NCT06916390

GUselkumAb inteRvention and DIet evaluAtioN for Pouchitis

Guselkumab Intervention and Diet Evaluation for Pouchitis

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Universitaire Ziekenhuizen KU Leuven · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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. Between 50% and 80% of those with an IPAA will experience pouchitis symptoms at any given moment with 10% of patients developing a chronic antibiotic refractory pouchitis. Symptomatic pouchitis for less than four weeks is considered acute pouchitis, while symptomatic pouchitis longer than four weeks is considered chronic pouchitis. Additionally, relapsing pouchitis can also occur when there are three or more episodes per year. The conventional treatment for acute and chronic pouchitis is antibiotics, such as metronidazole and ciprofloxacin. The clinical response of pouchitis to treatment with antibiotics such as metronidazole or ciprofloxacin, suggests that fecal stasis, Clostridium difficile infection, bacterial overgrowth or dysbiosis (qualitative or quantitative alterations in the bacterial communitiy) may be triggers. 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. Recently, vedolizumab has been shown to be efficacious in treating chronic pouchitis with remission rates of 31% at week 14. Nevertheless, the treatment of chronic pouchitis remains an unmet need for patients with inflammatory bowel diseases (IBD). Guselkumab, an interleukin-23 (IL-23) p19 subunit antagonist monoclonal antibody, is proven to be efficacious in patients with moderately-to-severely active UC. In the phase II GALAXI 1 trial (309 patients with UC, 2020), intravenous treatment with 200 mg, 600 mg or 1,200 mg guselkumab at weeks 0, 4 and 8 showed significantly greater reductions from baseline CDAI, outcomes of clinical response, clinical remission, Patient-Reported Outcome-2 (PRO-2) remission, clinical biomarker response and endoscopic response at week 12 compared with intravenous placebo. The QUASAR study (313 patients with UC, 2022), a Phase 2b/3 randomized, double-blind, placebo-controlled trial, demonstrated superiority of guselkumab to placebo for clinical response during induction at week 12 in patients with UC. Guselkumab also met key secondary endpoints of clinical remission, symptomatic remission, endoscopic improvement, and histo-endoscopic mucosal improvement. The efficacy and safety of guselkumab in patients with UC were further studied in the exploratory Phase 2a VEGA trial (214 patients with UC, 2023) evaluating combination treatment of guselkumab and golimumab during induction. Combination therapy was significantly more effective than either drug alone for clinical remission and endoscopic improvement. A meta-analysis (36 studies with 14270 patients with UC, 2024) comparing the relative efficacy of biologics and small molecules, proved Guselkumab to rank high in achieving clinical remission, endoscopic improvement and remission, and histological remission in patients with moderate to severe 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. Interestingly, lower fruit consumption has been associated with higher risk of pouchitis. Moreover, food colorants have been associated with colitis in mice with higher IL-23 expression. 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.

Conditions

• Pouchitis

Interventions

Type	Name	Description
DRUG	Guselkumab	All 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.
OTHER	Diet	Subjects 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.

Timeline

• Start date: 2025-09-30
• Primary completion: 2028-09-30
• Completion: 2028-09-30
• First posted: 2025-04-08
• Last updated: 2025-04-08

Locations

1 site across 1 country: Belgium