Evaluating the best first-line treatment for moderate-to-severe 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

This study is testing which of three approved treatments works best to help people with moderate-to-severe Crohn's disease feel better and stay off steroids for a year.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 297 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Calgary (Academic / other)
• Drugs / interventions: Infliximab, Adalimumab, Vedolizumab, Ustekinumab, Risankizumab
• Locations: 20 sites (Calgary, Alberta and 19 other locations)
• Trial ID: NCT05928039 on ClinicalTrials.gov

What this trial studies

This trial aims to compare the effectiveness of three classes of biologic treatments for patients with moderate-to-severe ileal-dominant Crohn's disease. Participants will be randomly assigned to receive either a TNF antagonist, anti-integrin, or anti-IL23 targeted therapy, all of which are approved treatments. The primary goal is to determine which treatment leads to the highest rate of endoscopic remission without the need for corticosteroids after one year. Participants will be monitored and assessed through standard care protocols, including various clinical evaluations and a video-recorded ileocolonoscopy at the end of the study period.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of moderate-to-severe ileal-dominant Crohn's disease who have not previously received biologic treatments.

Not a fit: Patients who are currently on corticosteroids or have previously been treated with biologics for Crohn's disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could help identify the most effective first-line treatment for patients with moderate-to-severe Crohn's disease, potentially improving their quality of life.

How similar studies have performed: Other studies have shown varying success with biologic treatments for Crohn's disease, but this trial's specific comparison of treatment classes is a novel approach.

Eligibility criteria

Inclusion Criteria:

1. Male or nonpregnant, nonlactating females, 18 years of age or older. Females of childbearing potential must have a negative serum or urine pregnancy test prior to randomization
2. Established CD diagnosis by conventional criteria
3. Baseline colonoscopy within 3 months of the first day of the screening period, with photo or video documentation of at least one large ileal ulcer \>5 mm and ileal segment SES-CD ≥4 (eligibility will be determined by local endoscopist, with subsequent confirmation by a CR at a later time, post enrolment)
4. HBI ≥5
5. Biologic-treatment naïve for CD-related therapies
6. Would otherwise have been eligible to start a biologic for moderate-to-severely active CD as part of their routine clinical care and for whom there is equipoise around which biologic class to start
7. Willing and able to participate fully in all aspects of this clinical trial, including adherence to study protocol and treatment algorithm
8. Written informed consent must be obtained and documented

Exclusion Criteria:

1. Condition(s) for which the biologics included in this study is contraindicated
2. CD-related complications such as symptomatic, endoscopically impassable strictures or abscesses that require imminent surgery (at investigator's discretion)
3. Participants with current or history of colonic dysplasia or neoplasia, toxic megacolon, or fulminant colitis
4. Recent bowel resection \<3 months before screening
5. Active enteric infection (positive stool culture), including but not limited to bacterial (including C. difficile), viral, or parasitic enteric infections
6. Known active hepatitis B, hepatitis C, or human immunodeficiency virus infection
7. Active COVID-19 infection during the screening period
8. Tested positive as part of SOC for tuberculosis (TB) at screening by QuantiFERON® TB Gold Test, tuberculin skin test, or history of untreated latent or active TB
9. History of malignancy within 5 years of screening, except fully treated carcinoma in-situ of the cervix, fully treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin
10. Active chronic or acute infections requiring treatment with systemic antibiotics, antivirals, antifungals, antiparasitics, or antiprotozoals during the screening period
11. Serious underlying disease other than CD that, in the opinion of the investigator, may interfere with the participant's ability to participate fully in the study
12. Not willing to withhold protocol-prohibited medications during the trial, or planned or anticipated use of any prohibited medications during screening
13. Received previously or currently receiving a TNF antagonist, anti-integrin, monoclonal antibody targeting IL-12/23 or IL-23, Janus kinase (JAK) inhibitors, or sphingosine 1 phosphate (S1P) receptor modulators (irrespective of indication)
14. History of alcohol or drug abuse that, in the opinion of the investigator, may interfere with the participant's ability to comply with the study procedures

Where this trial is running

Calgary, Alberta and 19 other locations

• University of Calgary — Calgary, Alberta, Canada (Recruiting)
• University of Alberta IBD Clinic — Edmonton, Alberta, Canada (Recruiting)
• GI Research Institute (G.I.R.I) — Vancouver, British Columbia, Canada (Not_yet_recruiting)
• West Coast Gastroenterology — Vancouver, British Columbia, Canada (Not_yet_recruiting)
• Nova Scotia Health Victoria — Halifax, Nova Scotia, Canada (Active_not_recruiting)
• GNRR Digestive Clinics and Research Center Inc. — Brampton, Ontario, Canada (Not_yet_recruiting)
• Rajbir Rai Medical Corporation — Brantford, Ontario, Canada (Not_yet_recruiting)
• McMaster University — Hamilton, Ontario, Canada (Recruiting)
• London Health Sciences Centre — London, Ontario, Canada (Active_not_recruiting)
• West GTA Research Inc. — Mississauga, Ontario, Canada (Not_yet_recruiting)
• ABP Research Services Corp. — Oakville, Ontario, Canada (Not_yet_recruiting)
• Taunton Surgical Center — Oshawa, Ontario, Canada (Not_yet_recruiting)
• The Ottawa Hospital Research Institute — Ottawa, Ontario, Canada (Recruiting)
• Thunder Bay Regional Health Research Institute — Thunder Bay, Ontario, Canada (Active_not_recruiting)
• Mount Sinai Hospital — Toronto, Ontario, Canada (Recruiting)
• TIDHI Clinic — Toronto, Ontario, Canada (Active_not_recruiting)
• Centre Hospitalier de l'Université de Montréal (CHUM) — Montreal, Quebec, Canada (Recruiting)
• Hôpital du Sacré-Cœur-de-Montréal — Montreal, Quebec, Canada (Recruiting)
• Research Institute of the McGill University Health Centre (MUHC) — Montreal, Quebec, Canada (Recruiting)
• Université de Sherbrooke — Sherbrooke, Quebec, Canada (Not_yet_recruiting)

Study contacts

• Study coordinator: Harsha Ashton

Conditions Crohn Disease