Tofacitinib for Hospitalized Acute Severe Ulcerative Colitis Management

• Register: ClinicalTrials.gov
• Last refreshed on: 6 November 2023
• Main ID: NCT04925973
• Date of registration: 08/06/2021
• Prospective Registration: No
• Primary sponsor: McMaster University
• Public title: Tofacitinib for Hospitalized Acute Severe Ulcerative Colitis Management TRIUMPH
• Scientific title: Tofacitinib for Hospitalized Acute Severe Ulcerative Colitis Management (the TRIUMPH Study)
• Date of first enrolment: June 1, 2021
• Target sample size: 24
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04925973
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Canada

Contacts

• Name: Neeraj Narula, MD
• Affiliation: McMaster University

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Adults ages 18 to 75 with ulcerative colitis (either known UC based on prior history
with histological confirmation or new diagnosis)

2. Symptoms consistent with severe acute ulcerative colitis as defined by modified
Truelove and Witts score (MTWSI) > 10 points

3. Primary non-response or secondary loss of response to anti-TNFa/anti-integrin
therapies/anti-interleukin therapies OR immunomodulators OR non-response to minimum 3
days and maximum of 7 days of intravenous corticosteroids (intravenous at dose
equivalent of prednisone 50mg daily / methylprednisolone 40mg daily).

a. For patients using anti-TNFa or anti-integrin or anti-interleukin therapies, they
must have been on a stable dose of one of the following: i. Adalimumab in the 14 days
prior to screening ii. Golimumab in the 28 days prior to screening iii. Infliximab in
the 28 days prior to screening iv. Vedolizumab in the 28 days prior to screening v.
Ustekinumab in the 28 days prior to screening b. Persons on biologic therapy will have
drug levels drawn during the time of hospitalization

4. Able to provide written informed consent

5. Treatment with concomitant corticosteroids or 5-ASA products is permitted, however
patients will be placed on a corticosteroid weaning regimen after initiating study
protocols. For patients using biologics or immunomodulators, these will be
discontinued prior to initiation of tofacitinib.

Exclusion Criteria:

1. Enteric infection confirmed before inclusion into study by stool microscopy, culture,
or histology (including Clostridum difficile, Campylobacter, Salmonella, Shigella,
Cytomegalovirus, Human Immunodeficiency Virus, Epstein Bar Virus)

2. Clinical signs of sepsis

3. Patient has indication for surgery instead of medical rescue therapy (ex. toxic
megacolon, massive exsanguination, or perforation)

4. Positive blood (beta-HCG) pregnancy test or currently lactating, or women of
childbearing potential not willing to use double barrier contraception for the
duration of the active part of the study and for 4 weeks after the last dose of
tofacitinib

a. Participants will be sufficiently educated to ensure compliance with double barrier
contraception prior to enrollment in the study

5. Current malignancy

6. Serious co-morbidity including but not limited to:

a. Immunodeficiency b. Recent myocardial infarction or stroke (in the past month) c.
History of heart, respiratory, renal, or hepatic failure i. Heart failure as defined
as ejection fraction of <50% as determined by transthoracic echo ii. Respiratory
failure as defined as PaO2 <60mmHg iii. Hepatic failure as defined as INR > 2.5 with
total bilirubin >30 iv. Renal failure as defined as a creatinine clearance of 40ml/min
(as estimated by the Cockroft-Gault equation) d. Infections such as abscess,
opportunistic infection, or sepsis

7. English not adequate in absence of local translation service

8. Currently taking part in another clinical trial

9. Treatment with tofacitinib in the 3 months prior to screening

10. Use of strong CYP (3A4 or 2C19) inhibitors or inducers such as antifungals
(ketoconazole, fluconazole), St John's wort or rifampin a. Patients will be told to
avoid consumption of grapefruit juice



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Ulcerative Colitis Acute

Intervention(s)

Drug: Tofacitinib 10 MG [Xeljanz]

Primary Outcome(s)

Clinical response at day 7 [Time Frame: 7 days]

Secondary Outcome(s)

Comparison of number of patients with severe colitis based on histology who are able to achieve histological improvement (mild or inactive colitis) at week 26 [Time Frame: Week 26]

Number of colectomies (emergency and planned) during the 52 weeks [Time Frame: 52 weeks]

1. Percentage of patients who achieve clinical remission at day 7, and weeks 12, 26, and 52 (Partial Mayo score < 2, with no subscore >1) [Time Frame: 52 weeks]

Number of patients requiring switch in therapy (i.e. initiation of another biological medication, start of a different clinical trial with another active drug, etc) during the 52 weeks [Time Frame: 52 weeks]

For patients who have response, to determine the mean number of days before detection of clinically significant response (MTWSI reduction of 3 or more points) population. [Time Frame: 7 days]

To determine the rate of corticosteroid-free clinical remission based on Number of patients with initial Mayo 2/3 disease at flexible sigmoidoscopy that achieve endoscopic improvement (Mayo score 0 or 1) at week 26 [Time Frame: Week 26]

Percentage of patients who achieve clinical response at weeks 12, 26, and 52 (MTWSI reduction 3 or more points and MTWSI < 10) [Time Frame: 52 weeks]

Comparison of absolute change from baseline endoscopic Mayo score at week 26 [Time Frame: Week 26]

Proportion of individuals who experience a severe adverse event over the course of treatment [Time Frame: 52 weeks]

Secondary ID(s)

11428

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

McGill University

University of Manitoba

University of Alberta

University of British Columbia