<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/NCT03837483</url>
  </required_header>
  <id_info>
    <org_study_id>OTL-103-4</org_study_id>
    <secondary_id>2018-003842-18</secondary_id>
    <nct_id>NCT03837483</nct_id>
  </id_info>
  <brief_title>A Clinical Study to Evaluate the Use of a Cryopreserved Formulation of OTL-103 in Subjects With Wiskott-Aldrich Syndrome</brief_title>
  <official_title>A Single Arm, Open-label Clinical Trial of Hematopoietic Stem Cell Gene Therapy With Cryopreserved Autologous CD34+ Cells Transduced With Lentiviral Vector Encoding WAS cDNA in Subjects With Wiskott-Aldrich Syndrome (WAS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Orchard Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ospedale San Raffaele</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Orchard Therapeutics</source>
  <oversight_info>
    <has_dmc>No</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>
      This is an open-label, single arm study to evaluate the cryopreserved formulation of OTL-103&#xD;
      Gene Therapy. OTL-103 consists of autologous CD34+ hematopoietic stem cells in which the gene&#xD;
      encoding for the Wiskott-Aldrich Syndrome is introduced by means of a third generation&#xD;
      lentiviral vector.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 21, 2019</start_date>
  <completion_date type="Anticipated">September 2027</completion_date>
  <primary_completion_date type="Anticipated">September 2025</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <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>Annualized rate of severe infections from 6 to 18 months after gene therapy compared with 1 year before gene therapy</measure>
    <time_frame>18 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Annualized rate of moderate and severe bleeding episodes up to 1 year after gene therapy compared with 1 year before gene therapy</measure>
    <time_frame>12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the overall survival</measure>
    <time_frame>36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with Vector copy number (VCN)/cell &gt; 0.1 measured in peripheral blood-derived CD3+ cells</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of WAS protein expression increased from pre-treatment levels in lymphocytes</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of WAS protein expression increased from pre-treatment levels in platelets</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with successful engraftment of OTL-103</measure>
    <time_frame>6 months</time_frame>
    <description>Engraftment of of OTL-103 is measured by hematological reconstitution of an absolute neutrophil count &gt; 500 cell/ul</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of subjects presenting with malignancies or abnormal clonal proliferation</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Wiskott-Aldrich Syndrome</condition>
  <arm_group>
    <arm_group_label>Gene Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OTL-103, Autologous CD34+ hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding the human WAS gene</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>OTL-103</intervention_name>
    <description>Autologous hematopoietic stem cells collected from mobilized peripheral blood transduced ex vivo with a lentiviral vector encoding the WAS cDNA</description>
    <arm_group_label>Gene Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: up to 65 years&#xD;
&#xD;
          -  Diagnosis of WAS defined by genetic mutation and at least one of the following&#xD;
             criteria:&#xD;
&#xD;
               -  Severe Wiskott-Aldrich Syndrome (WAS) gene mutation, defined by literature data&#xD;
                  (genotype/phenotype studies).;&#xD;
&#xD;
               -  Absent WASP expression, assessed by flow cytometry;&#xD;
&#xD;
               -  Severe clinical score (Zhu clinical score ≥ 3);&#xD;
&#xD;
          -  No human leukocyte antigen (HLA)-identical related donor available for hematopoietic&#xD;
             stem cells transplant (HSCT).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  End-organ dysfunction, severe active infection not responsive to treatment or other&#xD;
             severe disease or clinical condition which, in the judgment of the investigator, would&#xD;
             make the patient inappropriate for entry into this study.&#xD;
&#xD;
          -  Malignant neoplasia (except local skin cancer) or a documented history of hereditary&#xD;
             cancer syndrome.&#xD;
&#xD;
          -  Myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome and&#xD;
             acute myeloid leukaemia , or other serious haematological disorders&#xD;
&#xD;
          -  Documented human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Prior allogeneic hematopoietic stem cell transplantation, with evidence of residual&#xD;
             cells of donor origin&#xD;
&#xD;
          -  Symptomatic herpes zoster, not responsive to specific treatment&#xD;
&#xD;
          -  Evidence of acute tuberculosis&#xD;
&#xD;
          -  Acute or chronic stable Hepatitis B&#xD;
&#xD;
          -  Presence of positive Hepatitis C RNA test result at screening&#xD;
&#xD;
          -  Patients not eligible for mobilization protocols in order to obtain CD34+ cells&#xD;
&#xD;
          -  Previous Gene Therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Orchard Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Orchard Therapeutics (Europe) Limited</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta, Inc</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30329</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)</name>
      <address>
        <city>Milan</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>February 8, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>March 27, 2023</last_update_submitted>
  <last_update_submitted_qc>March 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 28, 2023</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>Wiskott-Aldrich Syndrome</mesh_term>
    <mesh_term>Syndrome</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/NCT03837483
org study id: OTL-103-4
secondary id: 2018-003842-18
nct id: NCT03837483
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label, single arm study to evaluate the cryopreserved formulation of OTL-103
      Gene Therapy. OTL-103 consists of autologous CD34+ hematopoietic stem cells in which the gene
      encoding for the Wiskott-Aldrich Syndrome is introduced by means of a third generation
      lentiviral vector.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Annualized rate of severe infections from 6 to 18 months after gene therapy compared with 1 year before gene therapy
time frame: 18 months
measure: Annualized rate of moderate and severe bleeding episodes up to 1 year after gene therapy compared with 1 year before gene therapy
time frame: 12 months
measure: Evaluation of the overall survival
time frame: 36 months
measure: Number of patients with Vector copy number (VCN)/cell > 0.1 measured in peripheral blood-derived CD3+ cells
time frame: 2 years
measure: Percentage of WAS protein expression increased from pre-treatment levels in lymphocytes
time frame: 2 years
measure: Percentage of WAS protein expression increased from pre-treatment levels in platelets
time frame: 2 years
measure: Number of participants with successful engraftment of OTL-103
time frame: 6 months
description: Engraftment of of OTL-103 is measured by hematological reconstitution of an absolute neutrophil count > 500 cell/ul
measure: The number of subjects presenting with malignancies or abnormal clonal proliferation
time frame: 2 years
arm group label: Gene Therapy
arm group type: Experimental
description: OTL-103, Autologous CD34+ hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding the human WAS gene
intervention type: Genetic
intervention name: OTL-103
description: Autologous hematopoietic stem cells collected from mobilized peripheral blood transduced ex vivo with a lentiviral vector encoding the WAS cDNA
arm group label: Gene Therapy
criteria: 
gender: All
minimum age: N/A
maximum age: 65 Years
healthy volunteers: No
last name: Orchard Clinical Trials
role: Study Director
affiliation: Orchard Therapeutics (Europe) Limited
facility: 
facility: 
country: Italy
country: United States
responsible party type: Sponsor
mesh term: Wiskott-Aldrich Syndrome
mesh term: Syndrome
sharing ipd: No