<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/NCT03279081</url>
  </required_header>
  <id_info>
    <org_study_id>Cx601-0303</org_study_id>
    <secondary_id>2017-000725-12</secondary_id>
    <nct_id>NCT03279081</nct_id>
  </id_info>
  <brief_title>Study to Assess Efficacy and Safety of Cx601, Adult Allogeneic Expanded Adipose-derived Stem Cells (eASC) for the Treatment of Complex Perianal Fistula(s) in Participants With Crohn's Disease (CD)</brief_title>
  <acronym>ADMIRE-CD-II</acronym>
  <official_title>A Phase-III, Randomized, Double-blind, Parallel-group, Placebo-controlled, International, Multicentre Study to Assess Efficacy and Safety of Cx601, Adult Allogeneic Expanded Adipose-derived Stem Cells (eASC) for the Treatment of Complex Perianal Fistula(s) in Patients With Crohn's Disease Over a Period of 24 Weeks and a Follow-up Period up to 52 Weeks</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tigenix S.A.U.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the combined remission of complex perianal fistulas,&#xD;
      defined as the clinical assessment at Week 24 of closure of all treated external openings&#xD;
      that were draining at baseline despite gentle finger compression, and absence of collections&#xD;
      greater than (&gt;) 2 centimeter (cm) (in at least 2 dimensions) confirmed by blinded central&#xD;
      magnetic resonance imaging (MRI) assessment at Week 24.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is to assess the efficacy and safety of Cx601, eASC, for the treatment of complex&#xD;
      perianal fistulas in participants with Crohn's disease.&#xD;
&#xD;
      The study will randomize approximately 554 participants.&#xD;
&#xD;
        -  Cx601 eASCs intralesional injection&#xD;
&#xD;
        -  Placebo - Cx601 placebo-matching eASCs intralesional injection&#xD;
&#xD;
      Study treatments will be allocated, on a 1:1 ratio, by central randomization through&#xD;
      interactive web response system (IWRS). The study will follow an add-on design, participants&#xD;
      receiving any ongoing concomitant medical treatment, at stable doses at the time of&#xD;
      screening, for the CD will be allowed to continue it throughout the study.&#xD;
&#xD;
      The primary efficacy analysis, will be conducted at Week 24 timepoint. The double blind&#xD;
      design will be maintained up to Week 52 (both participant and investigator) by a specific&#xD;
      blinding for study treatment administration and for evaluating its efficacy.&#xD;
&#xD;
      This multicenter trial will be conducted globally across 150 centers. The overall time to&#xD;
      participate in this study is approximately 5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Actual">July 26, 2023</completion_date>
  <primary_completion_date type="Actual">January 23, 2023</primary_completion_date>
  <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants with Combined Remission at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <description>Combined Remission is defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression and absence of collection(s) &gt;2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by blinded central MRI assessment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Clinical Remission at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <description>Clinical remission is defined as closure of all treated external openings that were draining at baseline despite gentle finger compression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Clinical Remission up to Week 24</measure>
    <time_frame>From the treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed (up to Week 24)</time_frame>
    <description>Time to clinical remission is defined as the time from treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Clinical Response at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <description>Clinical response is defined as closure of at least 50 percent (%) of all treated external openings that were draining at baseline despite gentle finger compression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Clinical Response up to Week 24</measure>
    <time_frame>From treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression, as clinically assessed (up to Week 24)</time_frame>
    <description>Time to clinical response is defined as the time from treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression, as clinically assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Combined Remission at Week 52</measure>
    <time_frame>Week 52</time_frame>
    <description>Combined Remission is defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of collections &gt;2 cm (in at least 2 dimensions) confirmed by blinded central MRI assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Clinical Remission at Week 52</measure>
    <time_frame>Week 52</time_frame>
    <description>Clinical remission is defined as closure of all treated external openings that were draining at baseline despite gentle finger compression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Clinical Response at Week 52</measure>
    <time_frame>Week 52</time_frame>
    <description>Clinical response is defined as closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Clinical Remission up to Week 52</measure>
    <time_frame>From treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed (up to Week 52)</time_frame>
    <description>Time to clinical remission is defined as the time from treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Clinical Response up to Week 52</measure>
    <time_frame>From treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed (up to Week 52)</time_frame>
    <description>Time to clinical response is defined as time from treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Relapse from Week 24 Combined Remission</measure>
    <time_frame>Week 24</time_frame>
    <description>Relapse is defined as reopening of any of the treated fistulas external openings with active drainage as clinically assessed, or the development of a perianal fluid collection &gt;2 cm of the treated perianal fistula confirmed by centrally read MRI assessment in participants who were in combined remission at week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs)</measure>
    <time_frame>Week 24 and Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With TEAEs Related to Vital Sign Parameters</measure>
    <time_frame>Week 24 and Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With TEAEs Related to Clinical Laboratory Parameters</measure>
    <time_frame>Week 24 and Week 52</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">569</enrollment>
  <condition>Crohn's Disease</condition>
  <arm_group>
    <arm_group_label>Cx601</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cx601 eASCs 120 million cells (5 million cells per milliliter [mL]) will be administered once by intralesional injection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>CX601 placebo-matching eASCs cells will be administered once by intralesional administration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cx601</intervention_name>
    <description>Cx601 eASCs intralesional injection.</description>
    <arm_group_label>Cx601</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Cx601 placebo-matching eASCs intralesional injection.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent.&#xD;
&#xD;
          2. Participants of either gender greater than or equal to (&gt;=) 18 years and less than or&#xD;
             equal to (&lt;=) 75 years of age.&#xD;
&#xD;
          3. Participants with CD diagnosed at least 6 months prior to Screening visit in&#xD;
             accordance with accepted clinical, endoscopic, histological and/or radiological&#xD;
             criteria.&#xD;
&#xD;
          4. Presence of complex perianal fistula(s) with a maximum of 2 internal openings and a&#xD;
             maximum of 3 external openings based on clinical assessment; a central reading of a&#xD;
             locally performed contrast enhanced (gadolinium) pelvic MRI will be performed to&#xD;
             confirm location of the fistula and potential associated perianal abscess(es).&#xD;
             Fistula(s) must have been draining for at least 6 weeks prior to Screening visit.&#xD;
             Actively draining simple subcutaneous fistula(s), at the time of Screening visit, are&#xD;
             not allowed in this study. A complex perianal fistula is defined as a fistula that&#xD;
             meets one or more of the following criteria :&#xD;
&#xD;
               -  High inter-sphincteric, high trans-sphincteric, extra-sphincteric or&#xD;
                  suprasphincteric.&#xD;
&#xD;
               -  Presence of &gt;=2 external openings.&#xD;
&#xD;
               -  Associated perianal abscess(es). Note: Abscesses that are larger than 2 cm at&#xD;
                  least 2 dimensions on MRI must be confirmed to have been drained adequately by&#xD;
                  the surgeon during the preparation curettage in order to be eligible.&#xD;
&#xD;
          5. Clinically controlled, nonactive or mildly active CD, during the last six months prior&#xD;
             to Screening visit with:&#xD;
&#xD;
               -  A patient reported outcomes (PRO-2) score &lt;14 at Screening, AND&#xD;
&#xD;
               -  A colonoscopy documenting the absence of ulcers larger than 0.5 cm in the colonic&#xD;
                  mucosa:&#xD;
&#xD;
                  - If colonoscopy data are not available within 6 months prior to Screening:&#xD;
&#xD;
               -  A simple endoscopic score for Crohn's Disease (SES-CD) &lt;=6 with absence of rectal&#xD;
                  ulcers larger than 0.5 cm must be documented in a colonoscopy performed at&#xD;
                  Screening before randomization.&#xD;
&#xD;
                  - If colonoscopy data are available within 6 months prior to Screening, the&#xD;
                  following must be documented, otherwise a new colonoscopy (as above) will be&#xD;
                  mandatory:&#xD;
&#xD;
               -  The absence of ulcers larger than 0.5 cm in the colonic mucosa AND&#xD;
&#xD;
               -  the improvement or no worsening in abdominal pain and/or in the diarrhea,&#xD;
                  sustained for one week or more, since the last colonoscopy was performed in the&#xD;
                  clinical records until Screening visit.&#xD;
&#xD;
             AND&#xD;
&#xD;
             o No hemoglobin decrease &gt;=2.0 gram per deciliter (g/dL) or an unexplained rising&#xD;
             C-reactive protein (CRP), &gt; 5.0 milligram per liter (mg/L) to a concentration above&#xD;
             the referenced upper limit of normal (ULN) (unless the rise is due to a known process&#xD;
             other than luminal Crohn's Disease), since the last colonoscopy was performed as&#xD;
             compared to results during the Screening visit.&#xD;
&#xD;
             AND&#xD;
&#xD;
             o no initiation or intensification of treatment with corticosteroids,&#xD;
             immunosuppressants or monoclonal antibodies (mAbs) dose regimen since the last&#xD;
             endoscopy up to Screening visit.&#xD;
&#xD;
          6. Participants whose perianal fistulas were previously treated and have shown an&#xD;
             inadequate response or a loss of response while they were receiving either an&#xD;
             immunosuppressive agent or tumour necrosis factor (TNF)-alpha antagonist or&#xD;
             vedolizumab or ustekinumab, or having documented intolerance to any of these&#xD;
             treatments administered at least at approved or recommended doses during the minimum&#xD;
             period mentioned:&#xD;
&#xD;
               -  Immunosuppressive agents: at least 3 months treatment with azathioprine (2-3&#xD;
                  milligram per kilogram per day [mg/kg/day]), 6-mercaptopurine (1-1.5 mg/kg/day),&#xD;
                  or subcutaneous/intramuscular methotrexate (25 mg/week) prior to Screening for&#xD;
                  the study.&#xD;
&#xD;
               -  TNFalpha antagonists:&#xD;
&#xD;
               -  Infliximab: at least 14 weeks treatment at the approved doses for induction&#xD;
                  and/or maintenance in Crohn´s disease prior to screening for the study. For&#xD;
                  induction: 1 intravenous dose of 5 milligram per kilogram (mg/kg) followed by the&#xD;
                  same dose 2 and 6 weeks after. For maintenance: 5-10 mg/kg intravenously every 8&#xD;
                  weeks, or more frequently.&#xD;
&#xD;
               -  Adalimumab: at least 14 weeks treatment at the approved doses for induction&#xD;
                  and/or maintenance in Crohn's disease prior to screening for the study. For&#xD;
                  induction: 1 subcutaneous dose of 160 milligram (mg), followed by 80 mg 2 weeks&#xD;
                  after. For maintenance: 40 mg subcutaneously every other week, or weekly.&#xD;
&#xD;
               -  Certolizumab l: at least 14 weeks treatment at the approved doses for induction&#xD;
                  and/or maintenance in Crohn´s disease prior to screening for the study. For&#xD;
                  induction: 1 subcutaneous dose of 400 mg, followed by the same dose 2 and 4 weeks&#xD;
                  after. For maintenance: 400 mg subcutaneously every 2 to 4 weeks.&#xD;
&#xD;
               -  Anti-integrin: at least 14 weeks treatment of the approved dose for induction&#xD;
                  and/or maintenance in Crohn´s disease prior to screening for the study. For&#xD;
                  induction: Vedolizumab 300 mg. For maintenance: Vedolizumab 300 mg every 4 to 8&#xD;
                  weeks.&#xD;
&#xD;
               -  Anti-interleukin (IL)-12/23: at least 16 weeks treatment of the approved dose in&#xD;
                  Crohn´s disease prior to screening for the study. For induction: Ustekinumab,&#xD;
                  approximately 6mg/kg intravenously initially then followed by 90 mg&#xD;
                  subcutaneously every 8 weeks.&#xD;
&#xD;
          7. Women of childbearing potential (WCBP) must have negative serum pregnancy test at&#xD;
             screening (sensitive to 25 international units [IU] human chorionic gonadotropin&#xD;
             [hCG]). Both WCBP or male participants participating in this study, with a WCBP as&#xD;
             partner, must agree to use an adequate method of contraception during the entire&#xD;
             duration of the study. An adequate method of contraception is defined as complete,&#xD;
             non-periodic sexual abstinence (refraining from heterosexual intercourse),&#xD;
             single-barrier method, vasectomy, adequate hormonal contraception (to have started at&#xD;
             least 7 days prior to Screening visit), or an intra-uterine device (to have been in&#xD;
             place for at least 2 months prior to Screening visit).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concomitant rectovaginal or rectovesical fistula(s).&#xD;
&#xD;
          2. Participant naïve to prior specific medical treatment for complex perianal fistula(s)&#xD;
             including immunosuppressant (IS) or anti-TNFs.&#xD;
&#xD;
          3. Presence of a perianal collection &gt;2 cm in at least two dimensions on the central&#xD;
             reading MRI at Screening visit that was not adequately drained as confirmed by the&#xD;
             surgeon during the preparation procedure (week -3 to day 0).&#xD;
&#xD;
          4. Severe rectal and/or anal stenosis and/or severe proctitis (defined as the presence of&#xD;
             large &gt;0.5 cm ulcers in the rectum) that make impossible to follow the surgery&#xD;
             procedure manual.&#xD;
&#xD;
          5. Participant with diverting stomas.&#xD;
&#xD;
          6. Active, uncontrolled infection requiring parenteral antibiotics.&#xD;
&#xD;
          7. Participant with ongoing systemic or rectal steroids for CD in the last 2 weeks prior&#xD;
             to the Preparation visit.&#xD;
&#xD;
          8. Participants with major alteration on any of the following laboratory tests or&#xD;
             increased risk for the surgical procedure:&#xD;
&#xD;
               -  Serum creatinine levels &gt;1.5 times the ULN&#xD;
&#xD;
               -  Total bilirubin &gt;1.5 ULN&#xD;
&#xD;
               -  Aspartate Transaminase (AST)/ Alanine Transaminase (ALT) &gt;3 times ULN&#xD;
&#xD;
               -  Hemoglobin &lt;10.0 g/dL&#xD;
&#xD;
               -  Platelets &lt;75.0*10^9/L&#xD;
&#xD;
               -  Albuminemia &lt;3.0 g/dL&#xD;
&#xD;
          9. Suspected or documented infectious enterocolitis within two weeks prior to Screening&#xD;
             visit.&#xD;
&#xD;
         10. Any prior invasive malignancy diagnosed within the last 5 years prior to Screening&#xD;
             visit. Participants with basal-cell carcinoma of the skin completely resected outside&#xD;
             the perineal region can be included.&#xD;
&#xD;
         11. Current or recent (within 6 months prior to the Screening visit) history of severe,&#xD;
             progressive, and/or uncontrolled hepatic, haematological, gastrointestinal (GI) (other&#xD;
             than CD), renal, endocrine, pulmonary, cardiac, neurological or psychiatric disease&#xD;
             that may result in participants increased risk from study participation and/or lack of&#xD;
             compliance with study procedures.&#xD;
&#xD;
         12. Participants with primary sclerosing cholangitis.&#xD;
&#xD;
         13. Participants with known chronically active hepatopathy of any origin, including&#xD;
             cirrhosis and participants with persistent positive Hepatitis B Virus (HBV) surface&#xD;
             antigen (HBsAg) and quantitative HBV polymerase chain reaction (PCR), or positive&#xD;
             serology for Hepatitis C Virus (HCV) and quantitative HCV PCR within 6 months prior to&#xD;
             Screening.&#xD;
&#xD;
         14. Congenital or acquired immunodeficiencies, including participants known to be HIV&#xD;
             carriers&#xD;
&#xD;
         15. Known allergies or hypersensitivity to penicillin or aminoglycosides; Dulbecco&#xD;
             Modified Eagle's Medium (DMEM); bovine serum; local anaesthetics or gadolinium (MRI&#xD;
             contrast).&#xD;
&#xD;
         16. Contraindication to MRI scan (example, due to the presence of pacemakers, hip&#xD;
             replacements or severe claustrophobia).&#xD;
&#xD;
         17. Severe trauma within 6 months prior to Screening visit.&#xD;
&#xD;
         18. Pregnant or breastfeeding women.&#xD;
&#xD;
         19. Participants who do not wish to or cannot comply with study procedures.&#xD;
&#xD;
         20. Participants currently receiving, or having received any investigational drug within 3&#xD;
             months prior to Screening visit.&#xD;
&#xD;
         21. Participants previously treated with Cx601 or other allogeneic stem-cell therapy&#xD;
             cannot be enrolled into this clinical study.&#xD;
&#xD;
         22. Any major surgery of the GI tract (including one or more segments of the colon or&#xD;
             terminal ileum) within 6 months prior the screening or any minor surgery of the GI&#xD;
             tract within 3 months prior to screening.&#xD;
&#xD;
         23. Participants who had local perianal surgery other than drainage for the fistula within&#xD;
             6 months prior to the Screening visit, or those who may need surgery in the perianal&#xD;
             region for reasons other than fistulas at the time of inclusion in the study.&#xD;
&#xD;
         24. Contraindication to the anaesthetic procedure.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Scottsdale Mayo Clinic</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC San Diego Health Systems</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Southern California (USC) Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Irvine Medical Center - Chao Family Comprehensive Cancer</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inland Empire Liver Foundation</name>
      <address>
        <city>Rialto</city>
        <state>California</state>
        <zip>92377</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permamente</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>91115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vallejo Hospital and Medical Offices</name>
      <address>
        <city>Vallejo</city>
        <state>California</state>
        <zip>94589</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedar-Sinai Medical Center</name>
      <address>
        <city>West Hollywood</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hartford Hospital - Gastroenterology</name>
      <address>
        <city>Farmington</city>
        <state>Connecticut</state>
        <zip>06032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06519</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MedStar Georgetown University Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic - Gastroenterology</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Hospital Orlando</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USF Health South Tampa Center for Advanced Healthcare</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Hospital Tampa</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Florida</name>
      <address>
        <city>Weston</city>
        <state>Florida</state>
        <zip>33331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Chicago Medicine - Colon &amp; Rectal Surgery</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carle Foundation Hospital</name>
      <address>
        <city>Urbana</city>
        <state>Illinois</state>
        <zip>61801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University - Colon and Rectal</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Sxchool of Medicine</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40292</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Digestive Health Center of Louisiana</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colon and Rectal Surgery Associates</name>
      <address>
        <city>Metairie</city>
        <state>Louisiana</state>
        <zip>70001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center - New Orleans</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>71103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Medicine - The Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachussetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>08807</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lahey Hospital &amp; Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Massachusetts</state>
        <zip>01803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Massachusetts - colon &amp; rectal surgery</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic College of Medicine - Division of Colon and Rectal Surgery - Division of Colon and Rectal Surgery</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barnes-Jewish Hospital - Gastroenterology</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nevada School of Medicine</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89154</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center - Cancer Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morristown Medical Center - Gastroenterology</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albany Medical Center</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Shore University Hospital - Gastroenterology</name>
      <address>
        <city>Manhasset</city>
        <state>New York</state>
        <zip>11030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Langone Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stony Brook University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Medical College of Cornell University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10028</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lenox Hill Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10075</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OHSU Digestive Health Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harvard Medical School-Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn State Hershey Medical Center - Surgery</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Surgical Associates-Rhode Island Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rapid City Medical Center</name>
      <address>
        <city>Rapid City</city>
        <state>South Dakota</state>
        <zip>57701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center - Gastroenterology - Gastroenterology</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine (BCM) - Gastroenterology</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carilion Clinic</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Mason Medical Center - Gastroenterology</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora St. Luke's Medical Center</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin Hub for Collaborative Medicine - Gastroenterology and Hepatology</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven - Campus Gasthuisberg</name>
      <address>
        <city>Leuven</city>
        <state>Vlaams Brabant</state>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Groeninge - Campus Kennedylaan - Gastro-enterology</name>
      <address>
        <city>Kortrijk</city>
        <state>West-Vlaanderen</state>
        <zip>8500</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Delta vzw - Maag-darm-leverziekten</name>
      <address>
        <city>Roeselare</city>
        <state>West-Vlaanderen</state>
        <zip>8800</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GZA ziekenhuizen - Campus Sint-Vincentius - Gastro-enterology</name>
      <address>
        <city>Antwerpen</city>
        <zip>2018</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imelda Ziekenhuis</name>
      <address>
        <city>Antwerpen</city>
        <zip>2820</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent - Gastroenterology</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Liege - Domaine Universitaire du Sart Tilman</name>
      <address>
        <city>Liege</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinique Saint-Joseph (CHC)</name>
      <address>
        <city>Liege</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Dinant Godinne UCL Namur</name>
      <address>
        <city>Namur</city>
        <zip>5530</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>(G.I.R.I.) GI Research Institute</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6Z 2K5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital - Toronto - Gastroenterology</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kensington Screening Clinic - Gastroenterology</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5T 3A9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Universite de Montreal</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 3J4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Health Centre - Montreal General Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3G 1A4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NH Hospital a.s.</name>
      <address>
        <city>Horovice</city>
        <state>Beroun</state>
        <zip>268 31</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FN Hradec Kralove</name>
      <address>
        <city>Hradec Kralove</city>
        <zip>500 05</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bispebjerg Hospital</name>
      <address>
        <city>Kobenhavn</city>
        <state>Copenhague</state>
        <zip>2400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aarhus University Hospital - Department of Hepatology and Gastroenterology, Lever-Mave- og Tarmsygdomme Klinik, krydspunkt C216</name>
      <address>
        <city>Aarhus</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Odense Universitetshospital</name>
      <address>
        <city>Odense</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Nice</name>
      <address>
        <city>Nice Cedex 03</city>
        <state>Alpes-Maritimes</state>
        <zip>06202</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Clermont-Ferrand - Estaing</name>
      <address>
        <city>Clermont-Ferrand cedex 1</city>
        <state>Auvergne</state>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire De Toulouse - Hopital De Ra</name>
      <address>
        <city>Toulouse cedex 09</city>
        <state>Haute-Garonne</state>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Beaujon</name>
      <address>
        <city>Clichy</city>
        <state>Ile-de-France</state>
        <zip>92110</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Louis - Gastro-hepatoenterologie</name>
      <address>
        <city>Paris</city>
        <state>Ile-de-France</state>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Hopital De Pontchaillou</name>
      <address>
        <city>Rennes</city>
        <state>Ille-et-Vilaine</state>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Saint Etienne</name>
      <address>
        <city>St Priest en Jarez</city>
        <state>Loire</state>
        <zip>42270</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU de Nancy -Hopital Brabois Adultes - Service d'Hepato- Gastroenterologie</name>
      <address>
        <city>Vandoeuvre-les-Nancy</city>
        <state>Lorraine</state>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU De Lille - Hopital Claude Huriez - Hepato-Gastro-Enterologie</name>
      <address>
        <city>Lille</city>
        <state>Nord</state>
        <zip>59000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Amiens-Picardie</name>
      <address>
        <city>AMIENS cedex 1</city>
        <state>Picardie</state>
        <zip>80054</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Lyon Sud</name>
      <address>
        <city>Pierre-Benite</city>
        <state>Rhone</state>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Paris St. Joseph Hospital</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Erlangen</name>
      <address>
        <city>Erlangen</city>
        <state>Bayern</state>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Universitat Munchen - Campus Grosshadern</name>
      <address>
        <city>Munchen</city>
        <state>Bayern</state>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Johann Wolfgang Goethe-Universitat</name>
      <address>
        <city>Frankfurt/Main</city>
        <state>Hessen</state>
        <zip>69590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Dresden</name>
      <address>
        <city>Dresden</city>
        <state>Sachsen</state>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont - I. sz. Belgyogyaszati Klinika</name>
      <address>
        <city>Szeged</city>
        <state>Csongrad</state>
        <zip>6720</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Debreceni Egyetem Klinikai Kozpont</name>
      <address>
        <city>Debrecen</city>
        <state>Hajdu-Bihar</state>
        <zip>H-4032</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MH Egeszsegugyi Kozpont - Gasztroenterologiai Osztaly</name>
      <address>
        <city>Budapest</city>
        <state>Pest</state>
        <zip>1062</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Semmelweis Egyetem</name>
      <address>
        <city>Budapest</city>
        <state>Pest</state>
        <zip>H-1088</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin Med Ctr Beilinson Hosp</name>
      <address>
        <city>Petah Tikva</city>
        <state>HaMerkaz</state>
        <zip>4941492</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Medical Centre</name>
      <address>
        <city>Haifa</city>
        <state>HaZafon</state>
        <zip>31096</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chaim sheba Medical Center</name>
      <address>
        <city>Tel Hashomer</city>
        <state>Tel-Aviv</state>
        <zip>5262000</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shaare Zedek Medical Center - Gastroenterology</name>
      <address>
        <city>Jerusalem</city>
        <state>Yerushalayim</state>
        <zip>9103102</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Medical Organization, Hadassah Medical Center, Ein-</name>
      <address>
        <city>Jerusalem</city>
        <state>Yerushalayim</state>
        <zip>91120</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Santissima Annunziata</name>
      <address>
        <city>Cento</city>
        <state>Ferrara</state>
        <zip>44042</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas Rozzano, IRCCS - IBD Center</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico S. Orsola Malpighi, AOU di Bologna-U.O. di Medicina Interna.</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU Policlinico di Modena - Gastroenterologia</name>
      <address>
        <city>Modena</city>
        <zip>41124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>II Universita degli Studi di Napoli</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gastroenterology Section</name>
      <address>
        <city>Palermo</city>
        <zip>90127</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universita degli studi di Pisa</name>
      <address>
        <city>Pisa</city>
        <zip>56126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Universitario Campus Biomedico - UOC di Gastroenterologia</name>
      <address>
        <city>Roma</city>
        <zip>00128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. San Camillo Forlanini</name>
      <address>
        <city>Roma</city>
        <zip>00152</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complesso Integrato Columbus</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Universitario Agostino Gemelli</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria S.Maria della Misericordia - Gastroenterologia</name>
      <address>
        <city>Udine</city>
        <zip>33100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Integrata Verona (AOUI) -</name>
      <address>
        <city>Verona</city>
        <zip>37134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Medyczne Melita Medical</name>
      <address>
        <city>Wroclaw</city>
        <state>Dolnoslaskie</state>
        <zip>50-449</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Kliniczny im. Wojskowej Akademii Medycznej Centralny Szpital Weteranow</name>
      <address>
        <city>Lodz</city>
        <state>Lodzkie</state>
        <zip>90-647</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Medyczne PROMED</name>
      <address>
        <city>Krakow</city>
        <state>Malopolskie</state>
        <zip>31-411</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wielospecjalistyczny Szpital Medicover</name>
      <address>
        <city>Warszawa</city>
        <state>Mazowieckie</state>
        <zip>03-984</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Endoskopia Sp z o.o.</name>
      <address>
        <city>Sopot</city>
        <state>Pomorskie</state>
        <zip>81-756</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>COPERNICUS Podmiot Leczniczy Sp. z o.o.</name>
      <address>
        <city>Gdansk</city>
        <zip>80-803</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centralny Szpital Kliniczny MSWiA w Warszawie</name>
      <address>
        <city>Warszawa</city>
        <zip>02-507</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Puerto Rico School of Medicine</name>
      <address>
        <city>San Juan</city>
        <zip>00936</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Son Espases</name>
      <address>
        <city>Palma de Mallorca</city>
        <state>Baleares</state>
        <zip>07120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H.U. G.Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Corporacio Sanitaria Parc Tauli</name>
      <address>
        <city>Sabadell</city>
        <state>Barcelona</state>
        <zip>8208</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Fuenlabrada</name>
      <address>
        <city>Fuenlabrada</city>
        <state>Madrid</state>
        <zip>28942</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Puerta de Hierro Majadahonda</name>
      <address>
        <city>Majadahonda</city>
        <state>Madrid</state>
        <zip>28222</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Sagunto</name>
      <address>
        <city>Sagunto</city>
        <state>Valencia</state>
        <zip>46520</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <zip>8003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Fundacion Jimenez Diaz</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>C.H.U. de Pontevedra</name>
      <address>
        <city>Pontevedra</city>
        <zip>36071</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H.U.V. del Rocio</name>
      <address>
        <city>Sevilla</city>
        <zip>21005</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linkoping University Hospital - Department of Surgery</name>
      <address>
        <city>Linkoping</city>
        <state>Ostergotlands Lan [se-05]</state>
        <zip>581 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Addenbrooke's Hospital</name>
      <address>
        <city>Cambridge</city>
        <state>Cambridgeshire</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHS Greater Glasgow and Clyde - Glasgow Royal Infirmary (GRI)</name>
      <address>
        <city>Glasgow</city>
        <state>Glasgow City</state>
        <zip>G52 3NQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Mark's Hospital</name>
      <address>
        <city>Harrow</city>
        <state>London, City Of</state>
        <zip>HA1 3UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guys &amp; St Thomas</name>
      <address>
        <city>London</city>
        <state>London, City Of</state>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospitals NHS Trust - Surgery</name>
      <address>
        <city>Nottingham</city>
        <state>Nottinghamshire</state>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Colleague London Hospital (UCLH)</name>
      <address>
        <city>London</city>
        <zip>NW1 2BU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wythenshawe Hospital - Gastroenterology</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northern General Hospital</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2JF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Poland</country>
    <country>Puerto Rico</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 21, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Crohn's disease</keyword>
  <keyword>complex perianal fistula(s)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</mesh_term>
    <mesh_term>Fistula</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_access_criteria>IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </patient_data>
  <!-- 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/NCT03279081
org study id: Cx601-0303
secondary id: 2017-000725-12
nct id: NCT03279081
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the combined remission of complex perianal fistulas,
      defined as the clinical assessment at Week 24 of closure of all treated external openings
      that were draining at baseline despite gentle finger compression, and absence of collections
      greater than (>) 2 centimeter (cm) (in at least 2 dimensions) confirmed by blinded central
      magnetic resonance imaging (MRI) assessment at Week 24.
This study is to assess the efficacy and safety of Cx601, eASC, for the treatment of complex
      perianal fistulas in participants with Crohn's disease.

      The study will randomize approximately 554 participants.

        -  Cx601 eASCs intralesional injection

        -  Placebo - Cx601 placebo-matching eASCs intralesional injection

      Study treatments will be allocated, on a 1:1 ratio, by central randomization through
      interactive web response system (IWRS). The study will follow an add-on design, participants
      receiving any ongoing concomitant medical treatment, at stable doses at the time of
      screening, for the CD will be allowed to continue it throughout the study.

      The primary efficacy analysis, will be conducted at Week 24 timepoint. The double blind
      design will be maintained up to Week 52 (both participant and investigator) by a specific
      blinding for study treatment administration and for evaluating its efficacy.

      This multicenter trial will be conducted globally across 150 centers. The overall time to
      participate in this study is approximately 5 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Participants with Combined Remission at Week 24
time frame: Week 24
description: Combined Remission is defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression and absence of collection(s) >2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by blinded central MRI assessment.
measure: Percentage of Participants with Clinical Remission at Week 24
time frame: Week 24
description: Clinical remission is defined as closure of all treated external openings that were draining at baseline despite gentle finger compression.
measure: Time to Clinical Remission up to Week 24
time frame: From the treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed (up to Week 24)
description: Time to clinical remission is defined as the time from treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed.
measure: Percentage of Participants with Clinical Response at Week 24
time frame: Week 24
description: Clinical response is defined as closure of at least 50 percent (%) of all treated external openings that were draining at baseline despite gentle finger compression.
measure: Time to Clinical Response up to Week 24
time frame: From treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression, as clinically assessed (up to Week 24)
description: Time to clinical response is defined as the time from treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression, as clinically assessed.
measure: Percentage of Participants with Combined Remission at Week 52
time frame: Week 52
description: Combined Remission is defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of collections >2 cm (in at least 2 dimensions) confirmed by blinded central MRI assessment.
measure: Percentage of Participants with Clinical Remission at Week 52
time frame: Week 52
description: Clinical remission is defined as closure of all treated external openings that were draining at baseline despite gentle finger compression.
measure: Percentage of Participants with Clinical Response at Week 52
time frame: Week 52
description: Clinical response is defined as closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression.
measure: Time to Clinical Remission up to Week 52
time frame: From treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed (up to Week 52)
description: Time to clinical remission is defined as the time from treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed.
measure: Time to Clinical Response up to Week 52
time frame: From treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed (up to Week 52)
description: Time to clinical response is defined as time from treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed.
measure: Percentage of Participants with Relapse from Week 24 Combined Remission
time frame: Week 24
description: Relapse is defined as reopening of any of the treated fistulas external openings with active drainage as clinically assessed, or the development of a perianal fluid collection >2 cm of the treated perianal fistula confirmed by centrally read MRI assessment in participants who were in combined remission at week 24.
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs)
time frame: Week 24 and Week 52
measure: Number of Participants With TEAEs Related to Vital Sign Parameters
time frame: Week 24 and Week 52
measure: Number of Participants With TEAEs Related to Clinical Laboratory Parameters
time frame: Week 24 and Week 52
arm group label: Cx601
arm group type: Experimental
description: Cx601 eASCs 120 million cells (5 million cells per milliliter [mL]) will be administered once by intralesional injection.
arm group label: Placebo
arm group type: Placebo Comparator
description: CX601 placebo-matching eASCs cells will be administered once by intralesional administration.
intervention type: Drug
intervention name: Cx601
description: Cx601 eASCs intralesional injection.
arm group label: Cx601
intervention type: Other
intervention name: Placebo
description: Cx601 placebo-matching eASCs intralesional injection.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Takeda
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country: Belgium
country: Canada
country: Czechia
country: Denmark
country: France
country: Germany
country: Hungary
country: Israel
country: Italy
country: Poland
country: Puerto Rico
country: Spain
country: Sweden
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Crohn Disease
mesh term: Fistula
sharing ipd: Yes
ipd description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
ipd url: https://vivli.org/ourmember/takeda/