Clinical trial NCT04089345: Stelara fOr ChRonic AntibioTic rEfractory pouchitiS
Official title: Stelara fOr ChRonic AntibioTic rEfractory pouchitiS (SOCRATES): A Belgian Open Label Multicenter Pilot-study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pouchitis
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Janssen Pharmaceuticals
First posted: 2019-09-13
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open label pilot study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: The percentage of subjects achieving clinically relevant steroid-free remission
timeFrame: 16 weeks after baseline
Secondary outcomes:
measure: The percentage of subjects achieving clinically relevant steroid-free remission
timeFrame: 48 weeks after baseline
measure: The percentage of subjects achieving partial response
timeFrame: 16 weeks after baseline
measure: The percentage of subjects achieving partial response
timeFrame: 48 weeks after baseline
measure: Time to clinically relevant remission
timeFrame: Within 48 weeks after baseline
measure: Change in mPDAI endoscopic subscore
timeFrame: At Week 16 and 48 compared to baseline
measure: Change in mPDAI symptomatic subscore
timeFrame: At Week 16 and 48 compared to baseline
measure: Change in total mPDAI score
timeFrame: At Week 16 and 48 compared to baseline
measure: Change in European Quality of Life 5 Dimensions (EQ-5D)
timeFrame: At Week 16, 32 and 48 compared to baseline
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaanderen
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Liège
country: Belgium
facility: CHU de Liège, Sart Tilman
Study officials:
affiliation: UZ Leuven
name: Marc Ferrante, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: