Stelara fOr ChRonic AntibioTic rEfractory pouchitiS

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

Detailed Description
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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.

Official Title
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Stelara fOr ChRonic AntibioTic rEfractory pouchitiS (SOCRATES): A Belgian Open Label Multicenter Pilot-study

Conditions
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Pouchitis

Intervention / Treatment
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* Drug: Ustekinumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open label pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open label ustekinumab<br>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. | Drug: Ustekinumab<br>* All patients will receive intravenously (IV) ustekinumab  6mg/kg at baseline and subcutaneously (SC) ustekinumab 90mg every 8 weeks thereafter until Week 48.<br>* Other names: Stelara;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of subjects achieving clinically relevant steroid-free remission | mPDAI score <5 and a reduction by ≥2 points from baseline | 16 weeks after baseline | 

Secondary Outcome Measures

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