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

NCT ID: NCT05928039

Last Updated: 2025-06-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

297 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-25

Study Completion Date

2028-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Crohn Disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

TNFα antagonist

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

Group Type ACTIVE_COMPARATOR

TNFa Antagonist - Infliximab

Intervention Type BIOLOGICAL

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

TNFa Antagonist - Adalimumab

Intervention Type BIOLOGICAL

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

Anti-IL12/23 or anti-IL23

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

Group Type ACTIVE_COMPARATOR

Anti-IL12/23 or anti-IL23 - Ustekinumab

Intervention Type BIOLOGICAL

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

Anti-IL12/23 or anti-IL23 - Risankizumab

Intervention Type BIOLOGICAL

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

Anti-integrin

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

Group Type ACTIVE_COMPARATOR

Anti-integrin - Vedolizumab IV

Intervention Type BIOLOGICAL

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

Anti-integrin - Vedolizumab IV and SC

Intervention Type BIOLOGICAL

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

TNFa Antagonist - Infliximab

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

Intervention Type BIOLOGICAL

TNFa Antagonist - Adalimumab

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

Intervention Type BIOLOGICAL

Anti-IL12/23 or anti-IL23 - Ustekinumab

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

Intervention Type 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

Intervention Type BIOLOGICAL

Anti-integrin - Vedolizumab IV

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

Intervention Type BIOLOGICAL

Anti-integrin - Vedolizumab IV and SC

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

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Alimentiv Inc.

OTHER

Sponsor Role collaborator

University of Calgary

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Calgary

Calgary, Alberta, Canada

Site Status RECRUITING

University of Alberta IBD Clinic

Edmonton, Alberta, Canada

Site Status RECRUITING

GI Research Institute (G.I.R.I)

Vancouver, British Columbia, Canada

Site Status NOT_YET_RECRUITING

West Coast Gastroenterology

Vancouver, British Columbia, Canada

Site Status NOT_YET_RECRUITING

Nova Scotia Health Victoria

Halifax, Nova Scotia, Canada

Site Status ACTIVE_NOT_RECRUITING

GNRR Digestive Clinics and Research Center Inc.

Brampton, Ontario, Canada

Site Status NOT_YET_RECRUITING

Rajbir Rai Medical Corporation

Brantford, Ontario, Canada

Site Status NOT_YET_RECRUITING

McMaster University

Hamilton, Ontario, Canada

Site Status RECRUITING

London Health Sciences Centre

London, Ontario, Canada

Site Status ACTIVE_NOT_RECRUITING

West GTA Research Inc.

Mississauga, Ontario, Canada

Site Status NOT_YET_RECRUITING

ABP Research Services Corp.

Oakville, Ontario, Canada

Site Status NOT_YET_RECRUITING

Taunton Surgical Center

Oshawa, Ontario, Canada

Site Status NOT_YET_RECRUITING

The Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Site Status RECRUITING

Thunder Bay Regional Health Research Institute

Thunder Bay, Ontario, Canada

Site Status ACTIVE_NOT_RECRUITING

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

TIDHI Clinic

Toronto, Ontario, Canada

Site Status ACTIVE_NOT_RECRUITING

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

Site Status RECRUITING

Hôpital du Sacré-Cœur-de-Montréal

Montreal, Quebec, Canada

Site Status RECRUITING

Research Institute of the McGill University Health Centre (MUHC)

Montreal, Quebec, Canada

Site Status RECRUITING

Université de Sherbrooke

Sherbrooke, Quebec, Canada

Site Status NOT_YET_RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Canada

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Harsha Ashton

Role: CONTACT

226-919-6959

Christopher Ma, MD MPH

Role: CONTACT

4035925013

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Ashley Clarke, MSc

Role: primary

4032109141

Heather Baylis

Role: backup

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 40357993 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

REB22-1641/RCT-01741

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.