<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/NCT03230175</url>
  </required_header>
  <id_info>
    <org_study_id>TTCRNE-1501</org_study_id>
    <nct_id>NCT03230175</nct_id>
  </id_info>
  <brief_title>Phase 2 Pilot Trial of Subjects With Complex Non-healing Diabetic Foot Ulcers Treated With Standard Care Plus Cryopreserved Umbilical Cord Allograft (TTAX01)</brief_title>
  <official_title>A Multicenter, Open Label Phase 2 Pilot Trial of Subjects With Complex Non-healing Diabetic Foot Ulcers Treated With Standard Care Plus Cryopreserved Umbilical Cord Allograft (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 of the human placental umbilical cord tissue TTAX01 to&#xD;
      the surface of a well debrided, complex diabetic foot ulcer will, with concomitant management&#xD;
      of infection, result in a higher proportion of wounds showing complete healing within 16&#xD;
      weeks of initiating therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The hypothesis under study is that one or more applications of TTAX01 to the wound surface of&#xD;
      a well debrided, complex diabetic foot ulcer managed with appropriate antibiotic therapy will&#xD;
      result in a higher probability of complete healing than would be expected from management&#xD;
      with standard care alone. In this open label Phase 2 pilot trial, all subjects will receive&#xD;
      the intervention over a maximum period of 16 weeks. Eligible consenting subjects will undergo&#xD;
      a baseline aggressive debridement in the operating room to remove infected and devitalized&#xD;
      bone and soft tissue. TTAX01 will be applied to the debrided wound bed at baseline, and if&#xD;
      healing is not evident, it will be applied again at 4 week intervals. At each weekly visit&#xD;
      the wound will be further debrided as necessary.&#xD;
&#xD;
      Consenting subjects who qualify for enrollment will undergo an aggressive surgical&#xD;
      debridement at the baseline visit, including biopsies of bone for histology and microbiologic&#xD;
      testing at the start and completion of debridement. Systemic antibiotics will be given&#xD;
      empirically, with adjustments made on the basis of culture and sensitivity results. New or&#xD;
      recurrent infections will be managed with additional debridement and adjustment or addition&#xD;
      of appropriate systemic antibiotics. The test article, TTAX01, will be sutured to the&#xD;
      debrided wound bed at baseline and again at 4 week intervals over the 16 week treatment&#xD;
      period for wounds that do not show evidence of healing. For wounds that do show evidence of&#xD;
      healing, additional applications of TTAX01 will be withheld, based on observations from&#xD;
      retrospective case series.&#xD;
&#xD;
      Subjects whose wounds close prior to 16 weeks will move directly to a 2 week confirmation of&#xD;
      closure period. Subjects whose wounds have not closed by the end of 16 weeks will exit the&#xD;
      trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 4, 2017</start_date>
  <completion_date type="Actual">April 1, 2019</completion_date>
  <primary_completion_date type="Actual">January 10, 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>Number of Subjects With Complete Wound Healing</measure>
    <time_frame>16-weeks</time_frame>
    <description>Proportion of subjects with complete wound healing observed over the 16-week treatment period. Complete wound healing was defined as an initial observation of closure, followed by two confirmatory visits two weeks apart.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Complete Wound Healing</measure>
    <time_frame>up to 16 weeks</time_frame>
    <description>Time in number of days to complete wound closure over the 16 week treatment period, starting from enrollment to the time of the initial observation of wound closure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Wound Surface Area</measure>
    <time_frame>at week 16</time_frame>
    <description>Rate of wound closure, specifically percent change in the wound surface area (cm2) at each visit from baseline for assessing the rate of wound closure in area. Only percent change in wound surface area at week 16 reported.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Non-healing Wound</condition>
  <condition>Non-healing Diabetic Foot Ulcer</condition>
  <condition>Diabetic Foot Infection</condition>
  <arm_group>
    <arm_group_label>TTAX01 plus standard care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible consenting subjects will undergo a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. A six week course of systemic antibiotics will be used to resolve baseline infection. TTAX01 will be applied to the debrided wound bed at baseline, and if healing is not evident, it will be applied again at 4 week intervals. At each weekly visit the wound will be further debrided as necessary.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TTAX01</intervention_name>
    <description>TTAX01 will be applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article should cover the entire open surface of the wound. The material is to be applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it may be replaced at any time.</description>
    <arm_group_label>TTAX01 plus standard care</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgical resection and debridement</intervention_name>
    <description>Perform surgical sharp debridement in the OR, to remove:&#xD;
infectious agents and biofilms (purulence),&#xD;
all debris, eschar, callus and macerated non-viable tissue from the wound base, and&#xD;
dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge.&#xD;
Surgical Resection will be performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate.</description>
    <arm_group_label>TTAX01 plus standard care</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Systemic antibiotics</intervention_name>
    <description>Six (6) weeks of systemic antibiotic therapy is required. A definitive therapy will be guided by the microbiological results based on bone biopsy.</description>
    <arm_group_label>TTAX01 plus standard care</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Off-loading</intervention_name>
    <description>Provide off-loading device appropriate to the location of wound with full length boot or total contact cast</description>
    <arm_group_label>TTAX01 plus standard care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The subject has signed the informed consent form&#xD;
&#xD;
          -  The subject is male or female, at least 18 years of age inclusive at the date of&#xD;
             Screening&#xD;
&#xD;
          -  The subject has confirmed diagnosis of Type I or Type II diabetes&#xD;
&#xD;
          -  The subject's index ulcer is located on the plantar surface, inter digital, heel, or&#xD;
             lateral or medial surface of the foot&#xD;
&#xD;
          -  The subject has an index ulcer with visible margins having an area ≥1.0 cm2 to ≤ 10.0&#xD;
             cm2 when measured by the electronic measuring device at Screening&#xD;
&#xD;
          -  The subject's index ulcer extends beyond the dermis, into subcutaneous tissue with&#xD;
             evidence of exposed bone, tendon, muscle and/or joint capsule&#xD;
&#xD;
          -  The subject presents with history, signs or symptoms leading to a clinical suspicion&#xD;
             of osteomyelitis in the opinion of the Investigator supported by positive Probe to&#xD;
             Bone (PTB) and any of the following: radiographic (x-ray, Magnetic Resonance Imaging&#xD;
             (MRI), or bone scan) or evidence of bone necrosis&#xD;
&#xD;
          -  The subject has an Ankle Brachial Index ≥ 0.7 to ≤ 1.3 or TcPO2 ≥ 40 mmHg on the&#xD;
             dorsum of the affected foot, or Great Toe Pressure ≥ 50 mmHg&#xD;
&#xD;
          -  The subject is under the care of a physician for the management of Diabetes Mellitus&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The subject's index ulcer is primarily located on the dorsal surface of the foot&#xD;
&#xD;
          -  The subject's index ulcer can be addressed by primary closure through the completion&#xD;
             of the initial or staged surgical procedure&#xD;
&#xD;
          -  The subject has a glycated hemoglobin A1c (HbA1c) level of &gt; 12%&#xD;
&#xD;
          -  The subject has a serum albumin level ≤ 2.0 g/dL&#xD;
&#xD;
          -  The subject has a white blood cell count &lt; 2.0 x109/L, neutrophils &lt; 1.0 x109/L, or&#xD;
             platelets &lt; 100 x109/L&#xD;
&#xD;
          -  The subject has malignancy or a history of cancer, other than non-melanoma skin&#xD;
             cancer, in five years before Screening&#xD;
&#xD;
          -  The subject is pregnant&#xD;
&#xD;
          -  The subject is a nursing mother&#xD;
&#xD;
          -  The subject's index ulcer is over an active Charcot deformity&#xD;
&#xD;
          -  The subject has had previous use of NEOX®, CLARIX®, or TTAX01 applied to the index&#xD;
             ulcer&#xD;
&#xD;
          -  Per Investigator's discretion the subject is not appropriate for inclusion in the&#xD;
             trial, e.g., undergoing surgical treatments listed in the protocol or the subject&#xD;
             currently has sepsis&#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</last_name>
    <role>Study Chair</role>
    <affiliation>Chief Technology Officer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner University Medical Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</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>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Village Podiatry Centers</name>
      <address>
        <city>Smyrna</city>
        <state>Georgia</state>
        <zip>30082</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>Ochsner Medical Center</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</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>University of North Carolina</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Futuro Clinical Trials, LLC</name>
      <address>
        <city>McAllen</city>
        <state>Texas</state>
        <zip>78501</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>May 2021</verification_date>
  <study_first_submitted>July 19, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <results_first_submitted>April 6, 2021</results_first_submitted>
  <results_first_submitted_qc>May 20, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 15, 2021</results_first_posted>
  <disposition_first_submitted>March 11, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>May 20, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">June 15, 2021</disposition_first_posted>
  <last_update_submitted>May 20, 2021</last_update_submitted>
  <last_update_submitted_qc>May 20, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2021</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>Diabetic Foot</mesh_term>
    <mesh_term>Foot 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>Anti-Bacterial Agents</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/75/NCT03230175/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 8, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/75/NCT03230175/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>TTAX01 Plus Standard Care</title>
          <description>Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. infection.&#xD;
TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was to be applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it may be replaced at any time.&#xD;
Surgical resection and debridement: Perform surgical sharp debridement in the OR, to remove:&#xD;
infectious agents and biofilms (purulence),&#xD;
all debris, eschar, callus and macerated non-viable tissue from the wound base, and&#xD;
dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge.&#xD;
Surgical Resection will be performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate.&#xD;
Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy is required. A definitive therapy will be guided by the microbiological results based on bone biopsy.&#xD;
Off-loading: Provide off-loading device appropriate to the location of wound with full length boot or total contact cast</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>TTAX01 Plus Standard Care</title>
          <description>Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue.&#xD;
TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it may be replaced at any time.&#xD;
Surgical resection and debridement: Perform surgical sharp debridement in the OR, to remove:&#xD;
infectious agents and biofilms (purulence),&#xD;
all debris, eschar, callus and macerated non-viable tissue from the wound base, and&#xD;
dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge.&#xD;
Surgical Resection will be performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate.&#xD;
Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy is required. A definitive therapy will be guided by the microbiological results based on bone biopsy.&#xD;
Off-loading: Provide off-loading device appropriate to the location of wound with full length boot or total contact cast</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="32"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt; 65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt; or = to 65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Alaskan Native/American Indian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black/African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White/Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other, not specified</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Subject presents with history, signs or symptoms leading to a clinical suspicion of osteomyelitis</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Subjects With Complete Wound Healing</title>
        <description>Proportion of subjects with complete wound healing observed over the 16-week treatment period. Complete wound healing was defined as an initial observation of closure, followed by two confirmatory visits two weeks apart.</description>
        <time_frame>16-weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TTAX01 Plus Standard Care</title>
            <description>Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue.&#xD;
TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it was replaced at any time.&#xD;
Surgical resection and debridement: Performed surgical sharp debridement in the OR, to remove:&#xD;
infectious agents and biofilms (purulence),&#xD;
all debris, eschar, callus and macerated non-viable tissue from the wound base, and&#xD;
dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge.&#xD;
Surgical Resection performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate.&#xD;
Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy was required. A definitive therapy was guided by the microbiological results based on bone biopsy.&#xD;
Off-loading: Provided off-loading device appropriate to the location of wound with full length boot or total contact cast</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Complete Wound Healing</title>
          <description>Proportion of subjects with complete wound healing observed over the 16-week treatment period. Complete wound healing was defined as an initial observation of closure, followed by two confirmatory visits two weeks apart.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Complete Wound Healing</title>
        <description>Time in number of days to complete wound closure over the 16 week treatment period, starting from enrollment to the time of the initial observation of wound closure</description>
        <time_frame>up to 16 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TTAX01 Plus Standard Care</title>
            <description>Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue.&#xD;
TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it was replaced at any time.&#xD;
Surgical resection and debridement: Performed surgical sharp debridement in the OR, to remove:&#xD;
infectious agents and biofilms (purulence),&#xD;
all debris, eschar, callus and macerated non-viable tissue from the wound base, and&#xD;
dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge.&#xD;
Surgical Resection performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate.&#xD;
Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy was required. A definitive therapy was guided by the microbiological results based on bone biopsy.&#xD;
Off-loading: Provided off-loading device appropriate to the location of wound with full length boot or total contact cast</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Complete Wound Healing</title>
          <description>Time in number of days to complete wound closure over the 16 week treatment period, starting from enrollment to the time of the initial observation of wound closure</description>
          <units>weeks</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.8" spread="4.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Wound Surface Area</title>
        <description>Rate of wound closure, specifically percent change in the wound surface area (cm2) at each visit from baseline for assessing the rate of wound closure in area. Only percent change in wound surface area at week 16 reported.</description>
        <time_frame>at week 16</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TTAX01 Plus Standard Care</title>
            <description>Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue.&#xD;
TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it was replaced at any time.&#xD;
Surgical resection and debridement: Performed surgical sharp debridement in the OR, to remove:&#xD;
infectious agents and biofilms (purulence),&#xD;
all debris, eschar, callus and macerated non-viable tissue from the wound base, and&#xD;
dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge.&#xD;
Surgical Resection performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate.&#xD;
Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy was required. A definitive therapy was guided by the microbiological results based on bone biopsy.&#xD;
Off-loading: Provided off-loading device appropriate to the location of wound with full length boot or total contact cast</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Wound Surface Area</title>
          <description>Rate of wound closure, specifically percent change in the wound surface area (cm2) at each visit from baseline for assessing the rate of wound closure in area. Only percent change in wound surface area at week 16 reported.</description>
          <units>Percent Change</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.93" lower_limit="84.54" upper_limit="95.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The maximum time in the study for any subject was 21 weeks, with 1 week in screening and assuming wound healing occurs at week 16 followed by 2 weeks of observation for confirmation of closure, and a final exit visit 14 days later.</time_frame>
      <desc>An Adverse Event (AE) is any untoward medical occurrence temporally associated with the use of an investigational medicinal product, whether or not considered causally related to that product. An Serious Adverse Event is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, requires hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.</desc>
      <group_list>
        <group group_id="E1">
          <title>TTAX01 Plus Standard Care</title>
          <description>Eligible consenting subjects underwent a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue.&#xD;
TTAX01: TTAX01 was applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article covered the entire open surface of the wound. The material was applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it was replaced at any time.&#xD;
Surgical resection and debridement: Performed surgical sharp debridement in the OR, to remove:&#xD;
infectious agents and biofilms (purulence),&#xD;
all debris, eschar, callus and macerated non-viable tissue from the wound base, and&#xD;
dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge.&#xD;
Surgical Resection performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate.&#xD;
Systemic antibiotics: Six (6) weeks of systemic antibiotic therapy was required. A definitive therapy was guided by the microbiological results based on bone biopsy.&#xD;
Off-loading: Provided off-loading device appropriate to the location of wound with full length boot or total contact cast</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (20.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>gastroparesis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bilateral Pleural Effusions</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>recurrent transient ischemic attack</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (20.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes mellitus inadequate control</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Diabetic Foot</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Osteomyelitis acute</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Limb injury</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Skin maceration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The one caveat is the lack of a control group. However, the study was designed to examine the safety and estimate the efficacy of TTAX01 plus standard care in achieving complete would closure of these complex non-healing diabetic foot ulcer with high risk factors.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Nick McCoy, Vice President Clinical Operations</name_or_title>
      <organization>TissueTech, Inc.</organization>
      <phone>7867340023</phone>
      <email>nmccoy@tissuetechinc.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03230175
org study id: TTCRNE-1501
nct id: NCT03230175
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
It is hypothesized that application of the human placental umbilical cord tissue TTAX01 to
      the surface of a well debrided, complex diabetic foot ulcer will, with concomitant management
      of infection, result in a higher proportion of wounds showing complete healing within 16
      weeks of initiating therapy.
The hypothesis under study is that one or more applications of TTAX01 to the wound surface of
      a well debrided, complex diabetic foot ulcer managed with appropriate antibiotic therapy will
      result in a higher probability of complete healing than would be expected from management
      with standard care alone. In this open label Phase 2 pilot trial, all subjects will receive
      the intervention over a maximum period of 16 weeks. Eligible consenting subjects will undergo
      a baseline aggressive debridement in the operating room to remove infected and devitalized
      bone and soft tissue. TTAX01 will be applied to the debrided wound bed at baseline, and if
      healing is not evident, it will be applied again at 4 week intervals. At each weekly visit
      the wound will be further debrided as necessary.

      Consenting subjects who qualify for enrollment will undergo an aggressive surgical
      debridement at the baseline visit, including biopsies of bone for histology and microbiologic
      testing at the start and completion of debridement. Systemic antibiotics will be given
      empirically, with adjustments made on the basis of culture and sensitivity results. New or
      recurrent infections will be managed with additional debridement and adjustment or addition
      of appropriate systemic antibiotics. The test article, TTAX01, will be sutured to the
      debrided wound bed at baseline and again at 4 week intervals over the 16 week treatment
      period for wounds that do not show evidence of healing. For wounds that do show evidence of
      healing, additional applications of TTAX01 will be withheld, based on observations from
      retrospective case series.

      Subjects whose wounds close prior to 16 weeks will move directly to a 2 week confirmation of
      closure period. Subjects whose wounds have not closed by the end of 16 weeks will exit the
      trial.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Subjects With Complete Wound Healing
time frame: 16-weeks
description: Proportion of subjects with complete wound healing observed over the 16-week treatment period. Complete wound healing was defined as an initial observation of closure, followed by two confirmatory visits two weeks apart.
measure: Time to Complete Wound Healing
time frame: up to 16 weeks
description: Time in number of days to complete wound closure over the 16 week treatment period, starting from enrollment to the time of the initial observation of wound closure
measure: Percent Change in Wound Surface Area
time frame: at week 16
description: Rate of wound closure, specifically percent change in the wound surface area (cm2) at each visit from baseline for assessing the rate of wound closure in area. Only percent change in wound surface area at week 16 reported.
arm group label: TTAX01 plus standard care
arm group type: Experimental
description: Eligible consenting subjects will undergo a baseline aggressive debridement in the operating room to remove infected and devitalized bone and soft tissue. A six week course of systemic antibiotics will be used to resolve baseline infection. TTAX01 will be applied to the debrided wound bed at baseline, and if healing is not evident, it will be applied again at 4 week intervals. At each weekly visit the wound will be further debrided as necessary.
intervention type: Biological
intervention name: TTAX01
description: TTAX01 will be applied directly to the wound surface and retained with non-absorbable sutures. A single layer of the test article should cover the entire open surface of the wound. The material is to be applied once every 4 weeks unless the wound shows evidence of healing, in which case dosing is suspended; or, if the test article has been accidentally dislodged, it may be replaced at any time.
arm group label: TTAX01 plus standard care
intervention type: Procedure
intervention name: Surgical resection and debridement
description: Perform surgical sharp debridement in the OR, to remove:
infectious agents and biofilms (purulence),
all debris, eschar, callus and macerated non-viable tissue from the wound base, and
dead (suprabasal epidermis), scarred (elevated/edematous) and necrotic/macerated tissue from the wound edge.
Surgical Resection will be performed to remove as much of the necrotic bone detected by the radiographic evidence as is appropriate.
arm group label: TTAX01 plus standard care
intervention type: Drug
intervention name: Systemic antibiotics
description: Six (6) weeks of systemic antibiotic therapy is required. A definitive therapy will be guided by the microbiological results based on bone biopsy.
arm group label: TTAX01 plus standard care
intervention type: Device
intervention name: Off-loading
description: Provide off-loading device appropriate to the location of wound with full length boot or total contact cast
arm group label: TTAX01 plus standard care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Scheffer Tseng, MD
role: Study Chair
affiliation: Chief Technology Officer
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetic Foot
mesh term: Foot Ulcer
mesh term: Ulcer
mesh term: Anti-Bacterial Agents
sharing ipd: Undecided
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The one caveat is the lack of a control group. However, the study was designed to examine the safety and estimate the efficacy of TTAX01 plus standard care in achieving complete would closure of these complex non-healing diabetic foot ulcer with high risk factors.
point of contact: 