Tofacitinib For Treatment Of Chronic Pouchitis

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

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

Study Overview

• Status: Terminated
• Conditions: Pouchitis; Ileal Pouch; Ileal Pouchitis
• Intervention / Treatment: Drug: Tofacitinib 10 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Elizabeth Khanishian; Phone Number: 310-423-2041; Email: elizabeth.khanishian@cshs.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	8 weeks
Change in mPDAI Endoscopic Sub-score	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.	8 weeks
Change in IBD-related Quality of Life	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.	8 weeks

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2021
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): May 15, 2023

Study Registration Dates

• First Submitted: October 2, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: tofacitinib; chronic pouchitis; antibiotic-refractory pouchitis; antibiotic-dependent pouchitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enteritis; Ileitis; Ileal Diseases; Pouchitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: STUDY00000693

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No