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

NCT05928039 | Recruiting Phase 4 DMC

• 1 other identifier: REB22-1641/RCT-01741
• Study Type: interventional
• Target: 297
• Locations: 1 country
• Sites: 20

Brief 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.

Conditions

Crohn Disease

Outcome Measures

Primary Outcomes (1)

• Corticosteroid-free endoscopic remission

  SES-CD ≤4, ileal segment SES-CD ≤2, and no ulcers in any segment \>5 mm, off corticosteroids for ≥ 16 weeks

  1 year

Secondary Outcomes (7)

• CD-related complications

  1 year

• Time to first Crohn's disease-related complication.

  From date of randomization until the date of first documented Crohn's disease-related complication or date of death from any cause, whichever came first, assessed up to 12 months

• Biomarker remission

  Months 4, 8, and 12

• Corticosteroid-free clinical remission

  Months 4, 8, and 12

• Treatment persistence

  1 year

Study Arms (3)

TNFα antagonist

ACTIVE COMPARATOR

Participants will receive either: * 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

Biological: TNFa Antagonist - Infliximab; Biological: TNFa Antagonist - Adalimumab

Anti-IL12/23 or anti-IL23

ACTIVE COMPARATOR

Participants will receive either: * 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

Biological: Anti-IL12/23 or anti-IL23 - Ustekinumab; Biological: Anti-IL12/23 or anti-IL23 - Risankizumab

Anti-integrin

ACTIVE COMPARATOR

Participants will receive either: * 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

Biological: Anti-integrin - Vedolizumab IV; Biological: Anti-integrin - Vedolizumab IV and SC

Interventions

TNFa Antagonist - Infliximab BIOLOGICAL

• Infliximab 5 mg/kg intravenously \[IV\] at weeks 0, 2, 6, then 5 mg/kg every 8 weeks

TNFα antagonist

TNFa Antagonist - Adalimumab BIOLOGICAL

• Adalimumab subcutaneously \[SC\] 160 mg at week 0, 80 mg at week 2, then 40 mg every 2 weeks

TNFα antagonist

Anti-IL12/23 or anti-IL23 - Ustekinumab BIOLOGICAL

• Ustekinumab \~6 mg/kg IV x1, then 90 mg SC every 8 weeks

Anti-IL12/23 or anti-IL23

Anti-IL12/23 or anti-IL23 - Risankizumab BIOLOGICAL

• Risankizumab 600 mg IV at weeks 0, 4, and 8, then 360 mg SC every 8 weeks

Anti-IL12/23 or anti-IL23

Anti-integrin - Vedolizumab IV BIOLOGICAL

• Vedolizumab 300 mg IV at weeks 0, 2, and 6, then every 8 weeks

Anti-integrin

Anti-integrin - Vedolizumab IV and SC BIOLOGICAL

• Vedolizumab 300 mg IV at weeks 0 and 2, then 108 mg SC every 2 weeks

Anti-integrin

Eligibility Criteria

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

You may qualify if:

• 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
• Established CD diagnosis by conventional criteria
• 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)
• HBI ≥5
• Biologic-treatment naïve for CD-related therapies
• 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
• Willing and able to participate fully in all aspects of this clinical trial, including adherence to study protocol and treatment algorithm
• Written informed consent must be obtained and documented

You may not qualify if:

• Condition(s) for which the biologics included in this study is contraindicated
• CD-related complications such as symptomatic, endoscopically impassable strictures or abscesses that require imminent surgery (at investigator's discretion)
• Participants with current or history of colonic dysplasia or neoplasia, toxic megacolon, or fulminant colitis
• Recent bowel resection \<3 months before screening
• Active enteric infection (positive stool culture), including but not limited to bacterial (including C. difficile), viral, or parasitic enteric infections
• Known active hepatitis B, hepatitis C, or human immunodeficiency virus infection
• Active COVID-19 infection during the screening period
• 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
• 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
• Active chronic or acute infections requiring treatment with systemic antibiotics, antivirals, antifungals, antiparasitics, or antiprotozoals during the screening period
• 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
• Not willing to withhold protocol-prohibited medications during the trial, or planned or anticipated use of any prohibited medications during screening
• 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)
• 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

Sponsors & Collaborators

• University of Calgary: lead
• Alimentiv Inc.: collaborator

Study Sites (20)

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

Related Publications (1)

• Hasskamp J, Meinhardt C, Timmer A. Anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2025 May 13;5(5):CD007572. doi: 10.1002/14651858.CD007572.pub4.

  PMID: 40357993 DERIVED

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Central Study Contacts

Harsha Ashton

CONTACT

226-919-6959; harsha.ashton@alimentiv.com

Christopher Ma, MD MPH

CONTACT

4035925013; christopher.ma@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This trial is a prospective, randomized, open-label, blinded-endpoint (PROBE) trial. The primary endpoint will be evaluated by a blinded, external central reviewer.

Study Record Dates

• First Submitted: June 13, 2023
• First Posted: July 3, 2023
• Study Start: October 25, 2023
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available after completion of the trial and publication of results. Data will be retained for 15 years.

Locations

CA (20)