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.
• 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)