A Study Testing How BI 655130 Works in Patients With Fistulizing Crohn's Disease

NCT03752970 | Completed Phase 2 Results DMC

• 2 other identifiers: 1368-00082017-003090-34
• Study Type: interventional
• Target: 27
• Locations: 8 countries
• Sites: 10

Brief Summary

This is a study in adults with Crohn's Disease who also have fistulas near the anus. The study has 2 parts. The first part is to find out more about what causes the fistulas. In this part of the study, tissue samples are taken from patients. The second part of the study tests whether a medicine called spesolimab (BI 655130) helps patients with Crohn's Disease. Participants get study medication for 24 weeks. The participants are put into 2 groups. It is decided by chance who gets into which group. One group gets an intravenous drip that contains spesolimab every 4 weeks. The other group gets a placebo drip every 4 weeks. The placebo drip looks like the spesolimab drip, but contains no medicine. The doctors regularly examine fistulas of the participants. The results of the fistula examinations are compared between the groups. The doctors also check the general health of the patients.

Conditions

Crohn Disease

Outcome Measures

Primary Outcomes (1)

• The Total Number of Deregulated Genes at Week 4

  The total number of deregulated genes based on biopsies from the inner fistula orifice at Week 4 comparing changes in gene expression from baseline between the two treatment groups. For each gene, a repeated measures linear regression model was utilized with treatment (BI 655130 or Placebo), visit (baseline, week 4), treatment by visit interaction as fixed effect and patient as a blocking factor. Changes will be quantified by log2 fold changes (FC) and associated False Discovery Rate (FDR) adjusted p-values. Genes will be considered deregulated if they fulfil the following criteria: * FDR adjusted p-value ≤ 0.05 * \|fold change\| ≥ 1.5 (\|log2 fold change\| ≥ 0.58)

  Biopsies taken at screening (Week -3) and at week 4 of treatment.

Secondary Outcomes (3)

• Number of Patients With Perianal Fistula Response at Week 12

  At baseline (day 1) and week 12 (day 85) of treatment.

• Number of Patients With Perianal Fistula Remission at Week 12

  At baseline (day 1) and week 12 (day 85) of treatment.

• Number of Patients With Combined Perianal Fistula Remission at Week 12

  At baseline (day 1) and week 12 (day 85) of treatment.

Study Arms (3)

Screening Cohort

NO INTERVENTION

Patients enrolled in the Screening Cohort did not receive study treatment. This was a feasibility phase for fistula preparation and seton placement to determine the tissue samples that were suitable for analysis of the primary endpoint in the Study Cohort.

Study Cohort - Placebo

PLACEBO COMPARATOR

Patients with perianal fistulising Crohn's disease received Placebo intravenously every 4 weeks (week 0, 4, 8). At week 12 achievement of combined perianal fistula remission was determined, patients without combined perianal fistula remission were switched to spesolimab and were treated with spesolimab 1200 milligram intravenously every 4 weeks (week 12, 16 and 20). Patients with combined perianal fistula remission remained on Placebo and were treated with placebo intravenously every 4 weeks (week 12, 16 and 20).

Drug: Spesolimab; Drug: Placebo

Study Cohort - Spesolimab

EXPERIMENTAL

Patients with perianal fistulising Crohn's disease received Spesolimab 1200 milligram intravenously every 4 weeks (week 0, 4, 8, 12, 16 and 20). At week 12 Placebo patients without combined perianal fistula remission were switched to spesolimab and were treated with spesolimab 1200 milligram intravenously every 4 weeks (week 12, 16 and 20).

Drug: Spesolimab

Interventions

Spesolimab DRUG

Spesolimab 1200 milligram intravenously every 4 weeks (week 0, 4, 8, 12, 16 and 20). At week 12 Placebo patients without combined perianal fistula remission were switched to spesolimab and were treated with spesolimab 1200 milligram intravenously every 4 weeks (week 12, 16 and 20).

Study Cohort - Placebo; Study Cohort - Spesolimab

Placebo DRUG

Placebo intravenously every 4 weeks (week 0, 4, 8). At week 12 achievement of combined perianal fistula remission was determined, patients without combined perianal fistula remission were switched to spesolimab and were treated with spesolimab 1200 milligram intravenously every 4 weeks (week 12, 16 and 20). Patients with combined perianal fistula remission remained on Placebo and were treated with placebo intravenously every 4 weeks (week 12, 16 and 20).

Study Cohort - Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years at date of signing informed consent
• Male or female patients. Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. Restrictions regarding women of childbearing potential. Restrictions regarding contraception for female patients are not applicable for Screening Cohort
• Diagnosis of clinical Crohn´s Disease ≥ 3 months prior to screening by clinical and endoscopic evidence and corroborated by a histopathology report
• Has ≥ 1 perianal active\* fistula(s) with clinical indication for seton drainage (≥ 4 weeks duration before enrolment, as a complication of CD) \*\*
• \* Criteria for Active Fistula: As per clinical evaluation: Presence of spontaneous drainage or drainage after gentle finger compression at the external openings \& as confirmed by radiological (MRI) exploration
• \*\* Patients who are screened with a seton drainage in place are eligible provided the drainage has not been in place for \> 3 months and the patient meets the rest of the eligibility criteria
• Absent, mild or moderate clinical activity with CDAI \< 250. CDAI is not applicable for Screening Cohort
• Demonstrated in the past inadequate fistula response or loss of response or have had unacceptable side effects with approved doses of at least one of the following compounds: immunosuppressive agents (e.g. thiopurines, methotrexate), TNFɑ antagonists (e.g. infliximab, adalimumab, certolizumab pegol; or respective biosimilars), vedolizumab, ustekinumab, azathioprine and / or antibiotics
• Patients with family history of colorectal cancer or personal history of increased colorectal cancer risk must have had a negative ileocolorectal cancer screening within \<1 year prior to screening per local guidance
• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial

You may not qualify if:

• Complications of Crohn's Disease such as symptomatic strictures, functional stenosis distal from fistula(s), short gut syndrome, or any other manifestation that might require surgery, could preclude the use of the PDAI and CDAI to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with BI 655130
• Rectovaginal fistulas
• Anticipated to require surgical intervention for CD including any fistula surgical procedures (except seton drainage)
• Has an abscess that the investigator feels requires drainage beyond fistula drainage with a seton (based on either clinical assessment or MRI)
• Any kind of bowel resection or diversion within 6 months or any other intraabdominal surgery within 3 months prior to screening.
• Ileostomy, colostomy or known fixed symptomatic stenosis of the intestine at screening
• Positive stool examinations for C. difficile or other intestinal pathogens \< 30 days prior to screening
• \-- Evidence of colonic mucosal dysplasia or colonic adenomas, unless properly removed (properly according to the investigator's assessment)
• Faecal Microbiota transplant (FMT) within 6 months prior to randomization
• Treatment with:
• any non-biologic medication (incl. cyclosporine, JAK inhibitors such as tofacitinib, tacrolimus, sirolimus, mycophenolate mofetile, S1P modulators, SMAD7 antisense inhibitors such as mongersen), other than those allowed per chapter 4.2.1 within 30 days prior to randomisation unless these patients show an undetectable plasma concentration
• any biologic treatment approved for CD other than anti-TNFα inhibitors within 8 weeks prior to randomization unless these patients show an undetectable plasma concentration
• any investigational or non-approved biologic for CD (including but not limited to IL-23 inhibitors) within 12 weeks prior to randomisation or etrolizumab within 8 weeks prior to randomization unless these patients show an undetectable plasma concentration
• rectal 5-ASA, rectal Tacrolimus, parenteral or rectal corticosteroids (incl. budesonide) within 2 weeks prior to randomisation
• any antibiotics within 1 week prior to randomisation

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (10)

AKH - Medical University of Vienna

Vienna, 1090, Austria

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Centre Hospitalier Universitaire de Liège

Liège, 4000, Belgium

Location

Herlev and Gentofte Hospital

Herlev, 2730, Denmark

Location

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Semmelweis University

Budapest, 1088, Hungary

Location

Amsterdam UMC, Locatie AMC

Amsterdam, 1105 AZ, Netherlands

Location

Inje University Haeundae Paik Hospital

Busan, 48108, South Korea

Location

Hospital Universitari de Girona Doctor Josep Trueta

Girona, 17007, Spain

Location

Related Publications (1)

• Lebwohl MG, Thoma C, Haeufel T. Spesolimab use in generalised pustular psoriasis flares - Authors' reply. Lancet. 2024 Aug 31;404(10455):847-848. doi: 10.1016/S0140-6736(24)01557-5. No abstract available.

  PMID: 39216969 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Crohn Disease

Interventions

spesolimab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Limitations and Caveats

For the primary endpoint, due to the limited number of evaluable samples from the curettage at baseline and at Week 4, curettage biopsies were not included in the gene expression analysis.

Results Point of Contact

• Title: Boehringer Ingelheim , Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2018
• First Posted: November 26, 2018
• Study Start: February 5, 2019
• Primary Completion: December 1, 2021
• Study Completion: July 4, 2022
• Last Updated: October 16, 2025
• Results First Posted: February 16, 2024

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); AU (1); HU (1); DE (2); DK (1); BE (2); KR (1); NL (1)