Tofacitinib For Treatment Of Chronic Pouchitis

Phase 2

Terminated

Conditions: Pouchitis
Ileal Pouchitis
Ileal Pouch

Interventions: Drug: Tofacitinib 10 mg

Registration Number: NCT04580277

Lead Sponsor: Cedars-Sinai Medical Center

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

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 6

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Chronic pouchitis	Tofacitinib 10 mg	This arm will include subjects with chronic pouchitis and will receive tofactinib 10 mg twice daily for 8 weeks

Primary Outcome Measures

Name	Time	Method
Number of Participants With Clinical Response/Remission	8 weeks	The proportion of subjects with clinical response at 8 weeks, defined as ≥2-point decrease in modified pouchitis disease activity index (mPDAI) with at least 1-point decrease in endoscopic subscore compared to the baseline.The mPDAI is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinical Response	8 weeks	The proportion of subjects with clinical remission at 8 weeks, defined as modified pouchitis disease activity index (mPDAI) \<5.
Number of Participants With Clinical Remission	8 weeks	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.
Change in mPDAI Score	8 weeks	change in median mPDAI score at 8 weeks compared to baseline. The mPDAI (modified pouchitis disease activity index) is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity.
Change in mPDAI Clinical Sub-score	8 weeks	change in median clinical mPDAI sub-score at 8 weeks compared to baseline. The mPDAI (modified pouchitis disease activity index) is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity.
Change in IBD-related Quality of Life	8 weeks	CGQL is a quality of life questionnaire used in inflammatory bowel diseases that incorporates three domains - quality of life, quality of health and energy level. Each domain is scored from 0 (worst) to 10 (best)and a total score is calculated by dividing the cumulative score by 30. The CGQL score can range from 0 to 1. Change in quality of life as measured by the Cleveland Global Quality of Life score (CGQL) at 8 weeks compared to baseline.
Change in mPDAI Endoscopic Sub-score	8 weeks	change in median endoscopic mPDAI sub-score at 8 weeks compared to baseline. The mPDAI (modified pouchitis disease activity index) is a 0- 18 point scale of pouchitis disease severity, with higher scores corresponding to worse disease severity.