Chronic, recurrent and/or antibiotic refractory pouchitis in patients with ulcerative colitis MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
Conditions
Interventions
Trade Name: Xeljanz 5mg film-coated tablets
Pharmaceutical Form: Film-coated tablet
Sponsors
Amsterdam UMC, location AMC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject has a history of ileal pouch anal anastomosis (IPAA) for UC, all stages completed at least 6 months prior to day one of the start of the study. 2. Subject has chronic, recurrent and/or antibiotic refractory pouchitis, defined as a PDAI = 7 , with either - = 2 recurrent pouchitis episodes within 1 year prior to screening, necessitating treatment with antibiotics or other prescription, or; - Requiring maintenance antibiotic therapy for = 4 weeks to maintain clinical remission and a history of at least two attempts in the last 24 months to stop this therapy, resulting in a relapse of the pouchitis episodes. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 11 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. Pouchitis due to surgery related conditions (such as an abscess, fistula, or sinus of the pouch). 2. Absence of a previous pelvic MRI to assess secondary causes of pouchitis. 3. Irritable pouch syndrome (symptoms without evidence of pouchitis on endoscopy and histology). 4. Mechanical complications of the pouch (e.g. pouch stricture or pouch fistula). 5. Diverting ileostomy. 6. Positive stool sample for C. difficile, enteric pathogens, pathogenic ova or parasites at screening. 7. Active herpes zoster infection or history of disseminated zoster infection. 8. Evidence of an active infection during screening, or known history of chronic HBV, HCV, HIV infection, or if subject is immunodeficient. 9. Active or latent infection with Mycobacterium tuberculosis (TB), regardless of treatment history.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess efficacy and safety of tofacitinib in the treatment of chronic, recurrent and/or antibiotic refractory pouchitis.;Secondary Objective: histologic disease activity, immune cell infiltration, gene expression of inflammatory cytokines and changes in the microbiome.;Primary end point(s): Proportion of subjects with chronic, recurrent and/or antibiotic refractory pouchitis achieving clinical relevant remission after 8 weeks of treatment with tofacitinib. Clinical relevant remission is defined as a PDAI score < 7 and a reduction of the overall score by = 3 points from baseline.;Timepoint(s) of evaluation of this end point: Week 8 of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of subjects achieving mPDAI < 5 and a reduction of the overall score by = 2 points from baseline to week 8 and week 12. • Proportion of subjects achieving a partial response after 8 weeks, defined as a reduction in PDAI = 2 points from baseline. • Proportion of subjects in sustained antibiotic-free remission and no need for rescue therapy until week 12. • Change in total PDAI. • Change in the endoscopic subscore of the PDAI at week 8, compared to baseline. • Change in histologic subscore of the PDAI at week 8, compared to baseline. • Time to clinical relevant remission. • Time to relapse. • Total number of patients in deep remission, defined as a PDAI of 0 at week 8. • Proportion of subjects not requiring further antibiotic treatment at week 8 and week 12. • Change in total scores of Inflammatory Bowel Disease Questionnaire (IBDQ) at week 8, compared to baseline. • Change in Cleveland Global Quality of Life (CGQL) at week 8, compared to baseline. • Change in SF-36 from baseline to week 8. • Incidence and severity of adverse events up to 84 days after initiating treatment. ;Timepoint(s) of evaluation of this end point: week 12 | — |
Countries
Netherlands
Contacts
Public ContactPhD candidate
Amsterdam UMC, location AMC
Outcome results
None listed