Tofacitinib for Hospitalized Acute Severe Ulcerative Colitis Management

NCT04925973 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 11428
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The TRIUMPH study was designed to build on the existing literature by studying the efficacy of tofacitinib in hospitalized patients with acute severe ulcerative colitis. This trial will provide evidence for a possible new indication for the use of tofacitinib.

Conditions

Ulcerative Colitis Acute

Outcome Measures

Primary Outcomes (1)

• Clinical response at day 7

  To determine the effectiveness (combined and endoscopic response) and safety of tofacitinib in patients with acute severe UC who experience treatment failure to steroids or anti-TNFα/anti-integrin therapies/anti-interleukin therapies. The primary outcome of this study is to assess clinical response at day 7 among patients who receive tofacitinib. This will be determined by the percentage of patients who achieve clinical response at day 7 (MTWSI reduction 3 or more points and MTWSI \< 10).

  7 days

Secondary Outcomes (9)

• 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)

  52 weeks

• Number of colectomies (emergency and planned) during the 52 weeks

  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

  52 weeks

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

  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.

  7 days

Study Arms (1)

Treatment arm

EXPERIMENTAL

Tofacitinib 10mg PO BID

Drug: Tofacitinib 10 MG [Xeljanz]

Interventions

Tofacitinib 10 MG [Xeljanz] DRUG

Tofacitinib 10mg PO BID

Treatment arm

Eligibility Criteria

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

You may qualify if:

• Adults ages 18 to 75 with ulcerative colitis (either known UC based on prior history with histological confirmation or new diagnosis)
• Symptoms consistent with severe acute ulcerative colitis as defined by modified Truelove and Witts score (MTWSI) \> 10 points
• Primary non-response or secondary loss of response to anti-TNFα/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-TNFα 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
• Able to provide written informed consent
• 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.

You may not qualify if:

• Clinical signs of sepsis
• Patient has indication for surgery instead of medical rescue therapy (ex. toxic megacolon, massive exsanguination, or perforation)
• 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
• Current malignancy
• 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
• English not adequate in absence of local translation service
• Currently taking part in another clinical trial
• Treatment with tofacitinib in the 3 months prior to screening
• 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

Sponsors & Collaborators

• McMaster University: lead
• University of Manitoba: collaborator
• University of British Columbia: collaborator
• McGill University: collaborator
• University of Alberta: collaborator

Study Sites (1)

McMaster University

Hamilton, Ontario, L8S 4K1, Canada

Location

Related Publications (1)

• Narula N, Pray C, Hamam H, Peerani F, Hansen T, Bessissow T, Bressler B, Arun A, Schmit M, Castelli J, Marshall JK. Tofacitinib for Hospitalized Acute Severe Ulcerative Colitis Management (The TRIUMPH Study). Crohns Colitis 360. 2025 Feb 15;7(1):otaf013. doi: 10.1093/crocol/otaf013. eCollection 2025 Jan.

  PMID: 40092634 DERIVED

MeSH Terms

Interventions

tofacitinib

Study Officials

• Neeraj Narula, MD

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 14, 2021
• Study Start: June 1, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: October 24, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)