<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/NCT04435249</url>
  </required_header>
  <id_info>
    <org_study_id>UK-2019-004939-24</org_study_id>
    <nct_id>NCT04435249</nct_id>
  </id_info>
  <brief_title>ENgineered Tissue Repair of BronchopleUral fiSTula</brief_title>
  <acronym>ENTRUST</acronym>
  <official_title>Phase I/II, Open Label Study to Assess the Safety and Efficacy Autologous Bone Marrow-derived Mesenchymal Stromal Cells Seeded on to Decellularised Airway Scaffold in Subjects With Clinically Significant Bronchopleural Fistula</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Videregen Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cell Therapy Catapult</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Papworth Hospital NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Royal Free Hospital NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Videregen Limited</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>
      Phase I/II Open-label Study to Assess the Safety and Efficacy of a Novel Tissue Engineered&#xD;
      Airway Product, Consisting of Expanded Autologous Bone Marrow (BM) Derived Mesenchymal&#xD;
      Stromal Cells (MSC) Seeded on to a Decellularised Allogeneic Patch of an Airway Scaffold in&#xD;
      Subjects With Clinically Significant Bronchopleural Fistula.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The proposed clinical trial is a phase I/II open-label study to assess the safety and&#xD;
      efficacy of a novel tissue engineered airway product, consisting of expanded autologous Bone&#xD;
      Marrow (BM) derived Mesenchymal Stromal Cells (MSC) seeded on to a decellularised allogeneic&#xD;
      patch of an airway scaffold in subjects with clinically significant bronchopleural fistula.&#xD;
      It is a phase I/II open-label study, which is an uncontrolled pilot in 5 subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">October 2023</start_date>
  <completion_date type="Anticipated">November 2027</completion_date>
  <primary_completion_date type="Anticipated">March 2025</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety: Emergent or worsening Serious Adverse Events (SAEs) related to the BPF implant during the 3 months post-defect repair</measure>
    <time_frame>3 months (90 days)</time_frame>
    <description>Safety: Emergent or worsening Serious Adverse Events (SAEs) related to the BPF implant during the 3 months post-defect repair.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy: Bronchopleural Fistula (BPF) closure at 3 months assessed by visual appearance and no clinical signs of leaks.</measure>
    <time_frame>3 months (90 days)</time_frame>
    <description>Closure of BPF with no need for further surgical closure. Efficacy will be deemed demonstrated if 2 or more subjects meet the primary endpoint.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Physiological and Quality of Life scores at 3, 6, 9, 12 months, Evaluation Questionnaire 5D (EQ-5D), 6-minute walking test (6MWT), ambulatory oxygen (O2).</measure>
    <time_frame>36 months</time_frame>
    <description>Impact as assessed in change from Baseline in Physiological and Quality of Life scores for each subject at 3, 6, 9, 12, 24 and up to 36 months post defect repair: QoL EQ-5D, 6-minute walking test, ambulatory O2 measurements.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability: - Adverse Events (AEs) including pre-defined postoperative AEs of special interest up to 30± 3 days post implantation- Related AEs reported after 3, 6, 9, 12, 24 and 36 months</measure>
    <time_frame>36 months</time_frame>
    <description>Adverse events related to the BPF implant procedures reported after 3, 6, 9, 12, 24 and 36 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Viability and the integrity of the repair area (closure) visually via bronchoscope. Integrity assessed by visual appearance of no visible leaks- Structural closure of the defect and visual health of the defect area and surrounding tissue</measure>
    <time_frame>36 months</time_frame>
    <description>viability of the repair area and integration with vascular supply at 6, 9, 12, 24 and 36 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absence of other surgical interventions at 6, 9, 12, 24 and 36 months</measure>
    <time_frame>36 months</time_frame>
    <description>Interventions at the operative sites up to 6, 9, 12, 24 and 36 months</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">5</enrollment>
  <condition>Bronchopleural Fistula</condition>
  <arm_group>
    <arm_group_label>Treatment Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will have a patch of expanded somatic mesenchymal stromal cells (MSCs) seeded onto a decellularised human tracheal-scaffold surgically implanted to repair bronchial fistula.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>BPF-001</intervention_name>
    <description>Expanded somatic mesenchymal stromal cells (MSCs) seeded onto a decellularised human tracheal-scaffold</description>
    <arm_group_label>Treatment Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female subjects 18 years or older.&#xD;
&#xD;
          -  Documented diagnoses of BPF through imaging and bronchoscopic examination.&#xD;
&#xD;
          -  BPF which involves the tracheobronchial junction or proximal bronchus.&#xD;
&#xD;
          -  Subjects who have failed primary repair.&#xD;
&#xD;
          -  Subjects who have no evidence of any primary or recurrent cancer (not limited to the&#xD;
             surgical site) at the time of pre-operative screening as evidenced by CT and/or&#xD;
             targeted biopsy (except for controlled or controllable basal cell carcinoma.&#xD;
&#xD;
          -  Subjects who have signed and dated written informed consent to participate in the&#xD;
             study.&#xD;
&#xD;
          -  Females of childbearing potential (i.e. not surgically sterilised or post-menopausal&#xD;
             for at least 2 years) must have a negative serum or urine pregnancy test.&#xD;
&#xD;
          -  Male and female subjects of childbearing potential (i.e. not surgically sterilised or&#xD;
             post-menopausal for at least 2 years) must use forms of highly effective methods of&#xD;
             contraception, which are defined as hormonal methods of contraception (oral, injection&#xD;
             or implant), barrier methods (condom or occlusive cap (diaphragm or cervical/vault&#xD;
             caps)) with spermicidal foam/gel/cream/film/suppository, or true abstinence for 1&#xD;
             month following surgery.&#xD;
&#xD;
          -  Subjects who have produced viable cells from Bone Marrow Aspirate.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who have received previous treatment with another Advanced Technology&#xD;
             Medicinal Product (ATMP).&#xD;
&#xD;
          -  Subjects with ECOG performance status of 3 or 4.&#xD;
&#xD;
          -  Subjects deemed not suitable for surgery by the MDT.&#xD;
&#xD;
          -  Uncontrolled diabetes, defined as HbA1c levels above 7.0 %.&#xD;
&#xD;
          -  Any medical condition contraindicating the ability to tolerate general anaesthetic in&#xD;
             the judgement of a consultant anaesthetist.&#xD;
&#xD;
          -  Subjects who have a severe acute or chronic medical or psychiatric condition or&#xD;
             laboratory abnormality that may increase the risk associated with trial participation&#xD;
             or investigational product administration or in the judgment of the investigator,&#xD;
             would make the subject inappropriate for entry into this trial.&#xD;
&#xD;
          -  Subjects with clinically significant renal and liver impairment.&#xD;
&#xD;
          -  Subjects undergoing an immunosuppression regimen or suffering from a primary&#xD;
             immunodeficiency syndrome.&#xD;
&#xD;
          -  Subjects with any known hypersensitivity to the culture and transport media compounds.&#xD;
&#xD;
          -  Subjects with current or recurrent disease that could affect the administration, the&#xD;
             action or disposition of the investigational product, or clinical or laboratory&#xD;
             assessments.&#xD;
&#xD;
          -  Subjects with clinically relevant or recent (within 2 years) history of substance&#xD;
             abuse, including alcohol.&#xD;
&#xD;
          -  Subject who has participated in any other interventional clinical trial within&#xD;
             previous 30 days of the start of this study.&#xD;
&#xD;
          -  Subjects with known presence of Human Immunodeficiency Virus (HIV) antibody, Hepatitis&#xD;
             B surface antigen (HBsAg) or Hepatitis C antibody.&#xD;
&#xD;
          -  Subject who, in the investigator's judgement, is unlikely to complete all protocol&#xD;
             required study visits or procedures, including follow-up visits, or comply with the&#xD;
             study requirements for participation&#xD;
&#xD;
          -  Subjects with any medical condition, that in the investigator's judgement, is likely&#xD;
             to interfere with assessment of safety or efficacy of study treatment.&#xD;
&#xD;
          -  Subject who is pregnant.&#xD;
&#xD;
          -  Subjects with cancer (except for controlled or controllable basal cell carcinoma).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Reg Affairs</last_name>
    <phone>+44203 728 9500</phone>
    <email>regulatory@ct.catapult.org.uk</email>
  </overall_contact>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>November 21, 2022</last_update_submitted>
  <last_update_submitted_qc>November 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 22, 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>Fistula</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>to follow</ipd_description>
  </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/NCT04435249
org study id: UK-2019-004939-24
nct id: NCT04435249
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Phase I/II Open-label Study to Assess the Safety and Efficacy of a Novel Tissue Engineered
      Airway Product, Consisting of Expanded Autologous Bone Marrow (BM) Derived Mesenchymal
      Stromal Cells (MSC) Seeded on to a Decellularised Allogeneic Patch of an Airway Scaffold in
      Subjects With Clinically Significant Bronchopleural Fistula.
The proposed clinical trial is a phase I/II open-label study to assess the safety and
      efficacy of a novel tissue engineered airway product, consisting of expanded autologous Bone
      Marrow (BM) derived Mesenchymal Stromal Cells (MSC) seeded on to a decellularised allogeneic
      patch of an airway scaffold in subjects with clinically significant bronchopleural fistula.
      It is a phase I/II open-label study, which is an uncontrolled pilot in 5 subjects.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety: Emergent or worsening Serious Adverse Events (SAEs) related to the BPF implant during the 3 months post-defect repair
time frame: 3 months (90 days)
description: Safety: Emergent or worsening Serious Adverse Events (SAEs) related to the BPF implant during the 3 months post-defect repair.
measure: Efficacy: Bronchopleural Fistula (BPF) closure at 3 months assessed by visual appearance and no clinical signs of leaks.
time frame: 3 months (90 days)
description: Closure of BPF with no need for further surgical closure. Efficacy will be deemed demonstrated if 2 or more subjects meet the primary endpoint.
measure: Change from Baseline in Physiological and Quality of Life scores at 3, 6, 9, 12 months, Evaluation Questionnaire 5D (EQ-5D), 6-minute walking test (6MWT), ambulatory oxygen (O2).
time frame: 36 months
description: Impact as assessed in change from Baseline in Physiological and Quality of Life scores for each subject at 3, 6, 9, 12, 24 and up to 36 months post defect repair: QoL EQ-5D, 6-minute walking test, ambulatory O2 measurements.
measure: Safety and tolerability: - Adverse Events (AEs) including pre-defined postoperative AEs of special interest up to 30± 3 days post implantation- Related AEs reported after 3, 6, 9, 12, 24 and 36 months
time frame: 36 months
description: Adverse events related to the BPF implant procedures reported after 3, 6, 9, 12, 24 and 36 months.
measure: Viability and the integrity of the repair area (closure) visually via bronchoscope. Integrity assessed by visual appearance of no visible leaks- Structural closure of the defect and visual health of the defect area and surrounding tissue
time frame: 36 months
description: viability of the repair area and integration with vascular supply at 6, 9, 12, 24 and 36 months.
measure: Absence of other surgical interventions at 6, 9, 12, 24 and 36 months
time frame: 36 months
description: Interventions at the operative sites up to 6, 9, 12, 24 and 36 months
arm group label: Treatment Arm
arm group type: Experimental
description: Patients will have a patch of expanded somatic mesenchymal stromal cells (MSCs) seeded onto a decellularised human tracheal-scaffold surgically implanted to repair bronchial fistula.
intervention type: Other
intervention name: BPF-001
description: Expanded somatic mesenchymal stromal cells (MSCs) seeded onto a decellularised human tracheal-scaffold
arm group label: Treatment Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: No
last name: Reg Affairs
phone: +44203 728 9500
email: regulatory@ct.catapult.org.uk
responsible party type: Sponsor
mesh term: Fistula
sharing ipd: No
ipd description: to follow