<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03752970</url>
  </required_header>
  <id_info>
    <org_study_id>1368-0008</org_study_id>
    <secondary_id>2017-003090-34</secondary_id>
    <nct_id>NCT03752970</nct_id>
  </id_info>
  <brief_title>A Study Testing How BI 655130 Works in Patients With Fistulizing Crohn's Disease</brief_title>
  <official_title>Mechanism of Action and Clinical Effect of BI 655130 in Patients With Fistulizing Crohn's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a study in adults with Crohn's Disease who also have fistulas near the anus. The&#xD;
      study has 2 parts. The first part is to find out more about what causes the fistulas. In this&#xD;
      part of the study, tissue samples are taken from patients. The second part of the study tests&#xD;
      whether a medicine called spesolimab (BI 655130) helps patients with Crohn's Disease.&#xD;
&#xD;
      Participants get study medication for 24 weeks. The participants are put into 2 groups. It is&#xD;
      decided by chance who gets into which group. One group gets an intravenous drip that contains&#xD;
      spesolimab every 4 weeks. The other group gets a placebo drip every 4 weeks. The placebo drip&#xD;
      looks like the spesolimab drip, but contains no medicine.&#xD;
&#xD;
      The doctors regularly examine fistulas of the participants. The results of the fistula&#xD;
      examinations are compared between the groups. The doctors also check the general health of&#xD;
      the patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 5, 2019</start_date>
  <completion_date type="Actual">July 4, 2022</completion_date>
  <primary_completion_date type="Actual">December 1, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total number of deregulated genes</measure>
    <time_frame>Week 4</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with perianal fistula response</measure>
    <time_frame>Week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with perianal fistula remission</measure>
    <time_frame>Week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with combined perianal fistula remission</measure>
    <time_frame>Week 12</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Crohn Disease</condition>
  <arm_group>
    <arm_group_label>Spesolimab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Spesolimab</intervention_name>
    <description>Solution for infusion</description>
    <arm_group_label>Spesolimab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Solution for infusion</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  18-75 years at date of signing informed consent&#xD;
&#xD;
          -  Male or female patients. Women of childbearing potential (WOCBP)1 must be ready and&#xD;
             able to use highly effective methods of birth control per ICH M3 (R2) that result in a&#xD;
             low failure rate of less than 1% per year when used consistently and correctly.&#xD;
             Restrictions regarding women of childbearing potential. Restrictions regarding&#xD;
             contraception for female patients are not applicable for Screening Cohort&#xD;
&#xD;
          -  Diagnosis of clinical Crohn´s Disease ≥ 3 months prior to screening by clinical and&#xD;
             endoscopic evidence and corroborated by a histopathology report&#xD;
&#xD;
          -  Has ≥ 1 perianal active* fistula(s) with clinical indication for seton drainage (≥ 4&#xD;
             weeks duration before enrolment, as a complication of CD) **&#xD;
&#xD;
             * Criteria for Active Fistula: As per clinical evaluation: Presence of spontaneous&#xD;
             drainage or drainage after gentle finger compression at the external openings &amp; as&#xD;
             confirmed by radiological (MRI) exploration&#xD;
&#xD;
             ** Patients who are screened with a seton drainage in place are eligible provided the&#xD;
             drainage has not been in place for &gt; 3 months and the patient meets the rest of the&#xD;
             eligibility criteria&#xD;
&#xD;
          -  Absent, mild or moderate clinical activity with CDAI &lt; 250. CDAI is not applicable for&#xD;
             Screening Cohort&#xD;
&#xD;
          -  Demonstrated in the past inadequate fistula response or loss of response or have had&#xD;
             unacceptable side effects with approved doses of at least one of the following&#xD;
             compounds: Immunesuppressive agents (e.g. thiopurines, methotrexate), TNFɑ antagonists&#xD;
             (e.g. infliximab, adalimumab, certolizumab pegol; or respective biosimilars),&#xD;
             vedolizumab, ustekinumab, azathioprine and / or antibiotics&#xD;
&#xD;
          -  Patients with family history of colorectal cancer or personal history of increased&#xD;
             colorectal cancer risk must have had a negative ileocolorectal cancer screening within&#xD;
             &lt;1 year prior to screening per local guidance&#xD;
&#xD;
          -  Signed and dated written informed consent in accordance with ICH-GCP and local&#xD;
             legislation prior to admission to the trial&#xD;
&#xD;
          -  Further inclusion criteria apply&#xD;
&#xD;
        Gastrointestinal Exclusion Criteria (Study cohort only)&#xD;
&#xD;
          -  Complications of Crohn's Disease such as symptomatic strictures, functional stenosis&#xD;
             distal from fistula(s), short gut syndrome, or any other manifestation that might&#xD;
             require surgery, could preclude the use of the PDAI and CDAI to assess response to&#xD;
             therapy, or would possibly confound the evaluation of benefit from treatment with BI&#xD;
             655130&#xD;
&#xD;
          -  Rectovaginal fistulas&#xD;
&#xD;
          -  Anticipated to require surgical intervention for CD including any fistula surgical&#xD;
             procedures (except seton drainage)&#xD;
&#xD;
          -  Has an abscess that the investigator feels requires drainage beyond fistula drainage&#xD;
             with a seton (based on either clinical assessment or MRI)&#xD;
&#xD;
          -  Any kind of bowel resection or diversion within 6 months or any other intraabdominal&#xD;
             surgery within 3 months prior to screening.&#xD;
&#xD;
          -  Ileostomy, colostomy or known fixed symptomatic stenosis of the intestine at screening&#xD;
&#xD;
          -  Positive stool examinations for C. difficile or other intestinal pathogens &lt; 30 days&#xD;
             prior to screening&#xD;
&#xD;
             -- Evidence of colonic mucosal dysplasia or colonic adenomas, unless properly removed&#xD;
             (properly according to the investigator's assessment)&#xD;
&#xD;
          -  Faecal Microbiota transplant (FMT) within 6 months prior to randomization&#xD;
&#xD;
          -  Treatment with:&#xD;
&#xD;
               -  any non-biologic medication (incl. cyclosporine, JAK inhibitors such as&#xD;
                  tofacitinib, tacrolimus, sirolimus, mycophenolate mofetile, S1P modulators, SMAD7&#xD;
                  antisense inhibitors such as mongersen), other than those allowed per chapter&#xD;
                  4.2.1 within 30 days prior to randomisation unless these patients show an&#xD;
                  undetectable plasma concentration&#xD;
&#xD;
               -  any biologic treatment approved for CD other than anti-TNFα inhibitors within 8&#xD;
                  weeks prior to randomization unless these patients show an undetectable plasma&#xD;
                  concentration&#xD;
&#xD;
               -  any investigational or non-approved biologic for CD (including but not limited to&#xD;
                  IL-23 inhibitors) within 12 weeks prior to randomisation or etrolizumab within 8&#xD;
                  weeks prior to randomization unless these patients show an undetectable plasma&#xD;
                  concentration&#xD;
&#xD;
               -  rectal 5-ASA, rectal Tacrolimus, parenteral or rectal corticosteroids (incl.&#xD;
                  budesonide) within 2 weeks prior to randomisation&#xD;
&#xD;
               -  any antibiotics within 1 week prior to randomisation&#xD;
&#xD;
               -  any prior autologous or allogeneic, haematopoietic (HSC) or mesenchymal stem cell&#xD;
                  (MSC) therapy&#xD;
&#xD;
               -  any prior exposure to BI 655130&#xD;
&#xD;
               -  any chronic use of NSAID within 2 weeks prior to randomisation (occasional use of&#xD;
                  NSAIDs and acetaminophen for headache, arthritis, myalgias, menstrual cramps,&#xD;
                  etc., and daily use of baby or low dose (81-162.5mg) aspirin for cardiovascular&#xD;
                  prophylaxis are permitted)&#xD;
&#xD;
               -  any life-attenuated vaccines within 6 weeks prior to randomization&#xD;
&#xD;
        Infectious Disease Exclusion Criteria (Study cohort only)&#xD;
&#xD;
          -  Increased risk of infectious complications (e.g. due to past organ or stem cell&#xD;
             transplantation)&#xD;
&#xD;
          -  Live or attenuated vaccination within 6 weeks prior to randomization&#xD;
&#xD;
          -  Patients with a positive QuantiFERON TB test during screening are excluded, unless:&#xD;
&#xD;
               -  Patient had previous diagnosis of active or latent TB and has completed&#xD;
                  appropriate treatment per local practice/guidelines within the last 3 years and&#xD;
                  at least 6 months before first administration of trial medication under this&#xD;
                  protocol (patients may be re-screened once to meet this criterion)&#xD;
&#xD;
               -  Patients with suspected false positive or indeterminate QuantiFERON TB result may&#xD;
                  be re-tested once&#xD;
&#xD;
               -  If Quantiferon not available or providing indeterminate results after repeat&#xD;
                  testing : A tuberculin skin test reaction ≥10mm (≥5mm if receiving ≥15mg/d&#xD;
                  prednisone or its equivalent)&#xD;
&#xD;
          -  Relevant chronic or acute infections including active tuberculosis, human&#xD;
             immunodeficiency virus (HIV) infection or viral hepatitis. A patient can be&#xD;
             re-screened if the patient was treated and is cured from the acute infection.&#xD;
&#xD;
        General Exclusion Criteria (Study cohort only)&#xD;
&#xD;
          -  Any documented active or suspected malignancy or history of malignancy within 5 years&#xD;
             prior to screening, except appropriately treated basal cell carcinoma of the skin,&#xD;
             squamous cell carcinoma of the skin, or in situ carcinoma of uterine cervix.&#xD;
&#xD;
          -  Major surgery (major according to the investigator's assessment) performed within 12&#xD;
             weeks prior to randomization or planned during study conduct, e.g. hip replacement.&#xD;
&#xD;
          -  Pathological safety lab parameters: haemoglobin &lt; 8 g/dL, total white blood count&#xD;
             (WBC) &lt; 3000 cells/μl, neutrophils &lt; 1000 cells/μl, thrombocytes &lt; 100.000/μl,&#xD;
             creatinine ≥ 2 mg/dL, total bilirubin &gt; 2 x ULN with ratio of direct/indirect &gt;1&#xD;
             (patients with Gilbert's syndrome are not excluded), Alkaline Phosphatase &gt;3 x ULN.&#xD;
&#xD;
          -  Patients who must or wish to continue the intake of restricted medications or any drug&#xD;
             considered likely to interfere with the safe conduct of the trial&#xD;
&#xD;
          -  Previous enrolment in this trial (exception: patients of screening cohort may be&#xD;
             enrolled in study cohort)&#xD;
&#xD;
          -  Currently enrolled in another investigational device or drug trial&#xD;
&#xD;
          -  Women who are pregnant, nursing, or who plan to become pregnant in the trial&#xD;
&#xD;
          -  Evidence of a current or previous disease, medical condition (including chronic&#xD;
             alcohol or drug abuse) other than Crohn´s disease, surgical procedure, medical&#xD;
             examination finding (including vital signs and electrocardiogram (ECG)), or laboratory&#xD;
             value at the screening visit outside the reference range that in the opinion of the&#xD;
             investigator is clinically significant and would make the study participant unreliable&#xD;
             to adhere to the protocol or to complete the trial, compromise the safety of the&#xD;
             patient, or compromise the quality of the data&#xD;
&#xD;
          -  History of allergy/hypersensitivity to the systemically administered trial medication&#xD;
             agent or its excipients or to contrast media&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>AKH - Medical University of Vienna</name>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire de Liège</name>
      <address>
        <city>Liège</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Herlev and Gentofte Hospital</name>
      <address>
        <city>Herlev</city>
        <zip>2730</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Erlangen</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Ulm</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Semmelweis University</name>
      <address>
        <city>Budapest</city>
        <zip>1088</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inje University Haeundae Paik Hospital</name>
      <address>
        <city>Busan</city>
        <zip>48108</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amsterdam UMC, Locatie AMC</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari de Girona Doctor Josep Trueta</name>
      <address>
        <city>Girona</city>
        <zip>17007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Denmark</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Spain</country>
  </location_countries>
  <link>
    <url>https://www.mystudywindow.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>November 22, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 26, 2018</study_first_posted>
  <last_update_submitted>July 7, 2022</last_update_submitted>
  <last_update_submitted_qc>July 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing clinical_submission_documents.html to request access to the clinical study documents regarding this study, and upon a signed &quot;Document Sharing Agreement&quot;. Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.&#xD;
The data shared are the raw clinical study data sets.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.</ipd_time_frame>
    <ipd_access_criteria>For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.</ipd_access_criteria>
    <ipd_url>https://www.mystudywindow.com/msw/datasharing</ipd_url>
  </patient_data>
  <pending_results>
    <submitted>June 30, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03752970
org study id: 1368-0008
secondary id: 2017-003090-34
nct id: NCT03752970
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Total number of deregulated genes
time frame: Week 4
measure: Proportion of patients with perianal fistula response
time frame: Week 12
measure: Proportion of patients with perianal fistula remission
time frame: Week 12
measure: Proportion of patients with combined perianal fistula remission
time frame: Week 12
arm group label: Spesolimab
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Spesolimab
description: Solution for infusion
arm group label: Spesolimab
intervention type: Drug
intervention name: Placebo
description: Solution for infusion
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Belgium
country: Denmark
country: Germany
country: Hungary
country: Korea, Republic of
country: Netherlands
country: Spain
url: https://www.mystudywindow.com
description: Related Info
responsible party type: Sponsor
mesh term: Crohn Disease
sharing ipd: Yes
ipd description: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing clinical_submission_documents.html to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
The data shared are the raw clinical study data sets.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
ipd access criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
ipd url: https://www.mystudywindow.com/msw/datasharing
submitted: June 30, 2023