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

TIDHI Innovation Inc.

Status: Enrolling

Conditions: Inflammatory Bowel Disease (IBD); IBD-unclassified (IBD-U); Ulcerative Colitis (UC); Crohn Disease (CD)

Treatments: Biological: Guselkumab (Tremfya)

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT07245394

TIDHI_001

ISRCTN13202059 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

200 participants in 2 patient groups

Early Switch Cohort (ESC)

Description:

Patients with CD or UC who had inadequate response to on-label maintenance ustekinumab (90 mg every 8 weeks) that requires a change in advanced therapy, as determined by the treating physician. Inadequate response could be either loss of response, partial response, or persistent endoscopic activity.

Treatment:

Biological: Guselkumab (Tremfya)

Exhausted Ustekinumab Cohort (EUC)

Description:

Patients with CD or UC who had inadequate response to off-label maintenance ustekinumab (90 mg every 6 or 4 weeks) that requires a change in advanced therapy, as determined by the treating physician. Inadequate response could be either loss of response, partial response, or persistent endoscopic activity.

Treatment:

Biological: Guselkumab (Tremfya)