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Trial registered on ANZCTR


Registration number
ACTRN12621000173897
Ethics application status
Approved
Date submitted
17/12/2020
Date registered
18/02/2021
Date last updated
25/09/2023
Date data sharing statement initially provided
18/02/2021
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
STOPit: Study of TOfacitinib for the treatment of chronic PouchITis
Secondary ID [1] 303042 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(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 intervention(s) / exposure
An open label induction with randomized, double blind, placebo-controlled withdrawal 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
Comparator / control treatment
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
End of induction phase (week 8 post commencement of study)
Secondary outcome [2] 390761 0
Clinical remission (a total mPDAI < 5)
Timepoint [2] 390761 0
At the end of induction (8 weeks post commencement of study)
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)
Timepoint [4] 390763 0
At the end of induction (8 weeks post commencement of study)
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)

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^

^ Recommend pre-treatment vaccinations for hepatitis B, varicella zoster and mumps, measles, rubella if serology testing is negative.
* Individuals with latent tuberculosis should be treated with standard antimycobacterial therapy before administering tofacitinib.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
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 withdrawal 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 data will be collected using REDCap and analyzed using R studio. Descriptive and analytical statistics of the series will be performed. Data will be presented as mean and standard deviation, or in median and range if the data shows a non-parametric distribution. Kaplan-Meier survival curves and Cox regression analyses will be used to evaluate patients who achieve clinical and endoscopic response to tofacitinib, and maintain a corticosteroid-free, antibiotic-free remission. Logistic regression analysis will be performed in search of pouch failure risk factors and to identify variables that could influence the long-term outcome and quality of life. Univariate and multivariate logistic regression will be completed by direct entry method.

A comparison of quality of life will be made between patients with or without treatment response, using chi-square, t student or Mann-Whitney as appropriate. Statistical significance is considered when p <0.05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/03/2021
Actual
16/07/2021
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
30/11/2025
Actual
Sample size
Target
120
Accrual to date
29
Final
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 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

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
Commercial sector/Industry
Name
Pfizer Australia
Address
Level 15-18, 151 Clarence Street
Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 308127 0
None
Name [1] 308127 0
Nil
Address [1] 308127 0
Nil
Country [1] 308127 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307532 0
Human Research Ethics Committee, The Prince Charles Hospital
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
Mater Hospital Brisbane
Raymond Terrace
South Brisbane QLD 4101
Country 107570 0
Australia
Phone 107570 0
+617 3163 2371
Fax 107570 0
Email 107570 0
jakob.begun@mater.uq.edu.au
Contact person for public queries
Name 107571 0
Emi Khoo
Address 107571 0
Mater Hospital Brisbane
Raymond Terrace
South Brisbane QLD 4101
Country 107571 0
Australia
Phone 107571 0
+61478117080
Fax 107571 0
Email 107571 0
emi.khoo@mater.org.au
Contact person for scientific queries
Name 107572 0
Emi Khoo
Address 107572 0
Mater Hospital Brisbane
Raymond Terrace
South Brisbane QLD 4101
Country 107572 0
Australia
Phone 107572 0
+61478117080
Fax 107572 0
Email 107572 0
emi.khoo@mater.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided 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.