SOCRATES: Stelara fOr ChRonic AntibioTic rEfractory pouchitiS
Study Details
Study Description
Brief Summary
To evaluate the efficacy and safety of ustekinumab in the treatment of chronic antibiotic refractory and relapsing pouchitis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Open label 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. |
Drug: Ustekinumab
All patients will receive intravenously (IV) ustekinumab ~6mg/kg at baseline and subcutaneously (SC) ustekinumab 90mg every 8 weeks thereafter until Week 48.
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- 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 [16 weeks after baseline]
reduction of mPDAI score by ≥2 points from baseline
- The percentage of subjects achieving partial response [48 weeks after baseline]
reduction of mPDAI score by ≥2 points 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
- Change in mPDAI endoscopic subscore [At Week 16 and 48 compared to baseline]
Change in mPDAI endoscopic subscore from baseline
- Change in mPDAI symptomatic subscore [At Week 16 and 48 compared to baseline]
Change in mPDAI symptomatic 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 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
The subject has a history of ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC)
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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
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Previous treatment with an anti-IL12/23 or an anti-IL23 antibody
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Any investigational or approved biologic agent within 30 days of baseline
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Nonbiologic investigational therapy or tofacitinib within 30 days prior to baseline
-
Active or untreated latent tuberculosis (TB)
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UZ Leuven | Leuven | Vlaanderen | Belgium | 3000 |
| 2 | Cliniques Universitaires Saint-Luc | Brussels | Belgium | 1200 | |
| 3 | CHU de Liège, Sart Tilman | Liège | Belgium | 4000 |
Sponsors and Collaborators
- Universitaire Ziekenhuizen Leuven
- Janssen, LP
Investigators
- Principal Investigator: Marc Ferrante, MD, PhD, UZ Leuven
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CNTO1275UCO2001