<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/NCT03288844</url>
  </required_header>
  <id_info>
    <org_study_id>CCD-GPLSCD01-03-FU</org_study_id>
    <secondary_id>2015-001344-11</secondary_id>
    <nct_id>NCT03288844</nct_id>
  </id_info>
  <brief_title>Follow-up Study After ACLSCT for Restoration of Corneal Epithelium in Patients With LSCD Due to Ocular Burns</brief_title>
  <acronym>HOLOCORE-FU</acronym>
  <official_title>Multinational, Multicenter, Prospective, Long-term Safety and Efficacy Follow-up Study After Autologous Cultivated Limbal Stem Cells Transplantation (ACLSCT) for Restoration of Corneal Epithelium in Patients With Limbal Stem Cell Deficiency Due to Ocular Burns</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Holostem Terapie Avanzate s.r.l.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cromsource</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Holostem Terapie Avanzate s.r.l.</source>
  <oversight_info>
    <has_dmc>No</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 is a multinational, multicentre, prospective, non-pharmacological follow-up study of the&#xD;
      clinical trial HOLOCORE. All patients transplanted with Holoclar in the HOLOCORE clinical&#xD;
      trial who consent to participate will be enrolled in this prospective study and observed for&#xD;
      at least 12 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      HOLOCORE FOLLOW-UP prospective study offers the opportunity to collect long-term efficacy and&#xD;
      safety data after one or two treatments with Holoclar. Moreover, since Holoclar (study drug&#xD;
      used in the main HOLOCORE interventional clinical trial) is suspected to improve the success&#xD;
      of keratoplasty in those patients candidate to receive this treatment but no data were&#xD;
      collected in the three previous retrospective studies (HLSTM01, HLSTM02 and HLSTM04) on&#xD;
      Holoclar, this follow-up study has been thought to observe the progress of the disease and to&#xD;
      collect data on keratoplasty and evaluate the benefits of Holoclar in subsequent keratoplasty&#xD;
      in patients treated once or two times with Holoclar.&#xD;
&#xD;
      All patients treated in the HOLOCORE clinical trial who consent to roll over to the present&#xD;
      extension study at the end of the HOLOCORE will be observed for a follow-up period which may&#xD;
      vary from a minimum of 12 month for the last patient to a maximum of 57 months for the first&#xD;
      patient entered.&#xD;
&#xD;
      A total of approximately 70 patients is expected (all patients who completed the HOLOCORE&#xD;
      study).&#xD;
&#xD;
      In case the last enrolled patient undergoes to Keratoplasty at the Last Visit of the&#xD;
      Follow-up study, this will consequently lead to a prolongation of the study up to further 12&#xD;
      months for all patients.&#xD;
&#xD;
      The subjects will be enrolled and observed at the same investigational centers where they&#xD;
      were recruited for the HOLOCORE clinical trial.&#xD;
&#xD;
      No drug will be administered for the scope of this study. Ophtalmological visits including&#xD;
      pictures collection and quality of life evaluations will be performed every 6 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 13, 2017</start_date>
  <completion_date type="Actual">March 31, 2023</completion_date>
  <primary_completion_date type="Actual">March 31, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Success of transplantation</measure>
    <time_frame>1 year</time_frame>
    <description>Transplantation will be considered with a clinically-relevant success if the severity of superficial corneal neo-vascularization will be judged as not exceeding one quadrant of invasion (without central cornea involvement) by the investigator and the degree of Epithelial defect as 'None' or 'Trace', respectively.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">47</enrollment>
  <condition>Limbal Stem Cell Deficiency Due to Ocular Burn</condition>
  <arm_group>
    <arm_group_label>HOLOCORE Patients</arm_group_label>
    <description>Patients who completed the main HOLOCORE clinical trial will undergo to Ophthalmologic examinations, Digital pictures collection and QoL questionnaires (NEI VFQ 25 and EQ-5D-3L/Y) will be performed/administered at each study visit</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Ophthalmologic examinations</intervention_name>
    <description>epithelial defects assessment by fluorescein staining; superficial corneal neo-vascularization assessment; ocular tonometry; slit lamp examination; conjunctival (both bulbar and limbal) inflammation assessment; corneal sensitivity; central cornea involvement (for opacity or central CNV); Best-Corrected Visual Acuity; evaluation of symptoms.</description>
    <arm_group_label>HOLOCORE Patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Digital pictures</intervention_name>
    <description>Digital pictures 2D to be taken at each visit</description>
    <arm_group_label>HOLOCORE Patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>QoL Questionnaires</intervention_name>
    <description>Quality of Life (NEI VFQ 25 and EQ-5D-3L/Y) questionnaires will be submitted at each visit</description>
    <arm_group_label>HOLOCORE Patients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All eligible patients who entered the core HOLOCORE study will be asked consent to roll&#xD;
        over into this extension study before their inclusion. Approximately 70 patients will be&#xD;
        enrolled in this study.&#xD;
&#xD;
        Safety population: all patients entering the study. The adult safety population will be&#xD;
        used to explore efficacy. Efficacy data collected on paediatric population will be only&#xD;
        listed.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients (adults and pediatrics) who completed the HOLOCORE core study and who&#xD;
             consent to roll over to the present extension study at the end of the HOLOCORE&#xD;
             follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No specific exclusion criterion is considered for this study, except for patients&#xD;
             dropping out from the HOLOCORE study or withdrawing consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Graziella Pellegrini, Professor</last_name>
    <role>Study Director</role>
    <affiliation>Holostem Terapie Avanzate s.r.l.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Paolo Rama, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital San Raffaele</name>
      <address>
        <city>Milan</city>
        <zip>20100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>May 25, 2023</last_update_submitted>
  <last_update_submitted_qc>May 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>LSCD, Holoclar, follow-up</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Limbal Stem Cell Deficiency</mesh_term>
    <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/NCT03288844
org study id: CCD-GPLSCD01-03-FU
secondary id: 2015-001344-11
nct id: NCT03288844
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a multinational, multicentre, prospective, non-pharmacological follow-up study of the
      clinical trial HOLOCORE. All patients transplanted with Holoclar in the HOLOCORE clinical
      trial who consent to participate will be enrolled in this prospective study and observed for
      at least 12 months.
HOLOCORE FOLLOW-UP prospective study offers the opportunity to collect long-term efficacy and
      safety data after one or two treatments with Holoclar. Moreover, since Holoclar (study drug
      used in the main HOLOCORE interventional clinical trial) is suspected to improve the success
      of keratoplasty in those patients candidate to receive this treatment but no data were
      collected in the three previous retrospective studies (HLSTM01, HLSTM02 and HLSTM04) on
      Holoclar, this follow-up study has been thought to observe the progress of the disease and to
      collect data on keratoplasty and evaluate the benefits of Holoclar in subsequent keratoplasty
      in patients treated once or two times with Holoclar.

      All patients treated in the HOLOCORE clinical trial who consent to roll over to the present
      extension study at the end of the HOLOCORE will be observed for a follow-up period which may
      vary from a minimum of 12 month for the last patient to a maximum of 57 months for the first
      patient entered.

      A total of approximately 70 patients is expected (all patients who completed the HOLOCORE
      study).

      In case the last enrolled patient undergoes to Keratoplasty at the Last Visit of the
      Follow-up study, this will consequently lead to a prolongation of the study up to further 12
      months for all patients.

      The subjects will be enrolled and observed at the same investigational centers where they
      were recruited for the HOLOCORE clinical trial.

      No drug will be administered for the scope of this study. Ophtalmological visits including
      pictures collection and quality of life evaluations will be performed every 6 months.
observational model: Case-Only
time perspective: Prospective
measure: Success of transplantation
time frame: 1 year
description: Transplantation will be considered with a clinically-relevant success if the severity of superficial corneal neo-vascularization will be judged as not exceeding one quadrant of invasion (without central cornea involvement) by the investigator and the degree of Epithelial defect as 'None' or 'Trace', respectively.
arm group label: HOLOCORE Patients
description: Patients who completed the main HOLOCORE clinical trial will undergo to Ophthalmologic examinations, Digital pictures collection and QoL questionnaires (NEI VFQ 25 and EQ-5D-3L/Y) will be performed/administered at each study visit
intervention type: Procedure
intervention name: Ophthalmologic examinations
description: epithelial defects assessment by fluorescein staining; superficial corneal neo-vascularization assessment; ocular tonometry; slit lamp examination; conjunctival (both bulbar and limbal) inflammation assessment; corneal sensitivity; central cornea involvement (for opacity or central CNV); Best-Corrected Visual Acuity; evaluation of symptoms.
arm group label: HOLOCORE Patients
intervention type: Other
intervention name: Digital pictures
description: Digital pictures 2D to be taken at each visit
arm group label: HOLOCORE Patients
intervention type: Other
intervention name: QoL Questionnaires
description: Quality of Life (NEI VFQ 25 and EQ-5D-3L/Y) questionnaires will be submitted at each visit
arm group label: HOLOCORE Patients
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Graziella Pellegrini, Professor
role: Study Director
affiliation: Holostem Terapie Avanzate s.r.l.
last name: Paolo Rama, MD
role: Study Chair
affiliation: Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Limbal Stem Cell Deficiency
mesh term: Burns
sharing ipd: No