Switching to guselkumab for adults with active IBD after ustekinumab

SHIFT-IBD: Switching to High-efficacy Anti-IL-23 Guselkumab in Ustekinumab-exposed Persons With Active IBD

We will try guselkumab (Tremfya) in adults with active IBD whose symptoms didn't improve enough on ustekinumab.

Quick facts

• Study type: Observational
• Enrollment: 200 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: TIDHI Innovation Inc. (Academic / other)
• Drugs / interventions: ustekinumab, infliximab, adalimumab, golimumab, certolizumab, vedolizumab, natalizumab, risankizumab, mirikizumab, guselkumab, tofacitinib, upadacitinib
• Locations: 9 sites (Fredericton, New Brunswick and 8 other locations)
• Trial ID: NCT07245394 on ClinicalTrials.gov

What this trial studies

This is a multi-center observational study in Canada following adults who start guselkumab as their treating doctor decides. Participants receive guselkumab according to local medical guidelines and clinicians may adjust treatment as part of routine care. Researchers will monitor symptoms, laboratory and endoscopy results, and overall health over one year. The goal is to see whether switching from ustekinumab to an IL-23 inhibitor provides better symptom control without worsening key test results.

Who should consider this trial

Good fit: Adults (≥18) with a confirmed diagnosis of CD, UC, or IBD-U for at least 6 months who have had an inadequate response to ustekinumab after at least 14 weeks and are starting guselkumab may be eligible.

Not a fit: Patients who are currently doing well on ustekinumab, who have started another advanced therapy since stopping ustekinumab, or who are unable to attend follow-up visits are unlikely to benefit from participating in this switching study.

Why it matters

Potential benefit: If successful, switching to guselkumab could provide improved symptom control for people with IBD who did not get sufficient benefit from ustekinumab.

How similar studies have performed: IL-23 inhibitors have shown promising results in recent IBD research, but direct evidence specifically about switching from ustekinumab to guselkumab is still limited and under study.

Eligibility criteria

Inclusion Criteria:

* Subjects of any gender aged ≥ 18.
* Confirmed diagnosis of IBD (CD, UC, or IBDU) for at least 6 months prior to baseline visit. Subjects with IBDU will be grouped with subjects with UC. The CD proportion of patients will be capped at 75%.
* Subjects have received ustekinumab for at least 14 weeks and who are currently on or recently discontinued ustekinumab therapy.
* For subjects that have recently discontinued ustekinumab, the last dose of ustekinumab must have been within 12 weeks before Week 0, and no other advanced therapy (i.e., infliximab, adalimumab, golimumab, certolizumab pegol, vedolizumab, natalizumab, risankizumab, mirikizumab, tofacitinib, upadacitinib, ozanimod, etrasimod) was started since stopping ustekinumab.
* Subjects with an inadequate response to ustekinumab who require a change in advanced therapy and are initiating guselkumab, as determined by the treating physician.
* For subjects on off-label ustekinumab dosing (90 mg every 4 or 6 weeks (off-label dosing), enrollment will be capped at 60%.
* Ability and willingness to give written informed consent and comply with the requirements of this study protocol.
* Subjects who have evidence of ongoing endoscopic evidence of disease activity within 3 months prior to Week 0, defined as:

  * For Crohn's Disease: Colonoscopy showing SES-CD score (excluding the presence of narrowing component) of ≥6 (or ≥4 for participants with isolated ileal disease), OR presence of ulcers larger than 5 mm in any segment.
  * For Ulcerative Colitis: Colonoscopy showing Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score ≥4, OR presence of erosions or ulcers in any segment.

Exclusion Criteria:

* History of prior exposure to any anti-p19 inhibitor (risankizumab or mirikizumab).
* Subjects with formal contraindication to guselkumab per the drug label.
* Use of guselkumab for an off-label indication, dosing regimen, or route of administration. Subjects who did not receive guselkumab induction will be excluded.
* Subjects with an ostomy or ileo-anal pouch.
* Subjects with a history of bowel surgery within 6 months prior to Week 0.
* Subjects displaying clinical signs of acute severe UC, fulminant colitis or toxic megacolon within 3 months prior to Week 0.
* Subjects who are expected to require bowel surgery by their IBD physician within the year of enrollment.
* Subjects on 1 or more concomitant biologics.
* Subjects with a history of colonic dysplasia (low-grade dysplasia, high-grade dysplasia, or colorectal cancer). Note: Patients with a history of indefinite for dysplasia would be eligible.
* Subjects with formal contraindication or unwilling to undergo lower endoscopy.
* The patient is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.

Where this trial is running

Fredericton, New Brunswick and 8 other locations

• MA MacMillan — Fredericton, New Brunswick, Canada (Recruiting)
• Barrie GI Associates — Barrie, Ontario, Canada (Recruiting)
• Brampton Gastroenterology Research Group Inc — Brampton, Ontario, Canada (Recruiting)
• GNRR Digestive Clinics and Research Center Inc. — Brampton, Ontario, Canada (Recruiting)
• LDDI Clinical Trials Inc. dba London Digestive Disease Institute — London, Ontario, Canada (Not_yet_recruiting)
• West Gta Research Inc. — Mississauga, Ontario, Canada (Recruiting)
• Abp Research Services Corporation — Oakville, Ontario, Canada (Recruiting)
• Taunton Surgical Center — Oshawa, Ontario, Canada (Recruiting)
• Toronto Immune and Digestive Health Institute — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Laura E. Targownik, MD, MSHS, FRCPC — TIDHI Innovation Inc.
• Study coordinator: Ajani Jeyakumar, HBSc BScN RN

Conditions Inflammatory Bowel Disease; Crohn Disease; Ulcerative Colitis; IBD-unclassified