<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/NCT03784131</url>
  </required_header>
  <id_info>
    <org_study_id>2015-004021-13</org_study_id>
    <nct_id>NCT03784131</nct_id>
  </id_info>
  <brief_title>Tissue Engineered Veins in Patients With Chronic Venous Insufficiency</brief_title>
  <acronym>TECVI-1</acronym>
  <official_title>Phase I Open-label, First-in-human Study to Evaluate Feasibility and Safety of Tissue Engineered Veins in Patients With Chronic Venous Insufficiency</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Verigraft AB</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Verigraft AB</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to evaluate the safety (incidence of adverse events including serious adverse&#xD;
      events and clinical significant laboratory abnormalities) of personalized tissue engineered&#xD;
      veins (P-TEV) with valves implanted in patients with severe chronic venous insufficiency&#xD;
      (CVI). For each patient a segment of the femoral vein containing the non-functioning valve&#xD;
      will be surgically replaced with a single P-TEV containing a functioning valve.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The advanced therapy medicinal product (ATMP) described herein is a personalized tissue-&#xD;
      engineered vein (P-TEV), a human vein segment graft for use in transplantation to replace a&#xD;
      defective or missing part of a patient's vein.&#xD;
&#xD;
      In this specific application a P-TEV segment with a functioning venous bicuspid valve is&#xD;
      implanted to replace a nonfunctioning venous valve in the femoral vein of a patient suffering&#xD;
      from severe CVI. The P-TEV is a hybrid tissue consisting of the extracellular matrix (ECM)&#xD;
      scaffold of an allogeneic vein segment derived from a cadaveric donor as well as autologous&#xD;
      components from a sample of peripheral blood of the recipient. As the allogeneic immunogenic&#xD;
      material from the donor has been removed and been replaced by autologous components, no&#xD;
      immunosuppression is required.&#xD;
&#xD;
      Successful implantation and treatment should prevent the reverse flow of blood, decrease&#xD;
      blood pooling in the lower leg, and thereby alleviate symptoms such as swelling, pain, and&#xD;
      ulcers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 15, 2021</start_date>
  <completion_date type="Anticipated">July 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">January 30, 2023</primary_completion_date>
  <phase>Phase 1</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>Thrombosis leading to occlusion of the graft measured by Color Duplex Ultrasound</measure>
    <time_frame>12 months</time_frame>
    <description>Ultrasonographic evaluation of occlusions of the graft.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Infection leading to surgical excision of the graft measured by blood samples</measure>
    <time_frame>12 months</time_frame>
    <description>White blood cells count: &gt;10 x10E9/L, C- Reactive Protein (CRP): &gt;4 mg/L, sedimentation rate: &gt;12mm).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Infection leading to surgical excision of the graft measured by Color Duplex Ultrasound</measure>
    <time_frame>12 months</time_frame>
    <description>Ultrasonographic examination to assess infection of the graft</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Infection leading to surgical excision of the graft measured by Computer Tomography</measure>
    <time_frame>12 months</time_frame>
    <description>Infection of the graft assessed by Computer Tomography</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Reporting of surgical complications</measure>
    <time_frame>12 months</time_frame>
    <description>Perioperative surgical complications related to the implanted graft (technical failure leading to surgical failure).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in symptoms assessed according to VCSS (Venous Clinical Severity Score)</measure>
    <time_frame>12 months</time_frame>
    <description>The VCSS includes 9 hallmarks of venous disease, each scored on a severity scale from 0 (absent) to 3 (severe), plus a category for compression with higher scores representing greater compliance (still scale 0-3).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in symptoms assessed according to CEAP classification (clinical, etiologic, anatomic, pathophysiologic)</measure>
    <time_frame>12 months</time_frame>
    <description>CEAP classification is assessed on scale from C0 (No visible or palpable signs of venous disease) to C6 (Active venous ulcer).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Related Quality of Life assessed by VEINES questionnaire</measure>
    <time_frame>12 months</time_frame>
    <description>Responses are made on a 2- to 7-point scale that rates intensity, frequency, and agreement. Higher scores are associated with better quality-of-life.The focus of VEINES is on physical symptoms as opposed to psychological or social aspects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Related Quality of Life assessed by EQ-5D questionnaire</measure>
    <time_frame>12 months</time_frame>
    <description>EQ-5D is a standardized self-assessment instrument for health status.It has two components; health state description and evaluation.&#xD;
The description part contains 5 items with three levels of response regarding five dimensions (mobility, hygiene, activities, pain and anxiety). The five questions are compounded into a health index according to a mathematical formula validated against the population in several countries. This index may vary between 1 and -0,594.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Durability of the P-TEV assessed by Color Duplex Ultrasound</measure>
    <time_frame>12 months</time_frame>
    <description>The time period in which the valve contained in the implant retains its function verified by ultrasonographic examination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vessel dilatation in the implant assessed by Duplex Color Ultrasound</measure>
    <time_frame>12 months</time_frame>
    <description>Ultrasonographic examination of vessel dilatation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Flow abnormalities in the implant assessed by Duplex Color Ultrasound</measure>
    <time_frame>12 months</time_frame>
    <description>Ultrasonographic examination of flow abnormalities</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wall degeneration in the implant assessed by Duplex Color Ultrasound</measure>
    <time_frame>12 months</time_frame>
    <description>Ultrasonographic examination of wall degeneration</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Chronic Venous Insufficiency</condition>
  <arm_group>
    <arm_group_label>Personalized Tissue Engineered Vein</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>P-TEV</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>P-TEV</intervention_name>
    <description>Replacement of vein with failing valves with personalized tissue engineering vein containing functional valves</description>
    <arm_group_label>Personalized Tissue Engineered Vein</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged between 18 and 65 years (inclusive)&#xD;
&#xD;
          -  CVI patients with skin changes and/or recurrent leg ulcer despite optimal conservative&#xD;
             treatment for a period of time according to the investigator's judgement&#xD;
&#xD;
          -  Patients with deep venous reflux (grade 4)&#xD;
&#xD;
          -  Anesthesiologically cleared and meeting ASA (American Society of Anesthesiologists&#xD;
             Classification) class 1 or 2&#xD;
&#xD;
          -  Laboratory values&#xD;
&#xD;
               -  INR &lt;1.7 (in case the patient uses Orfarin, the test might be repeated after the&#xD;
                  anticoagulant change)&#xD;
&#xD;
               -  Platelets ≥ 100 x 10 9 /L&#xD;
&#xD;
               -  Hemoglobin ≥ 100 g/L&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 × upper limit of normal (ULN)&#xD;
&#xD;
               -  ASAT ≤ 2.5 × ULN&#xD;
&#xD;
               -  ALAT ≤ 2.5 × ULN&#xD;
&#xD;
               -  Lipid profile within acceptable range according to investigator's opinion&#xD;
&#xD;
               -  Clinical chemistries (K, Ca) within acceptable range according to Investigator's&#xD;
                  opinion&#xD;
&#xD;
          -  Ability to understand the requirements of the study, provide written informed consent,&#xD;
             and comply with the study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients incapable to give written informed consent&#xD;
&#xD;
          -  Patients unlikely to cooperate fully in the study and/or with an anticipated poor&#xD;
             compliance&#xD;
&#xD;
          -  Non-walking patients or patients with lost ankle joint function&#xD;
&#xD;
          -  Patients previously organ-transplanted&#xD;
&#xD;
          -  Patients with cancer except in-situ stage cancer (basal-cell carcinomas and/or cervix&#xD;
             cancer) and five year recurrence free period after treatment&#xD;
&#xD;
          -  Patients with autoimmune diseases including rheumatoid arthritis, SLE and MS&#xD;
&#xD;
          -  Pregnant or breast feeding women&#xD;
&#xD;
          -  Patients with ongoing estrogen treatment/contraception. (intrauterine device,&#xD;
             bilateral tubal occlusion, vasectomized partner, sexual abstinence should be used for&#xD;
             contraception by women of childbearing period).&#xD;
&#xD;
          -  BMI ≥ 35&#xD;
&#xD;
          -  Patients who participate in other clinical trials&#xD;
&#xD;
          -  Patients with artery pathology (ankle-brachial pressure index &lt; 0,9 or &gt; 1,3)&#xD;
&#xD;
          -  Patients with thrombophilia according to the laboratory results at inclusion visit.&#xD;
             One of the following criteria is needed for thrombophilia: Protein C &lt; 40% or Protein&#xD;
             S &lt; 40 % or Leiden factor mutation or Antithrombin III &lt; 40 % or present Lupus&#xD;
             anticoagulant or Homocysteine &gt; 1.5 ULN&#xD;
&#xD;
          -  Patients with an active infection requiring systemic antibiotic treatment&#xD;
&#xD;
          -  Patients with clinically significant cardiac disease (New York Heart Association,&#xD;
             Class III or IV) or measured LVEF 40%&#xD;
&#xD;
          -  Patients with uncontrolled hypertension&#xD;
&#xD;
          -  Patients with renal dysfunction eGFR &lt; 45 ml/min (according to the MDRD calculation)&#xD;
&#xD;
          -  Patients with moderate or severe hepatic impairment (Child Pugh ≥ 7 points, i.e. class&#xD;
             B or C)&#xD;
&#xD;
          -  Patients with ongoing immunosuppression, Cortisol treatment etc.&#xD;
&#xD;
          -  Less than 3 months since previous ipsilateral venous intervention (e.g. Iliac&#xD;
             recanalization)&#xD;
&#xD;
          -  Clinically significant outflow disease&#xD;
&#xD;
          -  Heavy smoker: Has smoked 20 cigarettes or more per day for at least past 5 years&#xD;
&#xD;
          -  Other uncontrolled intercurrent illness that would jeopardize the patient's safety,&#xD;
             interfere with the objectives of the protocol, or limit the patient's compliance with&#xD;
             study requirements, as determined by the investigator in consultation with the sponsor&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Björquist</last_name>
    <role>Study Director</role>
    <affiliation>Verigraft AB</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Björquist</last_name>
    <phone>+46705979296</phone>
    <phone_ext>+46705979296</phone_ext>
    <email>info@verigraft.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Junta de Andalusia</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Petter Björquist, Dr</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>November 16, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>July 6, 2022</last_update_submitted>
  <last_update_submitted_qc>July 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CVI</keyword>
  <keyword>Leg Ulcer</keyword>
  <keyword>Tissue Engineering</keyword>
  <keyword>Personalized Vascular Graft</keyword>
  <keyword>Chronic Venous Insufficiency</keyword>
  <keyword>ATMP</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Venous Insufficiency</mesh_term>
  </condition_browse>
  <!-- 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/NCT03784131
org study id: 2015-004021-13
nct id: NCT03784131
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study aims to evaluate the safety (incidence of adverse events including serious adverse
      events and clinical significant laboratory abnormalities) of personalized tissue engineered
      veins (P-TEV) with valves implanted in patients with severe chronic venous insufficiency
      (CVI). For each patient a segment of the femoral vein containing the non-functioning valve
      will be surgically replaced with a single P-TEV containing a functioning valve.
The advanced therapy medicinal product (ATMP) described herein is a personalized tissue-
      engineered vein (P-TEV), a human vein segment graft for use in transplantation to replace a
      defective or missing part of a patient's vein.

      In this specific application a P-TEV segment with a functioning venous bicuspid valve is
      implanted to replace a nonfunctioning venous valve in the femoral vein of a patient suffering
      from severe CVI. The P-TEV is a hybrid tissue consisting of the extracellular matrix (ECM)
      scaffold of an allogeneic vein segment derived from a cadaveric donor as well as autologous
      components from a sample of peripheral blood of the recipient. As the allogeneic immunogenic
      material from the donor has been removed and been replaced by autologous components, no
      immunosuppression is required.

      Successful implantation and treatment should prevent the reverse flow of blood, decrease
      blood pooling in the lower leg, and thereby alleviate symptoms such as swelling, pain, and
      ulcers.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Thrombosis leading to occlusion of the graft measured by Color Duplex Ultrasound
time frame: 12 months
description: Ultrasonographic evaluation of occlusions of the graft.
measure: Infection leading to surgical excision of the graft measured by blood samples
time frame: 12 months
description: White blood cells count: >10 x10E9/L, C- Reactive Protein (CRP): >4 mg/L, sedimentation rate: >12mm).
measure: Infection leading to surgical excision of the graft measured by Color Duplex Ultrasound
time frame: 12 months
description: Ultrasonographic examination to assess infection of the graft
measure: Infection leading to surgical excision of the graft measured by Computer Tomography
time frame: 12 months
description: Infection of the graft assessed by Computer Tomography
measure: Reporting of surgical complications
time frame: 12 months
description: Perioperative surgical complications related to the implanted graft (technical failure leading to surgical failure).
measure: Change in symptoms assessed according to VCSS (Venous Clinical Severity Score)
time frame: 12 months
description: The VCSS includes 9 hallmarks of venous disease, each scored on a severity scale from 0 (absent) to 3 (severe), plus a category for compression with higher scores representing greater compliance (still scale 0-3).
measure: Change in symptoms assessed according to CEAP classification (clinical, etiologic, anatomic, pathophysiologic)
time frame: 12 months
description: CEAP classification is assessed on scale from C0 (No visible or palpable signs of venous disease) to C6 (Active venous ulcer).
measure: Health Related Quality of Life assessed by VEINES questionnaire
time frame: 12 months
description: Responses are made on a 2- to 7-point scale that rates intensity, frequency, and agreement. Higher scores are associated with better quality-of-life.The focus of VEINES is on physical symptoms as opposed to psychological or social aspects.
measure: Health Related Quality of Life assessed by EQ-5D questionnaire
time frame: 12 months
description: EQ-5D is a standardized self-assessment instrument for health status.It has two components; health state description and evaluation.
The description part contains 5 items with three levels of response regarding five dimensions (mobility, hygiene, activities, pain and anxiety). The five questions are compounded into a health index according to a mathematical formula validated against the population in several countries. This index may vary between 1 and -0,594.
measure: Durability of the P-TEV assessed by Color Duplex Ultrasound
time frame: 12 months
description: The time period in which the valve contained in the implant retains its function verified by ultrasonographic examination.
measure: Vessel dilatation in the implant assessed by Duplex Color Ultrasound
time frame: 12 months
description: Ultrasonographic examination of vessel dilatation
measure: Flow abnormalities in the implant assessed by Duplex Color Ultrasound
time frame: 12 months
description: Ultrasonographic examination of flow abnormalities
measure: Wall degeneration in the implant assessed by Duplex Color Ultrasound
time frame: 12 months
description: Ultrasonographic examination of wall degeneration
arm group label: Personalized Tissue Engineered Vein
arm group type: Experimental
description: P-TEV
intervention type: Drug
intervention name: P-TEV
description: Replacement of vein with failing valves with personalized tissue engineering vein containing functional valves
arm group label: Personalized Tissue Engineered Vein
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Björquist
role: Study Director
affiliation: Verigraft AB
last name: Björquist
phone: +46705979296
phone ext: +46705979296
email: info@verigraft.com
facility: 
status: Recruiting
contact: 
country: Spain
responsible party type: Sponsor
mesh term: Venous Insufficiency