Mirikizumab in the Treatment of Chronic Inflammatory Conditions of the Pouch

Обзор

The goal of this clinical trial is to learn if mirikizumab works to treat pouch disorders in adults. The main questions it aims to answer are: Does mirikizumab reduce symptoms of pouch disorders Participants will: Take mirikizumab every 4 weeks for one year Visit the clinic once every month for two months and at the end of the study Keep a diary of their symptoms

Вмешательства

• Препарат Mirikizumab - Intravenous (IV)
  300 mg mirikizumab at Weeks 0, 4, and 8
• Препарат Mirikizumab - Subcutaneous (SC)
  Pre-filled syringes administered at Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52.

Первичные конечные точки

• Remission as measured by Modified Pouchitis Disease Activity Index (mPDAI) [Срок оценки: Weeks 0, 24, and 52]

Вторичные конечные точки (5)

• Median change in the Endoscopic Pouch Score (EPS) [Срок оценки: Weeks 0, 24, and 52]
• Median change in the endoscopic subscore of the mPDAI [Срок оценки: Weeks 0, 24, and 52]
• Change in Cleveland Clinic Global Quality of Life (QoL) scale [Срок оценки: Weeks 0, 4, 8, 12, 24, 38, and 52]
• Change in Patient-Reported Outcomes Measurement Information System (PROMIS) incontinence measures [Срок оценки: Weeks 0, 4, 8, 12, 24, 38, and 52]
• Change in Urgency Numeric Rating Scale (NRS) [Срок оценки: Weeks 0, 4, 8, 12, 24, 38, and 52]

Критерии участия

Критерии включения

• Informed consent will be obtained before any study-related procedures
• Age >/= 18 and </= 80 years
• Diagnosis of Chronic Pouchitis or Crohn's-like disease of the pouch based on the following criteria:

• Chronic Antibiotic-Dependent Pouchitis: Recurrent symptoms of pouchitis (frequency, urgency, bleeding, abdominal pain or cramping, or pelvic discomfort) that respond to antibiotic therapy but relapse shortly after stopping antibiotics, thus necessitating continuous antibiotic therapy to achieve symptom control.
• Chronic Antibiotic Refractory Pouchitis: Lack of response to standard antibiotic therapy, requirement of a longer duration of antibiotic therapy than expected with minimal improvement in symptoms, in association with typical symptoms of pouchitis (frequency, urgency, bleeding, abdominal pain or cramping, or pelvic discomfort).
• Crohn's-like disease of the pouch: Presence of a perianal or other fistula that developed at least 12 months after the final stage of Ileal Pouch Anal Anastomosis (IPAA) surgery, stricture of the pouch body or pre-pouch ileum, or the presence of pre-pouch ileitis. Pouch body inflammation (pouchitis) may often coexist in the setting of Crohn's-like disease of the pouch.
• Participants with a proven history of ulcerative colitis and history of 1,2, modified -2 or 3 stage IPAA and ileostomy takedown
• Ability to access internet for electronic database entry
• Only those individuals for whom a provider is considering initiating mirikizumab for the treatment of chronic pouchitis or Crohn's-like disease of the pouch will be eligible for participation.

Критерии исключения

• Prior exposure to mirikizumab
• Known hypersensitivity to mirikizumab or its metabolites
• Current infection with Clostridioides difficile
• Known HIV or active Hepatitis B/C
• Clinically significant liver disease (Primary Sclerosing Cholangitis with LFT's <1.5 upper limit of normal can be included)
• Severe hepatic impairment, defined as Child-Pugh Class C
• Known decreased kidney function with a glomerular filtration rate <45 ml/min/1.732
• History of malignancy, except for basal cell carcinoma, non-metastatic squamous cell carcinoma of the skin, or prior malignancy with curative therapy completed at least 5 years prior to screening and no recurrence.
• Clinically significant laboratory results at screening or baseline, as judged by the Investigator from local testing.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
• Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.
• Any disorder, which in the investigator's opinion might jeopardize participant's safety or compliance with the protocol.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 5 центров

• UCLA Vatche & Tamar Manoukian Division of Digestive Diseases — Los Angeles
• Mayo Clinic — Rochester
• NYU Langone Health — New York
• University of North Carolina — Chapel Hill
• Allegheny Health Network — Pittsburgh

Публикации

• Weaver KN, Gregory M, Syal G, Hoversten P, Hicks SB, Patel D, Christophi G, Beniwal-Patel P, Isaacs KL, Raffals L, Deepak P, Herfarth HH, Barnes EL. Ustekinumab Is Effective for the Treatment of Crohn's Disease of the Pouch in a Multicenter Cohort. Inflamm Bowel Dis. 2019 Mar 14;25(4):767-774. doi: 10.1093/ibd/izy302. PMID 30295784
• Gregory M, Weaver KN, Hoversten P, Hicks SB, Patel D, Ciorba MA, Gutierrez AM, Beniwal-Patel P, Palam S, Syal G, Herfarth HH, Christophi G, Raffals L, Barnes EL, Deepak P. Efficacy of Vedolizumab for Refractory Pouchitis of the Ileo-anal Pouch: Results From a Multicenter US Cohort. Inflamm Bowel Dis. 2019 Aug 20;25(9):1569-1576. doi: 10.1093/ibd/izz030. PMID 30810748
• Ollech JE, Rubin DT, Glick L, Weisshof R, El Jurdi K, Israel A, Krugliak Cleveland N, Hyman N, Sakuraba A, Pekow J, Cohen RD, Dalal SR. Ustekinumab Is Effective for the Treatment of Chronic Antibiotic-Refractory Pouchitis. Dig Dis Sci. 2019 Dec;64(12):3596-3601. doi: 10.1007/s10620-019-05697-1. Epub 2019 Jun 11. PMID 31187322
• Akiyama S, Cohen NA, Kayal M, Dubinsky MC, Colombel JF, Rubin DT. Treatment of Chronic Inflammatory Pouch Conditions With Tofacitinib: A Case Series From 2 Tertiary IBD Centers in the United States. Inflamm Bowel Dis. 2023 Sep 1;29(9):1504-1507. doi: 10.1093/ibd/izad011. No abstract available. PMID 36745039
• Kayal M, Lambin T, Plietz M, Rizvi A, Radcliffe M, Khaitov S, Sylla P, Greenstein AJ, Colombel JF, Dubinsky MC, Ungaro RC. Recycling of Precolectomy Anti-Tumor Necrosis Factor Agents in Chronic Pouch Inflammation Is Associated With Treatment Failure. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1491-1493.e3. doi: 10.1016/j.cgh.2020.07.008. Epub 2020 Jul 12. PMID 32668342
• Shen B, Achkar JP, Connor JT, Ormsby AH, Remzi FH, Bevins CL, Brzezinski A, Bambrick ML, Fazio VW, Lashner BA. Modified pouchitis disease activity index: a simplified approach to the diagnosis of pouchitis. Dis Colon Rectum. 2003 Jun;46(6):748-53. doi: 10.1007/s10350-004-6652-8. PMID 12794576
• Barnes EL, Long MD, Raffals L, Isaacs K, Stidham RW, Herfarth HH; Contributors. Development of the Endoscopic Pouch Score for Assessment of Inflammatory Conditions of the Pouch. Clin Gastroenterol Hepatol. 2023 Jun;21(6):1663-1666.e3. doi: 10.1016/j.cgh.2022.04.026. Epub 2022 May 12. PMID 35568303
• Dubinsky MC, Irving PM, Panaccione R, Naegeli AN, Potts-Bleakman A, Arora V, Shan M, Travis S. Incorporating patient experience into drug development for ulcerative colitis: development of the Urgency Numeric Rating Scale, a patient-reported outcome measure to assess bowel urgency in adults. J Patient Rep Outcomes. 2022 Apr 1;6(1):31. doi: 10.1186/s41687-022-00439-w. PMID 35362902

Идентификаторы

NCT: NCT06864403 · 24-2214

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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