Tofacitinib For Treatment Of Chronic Pouchitis

NCT04580277 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: STUDY00000693
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Pouchitis; Ileal Pouchitis; Ileal Pouch

Keywords

chronic pouchitis; tofacitinib; antibiotic-refractory pouchitis; antibiotic-dependent pouchitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Number of Participants With Clinical Response

  8 weeks

• Number of Participants With Clinical Remission

  8 weeks

• Change in mPDAI Score

  8 weeks

• Change in mPDAI Clinical Sub-score

  8 weeks

• Change in mPDAI Endoscopic Sub-score

  8 weeks

Study Arms (1)

Chronic pouchitis

EXPERIMENTAL

This arm will include subjects with chronic pouchitis and will receive tofactinib 10 mg twice daily for 8 weeks

Drug: Tofacitinib 10 mg

Interventions

Tofacitinib 10 mg DRUG

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

Chronic pouchitis

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Pouchitis

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Ileitis; Enteritis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Ileal Diseases

Limitations and Caveats

Limitations of this study included a single center design, small sample size, and absence of a control arm. This study also lacked long-term follow-up data to assess durability of response to tofacitinib and its long-term safety in chronic pouchitis. This study also only included patients with chronic pouchitis and its findings may not be applicable to other chronic inflammatory pouch disorders. Study recruitment was terminated prematurely due to COVID-19 pandemic-related recruitment challenges.

Results Point of Contact

• Title: Dr. Gil Y. Melmed
• Organization: Cedars Sinai Inflammatory Bowel Disease Center

gil.melmed@cshs.org

310-423-4100

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 8, 2020
• Study Start: January 25, 2021
• Primary Completion: December 1, 2022
• Study Completion: May 15, 2023
• Last Updated: April 4, 2024
• Results First Posted: April 4, 2024

Record last verified: 2024-03

Locations

US (1)