<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/NCT03022019</url>
  </required_header>
  <id_info>
    <org_study_id>NL57683.018.16</org_study_id>
    <nct_id>NCT03022019</nct_id>
  </id_info>
  <brief_title>ReNovaCell in Non-segmental Vitiligo</brief_title>
  <official_title>Autologous Cell Suspension Grafting Using ReNovaCell in Non-segmental Vitiligo Patients: a Randomized Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Netherlands Institute for Pigment Disorders</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Avita Medical</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Netherlands Institute for Pigment Disorders</source>
  <brief_summary>
    <textblock>
      Rationale:&#xD;
&#xD;
      Autologous epidermal cell suspension grafting is an effective method of surgical treatment in&#xD;
      vitiligo, which is suitable for treating large areas with good cosmetic results. The&#xD;
      RenovaCell Autologous Cell Harvesting Device (Avita Medical Europe Limited, Cambridge, UK)&#xD;
      (previous name: ReCell) is a device which, compared to other forms of autologous epidermal&#xD;
      cell suspension grafting, is easier in use showing similar results. Efficacy and safety of&#xD;
      the ReCell device was proven in segmental vitiligo and piebaldism. However, the efficacy in&#xD;
      non-segmental vitiligo is not yet confirmed in randomized controlled trials. The&#xD;
      investigators hypothesize that grafting using the ReNovaCell device in combination with&#xD;
      standard of care is also effective in stable non-segmental vitiligo and more effective than&#xD;
      standard of care alone.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      Primary: to assess the efficacy and safety of ReNovaCell grafting combined with 311 nm UVB&#xD;
      therapy and topical anti-inflammatory therapy for the treatment of stable non-segmental&#xD;
      vitiligo. Secondary: to assess, satisfaction, cosmetic acceptability, noticeability and&#xD;
      persistence of repigmentation after ReNovaCell transplantation.&#xD;
&#xD;
      Study design: Prospective, observer-blinded, randomised, within subject, controlled, study.&#xD;
&#xD;
      Study population: 20 patients ≥ 18 years with stable non-segmental vitiligo receiving&#xD;
      standard of care (311 nm UVB therapy and topical anti-inflammatory therapy) for at least 6&#xD;
      months at the Netherlands Institute for Pigment Disorders (NIPD) at the Academic Medical&#xD;
      Centre, University of Amsterdam.&#xD;
&#xD;
      Intervention: In patients already receiving standard of care (311 nm UVB therapy + topical&#xD;
      anti-inflammatory therapy) 2 comparable depigmented regions are randomised to receive&#xD;
      ReNovaCell grafting or no grafting. Standard of care will be given according to the standard&#xD;
      treatment protocol of our institute.&#xD;
&#xD;
      Main study parameters/endpoints:&#xD;
&#xD;
      Primary outcome:&#xD;
&#xD;
      Objective assessment of the degree of repigmentation three and six months after ReNovaCell&#xD;
      grafting with a digital image analysis system. To assess the pigmentation, the contours of&#xD;
      pigmentation are copied on a transparent sheet before, three and six months after treatment,&#xD;
      after which the sheets are scanned and digital image analysis is used to compute the affected&#xD;
      surface. By comparing pre- and post-treatment pictures, the relative surface showing&#xD;
      repigmentation expressed as percentage of the selected treated patch is computed.&#xD;
&#xD;
      Secondary outcomes:&#xD;
&#xD;
        -  Patient Reported Outcomes: satisfaction, cosmetic acceptability, noticeability&#xD;
&#xD;
        -  General patient assessed outcome per treatment region on a scale from 0-3 (poor,&#xD;
           moderate, good or excellent).&#xD;
&#xD;
        -  Visual assessment of percentage repigmentation by blinded observer and color match to&#xD;
           normal skin&#xD;
&#xD;
        -  Visual assessment of side effects per treatment region (hyperpigmentation,&#xD;
           hypopigmentation and scarring on a scale from 0-3) by a blinded investigator.&#xD;
&#xD;
        -  A small amount of the suspension of the included patients and the redundant lesional&#xD;
           punchgrafts of all patients will be used for flow cytometric analyses of the cellular&#xD;
           composition of the grafted cell suspension, and expression analysis of melanin&#xD;
           synthesis-related genes. These data will be correlated to the clinical data.&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
      relatedness: As the study involves large depigmented lesions, which are too large to treat in&#xD;
      regular surgical treatment (punch grafting), patients will not miss any regular treatment.&#xD;
      The time investment for the patient will be approximately 20 minutes for the punchgrafting&#xD;
      session, 75 minutes for the cell suspension grafting session and 15 minutes for the three&#xD;
      follow-up visits. Two of the five visits are part of the standard of care UVB follow-up&#xD;
      regimen and are therefore not additional due to the study. Infection in the grafted area or&#xD;
      the donor site may occur but is very rare; the risk of mild textural changes in the donor&#xD;
      site is moderate. Hyperpigmentation of the treated area does occur often, although this&#xD;
      improves over time in most cases. In case of improvement of the depigmentation, patients may&#xD;
      receive another treatment for the (contralateral) untreated side.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Futility&#xD;
  </why_stopped>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">May 14, 2019</completion_date>
  <primary_completion_date type="Actual">May 14, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
  </study_design_info>
  <primary_outcome>
    <measure>degree of repigmentation</measure>
    <time_frame>3 and 6 months</time_frame>
    <description>Objective assessment of the degree of repigmentation three and six months after ReNovaCell grafting with a digital image analysis system.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Patient Reported Outcomes: satisfaction, cosmetic acceptability, noticeability</measure>
    <time_frame>6 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Visual assessment of percentage repigmentation by blinded observer and color match to normal skin</measure>
    <time_frame>6 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Visual assessment of side effects per treatment region</measure>
    <time_frame>6 months</time_frame>
    <description>Visual assessment of side effects per treatment region (hyperpigmentation, hypopigmentation and scarring on a scale from 0-3) by a blinded investigator</description>
  </other_outcome>
  <other_outcome>
    <measure>flow cytometric analyses of the cellular composition of the grafted cell suspension</measure>
    <time_frame>at time of autologous cell suspension grafting</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Non-segmental Vitiligo</condition>
  <condition>Vitiligo</condition>
  <arm_group>
    <arm_group_label>No ReNovaCell treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Lesion on the same patient that receives only standard therapy, no ReNovaCell treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ReNovaCell treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lesion on the same patient that receives the ReNovaCell treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>ReNovaCell</intervention_name>
    <arm_group_label>ReNovaCell treatment</arm_group_label>
    <other_name>Autologous cell suspension grafting</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with, non-segmental vitiligo receiving 6 months of standard of care,&#xD;
             consisting of topical corticosteroids or immune modulators and NB-UVB phototherapy&#xD;
&#xD;
          -  Age ≥18&#xD;
&#xD;
          -  Patient is willing and able to give written informed consent&#xD;
&#xD;
          -  At least two comparable (in location and diameter) depigmented lesions of at least 10&#xD;
             cm2 or one large lesion of at least 30 cm2 on the extremities, face or trunk.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with signs of activity (spreading of lesions and/or koebnerisation) during&#xD;
             standard of care treatment or showing depigmentation in the test punch grafting&#xD;
&#xD;
          -  Skin type I&#xD;
&#xD;
          -  Recurrent HSV skin infections&#xD;
&#xD;
          -  Hypertrophic scars&#xD;
&#xD;
          -  Keloid&#xD;
&#xD;
          -  Cardiac insufficiency&#xD;
&#xD;
          -  Patients with a history of hypersensitivity to (UVB or UVA) light and/or allergy to&#xD;
             local anaesthesia.&#xD;
&#xD;
          -  Patients who are pregnant or breast-feeding&#xD;
&#xD;
          -  Patients not competent to understand what the procedures involves&#xD;
&#xD;
          -  Patients with a personal history of melanoma or non-melanoma skin cancer&#xD;
&#xD;
          -  Patients with atypical nevi.&#xD;
&#xD;
          -  Known allergy to clarithromycin&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Nipd / Amc</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 16, 2017</study_first_posted>
  <last_update_submitted>September 12, 2019</last_update_submitted>
  <last_update_submitted_qc>September 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>autologous cell suspension grafting</keyword>
  <keyword>vitiligo</keyword>
  <keyword>non-segmental</keyword>
  <keyword>ReNovaCell</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitiligo</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/NCT03022019
org study id: NL57683.018.16
nct id: NCT03022019
lead sponsor: 
collaborator: 
collaborator: 
Rationale:

      Autologous epidermal cell suspension grafting is an effective method of surgical treatment in
      vitiligo, which is suitable for treating large areas with good cosmetic results. The
      RenovaCell Autologous Cell Harvesting Device (Avita Medical Europe Limited, Cambridge, UK)
      (previous name: ReCell) is a device which, compared to other forms of autologous epidermal
      cell suspension grafting, is easier in use showing similar results. Efficacy and safety of
      the ReCell device was proven in segmental vitiligo and piebaldism. However, the efficacy in
      non-segmental vitiligo is not yet confirmed in randomized controlled trials. The
      investigators hypothesize that grafting using the ReNovaCell device in combination with
      standard of care is also effective in stable non-segmental vitiligo and more effective than
      standard of care alone.

      Objective:

      Primary: to assess the efficacy and safety of ReNovaCell grafting combined with 311 nm UVB
      therapy and topical anti-inflammatory therapy for the treatment of stable non-segmental
      vitiligo. Secondary: to assess, satisfaction, cosmetic acceptability, noticeability and
      persistence of repigmentation after ReNovaCell transplantation.

      Study design: Prospective, observer-blinded, randomised, within subject, controlled, study.

      Study population: 20 patients ≥ 18 years with stable non-segmental vitiligo receiving
      standard of care (311 nm UVB therapy and topical anti-inflammatory therapy) for at least 6
      months at the Netherlands Institute for Pigment Disorders (NIPD) at the Academic Medical
      Centre, University of Amsterdam.

      Intervention: In patients already receiving standard of care (311 nm UVB therapy + topical
      anti-inflammatory therapy) 2 comparable depigmented regions are randomised to receive
      ReNovaCell grafting or no grafting. Standard of care will be given according to the standard
      treatment protocol of our institute.

      Main study parameters/endpoints:

      Primary outcome:

      Objective assessment of the degree of repigmentation three and six months after ReNovaCell
      grafting with a digital image analysis system. To assess the pigmentation, the contours of
      pigmentation are copied on a transparent sheet before, three and six months after treatment,
      after which the sheets are scanned and digital image analysis is used to compute the affected
      surface. By comparing pre- and post-treatment pictures, the relative surface showing
      repigmentation expressed as percentage of the selected treated patch is computed.

      Secondary outcomes:

        -  Patient Reported Outcomes: satisfaction, cosmetic acceptability, noticeability

        -  General patient assessed outcome per treatment region on a scale from 0-3 (poor,
           moderate, good or excellent).

        -  Visual assessment of percentage repigmentation by blinded observer and color match to
           normal skin

        -  Visual assessment of side effects per treatment region (hyperpigmentation,
           hypopigmentation and scarring on a scale from 0-3) by a blinded investigator.

        -  A small amount of the suspension of the included patients and the redundant lesional
           punchgrafts of all patients will be used for flow cytometric analyses of the cellular
           composition of the grafted cell suspension, and expression analysis of melanin
           synthesis-related genes. These data will be correlated to the clinical data.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: As the study involves large depigmented lesions, which are too large to treat in
      regular surgical treatment (punch grafting), patients will not miss any regular treatment.
      The time investment for the patient will be approximately 20 minutes for the punchgrafting
      session, 75 minutes for the cell suspension grafting session and 15 minutes for the three
      follow-up visits. Two of the five visits are part of the standard of care UVB follow-up
      regimen and are therefore not additional due to the study. Infection in the grafted area or
      the donor site may occur but is very rare; the risk of mild textural changes in the donor
      site is moderate. Hyperpigmentation of the treated area does occur often, although this
      improves over time in most cases. In case of improvement of the depigmentation, patients may
      receive another treatment for the (contralateral) untreated side.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
measure: degree of repigmentation
time frame: 3 and 6 months
description: Objective assessment of the degree of repigmentation three and six months after ReNovaCell grafting with a digital image analysis system.
measure: Patient Reported Outcomes: satisfaction, cosmetic acceptability, noticeability
time frame: 6 months
measure: Visual assessment of percentage repigmentation by blinded observer and color match to normal skin
time frame: 6 months
measure: Visual assessment of side effects per treatment region
time frame: 6 months
description: Visual assessment of side effects per treatment region (hyperpigmentation, hypopigmentation and scarring on a scale from 0-3) by a blinded investigator
measure: flow cytometric analyses of the cellular composition of the grafted cell suspension
time frame: at time of autologous cell suspension grafting
arm group label: No ReNovaCell treatment
arm group type: No Intervention
description: Lesion on the same patient that receives only standard therapy, no ReNovaCell treatment.
arm group label: ReNovaCell treatment
arm group type: Experimental
description: Lesion on the same patient that receives the ReNovaCell treatment
intervention type: Device
intervention name: ReNovaCell
arm group label: ReNovaCell treatment
other name: Autologous cell suspension grafting
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Vitiligo