GUselkumAb inteRvention and DIet evaluAtioN for Pouchitis
ConditionPouchitis
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversitaire Ziekenhuizen KU Leuven
About this trial
Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) is considered the procedure of choice in patients with ulcerative colitis (UC) refractory to medical therapy or with neoplasia. The most common complication after IPAA is the development of pouchitis. Pouchitis is clinically characterized by variable symptoms including increased stool frequency, altered consistency, bloody stools, abdominal cramping, urgency, and incontinence. Symptomatic pouchitis longer than four weeks is considered chronic pouchitis.
The conventional treatment for acute and chronic pouchitis is antibiotics, such as metronidazole and ciprofloxacin. The disease course of antibiotic responsive pouchitis may evolve into antibiotic dependent (requiring antibiotic maintenance therapy) pouchitis and then antibiotic refractory (no response to antibiotic treatment) pouchitis. Although many patients respond to antibiotic therapy, there is also evidence that suggest that aberrant regulation of the mucosal immune system might play a part in the pathogenesis of pouchitis arising from an abnormal mucosal immune response to a dysbiosis of the pouch microbiota. If individuals fail to respond to antibiotics, anti-tumor necrosis factor (anti-TNF) agents and vedolizumab have been proposed for the treatment of chronic pouchitis.
Guselkumab, an interleukin-23 (IL-23) p19 subunit antagonist monoclonal antibody, is proven to be efficacious in patients with moderately-to-severely active UC. Efficacy of guselkumab in treating UC has been shown in multiple large clinical trials. However, patients with pouchitis were never the targeted population and were even often excluded from the trials.
Pouchitis becomes a chronic problem with a huge impact in the quality of life of these patients. The incidence of pouchitis has been rising in the last decades. This increase might be explained by a change in dietary habits of this population.
This open label single center trial at UZ Leuven aims to evaluate the efficacy and safety of guselkumab in the treatment of chronic antibiotic refractory pouchitis during a 48-week treatment period, with or without a dietary intervention. Twenty subjects with a proctocolectomy and IPAA for UC who have developed chronic or relapsing pouchitis will be enrolled.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
At least 18 years of age at the time of signing the Informed Consent Form (ICF)
Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.
≥2 recurrent episodes within 1 year prior to the screening visit, each treated with ≥2 weeks of antibiotic or other prescription therapy, or
Disqualifiers
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, infectious 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 screening
Nonbiologic investigational therapy or JAK inhibitors within 30 days prior to screening
Trial design
Design model
Parallel
Treatments tested in this trial
Guselkumab
DrugAll patients will receive guselkumab 400 mg intravenous at week 0, week 4, and week 8, followed by subcutaneous guselkumab 200 mg at week 12, week 16, week 20, week 24, week 28, week 32, week 36, week 40, week 44, and week 48. All subjects will receive concomitant antibiotic treatment with ciprofloxacin 500mg twice daily from randomization through week 4.
Diet
Other interventionSubjects randomized to the group with the dietary intervention will be advised to follow a low-UPF, high-fruit diet. Patients will be instructed to restrict the intake of NOVA 4 food products during the first 16 weeks of the trial, and to increase the intake of fruits (minimum 3 servings per day) during the full trial. Dietary education will be provided by certified IBD dietitians, lists of products to avoid, and week menu's will also be provided to increase dietary adherence. Dietary information will be collected with food records and food frequency questionnaires.
Treatment groups
20 Participants
are divided into 2 treatment groupsGroup A: intervention with guselkumabActive comparator 1 intervention
Group B: intervention with guselkumab and dietActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
percentage of subjects achieving clinical remission after 16 weeks of treatment with guselkumab with/without diet
the percentage of subjects with chronic or recurrent pouchitis achieving clinical remission (mPDAI score \<5 and a reduction of overall score by ≥2 points from Baseline) after 16 weeks of treatment with guselkumab compared to 16 weeks of guselkumab and a dietary intervention.
Time frame
16 weeksSecondary outcomes
1
percentage of subjects achieving clinical remission after 48 weeks
The percentage of subjects achieving clinical remission (mPDAI score \<5 and a reduction of overall score by ≥2 points from Baseline) after 48 weeks in both groups
Time frame
48 weeks2
percentage of subjects achieving antibiotic free clinical remission by week 16 and 48
The percentage of subjects achieving antibiotic free clinical remission by week 16 and 48
Time frame
week 16 and week 483
percentage of subjects achieving partial response after 16 and 48 weeks
The percentage of subjects achieving partial response (reduction of mPDAI score by ≥2 points from Baseline) after 16 and 48 weeks in both groups
Time frame
week 16 and week 484
Time to clinically relevant remission
Time to clinically relevant remission in both groups
Time frame
48 weeksOther outcomes
1
Time to relapse of pouchitis symptoms and number of relapses
Time to relapse of pouchitis symptoms and number of relapses in both groups
Time frame
48 weeks2
Change in CRP at Week 8, 16, 24, 32, 40 and 48
Change in CRP at Week 8, 16, 24, 32, 40 and 48 compared to Baseline in both groups
Time frame
baseline, week 8, 16, 24, 32, 40 and week 483
Change in faecal calprotectin at Week 8, 16, 24, 32 and 48
Change in faecal calprotectin at Week 8, 16, 24, 32 and 48 compared to Baseline in both groups
Time frame
baseline, week 8, 16, 24, 32, 40 and week 484
Evolution of guselkumab serum levels
Evolution of guselkumab serum levels between Baseline and Week 8, 16, 24, 32, 40 and 48 in both groups
Time frame
baseline, week 8, 16, 24, 32, 40 and week 48Sponsors and contacts
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Source ClinicalTrials.gov