Tofacitinib For Treatment Of Chronic Pouchitis

Phase 2TerminatedNCT04580277

Cedars-Sinai Medical Center6 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pouchitis Ileal Pouchitis Ileal Pouch

Interventions

Tofacitinib 10 mgDRUG

Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male or female subjects ages 18 to 80 2. Subjects with a history of proctocolectomy with ileal pouch anal anastomosis (IPAA) for UC at least 6 months prior to screening. 3. 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 4. 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: 1. Subjects with IPAA surgery done for Crohn's disease (CD) or familial adenomatous polyposis (FAP) indications. 2. Subjects with primary CD of pouch, isolated or predominant cuffitis or mechanical complications of the ileal pouch. 3. Subjects with prior exposure to tofacitinib. 4. Subjects with a diverting stoma. 5. Subjects with a prior history or risk factors for venous thromboembolism. 6. Subjects with active bacterial, parasitic, fungal, mycobacterial, or viral infection. 7. Subjects with a history of latent or active tuberculosis. 8. 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. 9. Female subjects who are pregnant or lactating. 10. 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. 11. Subjects with clinically significant laboratory abnormalities at study screening. * Other eligibility criteria apply

Locations (1)

Cedars-Sinai Medical Center

Los Angeles, California, United States

Outcomes

Primary Outcomes

Number of Participants With Clinical Response/Remission

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.

Time frame: 8 weeks

Secondary Outcomes

Number of Participants With Clinical Response

The proportion of subjects with clinical remission at 8 weeks, defined as modified pouchitis disease activity index (mPDAI) \<5.

Time frame: 8 weeks

Number of Participants With 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.

Time frame: 8 weeks

Change in mPDAI Score

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.

Time frame: 8 weeks

Change in mPDAI Clinical Sub-score

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.

Time frame: 8 weeks

Change in mPDAI Endoscopic Sub-score

Data from ClinicalTrials.gov

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