Etrasimod as Prevention of Pouchitis (ESPIRIT)

Etrasimod as Primary and Secondary Prevention of Pouchitis (ESPIRIT)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pouchitis
• Intervention / Treatment: Drug: etrasimod; Drug: Placebo

Detailed Description

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
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Maia Kayal, MD; Phone Number: 212-241-8100; Email: maia.kayal@mountsinai.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
      • Principal Investigator: Maia Kayal
      • Contact: Maia Kayal; Phone Number: 212-241-8100; Email: maia.kayal@mssm.edu
      • Contact: Sari Feldman; Phone Number: 212-241-8100; Email: sari.feldman@mssm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female aged ≥ 18 years (verified at screening)
• Ability to provide written informed consent and to be compliant with protocol assessments (verified at screening)
• Diagnosed with UC and underwent TPC with IPAA for medically refractory disease or dysplasia (verified at screening)
• Screening may take place at any time from one month to two years after the final surgical stage
• High-risk of developing acute pouchitis - defined as fulfilling at least one of the criteria defined in section 2 (verified at screening)
• Patients with 1 prior episode of acute pouchitis can be enrolled - after a minimum period of 4 weeks after completion of a course of antibiotics and resolution of symptoms of pouchitis
• Symptomatic remission defined by a symptom mPDAI subscore ≤2 points at the baseline visit (verified at screening, baseline)
• Adequate hematological function defined by white blood cell count ≥ 3.5 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, absolute lymphocyte count (ALC) ≥ 0.8 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 8 g/dL (verified at screening)
• Healthcare professional-confirmed history of varicella or a full course of vaccination against varicella zoster virus (VZV) or a positive antibody test to VZV (verified at screening)
• 12-lead electrocardiogram (ECG) that showed no clinically significant abnormalities as defined by the clinician's judgement (verified at screening)
• Females must be non-pregnant, as determined by qualitative urine hCG testing, non-lactating, and if premenopausal, must agree to using a highly effective contraception method (that can achieve a failure rate of less than 1% per year when used consistently and correctly) during treatment and for one week after stopping treatment with etrasimod (verified at screening)

Exclusion Criteria:

• Isolated cuffitis (verified at screening pouchoscopy)
• Diagnosis of Crohn's disease (verified at screening)

• Diagnosis of Crohn's disease-like pouch inflammation (verified at screening)

  o Crohn's disease-like pouch inflammation is defined as ulcerations of the pre-pouch ileum extending > 10 cm above the inlet, strictures in the pre-pouch ileum or pouch body outside of the anastomoses, and/or fistulae of the pre-pouch ileum, pouch body, or perineum

• Diagnosis of chronic pouchitis (verified at screening)

  o Chronic pouchitis is defined as persistent (> 4 weeks) or recurrent (> 4 episodes/year) symptoms of pouchitis

• Anastomotic stenosis or other mechanical complications of the pouch (verified at screening pouchoscopy)
• Treatment with probiotics ≤ 3 months prior to screening (verified at screening)
• Treatment with topical rectal 5-ASA, or steroids ≤ 2 weeks prior to or during screening (verified at screening)
• Any use of a biologic or small molecule approved for moderately to severely active UC or investigational, after TPC with IPAA (verified at screening)
• Any prior exposure to a S1P receptor modulator therapy, at any time (verified at screening)
• Any investigational or biologic agent within 30 days of screening pouchoscopy (verified at screening)

• Have the following cardiovascular history (verified at screening):

  • In the last 6 months, have experienced a myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III or IV heart failure
  • Have a history or presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker
  • A history of symptomatic bradycardia, recurrent cardiogenic syncope, Mobitz type I second-degree AV block, or severe untreated sleep apnea
  • Significant QT prolongation (QTcF interval ≥ 450 ms in male or ≥ 470 ms in females)
  • Arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugs or QT prolonging drugs

• Clinically significant or serious active infection ≤ 28 days prior to baseline - including but not limited to (verified at screening):

  • Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or
  • positive test for Clostridioides difficile toxin at screening
  • Active tuberculosis
  • Acute or chronic hepatitis B or hepatitis C
  • HIV infection
• Pregnancy, lactation, or a positive urine pregnancy test measured during screening
• Severe hepatic impairment (Child Pugh Class C) (verified at screening)
• Have a known history of macular edema or retinopathy (verified at screening)
• History of cancer within the last 5 years (excluding in situ squamous or basal cell carcinoma of the skin that has been excised and resolved) or current malignancy (verified at screening)
• History of posterior reversible encephalopathy syndrome (PRES)
• Have a history of any clinically significant medical condition that, in the investigator's opinion, precludes participation in the study (verified at screening)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: etrasimod; study drug etrasimod 2 mg once daily for 48 weeks	Drug: etrasimod; 2 mg once daily for 48 weeks
Placebo Comparator: Placebo; Placebo for 48 weeks	Drug: Placebo; matching placebo for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first episode of acute pouchitis	Time to first episode of acute pouchitis (days)	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)	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.	end of study at 48 weeks
Number of episodes of acute pouchitis	Number of episodes of acute pouchitis during the 48-week treatment period	end of study at 48 weeks
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	Baseline and at Weeks 12, 24, 36 and 48

Collaborators and Investigators

• Sponsor: Maia Kayal
• Collaborators: Pfizer
• Investigators: Principal Investigator: Maia Kayal, MD, Principal Investigator

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): February 6, 2030
• Study Completion (Estimated): February 6, 2030

Study Registration Dates

• First Submitted: March 17, 2026
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 23, 2026

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Enteritis; Ileitis; Ileal Diseases; Pouchitis; etrasimod
• Other Study ID Numbers: STUDY-25-01158

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: PD will not be shared due to privacy concerns and consent limitations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No