NCT05928039

PATHFINDER: Evaluating the Optimal First-Line Treatment Strategy for Moderate-to-Severely Active Ileal-dominant Crohn's Disease

PATHFINDER: A Pragmatic, Active-comparator, Parallel-group, Randomized Trial to Evaluate the Optimal First-line Treatment Strategy for Moderate-to-Severely Active Ileal-dominant Crohn's Disease

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 297 (estimated)
• Sponsor: University of Calgary · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

There are currently three classes of biologic treatments approved in Canada for the management of moderate-to-severe Crohn's disease: anti-tumor necrosis factor \[TNF\] alpha, anti-integrin, and anti-interleukin \[IL\]-23 targeted agents. The purpose of this trial is to determine which of these three classes of biologics results in the highest percentage of patients with small bowel (ileal) Crohn's disease entering into endoscopic remission without needing corticosteroids at 1 year. Endoscopic remission means that the ulcers in the small bowel from Crohn's disease have healed. All treatments in this trial are approved by Health Canada. No experimental drugs will be included.

Detailed description

This is a pragmatic, real-world trial of patients with moderate-to-severe, ileal-dominant Crohn's disease. At week 0, participants who meet the eligibility criteria will be randomized in a 1:1:1 ratio to a TNF antagonist; anti-integrin; or anti-IL23 targeted treatment. All interventions will be offered according to standard of care. The dosing will be as follows: TNFα antagonist * Infliximab 5 mg/kg intravenously \[IV\] at weeks 0, 2, 6, then 5 mg/kg every 8 weeks; OR * Adalimumab subcutaneously \[SC\] 160 mg at week 0, 80 mg at week 2, then 40 mg every 2 weeks Anti-integrin * Vedolizumab 300 mg IV at weeks 0, 2, and 6, then every 8 weeks; OR * Vedolizumab 300 mg IV at weeks 0 and 2, then 108 mg SC every 2 weeks Anti-IL23 targeted agents * Ustekinumab \~6 mg/kg IV x1, then 90 mg SC every 8 weeks; OR * Risankizumab 600 mg IV at weeks 0, 4, and 8, then 360 mg SC every 8 weeks All treatments will be administered as part of the participant's routine care. All participants will be monitored per standard of care. Participants on corticosteroids at baseline will begin a steroid taper within 6 weeks of starting their biologic. At months 4, 8 and 12 participants will be evaluated for the Harvey Bradshaw Index (HBI), EuroQOL 5-domain questionnaire (EQ-5D), and be tested for C-reactive protein and fecal calprotectin concentrations. At month 12 patients will undergo a video-recorded ileocolonoscopy to determine if they have achieved endoscopic remission.

Conditions

• Crohn Disease

Interventions

Type	Name	Description
BIOLOGICAL	TNFa Antagonist - Infliximab	• Infliximab 5 mg/kg intravenously \[IV\] at weeks 0, 2, 6, then 5 mg/kg every 8 weeks
BIOLOGICAL	TNFa Antagonist - Adalimumab	• Adalimumab subcutaneously \[SC\] 160 mg at week 0, 80 mg at week 2, then 40 mg every 2 weeks
BIOLOGICAL	Anti-IL12/23 or anti-IL23 - Ustekinumab	• Ustekinumab \~6 mg/kg IV x1, then 90 mg SC every 8 weeks
BIOLOGICAL	Anti-IL12/23 or anti-IL23 - Risankizumab	• Risankizumab 600 mg IV at weeks 0, 4, and 8, then 360 mg SC every 8 weeks
BIOLOGICAL	Anti-integrin - Vedolizumab IV	• Vedolizumab 300 mg IV at weeks 0, 2, and 6, then every 8 weeks
BIOLOGICAL	Anti-integrin - Vedolizumab IV and SC	• Vedolizumab 300 mg IV at weeks 0 and 2, then 108 mg SC every 2 weeks

Timeline

• Start date: 2023-10-25
• Primary completion: 2027-07-30
• Completion: 2028-12-31
• First posted: 2023-07-03
• Last updated: 2025-06-11

Locations

20 sites across 1 country: Canada