Pouchitis
Conditions
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.
Interventions
DRUGUstekinumab
All patients will receive intravenously (IV) ustekinumab \ 6mg/kg at baseline and subcutaneously (SC) ustekinumab 90mg every 8 weeks thereafter until Week 48.
Sponsors
Janssen Pharmaceuticals
Universitaire Ziekenhuizen KU Leuven
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
open label pilot study
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| The percentage of subjects achieving partial response | 16 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 |
| 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 |
| 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 |
| Change in mPDAI symptomatic subscore | At Week 16 and 48 compared to baseline | Change in mPDAI symptomatic subscore from baseline |
Countries
Belgium
Outcome results
None listed