A Study Testing How BI 655130 Works in Patients With Fistulizing Crohn's Disease
Condition: Crohn Disease
MeSH terms: Crohn Disease
Intervention: Spesolimab; Placebo
Intervention description: 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).; 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).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion criteria

          -  18-75 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

          -  Further inclusion criteria apply

        Gastrointestinal Exclusion Criteria (Study cohort only)

          -  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

               -  any prior autologous or allogeneic, haematopoietic (HSC) or mesenchymal stem cell
                  (MSC) therapy

               -  any prior exposure to BI 655130

               -  any chronic use of NSAID within 2 weeks prior to randomisation (occasional use of
                  NSAIDs and acetaminophen for headache, arthritis, myalgias, menstrual cramps,
                  etc., and daily use of baby or low dose (81-162.5mg) aspirin for cardiovascular
                  prophylaxis are permitted)

               -  any life-attenuated vaccines within 6 weeks prior to randomization

        Infectious Disease Exclusion Criteria (Study cohort only)

          -  Increased risk of infectious complications (e.g. due to past organ or stem cell
             transplantation)

          -  Live or attenuated vaccination within 6 weeks prior to randomization

          -  Patients with a positive QuantiFERON TB test during screening are excluded, unless:

               -  Patient had previous diagnosis of active or latent TB and has completed
                  appropriate treatment per local practice/guidelines within the last 3 years and
                  at least 6 months before first administration of trial medication under this
                  protocol (patients may be re-screened once to meet this criterion)

               -  Patients with suspected false positive or indeterminate QuantiFERON TB result may
                  be re-tested once

               -  If Quantiferon not available or providing indeterminate results after repeat
                  testing : A tuberculin skin test reaction ≥10mm (≥5mm if receiving ≥15mg/d
                  prednisone or its equivalent)

          -  Relevant chronic or acute infections including active tuberculosis, human
             immunodeficiency virus (HIV) infection or viral hepatitis. A patient can be
             re-screened if the patient was treated and is cured from the acute infection.

        General Exclusion Criteria (Study cohort only)

          -  Any documented active or suspected malignancy or history of malignancy within 5 years
             prior to screening, except appropriately treated basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, or in situ carcinoma of uterine cervix.

          -  Major surgery (major according to the investigator's assessment) performed within 12
             weeks prior to randomization or planned during study conduct, e.g. hip replacement.

          -  Pathological safety lab parameters: haemoglobin < 8 g/dL, total white blood count
             (WBC) < 3000 cells/μl, neutrophils < 1000 cells/μl, thrombocytes < 100.000/μl,
             creatinine ≥ 2 mg/dL, total bilirubin > 2 x ULN with ratio of direct/indirect >1
             (patients with Gilbert's syndrome are not excluded), Alkaline Phosphatase >3 x ULN.

          -  Patients who must or wish to continue the intake of restricted medications or any drug
             considered likely to interfere with the safe conduct of the trial

          -  Previous enrolment in this trial (exception: patients of screening cohort may be
             enrolled in study cohort)

          -  Currently enrolled in another investigational device or drug trial

          -  Women who are pregnant, nursing, or who plan to become pregnant in the trial

          -  Evidence of a current or previous disease, medical condition (including chronic
             alcohol or drug abuse) other than Crohn´s disease, surgical procedure, medical
             examination finding (including vital signs and electrocardiogram (ECG)), or laboratory
             value at the screening visit outside the reference range that in the opinion of the
             investigator is clinically significant and would make the study participant unreliable
             to adhere to the protocol or to complete the trial, compromise the safety of the
             patient, or compromise the quality of the data

          -  History of allergy/hypersensitivity to the systemically administered trial medication
             agent or its excipients or to contrast media