Stelara fOr ChRonic AntibioTic rEfractory pouchitiS (SOCRATES)

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

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

Study Overview

• Status: Completed
• Conditions: Pouchitis
• Intervention / Treatment: Drug: Ustekinumab

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Liège, Belgium, 4000
    • CHU de Liège, Sart Tilman
  • Vlaanderen
    • Leuven, Vlaanderen, Belgium, 3000
      • UZ Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Stelara

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: Janssen Pharmaceuticals
• Investigators: Principal Investigator: Marc Ferrante, MD, PhD, UZ Leuven

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): May 1, 2023

Study Registration Dates

• First Submitted: September 9, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Estimated): December 11, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Enteritis; Ileitis; Ileal Diseases; Pouchitis; Dermatologic Agents; Ustekinumab
• Other Study ID Numbers: CNTO1275UCO2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No