Acute Pouchitis Inflammatory bowel disease
Conditions
Interventions
None listed
Sponsors
Alimentiv B.V.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Participants must meet each of the following criteria for enrollment into the study: 1. Adults >=18 years of age. 2. Ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) (J-pouch only) >= 6 months prior to screening. 3. Diagnosis of acute pouchitis at screening by stool frequency (an absolute value of >= 6 stools / day ANDan increase of >= 3 stools / day above the post-IPAA baseline), and local endoscopy (presence of >= 1 erosion or ulceration of the pouch on endoscopy [not including ulceration occurring within 1 cm of the pouch staple or pouch suture line]). 4. Not currently taking antibiotics for pouchitis and no previous systemic antibiotic use for any reason within 4 weeks prior to the Screening pouchoscopy. Note: Initiation of antibiotics for treatment of acute pouchitis prior to the Screening pouchoscopy will be permitted only if the participant initiates treatment within 48 hours prior to the Screening pouchoscopy; use outside of the 48-hour window will not be permitted and these patients should not be included in the study. 5. Current treatment with 5-aminosalicylic acid drugs, immunosuppressants, antidiarrheals, antimotility agents, and probiotics is permitted, if patient has received a stable dose for >= 4 weeks prior to screening. Dose of concomitant therapy must remain stable during the study period. 6. Able to participate fully in all aspects of this clinical study. 7. Written informed consent must be obtained and documented.
Exclusion criteria
Exclusion criteria: Participants who exhibit any of the following conditions are to be excluded from the study: 1. Pouch formations besides J-pouch (e.g., W-, S- and Kock pouches). 2. IPAA for familial adenomatous polyposis. 3. Pouchitis caused by other inflammatory etiologies (e.g., ischemia or infection). 4. Antibiotic-dependent pouchitis, defined by >= 3 months of cumulative antibiotic use over the 12 months prior to screening. 5. Isolated cuffitis, pouch-anal or pouch-ileal anastomotic stricture, perforating complications, or pelvic sepsis. 6. Known Crohn*s disease (CD) or suspected CD of the pouch, defined as complex perianal/pouch fistula and/or extensive length of prepouch ileitis with deep ulceration. 7. Anticipated changes in therapy during study period. 8. Use of oral corticosteroids. Participants must have discontinued oral corticosteroids within 1 month prior to screening. 9. Current use of any advanced oral small molecule drug (e.g., Janus kinase [JAK] inhibitors) for the treatment of pouchitis. Participants must have discontinued oral small molecule therapy within 2 weeks prior to screening. 10. Failed (i.e., inadequate response with, loss of response to, or intolerance to) 2 or more compounds or classes of advanced therapies such as biologics and/or small molecule drugs (i.e., 1 biologic and 1 JAK inhibitor, 2 biologics in the same class, or 2 biologics from different classes) for the treatment of pouchitis. 11. Participants who are pregnant or breastfeeding. 12. Known history of allergy, intolerance, or are refractory to ciprofloxacin AND metronidazole AND any component of amoxicillin/potassium clavulanate combination. 13. Unable to undergo endoscopic evaluation. 14. Serious underlying disease other than acute pouchitis and UC that in the opinion of the investigator may interfere with the participant*s ability to participate fully in the study. 15. History of alcohol or drug abuse that in the opinion of the investigator may interfere with the participant*s ability to comply with the study procedures. 16. Prior enrollment in the current study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Participants will undergo a pouchoscopy with biopsies at Screening and Week 6 (EOS) for assessing the reliability and responsiveness of endoscopic and histologic items for assessing pouchitis disease activity. In addition, participants will complete a Patient eDiary daily for the duration of the study to evaluate the responsiveness of symptoms to change following treatment. Blood, mucosal biopsy, and stool samples will be collected to identify biomarkers of pouchitis disease activity, biomarkers associated with responsiveness to antibiotic therapy, and to evaluate changes to the microbiome following antibiotic therapy and therapy withdrawal. Pouchitis Symptoms Site investigators will rate the severity of pouchitis symptoms using the Clinical Global Impressions of Severity (CGI-S) at Screening and Week 6 (EOS) and change in pouchitis symptoms using the CGI of Change (CGI-C) scale at Week 6. Participants will rate their symptoms using the Patient*s Global Impression of Severity (PGI-S) and a 100-mm visual analog scale (VAS) at Screening and change in symptoms using the Patient*s Global Impression of Change (PGI-C) at Week 6. In addition, participants will record stool frequency and rate rectal bleeding, fecal urgency, and abdominal cramps in the Patient eDiary at Screening and throughout the duration of the study. At Screening and Week 6, participants will also complete the St. Mark*s Fecal Incontinence Score (Vaizey Score) and a Symptoms and Impacts Questionnaire for Pouchitis. Endoscopic Disease Activity Trained central endoscopy readers will score pouchitis endoscopic disease activity in the worst affected area of the pouch body with the Endoscopic Pouch Activity Index, Mayo endoscopic subscore, and Simple Endoscopic Score for CD, endoscopic component items of the Pouchitis Disease Activity Index (PDAI), St. Mark*s Criteria, Heidelberg Pouchitis Activity Score (HPAS), Japanese Diagnostic Criteria for Pouchitis (JDCP), novel items identifi | — |
Countries
Netherlands
Outcome results
None listed