<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/NCT03818828</url>
  </required_header>
  <id_info>
    <org_study_id>TTAX01-CR002</org_study_id>
    <nct_id>NCT03818828</nct_id>
  </id_info>
  <brief_title>Subjects With Non-Healing Venous Leg Ulcers Treated With Standard Care Plus Cryopreserved Human Umbilical Cord (TTAX01)</brief_title>
  <official_title>A Multicenter, Open Label Phase 2 Pilot Trial of Subjects With Non-Healing Venous Leg Ulcers Treated With Standard Care Plus Cryopreserved Human Umbilical Cord (TTAX01)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tissue Tech Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tissue Tech Inc.</source>
  <oversight_info>
    <has_dmc>Yes</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>
      It is hypothesized that application at 4-week intervals of the human umbilical cord tissue&#xD;
      TTAX01 to the surface of a well debrided, nonhealing venous leg ulcer (VLU) will result in a&#xD;
      high proportion of wounds showing complete healing within 12 weeks of initiating therapy.&#xD;
      This open label pilot study provides a framework for a larger, controlled study. The purposes&#xD;
      for conducting this study are to evaluate the functionality of the protocol and to obtain an&#xD;
      estimate of product safety and efficacy when applied according to the protocol instructions,&#xD;
      and measured according to the stated endpoints.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 14, 2019</start_date>
  <completion_date type="Actual">January 28, 2020</completion_date>
  <primary_completion_date type="Actual">December 20, 2019</primary_completion_date>
  <phase>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>Complete wound healing</measure>
    <time_frame>12-weeks</time_frame>
    <description>Proportion of subjects who achieve complete wound closure over the 12-week treatment period from baseline with a 4 week followup to confirm wound healing.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to complete wound healing</measure>
    <time_frame>up to 12 weeks</time_frame>
    <description>Time, in days, from baseline to initial observation of closure, in cases where healing is later confirmed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete wound healing</measure>
    <time_frame>up to 12 weeks</time_frame>
    <description>Proportion of subjects with complete wound closure at each of the 12 treatment weeks from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in pain using the numeric rating scale</measure>
    <time_frame>up to 12 weeks</time_frame>
    <description>Change from baseline in pain level as reported using a numeric rating scale for the target ulcer and the affected leg, separately. Subjects will be asked to rate the level of pain they experience on a scale from 0 to 10, with 0 representing &quot;no pain&quot; and 10 representing &quot;the worst possible pain&quot;.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Sheffield Preference-based Venous Ulcer questionnaire (SPVU-5D) quality of life questionnaire</measure>
    <time_frame>up to 17 weeks</time_frame>
    <description>The SPVU-5D is a condition-specific preference-based measure of health-related quality of life for use in the assessment of the impact of venous ulceration. It has five dimensions encompassing physical, psychological and social aspects. The dimensions have between three and five levels. The measure was developed from the bottom-up and incorporates items generated from patients. The measure has been shown to have good practicality and validity. Preference-weights and a scoring algorithm were produced based on valuations from the UK population.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Venous Leg Ulcer</condition>
  <arm_group>
    <arm_group_label>TTAX01</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TTAX01 will be applied directly to the wound surface and fixed with sterile adhesive strips, plus a secondary foam dressing held in place by multi-layer compression bandaging. A single layer of the test article should cover the entire open surface of the wound. TTAX01 may overlap onto adjacent healthy tissue and must be fenestrated prior to or after fixture. The material is to be applied once every 4 weeks unless the wound shows evidence of healing, in which case product will be withheld; or, if the test article has been accidentally dislodged within 1-week post application, it may be replaced at the subsequent treatment visit.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TTAX01</intervention_name>
    <description>TTAX01 is a cryopreserved human umbilical cord product derived from donated human placental tissue following healthy, live, caesarian section, full-term births after determination of donor eligibility and placenta suitability. TTAX01 is manufactured by TissueTech Inc. utilizing a proprietary CRYOTEK® process, which devitalizes the living cells but retains the natural structural and biological characteristics relevant to this tissue. TTAX01 is aseptically processed in compliance with current Good Tissue Practices (cGTP). TTAX01 will be manufactured in various sizes, stored in a medium of Dulbecco's Modified Eagle Medium/Glycerol (1:1) containing Amphotericin B.</description>
    <arm_group_label>TTAX01</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Profore Compression Therapy</intervention_name>
    <description>Subjects will utilize the compression system for the duration of the trial, with weekly re-applications of the compression system during study visits</description>
    <arm_group_label>TTAX01</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cadexomer Iodine dressing</intervention_name>
    <description>During the 2-week Screening Run-in period, subjects should be applied cadexomer iodine on the VLU.</description>
    <arm_group_label>TTAX01</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provide informed consent.&#xD;
&#xD;
          -  Age ≥ 18 years and of either sex.&#xD;
&#xD;
          -  Willing to comply with protocol instructions, including allowing all study&#xD;
             assessments.&#xD;
&#xD;
          -  Have a venous leg ulcer (VLU) between the knee and ankle (at or above the malleolus),&#xD;
             with a surface area in the range of ≥ 2.0 cm2 and ≤ 18.0 cm2 confirmed using the wound&#xD;
             imaging and measurement device.&#xD;
&#xD;
          -  Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular&#xD;
             or venous incompetence.&#xD;
&#xD;
          -  Arterial supply adequacy confirmed by any one of the following: Great toe pressure ≥&#xD;
             50 mm/Hg; Systolic blood pressure Ankle Brachial Index (ABI) in the range ≥ to 0.8 to&#xD;
             ≤ 1.1; TcPO2 ≥ to 40 mmHg from the foot&#xD;
&#xD;
          -  Target ulcer involves a full thickness skin loss, but WITHOUT exposure of tendon,&#xD;
             muscle, or bone&#xD;
&#xD;
          -  Target ulcer duration ≥ 6 weeks but ≤ 104 weeks&#xD;
&#xD;
          -  For diabetic subjects an HbA1C &lt; 12.0% per the local lab report&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Therapy with another investigational agent within thirty (30) days of Screening, or&#xD;
             during the study.&#xD;
&#xD;
          -  A target ulcer of non-venous etiologies (e.g., sickle cell anemia, necrobiosis&#xD;
             lipoidica diabeticorum, pyoderma gangrenosum, vasculopathic or vasculitic).&#xD;
&#xD;
          -  Deep Vein Thrombosis (DVT) that is acute, defined as the first 10 days from onset of&#xD;
             symptoms, or any DVT for which compression bandaging is considered by the Investigator&#xD;
             to be contraindicated.&#xD;
&#xD;
          -  Clinical evidence of ulcer bed infection as described in the Study Guide.&#xD;
&#xD;
          -  Documented history of osteomyelitis at the target wound location within 6 months&#xD;
             preceding the Screening Visit.&#xD;
&#xD;
          -  Refusal of or inability to tolerate compression therapy.&#xD;
&#xD;
          -  The subject is pregnant&#xD;
&#xD;
          -  The subject is a nursing mother&#xD;
&#xD;
          -  The subject is a woman of child-bearing potential who is unwilling to avoid pregnancy&#xD;
             or use an appropriate form of birth control (adequate birth control methods are&#xD;
             defined as: topical, oral, implantable, or injectable contraceptives; spermicide in&#xD;
             conjunction with a barrier such as a condom or diaphragm; IUD; or surgical&#xD;
             sterilization of partner).&#xD;
&#xD;
          -  Therapy of the target ulcer with other birth tissue products, autologous skin graft,&#xD;
             Apligraf®, or Dermagraft® within 30 days preceding the Screening Visit.&#xD;
&#xD;
          -  Therapy of the target ulcer with topical growth factors within 1 week preceding the&#xD;
             Screening Visit.&#xD;
&#xD;
          -  Current therapy with systemic antibiotics.&#xD;
&#xD;
          -  Current systemic therapy with cytotoxic drugs.&#xD;
&#xD;
          -  Current therapy with chronic (&gt; 10 days) oral corticosteroids.&#xD;
&#xD;
          -  Current therapy with TNF alpha inhibitors other than Trental® (pentoxifylline).&#xD;
&#xD;
          -  History of cancer in the preceding 5 years (other than carcinoma in situ of the cervix&#xD;
             or adequately treated non-melanoma skin cancers).&#xD;
&#xD;
          -  The subject has had previous use of NEOX® CORD 1K®, CLARIX® CORD 1K®, or TTAX01&#xD;
             applied to the index ulcer&#xD;
&#xD;
          -  The subject has an allergy to Amphotericin B or glycerol&#xD;
&#xD;
          -  The subject has an allergy to primary or secondary dressing materials used in this&#xD;
             trial&#xD;
&#xD;
          -  Per Investigator's discretion the subject is not appropriate for inclusion in the&#xD;
             trial, e.g., undergoing surgical treatments or the subject currently has sepsis, i.e.,&#xD;
             life-threatening organ dysfunction caused by a dysregulated host response to infection&#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>Scheffer Tseng, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Chief Technology Officer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ILD Consulting, Inc.</name>
      <address>
        <city>Carlsbad</city>
        <state>California</state>
        <zip>92009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA Olive View</name>
      <address>
        <city>Sylmar</city>
        <state>California</state>
        <zip>91342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rosalind Franklin University</name>
      <address>
        <city>North Chicago</city>
        <state>Illinois</state>
        <zip>60064</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Foot &amp; Ankle Center</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Luke's-Roosevelt Hospital Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carilion Clinic</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <disposition_first_submitted>August 12, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>August 25, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 1, 2020</disposition_first_posted>
  <last_update_submitted>August 31, 2020</last_update_submitted>
  <last_update_submitted_qc>August 31, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 3, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>venous stasis</keyword>
  <keyword>VLU</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Varicose Ulcer</mesh_term>
    <mesh_term>Leg Ulcer</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Iodine</mesh_term>
    <mesh_term>Cadexomer iodine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT03818828
org study id: TTAX01-CR002
nct id: NCT03818828
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
It is hypothesized that application at 4-week intervals of the human umbilical cord tissue
      TTAX01 to the surface of a well debrided, nonhealing venous leg ulcer (VLU) will result in a
      high proportion of wounds showing complete healing within 12 weeks of initiating therapy.
      This open label pilot study provides a framework for a larger, controlled study. The purposes
      for conducting this study are to evaluate the functionality of the protocol and to obtain an
      estimate of product safety and efficacy when applied according to the protocol instructions,
      and measured according to the stated endpoints.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete wound healing
time frame: 12-weeks
description: Proportion of subjects who achieve complete wound closure over the 12-week treatment period from baseline with a 4 week followup to confirm wound healing.
measure: Time to complete wound healing
time frame: up to 12 weeks
description: Time, in days, from baseline to initial observation of closure, in cases where healing is later confirmed.
measure: Complete wound healing
time frame: up to 12 weeks
description: Proportion of subjects with complete wound closure at each of the 12 treatment weeks from baseline
measure: Changes in pain using the numeric rating scale
time frame: up to 12 weeks
description: Change from baseline in pain level as reported using a numeric rating scale for the target ulcer and the affected leg, separately. Subjects will be asked to rate the level of pain they experience on a scale from 0 to 10, with 0 representing "no pain" and 10 representing "the worst possible pain".
measure: Sheffield Preference-based Venous Ulcer questionnaire (SPVU-5D) quality of life questionnaire
time frame: up to 17 weeks
description: The SPVU-5D is a condition-specific preference-based measure of health-related quality of life for use in the assessment of the impact of venous ulceration. It has five dimensions encompassing physical, psychological and social aspects. The dimensions have between three and five levels. The measure was developed from the bottom-up and incorporates items generated from patients. The measure has been shown to have good practicality and validity. Preference-weights and a scoring algorithm were produced based on valuations from the UK population.
arm group label: TTAX01
arm group type: Experimental
description: TTAX01 will be applied directly to the wound surface and fixed with sterile adhesive strips, plus a secondary foam dressing held in place by multi-layer compression bandaging. A single layer of the test article should cover the entire open surface of the wound. TTAX01 may overlap onto adjacent healthy tissue and must be fenestrated prior to or after fixture. The material is to be applied once every 4 weeks unless the wound shows evidence of healing, in which case product will be withheld; or, if the test article has been accidentally dislodged within 1-week post application, it may be replaced at the subsequent treatment visit.
intervention type: Biological
intervention name: TTAX01
description: TTAX01 is a cryopreserved human umbilical cord product derived from donated human placental tissue following healthy, live, caesarian section, full-term births after determination of donor eligibility and placenta suitability. TTAX01 is manufactured by TissueTech Inc. utilizing a proprietary CRYOTEK® process, which devitalizes the living cells but retains the natural structural and biological characteristics relevant to this tissue. TTAX01 is aseptically processed in compliance with current Good Tissue Practices (cGTP). TTAX01 will be manufactured in various sizes, stored in a medium of Dulbecco's Modified Eagle Medium/Glycerol (1:1) containing Amphotericin B.
arm group label: TTAX01
intervention type: Other
intervention name: Profore Compression Therapy
description: Subjects will utilize the compression system for the duration of the trial, with weekly re-applications of the compression system during study visits
arm group label: TTAX01
intervention type: Other
intervention name: Cadexomer Iodine dressing
description: During the 2-week Screening Run-in period, subjects should be applied cadexomer iodine on the VLU.
arm group label: TTAX01
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Scheffer Tseng, MD, PhD
role: Study Chair
affiliation: Chief Technology Officer
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Varicose Ulcer
mesh term: Leg Ulcer
mesh term: Ulcer
mesh term: Iodine
mesh term: Cadexomer iodine
sharing ipd: No