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

Last updated: December 1, 2023
Sponsor: University of Calgary
Overall Status: Active - Recruiting

Phase

4

Condition

N/A

Treatment

Anti-IL12/23 or anti-IL23 - Ustekinumab

TNFa Antagonist - Adalimumab

TNFa Antagonist - Infliximab

Clinical Study ID

NCT05928039
REB22-1641/RCT-01741
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Male or nonpregnant, nonlactating females, 18 years of age or older. Females ofchildbearing potential must have a negative serum or urine pregnancy test prior torandomization
  2. Established CD diagnosis by conventional criteria
  3. Baseline colonoscopy within 3 months of the first day of the screening period, withphoto or video documentation of at least one large ileal ulcer >5 mm and ileal segmentSES-CD ≥4 (eligibility will be determined by local endoscopist, with subsequentconfirmation 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 activeCD as part of their routine clinical care and for whom there is equipoise around whichbiologic class to start
  7. Willing and able to participate fully in all aspects of this clinical trial, includingadherence to study protocol and treatment algorithm
  8. Written informed consent must be obtained and documented

Exclusion

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 orabscesses that require imminent surgery (at investigator's discretion)
  3. Participants with current or history of colonic dysplasia or neoplasia, toxicmegacolon, or fulminant colitis
  4. Recent bowel resection <3 months before screening
  5. Active enteric infection (positive stool culture), including but not limited tobacterial (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® TBGold Test, tuberculin skin test, or history of untreated latent or active TB
  9. History of malignancy within 5 years of screening, except fully treated carcinomain-situ of the cervix, fully treated and resolved nonmetastatic squamous or basal cellcarcinoma 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, mayinterfere with the participant's ability to participate fully in the study
  12. Not willing to withhold protocol-prohibited medications during the trial, or plannedor anticipated use of any prohibited medications during screening
  13. Received previously or currently receiving a TNF antagonist, anti-integrin, monoclonalantibody targeting IL-12/23 or IL-23, Janus kinase (JAK) inhibitors, or sphingosine 1phosphate (S1P) receptor modulators (irrespective of indication)
  14. History of alcohol or drug abuse that, in the opinion of the investigator, mayinterfere with the participant's ability to comply with the study procedures

Study Design

Total Participants: 297
Treatment Group(s): 6
Primary Treatment: Anti-IL12/23 or anti-IL23 - Ustekinumab
Phase: 4
Study Start date:
October 25, 2023
Estimated Completion Date:
December 31, 2028

Study 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.

Connect with a study center

  • University of Calgary

    Calgary, Alberta
    Canada

    Active - Recruiting

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