. Eligible patients will be randomized (1:1 ratio) to receive either etrasimod (2 mg once daily) or placebo for 48 weeks. Randomization will be stratified by the presence of medical history of primary sclerosing cholangitis (yes or no) and by the presence of medical history of at least one prior episode of acute pouchitis (yes or no).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
40
Icahn School Of Medicine at Mount Sinai
New York, New York, United States
Proportion of participants with at least 1 episode of acute pouchitis
The proportion of patients with at least 1 episode of acute pouchitis during the 48 weeks of treatment. Acute Pouchitis defined as: modified pouchitis disease activity index (mPDAI) score ≥ 5 points OR an increase of ≥ 2 points vs. baseline, AND Endoscopic component of the mPDAI Score \>= 2 points (within 7 days prior or post the collection date of the symptomatic component of the mPDAI score)
Time frame: 48 weeks
Time to first episode of acute pouchitis
Time to first episode of acute pouchitis (days)
Time frame: end of study at 48 weeks
Proportion of patients with acute pouchitis
Proportion of patients with acute pouchitis by Weeks 12, 24 and 36 Acute Pouchitis defined as: mPDAI\* score ≥ 5 points OR an increase of ≥ 2 points vs. baseline, AND Endoscopic component of the mPDAI Score \>= 2 points (within 7 days prior or post the collection date of the symptomatic component of the mPDAI score)
Time frame: Weeks 12, 24 and 36
Number of participants with clinical remission
Clinical remission based on mPDAI score at Week 48 Clinical remission is defined as a mPDAI score \< 5 points. The modified PDAI (mPDAI) is calculated from 2 separate 6-point scales assessing clinical symptoms and endoscopic findings with full scale scored from 0-12. Patients are classified as either having pouchitis (PDAI score ≥5) or as not having pouchitis (PDAI score \<5). Greater clinical scores and endoscopy scores correspond to worse disease severity.
Time frame: end of study at 48 weeks
Number of episodes of acute pouchitis
Number of episodes of acute pouchitis during the 48-week treatment period
Time frame: end of study at 48 weeks
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Change in Inflammatory Bowel Disease (IBD) Disability Index
Change from baseline in total score on the IBD Disability Index at Weeks 12, 24, 36 and 48 Total score on scale from 0-100. Higher score indicates more disability
Time frame: Baseline and at Weeks 12, 24, 36 and 48