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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12621000173897
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
17/12/2020
Date registered
Help: Date registered
18/02/2021
Date last updated
Help: Date last updated
29/09/2026
Date data sharing statement initially provided
Help: Data sharing statement date
18/02/2021
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
A study to assess the efficacy of tofacitinib for the treatment of chronic pouchitis in adults
Scientific title
Study of TOfacitinib for the treatment of chronic PouchITis (STOPit) – An open label induction with randomized, double blind, placebo-controlled maintenance trial
Additional trial identifiers [1] 303042 0
None
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(s) studied:
Chronic pouchitis 320112 0
Condition category
Condition code
Inflammatory and Immune System 318052 318052 0 0
Autoimmune diseases
Oral and Gastrointestinal 318270 318270 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
An open label induction with randomized, double blind, placebo-controlled maintenance trial

The study comprises two phases: An 8-week induction phase, with optional 8-week extension for non-responders, followed by a 24-week maintenance phase. During the induction phase, all participants will receive oral tablets of tofacitinib 10mg twice daily dosing for 8 weeks. At the end of induction, non-responders will proceed to extended induction, receiving another 8 weeks of tofacitinib 10mg twice daily dosing. Responders to standard or extended induction will proceed to randomization (1:1 allocation), to either oral tofacitinib 5mg twice daily or placebo (identical appearing oral tablet BD) during maintenance phase. The non-responders at the end of extended induction phase will discontinue from study. Any participants who experience a flare of symptoms would proceed to the open label extension study for 12 weeks, receiving either 5mg or 10mg twice daily dosing of tofacitinib, at the treating physician’s discretion.

A total of 5 study visits are planned during the follow up period, including 3 pouchoscopies to assess pouch inflammation. At each of the study visits, there are several measurement tools involved, including study visit review, blood and stool tests, as well as questionnaires
Intervention code [1] 319331 0
Treatment: Drugs
Description of the comparator or control
Matching placebo as control treatment
The placebo tablets use all precedented excipients. The ingredients are considered confidential to Pfizer
Control group
Placebo

Outcomes
Primary outcome [1] 326038 0
The primary outcome is the proportion of patients with a clinical response to tofacitinib at the end of maintainence phase compared to placebo in patients with chronic pouchitis. This is evaluated using the validated modified Pouchitis Disease Activity Index (mPDAI) scoring system.
Timepoint [1] 326038 0
End of maintenance phase, which is 24 weeks post randomisation.
Secondary outcome [1] 389946 0
Clinical response (a reduction of modified Pouchitis Disease Activity Index of >2)
Timepoint [1] 389946 0
At the end of induction phase (8 weeks post commencement of study) and the end of maintenance phase (24 weeks post randomisation)
Secondary outcome [2] 390761 0
Clinical remission (a total mPDAI < 5)
Timepoint [2] 390761 0
At the end of induction phase (8 weeks post commencement of study) and the end of maintenance phase (24 weeks post randomisation)
Secondary outcome [3] 390762 0
Corticosteroid free remission, by assessing patient medical records
Timepoint [3] 390762 0
At the end of maintenance phase (24 weeks post randomisation)
Secondary outcome [4] 390763 0
Endoscopic response (a reduction of endoscopic Pouchitis Disease Activity Index of > 2) and Mucosal healing (endoscopic Pouchitis Disease Activity Index <2)
Timepoint [4] 390763 0
At the end of induction phase (8 weeks post commencement of study) and the end of maintenance phase (24 weeks post randomisation)
Secondary outcome [5] 390765 0
Change in inflammatory biomarkers, including faecal calprotectin and C-reactive protein
Timepoint [5] 390765 0
At the end of induction phase ( 8 weeks post commencement of study)
Secondary outcome [6] 390766 0
Change in inflammatory biomarkers, including faecal calprotectin and c-reactive protein
Timepoint [6] 390766 0
At the end of maintenance phase (24 weeks post randomisation)
Secondary outcome [7] 390767 0
Change in quality of life using validated questionnaire tools: 1. Short Inflammatory Bowel Disease Questionnaire (SIBDQ) 2. Patient-Reported Outcomes Measurement Information System (PROMIS-29) 3. Oresland Score
Timepoint [7] 390767 0
At the end of induction phase (8 weeks post commencement of study)
Secondary outcome [8] 390768 0
Change in quality of life using validated questionnaire tools: 1. Short Inflammatory Bowel Disease Questionnaire (SIBDQ) 2. Patient-Reported Outcomes Measurement Information System (PROMIS-29) 3. Oresland Score
Timepoint [8] 390768 0
At the end of maintenance phase (24 weeks post randomisation)
Secondary outcome [9] 390769 0
The safety profile over the course of the study, including pouch failure, adverse events and serious adverse events. This will be assessed through patient medical records
Timepoint [9] 390769 0
At the each study visits throughout study period
Secondary outcome [10] 391851 0
Antibiotic free remission, by assessing patient medical records
Timepoint [10] 391851 0
At end of maintenance phase (24 weeks post randomisation)
Secondary outcome [11] 468699 0
Time to flare of symptoms post randomisation, assessed by change in clinical Pouchitis Disease Activity Index score - this new outcome was added prior to enrolment commencement
Timepoint [11] 468699 0
Post randomisation

Eligibility
Key inclusion criteria
1. Adult patients age 18 to 65
2. Previous diagnosis of ulcerative colitis (UC) and have undergone total proctocolectomy and ileal pouch-anal anastomosis (IPAA)
3. Chronic or recurrent pouchitis that required > 4 weeks of antibiotics (CADP) in the previous 12 months OR pouchitis that is refractory to antibiotic therapy (CARP)
4. A total modified pouchitis disease activity index (mPDAI) score > 5 with endoscopic evidence of active disease
5. Completed pre-screening tests (blood test and chest x-ray) for tofacitinib therapy, including hepatitis B, hepatitis C, human immunodeficiency virus, varicella zoster virus, tuberculosis, mumps, measles and rubella
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
1. Crohn’s disease of pouch (defined as the presence of stricture or fistula in the pouch)
2. IPAA surgery was performed for an indication other than ulcerative colitis such as familial adenomatous polyposis syndrome (FAP), hereditary nonpolyposis colorectal cancer, or Crohn’s disease (CD)
3. High cardiovascular risk factors (CHADS2 score > 2)
4. Bradycardia at baseline (<60 beats per minute), sick sinus syndrome, sinoatrial block, atrioventricular block
5. Chronic renal impairment (eGFR < 50mL/min)
6. Chronic liver disease (Child Pugh score B or C) or chronic hepatitis B
7. Active infections, including hepatitis B, hepatitis C, human immunodeficiency virus, varicella zoster virus, tuberculosis, mumps, measles and rubella
8. History of organ transplantation on immunosuppressive medications
9. Previous use of lymphocyte-depleting therapies (ie. alemtuzumab, cyclophosphamide, total lymphoid irradiation, rituximab, and any other lymphocyte depleting therapies)
10. History of unprovoked thromboembolism or hypercoagulable condition
11. Active or past malignancy (except non-melanoma skin cancer) or lymphoproliferative disorder
12. Significant lymphopenia (absolute lymphocyte count < 0.75x109cells/L), or neutropenia (absolute neutrophil count < 1.0 x109cells/L), or anaemia (hemoglobin < 80g/L)
13. Pregnancy or lactation
14. History of hypersensitivity or adverse events to other JAK inhibitor

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This is an open label induction study of tofacitinib in chronic pouchitis with a randomized, double blind, placebo-controlled maintenance trial for responders. A sample size of 72 patients will be sufficient to detect a difference in study group with a power of 80% with an a-value = 0.05. This calculation was based on the effect size observed in previous studies of tofacitinib in ulcerative colitis, where a sustained clinical response with tofacitinib treatment was achieved in 50% of patients and a 19% response in the placebo group with an initial response rate of 60%. Hence, we aim to recruit up to 120 subjects into the open label induction study in order to recruit 72 patients into the maintenance phase, in order to determine if a similar effect is seen in pouchitis compared to ulcerative colitis.

The primary outcome will be assessed with a two-tailed test and P values of < 0.05 deemed statistically significant. Treatment evaluations will be performed on the principle of `intention to treat` (ITT) unless otherwise specified. Methods of handling missing data for the primary and secondary endpoints are described below. No formal adjustments for multiplicity are planned due to exploratory nature of this trial. However, all the results will be reported and interpreted in light of the multiple comparisons made and by considering both the strength of the evidence and the consistency of effects across endpoints.

Data will be collected using REDCap and statistical software R and R studio will be used to perform data cleaning and statistical analysis. Data cleaning for measurements from validated metrics will be cleaned as recommended by its manual. In cases where this is not possible, data cleaning rules will be developed and implemented based on team consensus. For blood work data, where there are censored endpoints, floor endpoints will be replaced with half of the value, while ceiling censored endpoints will be replaced with the ceiling value. Safety analyses will be based on all participants who underwent any induction.

Summaries of continuous variables which are normally distributed will be presented as means and standard deviations, or as medians and inter-quartile ranges for skewed data. Categorical variables will be presented as frequencies and percentages.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
1/03/2021
Actual
16/07/2021
Date of last participant enrolment
Anticipated
5/09/2025
Actual
7/05/2025
Date of last data collection
Anticipated
1/10/2026
Actual
27/01/2026
Sample size
Target
120
Accrual to date
Final
54
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 25578 0
Mater Hospital Brisbane - South Brisbane
Recruitment hospital [2] 25579 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 25580 0
The Alfred - Melbourne
Recruitment hospital [4] 25581 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [5] 25582 0
Liverpool Hospital - Liverpool
Recruitment hospital [6] 25583 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [7] 25584 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [8] 25585 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [9] 28521 0
Gold Coast University Hospital - Southport
Recruitment hospital [10] 28522 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [11] 28523 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [12] 28524 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [13] 28525 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [14] 28526 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [15] 28527 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 41400 0
4101 - South Brisbane
Recruitment postcode(s) [2] 41401 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 41402 0
3004 - Melbourne
Recruitment postcode(s) [4] 41403 0
3084 - Heidelberg
Recruitment postcode(s) [5] 41404 0
2170 - Liverpool
Recruitment postcode(s) [6] 41405 0
5011 - Woodville
Recruitment postcode(s) [7] 41406 0
5000 - Adelaide
Recruitment postcode(s) [8] 41407 0
2109 - Macquarie Park
Recruitment postcode(s) [9] 44750 0
4215 - Southport
Recruitment postcode(s) [10] 44751 0
6150 - Murdoch
Recruitment postcode(s) [11] 44752 0
4575 - Birtinya
Recruitment postcode(s) [12] 44753 0
4029 - Herston
Recruitment postcode(s) [13] 44754 0
3065 - Fitzroy
Recruitment postcode(s) [14] 44755 0
3168 - Clayton
Recruitment postcode(s) [15] 44756 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 307454 0
Other
Name [1] 307454 0
2021 Gastroenterology Society of Australia Celltrion Healthcare IBD Fellowship Grant
Country [1] 307454 0
Australia
Funding source category [2] 307627 0
Commercial sector/Industry
Name [2] 307627 0
Pfizer Global Medical Grants
Country [2] 307627 0
Australia
Primary sponsor type
Hospital
Name
Mater Research Limited
Address
Level 15-18, 151 Clarence Street
Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 308127 0
Commercial sector/Industry
Name [1] 308127 0
Pfizer Pharmaceutical
Address [1] 308127 0
Nil
Country [1] 308127 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307532 0
Metro North Health HREC
Ethics committee address [1] 307532 0
Ethics committee country [1] 307532 0
Australia
Date submitted for ethics approval [1] 307532 0
23/07/2020
Approval date [1] 307532 0
23/10/2020
Ethics approval number [1] 307532 0
Project ID 66809

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107570 0
A/Prof Jakob Begun
Address 107570 0
IBD Research Group Mater Research Limited
Country 107570 0
Australia
Phone 107570 0
+61 7 3163 6171
Fax 107570 0
Email 107570 0
[email protected]
Contact person for public queries
Name 107571 0
Emi Khoo
Address 107571 0
IBD Research Group Mater Research Limited
Country 107571 0
Australia
Phone 107571 0
+61 7 3163 6171
Fax 107571 0
Email 107571 0
[email protected]
Contact person for scientific queries
Name 107572 0
Emi Khoo
Address 107572 0
IBD Research Group Mater Research Limited
Country 107572 0
Australia
Phone 107572 0
+61 7 3163 6171
Fax 107572 0
Email 107572 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: Data will not be shared as the patient consent form is only applicable to this specific study.



What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.