Back to resultsTofacitinib For Treatment Of Chronic Pouchitis
Primary Purpose
Pouchitis, Ileal Pouchitis, Ileal Pouch
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tofacitinib 10 mg
Sponsored by
About this trial
This is an interventional treatment trial for Pouchitis focused on measuring chronic pouchitis, tofacitinib, antibiotic-refractory pouchitis, antibiotic-dependent pouchitis
Eligibility Criteria
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
Sites / Locations
- Cedars-Sinai Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Chronic pouchitis
Arm Description
This arm will include subjects with chronic pouchitis and will receive tofactinib 10 mg twice daily for 8 weeks
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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).
Full Information
NCT ID
NCT04580277
First Posted
October 2, 2020
Last Updated
May 19, 2023
Sponsor
Cedars-Sinai Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT04580277
Brief Title
Tofacitinib For Treatment Of Chronic Pouchitis
Official Title
A Single Center Open-Label Prospective Study Of Oral Tofacitinib In Patients With Chronic Pouchitis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
low recruitment
Study Start Date
January 25, 2021 (Actual)
Primary Completion Date
December 1, 2022 (Actual)
Study Completion Date
May 15, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cedars-Sinai Medical Center
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pouchitis, Ileal Pouchitis, Ileal Pouch
Keywords
chronic pouchitis, tofacitinib, antibiotic-refractory pouchitis, antibiotic-dependent pouchitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Chronic pouchitis
Arm Type
Experimental
Arm Description
This arm will include subjects with chronic pouchitis and will receive tofactinib 10 mg twice daily for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Tofacitinib 10 mg
Intervention Description
Subjects in this arm will receive tofactinib 10 mg twice daily for 8 weeks
Primary Outcome Measure Information:
Title
Clinical response or remission
Description
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.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Clinical response
Description
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.
Time Frame
8 weeks
Title
Clinical remission
Description
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
Title
Change in mPDAI score
Description
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.
Time Frame
8 weeks
Title
Change in mPDAI clinical sub-score
Description
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.
Time Frame
8 weeks
Title
Change in mPDAI endoscopic sub-score
Description
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.
Time Frame
8 weeks
Title
IBD-related quality of life
Description
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).
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
12. IPD Sharing Statement
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Tofacitinib For Treatment Of Chronic Pouchitis
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