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
Principal Investigator: Dr. Christopher Ma, University of Calgary
Dr. Remo Panacciones
Dr. Vipul Jairath
Dr. Cathy Lu
Dr. Talat Bessissow
Dr. GY Zou
Dr. Susan Elliott
The primary aim of PATHFINDER is to compare available biologic classes as first-line treatment for achieving 1-year corticosteroid-free endoscopic remission in adult participants with moderate- to-severely active ileal or ileocolonic Crohn’s disease (CD). The primary comparison will evaluate the noninferiority of anti-integrin therapy compared to anti-tumor necrosis factor (TNF) alpha or anti-interleukin (IL)-23 targeted biologics.
This is a pragmatic, multicenter, Canadian, active-comparator, parallel-group, prospective, randomized, open-label, blinded-endpoint (PROBE) trial. Biologic-naïve adults with CD and at least one large ileal ulcer >5 mm and ileal segment Simple Endoscopic Score for Crohn’s Disease (SES-CD) ≥4 at baseline will be randomized equally to one of 3 biologic classes of therapy (tumor necrosis factor alpha [TNFα] antagonist, anti-IL12/23, or anti-integrin). All participants will receive all treatments as per standard of care (SOC); initiation will be coordinated through the corresponding patient support program (PSP). Post-randomization, participants will be monitored by symptoms and biomarkers at approximately 4-month intervals and undergo video-recorded ileocolonoscopy at 1 year. Participants with active disease (defined by persistent symptoms and elevated biomarkers) will be permitted to dose optimize their biologic or add immunomodulators per SOC at 4-monthly intervals. The primary endpoint is corticosteroid-free (off systemic corticosteroids x16 weeks) endoscopic remission, defined by a blinded, central reader.
Participating Sites (N=30)
Anticipated sample size: 264
Anticipated start date: Ocotber 2023
Anticipated end: January 2028