Starting soon
Phase 4
Risankizumab for Refractory Perianal Fistulizing Crohn's Disease
Condition(s) studied
Crohn DiseasePerianal FistulaPerianal Fistula Due to Crohn's DiseasePerianal Crohn's Disease
Investigational drug(s) / intervention(s)
Risankizumab: Risankizumab (Skyrizi®, AbbVie Inc.) is a humanized IgG1 monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23). For Crohn's disease, participants receive 600 mg intravenously (IV) at Weeks 0, 4, and 8 as induction therapy, followed by 360 mg subcutaneously (SC) at Week 12 and every 8 weeks thereafter as maintenance therapy. If efficacy diminishes 16 weeks or later after initiating maintenance therapy with the subcutaneous formulation of risankizumab, a single intravenous infusion of 1200 mg may be administered (rescue therapy).
Study summary
Crohn's disease is an inflammatory bowel disease characterized by relapses and remissions, causing lesions throughout the digestive tract and accompanied by diarrhea, abdominal pain, and nutritional disorders. In Japan particularly, the incidence of anal lesions is high, with approximately half of patients developing fistulas or abscesses, significantly impairing quality of life (QOL). For perianal fistulizing Crohn's disease (PFCD), combined treatment with surgical intervention (e.g., seton placement) and medical therapy centered on anti-TNF agents is standard. However, challenges remain regarding efficacy rates and evaluation criteria. Novel therapies such as stem cell therapy, JAK inhibitors, and IL-23 inhibitors are gaining attention. This study using risankizumab aims to be the first in Japan to comprehensively evaluate the therapeutic efficacy of PFCD using both clinical and MRI assessments, thereby contributing to future treatment standardization and guideline development.
Eligibility
Inclusion Criteria:
1. 15 years of age or older
2. Patients with an MRI-confirmed perianal fistula due to Crohn's disease
3. Patients with a draining anal fistula (maximum of 2 internal openings and maximum of 3 external openings) persisting for at least 2 weeks
4. Patients who have experienced inadequate response, diminished response, or intolerance to one or more of the following treatments in the past:
① Antibiotics (ciprofloxacin or metronidazole): Treatment lasting one month or longer.
② Immunomodulators (azathioprine, 6-mercaptopurine, or methotrexate): Treatment for 3 months or longer.
③ Advanced therapies (infliximab, adalimumab, vedolizumab, ustekinumab, and upadacitinib): Standard therapy administered for 14 weeks or longer as induction or maintenance therapy.
5. Patients who can agree to removal of the perianal seton by week 20 (week 20 ± 1 week) of administration, if patients already have setons inserted.
6. Patients with draining fistulas that were drained at least 6 weeks prior to enrollment.
7. Patients who have received a sufficient explanation regarding participation in this study, understood it fully, and provided their voluntary written consent, or patients whose legal representative received a sufficient explanation regarding participation in this study, understood it fully, and provided their voluntary written assent, if participating hospital/clinic requires.
Exclusion Criteria:
1. Patients with a rectovaginal fistula at baseline (excluding past rectovaginal fistulas)
2. Patients with severe rectal and/or anal stricture and/or severe proctitis (defined as the presence of large ulcers exceeding 0.5 cm in the rectum)
3. Patients with abscesses or fluid collections exceeding 2 cm
4. Patients for whom MRI is contraindicated
5. Patients with a history of risankizumab, mirikizumab, or guselkumab administration
6. Patients who are refractory to three or more prior lines of advanced therapy
7. Patients who are intolerant to two or more prior lines of advanced therapy
8. Patients previously treated with darvadstrocel
9. Patients with a colostomy or ileostomy
10. Patients with disease activity (CDAI) \> 400
11. Patients receiving systemic steroids
12. Patients requiring new treatment with immunomodulators or advanced therapies during the screening period
13. Patients undergoing cytapheresis
14. Patients with a history of malignancy (excluding carcinoma in situ)
15. Patients with concomitant uncontrolled liver disease, hematologic disease, gastrointestinal disease (excluding Crohn's disease), endocrine disease, pulmonary disease, cardiac disease, neurological disease, psychiatric disease, brain disease, or active infection
16. Patients who underwent major surgery or suffered severe trauma within the past 6 months
17. Patients who are breastfeeding, pregnant, or may be pregnant, or who plan to become pregnant during the study period
18. Patients who showed persistent positivity for HBsAg and HBV-PCR, or seropositivity for HCV and quantitative HCV-PCR within 6 months prior to the start of the screening period
19. Patients who received a live vaccine within 4 weeks prior to the start of risankizumab administration
20. Patients with active tuberculosis
21. Other patients deemed inappropriate for trial participation by the principal/ sub-investigator responsible
Primary outcome measure(s)
- The proportion of participants achieving combined fistula remission at Week 28 — at Week 28
To confirm the efficacy of risankizumab, a combined evaluation of clinical symptoms and objective MRI findings will be used.
Trial sites (4)
| Facility | City | Region | Status |
|---|
| Hyogo Medical University |
Nishinomiya |
Japan |
|
| Department of Coloproctology, Tokyo Yamate Medical Center |
Shinjuku-Ku |
Japan |
|
| Department of Inflammatory Bowel Disease (IBD), Yokohama Municipal Citizen's Hospital |
Yokohama |
Japan |
|
| Inflammatory Bowel Disease Center, YCU Medical Center, Yokohama City University |
Yokohama |
Japan |
|
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