Switching to the IL-23 Inhibitor Guselkumab for People With Active IBD Who Previously Used Ustekinumab (SHIFT-IBD)

Official title

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

Overview

The SHIFT-IBD Study is being conducted at multiple medical centers across Canada to evaluate how well guselkumab (Tremfya) works for people with inflammatory bowel disease (IBD) who haven't responded well enough to ustekinumab. Patients will begin guselkumab based on their doctor's decision. If eligible, they may be invited to participate in the study, which involves monitoring symptoms, test results, and overall health over the course of one year. Guselkumab will be given according to local medical guidelines. Doctors can adjust the treatment as needed, just like in routine care. Researchers believe that switching to guselkumab may be as effective as other advanced treatments. For those who saw some improvement on ustekinumab but not enough, guselkumab may offer better symptom control-without worsening results on medical tests like endoscopy. The goal is to explore better treatment options for people whose IBD has not been well controlled with current therapies.

Interventions

• Biological Guselkumab (Tremfya)
  Switching to Guselkumab (Tremfya) in People With Active IBD Previously Treated With Ustekinumab.

Primary outcome measures

• Rate of participants achieving deep remission in IBD patients treated with guselkumab after switching from ustekinumab [Time frame: Week 52]
• Rate of participants achieving deep remission, stratified by cohorts [Time frame: Week 52]

Secondary outcome measures (7)

• Rate of participants with absence of symptomatic worsening [Time frame: Week 52]
• Rate of participants achieving endoscopic remission [Time frame: Week 52]
• Rate of participants achieving endoscopic response [Time frame: Week 52]
• Rate of participants with absence of symptomatic worsening [Time frame: Any study visit (Week 4, Week 12, Week 32, Week 52)]
• Rate of participants achieving symptomatic remission among those not in remission at baseline [Time frame: Week 12 and Week 52]
• Rate of participants achieving steroid-free remission among corticosteroid users at baseline [Time frame: Week 52]
• Rate of participants discontinuing guselkumab therapy [Time frame: Any study visit (Week 4, Week 12, Week 32, Week 52)]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Canada · 12 centers

• University of Calgary — Calgary
• MA MacMillan — Fredericton
• Hamilton Health Sciences Corporation — Hamilton
• Barrie GI Associates — Barrie
• Brampton Gastroenterology Research Group Inc — Brampton
• GNRR Digestive Clinics and Research Center Inc. — Brampton
• LDDI Clinical Trials Inc. dba London Digestive Disease Institute — London
• West Gta Research Inc. — Mississauga
• … and 4 more centers

Identifiers

NCT: NCT07245394 · TIDHI_001 · ISRCTN13202059

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗