Crohn's Disease, Perianal Fistula
Conditions
Keywords
Perianal Fistula, Perianal Fistulizing Crohn's Disease, Mirikizumab, Interleukin-23 inhibitor, Magnetic resonance imaging, Crohn's Disease
Brief summary
This Phase 4, single-arm, open-label study will evaluate the effectiveness and safety of mirikizumab combined with surgical curettage and closure in adults with active perianal fistulizing Crohn's disease. Fifty participants with complex draining fistulas will undergo staged surgical management followed by mirikizumab induction and maintenance therapy. The primary endpoint is combined clinical remission and radiologic response at Week 24. Participants will be followed through Week 48.
Detailed description
Perianal fistulizing Crohn disease is a severe manifestation of Crohn disease associated with persistent fistula drainage, impaired quality of life, and substantial morbidity. Although biologic therapies have improved outcomes, durable fistula healing remains uncommon, and optimal treatment strategies continue to be defined. Mirikizumab is an interleukin-23 p19 antagonist approved for the treatment of moderately to severely active Crohn disease. Surgical management, including fistula tract curettage and closure of the internal opening, has demonstrated favorable outcomes when incorporated into multidisciplinary treatment approaches for complex perianal fistulas. This Phase 4, multicenter, single-arm, open-label study will enroll approximately 50 adults with active complex perianal fistulizing Crohn disease. Participants will undergo examination under anesthesia with fistula tract curettage and seton placement prior to initiation of mirikizumab induction therapy. After 8 to 10 weeks of treatment, participants will undergo repeat examination under anesthesia with seton removal, repeat curettage, and closure of the internal fistula opening. Participants will receive mirikizumab induction followed by maintenance therapy and will be followed for 48 weeks. Pelvic MRI will be performed at Weeks 12, 24, and 48 and evaluated using standardized MAGNIFI-CD and TOpCLASS criteria. Clinical assessments, patient-reported outcome measures, safety evaluations, and quality-of-life assessments will be collected throughout the study. The primary objective is to evaluate the proportion of participants achieving combined clinical remission and radiologic response at Week 24. Secondary objectives include evaluation of clinical remission, radiologic remission, fistula healing, quality of life, disease activity, and safety through Week 48.
Interventions
DRUGMirikizumab
Mirikizumab is administered as a 900 mg intravenous infusion at Weeks 0, 4, and 8, followed by a 300 mg subcutaneous maintenance injection beginning at Week 12 and every 4 weeks thereafter through the end of the study.
PROCEDUREFistula Tract Curettage and Closure
Participants undergo an initial examination under anesthesia with fistula tract curettage and seton placement before initiation of mirikizumab therapy. After 8 to 10 weeks of induction therapy, participants undergo a second examination under anesthesia with seton removal, repeat fistula tract curettage, and closure of the internal fistula opening(s).
Sponsors
Icahn School of Medicine at Mount Sinai
Eli Lilly and Company
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label, single-arm study. All participants and study personnel are aware that participants receive mirikizumab in combination with staged surgical curettage and closure. No masking or blinding is performed.
Intervention model description
All participants are assigned to a single treatment group receiving mirikizumab in combination with staged surgical curettage and closure for active perianal fistulizing Crohn's disease.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults ≥18 years * Diagnosis of Crohn disease for at least 3 months * Active draining complex perianal fistula * Able to provide informed consent
Exclusion criteria
* Rectovaginal fistula * Only low intersphincteric or submucosal fistulas * Severe proctitis preventing surgical closure * Stoma * Active tuberculosis * Active hepatitis B * Active serious infection * Pregnancy * Concurrent investigational drug trial * MRI contraindication * Additional laboratory exclusions as specified in the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving combined clinical remission and radiologic response | Week 24 | Proportion of participants achieving combined clinical remission and radiologic response. Clinical remission is defined as complete closure of all treated external fistula openings without spontaneous drainage or drainage upon gentle finger compression and without development of new fistulas or abscesses greater than 1 cm. Radiologic response is defined using MAGNIFI-CD criteria as greater than 50% reduction in MAGNIFI-CD score together with improvement in fibrosis-to-fluid ratio compared with baseline MRI. The MAGNIFI-CD is an MRI-based composite index that assesses perianal fistulizing Crohn disease activity using six weighted domains, including fistula complexity, tract length, fistula composition, tract enhancement, extension, and inflammatory mass/abscess. Total scores range from 0 to 25, with higher scores indicating greater disease activity and lower scores indicating improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving combined clinical remission and radiologic response | 48 week | Proportion of participants achieving combined clinical remission and radiologic response. Clinical remission is defined as complete closure of all treated external fistula openings without spontaneous drainage or drainage upon gentle finger compression and without development of new fistulas or abscesses greater than 1 cm. Radiologic response is defined using MAGNIFI-CD criteria as greater than 50% reduction in MAGNIFI-CD score together with improvement in fibrosis-to-fluid ratio compared with baseline MRI. The MAGNIFI-CD is an MRI-based composite index that assesses perianal fistulizing Crohn disease activity using six weighted domains, including fistula complexity, tract length, fistula composition, tract enhancement, extension, and inflammatory mass/abscess. Total scores range from 0 to 25, with higher scores indicating greater disease activity and lower scores indicating improvement. |
Countries
United States
Contacts
CONTACTSerre-Yu Wong, MD, PhD
PRINCIPAL_INVESTIGATORSerre-Yu Wong, MD, PhD
Icahn School of Medicine at Mount Sinai
PRINCIPAL_INVESTIGATORParakkal Deepak, MBBS, MS
Washington University School of Medicine
Outcome results
None listed