Stelara fOr ChRonic AntibioTic rEfractory pouchitiS

Phase 3

Completed

• Conditions: Pouchitis
• Interventions: Drug: Ustekinumab

• Registration Number: NCT04089345
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

Brief Summary

To evaluate the efficacy and safety of ustekinumab in the treatment of chronic antibiotic refractory and relapsing pouchitis.

Detailed Description

This study is a Belgian prospective open label multicenter study to evaluate the efficacy and safety of ustekinumab in the treatment of relapsing or chronic antibiotic refractory pouchitis during a 48-week treatment period. Twenty subjects with a RPC and IPAA for UC who have developed relapsing or chronic antibiotic refractory pouchitis will be enrolled.

All patients will receive intravenously (IV) ustekinumab \~6mg/kg at baseline and subcutaneously (SC) ustekinumab 90mg every 8 weeks thereafter until Week 48. All subjects will receive concomitant antibiotic treatment with ciprofloxacin or metronidazole from baseline through Week 4. Intravenous induction doses will be 260mg for patients \<55kg, 390mg for patients between 55 and 85kg, and 520mg for patients with a body weight \>85 kg.

Clinical and biochemical evaluation will be planned every 8 weeks. Efficacy will be assessed at Week 16 and Week 48 using mPDAI and PDAI scores, therefor a pouchoscopy with biopsy sampling will be performed. Patients who do not achieve partial response (reduction of mPDAI score by ≥2 points from baseline) at Week 16 will be discontinued.

Study Timeline

• Study First Submitted: 2019-09-09
• Study First Submitted QC: 2019-09-12
• Study First Posted: 2019-09-13
• Study Start: 2020-06-15
• Status Verified: 2021-04
• Primary Completion: 2022-12-01
• Study Completion: 2023-05-01
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• The subject has a history of ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC)
• The subject has pouchitis that is (a) relapsing or (b) chronic antibiotic refractory, defined by an mPDAI score ≥5 assessed as the average from 3 days immediately prior to the baseline endoscopy visit and a minimum endoscopic subscore of 2 (outside the staple or suture line) with either (a) ≥3 recurrent episodes within the last year, each treated with ≥2 weeks of antibiotic or other prescription therapy, or (b) requiring maintenance antibiotic therapy taken continuously for ≥4 weeks immediately prior to the baseline endoscopy visit

Exclusion Criteria

• Crohn's disease (CD), CD-related complications of the pouch (pouch fistula, pouch strictures, ulcerations in the pre-pouch ileum without pouchitis), irritable pouch syndrome (IPS), isolated or predominant cuffitis, infectiouw pouchitis, diverting ostomy or mechanical complications of the pouch
• Previous treatment with an anti-IL12/23 or an anti-IL23 antibody
• Any investigational or approved biologic agent within 30 days of baseline
• Nonbiologic investigational therapy or tofacitinib within 30 days prior to baseline
• Active or untreated latent tuberculosis (TB)
• Chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, a known history of human immunodeficiency virus (HIV) infection (or is found to be seropositive at screening) or subject is immunodeficient
• Active severe infection (e.g. sepsis, cytomegalovirus, listeriosis or C. difficile)
• History of malignancy or current malignancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open label ustekinumab	Ustekinumab	All patients will receive intravenously (IV) ustekinumab \~6mg/kg at baseline and subcutaneously (SC) ustekinumab 90mg every 8 weeks thereafter until Week 48. All subjects will receive concomitant antibiotic treatment with ciprofloxacin or metronidazole from baseline through Week 4. Intravenous induction doses will be 260mg for patients \<55kg, 390mg for patients between 55 and 85kg, and 520mg for patients with a body weight \>85 kg.

Primary Outcome Measures

Name	Time	Method
The percentage of subjects achieving clinically relevant steroid-free remission	16 weeks after baseline	mPDAI score \<5 and a reduction by ≥2 points from baseline

Secondary Outcome Measures

Name	Time	Method
The percentage of subjects achieving clinically relevant steroid-free remission	48 weeks after baseline	mPDAI score \<5 and a reduction by ≥2 points from baseline, without need for steroids
The percentage of subjects achieving partial response	48 weeks after baseline	reduction of mPDAI score by ≥2 points from baseline
Change in mPDAI endoscopic subscore	At Week 16 and 48 compared to baseline	Change in mPDAI endoscopic subscore from baseline
Change in total mPDAI score	At Week 16 and 48 compared to baseline	Change in total mPDAI score from baseline
Change in mPDAI symptomatic subscore	At Week 16 and 48 compared to baseline	Change in mPDAI symptomatic subscore from baseline
Change in European Quality of Life 5 Dimensions (EQ-5D)	At Week 16, 32 and 48 compared to baseline	Change in European Quality of Life 5 Dimensions (EQ-5D) from baseline
Time to clinically relevant remission	Within 48 weeks after baseline	Time to mPDAI score \<5 and a reduction by ≥2 points from baseline

Trial Locations

Locations (3)

Cliniques Universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

CHU de Liège, Sart Tilman; 🇧🇪 Liège, Belgium

UZ Leuven; 🇧🇪 Leuven, Vlaanderen, Belgium