<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/NCT03229564</url>
  </required_header>
  <id_info>
    <org_study_id>TBRU-dS-BC-PIIb</org_study_id>
    <nct_id>NCT03229564</nct_id>
  </id_info>
  <brief_title>Study With an Autologous Dermo-epidermal Skin Substitute for the Treatment of Burns in Children</brief_title>
  <official_title>A Phase IIb, Prospective, Intra-patient Randomised Controlled, Multicentre Study to Evaluate the Safety and Efficacy of an Autologous Bio-engineered Dermo-epidermal Skin Substitute (EHSG-KF) for the Treatment of Partial Deep Dermal and Full Thickness Burns in Children in Comparison to Autologous Split-thickness Skin Grafts (STSG)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CUTISS AG</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Wyss Zurich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Julius Clinical</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sintesi Research Srl</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Zürich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Zurich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>CUTISS AG</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>
      This phase IIb trial aims to evaluate the efficacy and safety of EHSG-KF (synonym denovoSkin)&#xD;
      in comparison to meshed STSG in children with partial deep dermal and full thickness burns.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This multicentre phase IIb clinical trial will target patients from 1-17 years with severe&#xD;
      burns to elucidate the benefit of a tissue-engineered autologous skin substitute for the&#xD;
      patient group with the highest mortality rates. Particular emphasis, apart from safety, will&#xD;
      be placed on efficacy, including the ratio of covered surface area to harvested surface area&#xD;
      and scar quality, in comparison to meshed STSG.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 25, 2017</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Efficacy of EHSG-KF in comparison to meshed STSG based on ratio of covered surface</measure>
    <time_frame>4 weeks post grafting</time_frame>
    <description>Efficacy of EHSG-KF in comparison to meshed STSG based on ratio of covered surface area to biopsy site/donor site surface area</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of EHSG-KF in comparison to meshed STSG based on clinical signs of infection</measure>
    <time_frame>4-11 days post grafting and 21 +/-2 days post grafting</time_frame>
    <description>Evaluation of clinical signs of infection at experimental area and control area</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of EHSG-KF in comparison to meshed STSG based on microbiological signs of infection</measure>
    <time_frame>4-11 days post grafting and 21 +/-2 days post grafting</time_frame>
    <description>Evaluation of microbiologic signs of infection at experimental area and control area</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of EHSG-KF in comparison to meshed STSG based on evaluation of scar quality by measurement of the elasticity using Cutometer(R)</measure>
    <time_frame>1 year +/-30 days post grafting</time_frame>
    <description>Assessment of elasticity of experimental area and control area using Cutometer(R)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of EHSG-KF in comparison to meshed STSG based on evaluation of scar quality by assessment of general scar quality using POSAS assessment tool</measure>
    <time_frame>1 year +/-30 days post grafting</time_frame>
    <description>Assessment of general scar quality of experimental area and control area using POSAS assessment tool</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Burns</condition>
  <arm_group>
    <arm_group_label>EHSG-KF and STSG Transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transplantation of EHSG-KF to the experimental area and transplantation of STSG (split-thickness skin graft) to the control area</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>EHSG-KF</intervention_name>
    <description>Transplantation of autologous dermo-epidermal skin substitute EHSG-KF to the experimental area</description>
    <arm_group_label>EHSG-KF and STSG Transplantation</arm_group_label>
    <other_name>denovoSkin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>STSG</intervention_name>
    <description>Transplantation of autologous split-thickness skin graft to the control area</description>
    <arm_group_label>EHSG-KF and STSG Transplantation</arm_group_label>
    <other_name>Split-thickness skin graft</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: &lt;12 years of age&#xD;
&#xD;
          -  Deep partial thickness and/or full-thickness burns requiring surgical wound coverage&#xD;
&#xD;
          -  Expected that ≥90 cm2 of wound (not counting the head and neck area for study patients&#xD;
             in The Netherlands) will remain open at 4 weeks post burn despite proceeding with&#xD;
             treatment in accordance with the standard of care. &gt;20% TBSA burns can be taken as&#xD;
             guideline, but TBSA is not an inclusion criterion.&#xD;
&#xD;
          -  Signed Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients tested positive for HBV, HCV, syphilis or HIV&#xD;
&#xD;
          -  Patients with known underlying or concomitant medical conditions that may interfere&#xD;
             with normal wound healing (e.g. systemic skin and connective tissue diseases, any kind&#xD;
             of congenital defect of metabolism including insulin-dependent diabetes mellitus,&#xD;
             Cushing syndrome or disease, scurvy, chronic hypothyroidism, congenital or acquired&#xD;
             immunosuppressive condition, chronic renal failure, or chronic hepatic dysfunction&#xD;
             (Child-Pugh class B or C), severe malnutrition, or other concomitant illness which, in&#xD;
             the opinion of the Investigator, has the potential to significantly delay wound&#xD;
             healing)&#xD;
&#xD;
          -  Severe drug and alcohol abuse&#xD;
&#xD;
          -  Patients with a known history of malignancy&#xD;
&#xD;
          -  Pre-existing coagulation disorders as defined by INR outside its normal value, PTT&#xD;
             &gt;ULN and fibrinogen &lt;LLN prior to the current hospital admission and / or at the&#xD;
             Investigator's discretion&#xD;
&#xD;
          -  Patients with known allergies to amphotericin B, gentamicin, penicillin, streptomycin,&#xD;
             or bovine collagen&#xD;
&#xD;
          -  Previous enrolment of the patient into the current phase II study&#xD;
&#xD;
          -  Participation of the patient in another study with conflicting endpoints within 30&#xD;
             days preceding and during the present study&#xD;
&#xD;
          -  Patients or parents/legal guardian expected not to comply with the study protocol&#xD;
             (including patients with severe cognitive dysfunction/impairment and severe&#xD;
             psychiatric disorders)&#xD;
&#xD;
          -  Pregnant or breast feeding females&#xD;
&#xD;
          -  Suspicion of child abuse&#xD;
&#xD;
          -  Wounds in the head and neck area as study target area (only applicable for study&#xD;
             patients in The Netherlands)&#xD;
&#xD;
          -  Enrolment of the Investigator, his/her family members, employees and other dependent&#xD;
             persons&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clemens Schiestl, Prof.</last_name>
    <role>Study Chair</role>
    <affiliation>University Children's Hospital, Zurich</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Clemens Schiestl, Prof.</last_name>
    <phone>+41 44 266 73 93</phone>
    <email>clemens.schiestl@kispi.uzh.ch</email>
  </overall_contact>
  <location>
    <facility>
      <name>Unità di Chirurgia Plastica e Ustioni Ospedale Santobono</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marcello Zamparelli, Dr.</last_name>
    </contact>
    <investigator>
      <last_name>Marcello Zamparelli, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>U.O.C. Grandi Ustionati Azienda Ospedale Università Padova</name>
      <address>
        <city>Padova</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bruno Azzena, Prof.</last_name>
    </contact>
    <investigator>
      <last_name>Bruno Azzena, Prof.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Città della Salute</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Maurizio Stella, Dott.</last_name>
      <phone>+39 11 693 34 25</phone>
    </contact>
    <investigator>
      <last_name>Maurizio Stella, Dott.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>U.O. Chirurgia Plastica e Centro Ustioni Azienda Ospedaliera Universitaria Integrata Verona</name>
      <address>
        <city>Verona</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jasminka Minic, Dr.</last_name>
    </contact>
    <investigator>
      <last_name>Jasminka Minic</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Rode Kruis Ziekenhuis</name>
      <address>
        <city>Beverwijk</city>
        <zip>1940</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Esther Middelkoop, Prof.</last_name>
      <phone>+31 251 265 555</phone>
    </contact>
    <investigator>
      <last_name>Esther Middelkoop, Prof.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Children's Hospital Zurich</name>
      <address>
        <city>Zurich</city>
        <zip>8032</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sophie Böttcher, PD Dr. med.</last_name>
      <phone>+41 44 266 73 93</phone>
    </contact>
    <investigator>
      <last_name>Sophie Böttcher, PD Dr. med.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Switzerland</country>
  </location_countries>
  <removed_countries>
    <country>United Kingdom</country>
  </removed_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 7, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <last_update_submitted>February 7, 2023</last_update_submitted>
  <last_update_submitted_qc>February 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Burns</keyword>
  <keyword>Scar</keyword>
  <keyword>Skin</keyword>
  <keyword>Wound healing</keyword>
  <keyword>Tissue Engineering</keyword>
  <keyword>Dermis</keyword>
  <keyword>Epidermis</keyword>
  <keyword>Thermal Injuries</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burns</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03229564
org study id: TBRU-dS-BC-PIIb
nct id: NCT03229564
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This phase IIb trial aims to evaluate the efficacy and safety of EHSG-KF (synonym denovoSkin)
      in comparison to meshed STSG in children with partial deep dermal and full thickness burns.
This multicentre phase IIb clinical trial will target patients from 1-17 years with severe
      burns to elucidate the benefit of a tissue-engineered autologous skin substitute for the
      patient group with the highest mortality rates. Particular emphasis, apart from safety, will
      be placed on efficacy, including the ratio of covered surface area to harvested surface area
      and scar quality, in comparison to meshed STSG.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy of EHSG-KF in comparison to meshed STSG based on ratio of covered surface
time frame: 4 weeks post grafting
description: Efficacy of EHSG-KF in comparison to meshed STSG based on ratio of covered surface area to biopsy site/donor site surface area
measure: Safety of EHSG-KF in comparison to meshed STSG based on clinical signs of infection
time frame: 4-11 days post grafting and 21 +/-2 days post grafting
description: Evaluation of clinical signs of infection at experimental area and control area
measure: Safety of EHSG-KF in comparison to meshed STSG based on microbiological signs of infection
time frame: 4-11 days post grafting and 21 +/-2 days post grafting
description: Evaluation of microbiologic signs of infection at experimental area and control area
measure: Efficacy of EHSG-KF in comparison to meshed STSG based on evaluation of scar quality by measurement of the elasticity using Cutometer(R)
time frame: 1 year +/-30 days post grafting
description: Assessment of elasticity of experimental area and control area using Cutometer(R)
measure: Efficacy of EHSG-KF in comparison to meshed STSG based on evaluation of scar quality by assessment of general scar quality using POSAS assessment tool
time frame: 1 year +/-30 days post grafting
description: Assessment of general scar quality of experimental area and control area using POSAS assessment tool
arm group label: EHSG-KF and STSG Transplantation
arm group type: Experimental
description: Transplantation of EHSG-KF to the experimental area and transplantation of STSG (split-thickness skin graft) to the control area
intervention type: Biological
intervention name: EHSG-KF
description: Transplantation of autologous dermo-epidermal skin substitute EHSG-KF to the experimental area
arm group label: EHSG-KF and STSG Transplantation
other name: denovoSkin
intervention type: Biological
intervention name: STSG
description: Transplantation of autologous split-thickness skin graft to the control area
arm group label: EHSG-KF and STSG Transplantation
other name: Split-thickness skin graft
criteria: 
gender: All
minimum age: N/A
maximum age: 12 Years
healthy volunteers: No
last name: Clemens Schiestl, Prof.
role: Study Chair
affiliation: University Children's Hospital, Zurich
last name: Clemens Schiestl, Prof.
phone: +41 44 266 73 93
email: clemens.schiestl@kispi.uzh.ch
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Italy
country: Netherlands
country: Switzerland
country: United Kingdom
responsible party type: Sponsor
mesh term: Burns
sharing ipd: No