Tofacitinib For Treatment Of Chronic Pouchitis

Study Overview
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Brief Summary
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A phase 2 pilot study to evaluate the effectiveness of tofacitinib in subjects with chronic pouchitis

Detailed Description
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The proposed study is a phase 2, open-label study of tofactinib in treatment of patients with chronic pouchitis. Subjects with chronic active pouchitis will be screened and recruited if they meet eligibility criteria. Eligible subjects will undergo baseline clinical evaluation, laboratory testing and a pouch endoscopy. They will then receive oral tofacitinib 10 mg twice daily for 8 weeks. Clinical and laboratory data will be collected at week 4 and week 8, and all subjects will undergo a end of treatment pouch endoscopy at 8 weeks. Clinical, laboratory and endoscopic data at 8 weeks will be compared to the baseline data to evaluate study outcomes.

Official Title
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A Single Center Open-Label Prospective Study Of Oral Tofacitinib In Patients With Chronic Pouchitis

Conditions
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Pouchitis, Ileal Pouchitis, Ileal Pouch

Intervention / Treatment
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* Drug: Tofacitinib 10 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects ages 18 to 80 Subjects with a history of proctocolectomy with ileal pouch anal anastomosis (IPAA) for UC at least 6 months prior to screening. Subjects with pouchitis that is chronic, defined by a mPDAI score ≥5 assessed as the average from 3 days immediately prior to the baseline study visit and a minimum endoscopic sub-score of 2 (outside the staple or suture line) with either (a) ≥ 3 recurrent episodes within 1 year prior to the screening treated with ≥2 weeks of antibiotic or other prescription therapy, (b) requiring maintenance antibiotic therapy taken continuously for ≥4 weeks immediately prior to the baseline study visit Women of childbearing potential must have documentation of a negative pregnancy test at screening and must agree to use two highly effective methods of birth control during the study and for at least 1 month after completion of study drug dosing. Exclusion Criteria: Subjects with IPAA surgery done for Crohn's disease (CD) or familial adenomatous polyposis (FAP) indications. Subjects with primary CD of pouch, isolated or predominant cuffitis or mechanical complications of the ileal pouch. Subjects with prior exposure to tofacitinib. Subjects with a diverting stoma. Subjects with a prior history or risk factors for venous thromboembolism. Subjects with active bacterial, parasitic, fungal, mycobacterial, or viral infection. Subjects with a history of latent or active tuberculosis. Subjects positive for hepatitis B virus (HBV) surface antigen, hepatitis B virus core antibody with a negative hepatitis B surface antibody or with detectable serum hepatitis B DNA. Female subjects who are pregnant or lactating. Female subjects of childbearing potential who are sexually active and do not agree to using two highly effective methods of contraception during the study period. Subjects with clinically significant laboratory abnormalities at study screening. Other eligibility criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chronic pouchitis<br>This arm will include subjects with chronic pouchitis and will receive tofactinib 10 mg twice daily for 8 weeks | Drug: Tofacitinib 10 mg<br>* Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response or remission | Proportion of subjects with clinical response defined as reduction in modified pouch disease activity index (mPDAI) score ≥2 from baseline at 8 weeks. The mPDAI is an 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response | The proportion of subjects with clinical response, defined as a modified pouch disease activity index (mPDAI) score of ≥5 at 8 weeks with ≥2-point decrease from the baseline score at 8 weeks. The mPDAI is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity. | 8 weeks | 
| Clinical remission | The proportion of subjects with clinical remission at 8 weeks, defined as a modified pouch disease activity index (mPDAI) score of <5 with a ≥2-point decrease from the baseline mPDAI score. The mPDAI is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity. | 8 weeks | 
| Change in mPDAI score | Change in modified pouch disease activity index (mPDAI) score at 8 weeks compared to baseline. The mPDAI is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity. | 8 weeks | 
| Change in mPDAI clinical sub-score | Change in modified pouch disease activity index (mPDAI) clinical sub-score at week 8 compared to baseline. The mPDAI is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity. | 8 weeks | 
| Change in mPDAI endoscopic sub-score | Change in modified pouch disease activity index (mPDAI) endoscopic sub-score at week 8 compared to baseline. The mPDAI is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity. | 8 weeks | 
| IBD-related quality of life | Change in IBD-related quality of life as measured by Short Inflammatory Bowel Disease Questionnaire (SIBD-Q) at week 4 and week 8 compared to baseline. The Short Inflammatory Bowel Disease Questionnaire ranges from 10 (poor health-related quality of life) to 70 (optimum health-related quality of life). | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic pouchitis, tofacitinib, antibiotic-refractory pouchitis, antibiotic-dependent pouchitis