<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/NCT03275051</url>
  </required_header>
  <id_info>
    <org_study_id>207757</org_study_id>
    <secondary_id>2017-001366-14</secondary_id>
    <nct_id>NCT03275051</nct_id>
  </id_info>
  <brief_title>Long-term Follow-up of Subjects Treated With OTL-300 for Transfusion Dependent Beta-thalassemia Study (TIGET-BTHAL)</brief_title>
  <official_title>A Long-term Safety and Efficacy follow-on Study in Participants With Transfusion Dependent Beta-thalassemia Who Have Previously Received OTL-300 (Formerly Know as GSK2696277)) and Completed the TIGET-BTHAL Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IRCCS San Raffaele</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Telethon Institute for Gene Therapy (OSR-TIGET)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>IRCCS San Raffaele</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>
      OTL-300 is a gene therapy drug product consisting of autologous hematopoietic stem/progenitor&#xD;
      cluster of differentiation (CD) 34+ cells genetically modified with a lentiviral vector&#xD;
      (GLOBE) encoding the human beta globin gene. The TIGET-BTHAL is a phase I/II study evaluating&#xD;
      safety and efficacy of OTL-300 in subjects with transfusion dependent beta-thalassemia for&#xD;
      two years post gene-therapy. Subjects with rare disease who have undergone gene therapy are&#xD;
      followed for efficacy and possible delayed adverse events. Thus, this study is designed to&#xD;
      follow patients who have received gene therapy on TIGET-BTHAL for an additional six years&#xD;
      (for a total of eight years).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 4, 2017</start_date>
  <completion_date type="Anticipated">June 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2025</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>No study treatment will be administered in this study. Subjects who have received treatment with OTL-300 in and completed study TIGET-BTHAL will be included in this study.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>No study treatment will be administered.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects with absence of abnormal clonal proliferation (ACP)</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>Clonal proliferation describes the selection and reproduction of only one type of cell.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with Polyclonal engraftment</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>Integration site analysis will be performed on different hematopoietic lineages from peripheral blood and/or bone marrow. Polyclonality of hematopoiesis is defined as &gt;1000 unique integration sites retrieved at specified time points. The number of subjects with polyclonality of hematopoiesis will be estimated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with reduction in red blood cells (RBC) transfusion volume</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with reduction in transfusion rate up to transfusion independence</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with transfusion independence</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>Transfusion independence is defined as &lt;= 1 transfusion in the previous 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin (Hb) levels in subjects achieving transfusion independence</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with sustained engraftment of genetically corrected cells</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>Engraftment will be assessed by vector-specific quantitative polymerase chain reaction (PCR) on bone marrow. Sustained engraftment is defined as &gt;=0.15 vector copy number (VCN)/genome in bone marrow erythroid cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with overall survival</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The number of subjects alive over all the trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events (AEs), serious AEs (SAEs)</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical chemistry laboratory parameters as a measure of safety</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematology laboratory parameters as a measure of safety</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urinalysis as a measure of safety</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of viral infections as a measure of safety</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>Microbiological laboratory tests will be performed to analyze the presence of hepatitis C virus ribonucleic acid (RNA), hepatitis B virus RNA, hepatitis B surface antigen, human T cell lymphotropic virus type 1-2 antibodies. Molecular tests will be performed for human immunodeficiency virus in peripheral blood or plasma.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Screening for occurrence of antibodies against viruses and toxoplasma as a measure of safety</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>Immunological laboratory tests will be performed to analyze antibodies to Epstein-Barr virus, cytomegalovirus, herpes simplex virus 1-2, varicella zoster virus, toxoplasma.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) scores</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short-Form-36 (SF-36) scores</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>Impact of disease on overall QoL in adults will be measured using the SF-36.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pediatric Quality of Life (PedsQL) questionnaire scores</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The PedsQL 4.0 generic core scale will be used to measure QoL in pediatric subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of growth in pediatric subjects</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>Growth will be assessed by changes in height versus national growth charts and predicted genetic height.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of hormonal levels in pediatric subjects</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in puberty status as assessed by clinical examination</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in puberty status as assessed by Tanner scale (TS)</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>Puberty will be assessed using TS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in puberty status as assessed by general questioning</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Beta Thalassaemia</condition>
  <arm_group>
    <arm_group_label>All subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects who have received treatment with OTL-300 in and completed study TIGET-BTHAL will be included in this study. Subjects received OTL-300 injection administered intraosseously in TIGET-BTHAL study. No study treatment will be administered in this study (207757).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Safety and Efficacy assessments</intervention_name>
    <description>Safety and efficacy assessment of OTL-300 in subjects with transfusion dependent beta-thalassemia will be performed.</description>
    <arm_group_label>All subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects who have completed study TIGET-BTHAL i.e. who have received treatment and&#xD;
             been followed for two years post treatment with OTL-300.&#xD;
&#xD;
          -  For adults; capable of giving signed informed consent. For children; informed assent&#xD;
             and/or consent in writing signed by the subject and/or parent(s) / legal&#xD;
             representative (according to local regulations and age of the subject).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  None&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Orchard Clinical Trials</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ospedale San Raffaele- Telething Institute for Gene Therapy (SR-TIGET)</affiliation>
  </overall_official>
  <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>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>November 22, 2022</last_update_submitted>
  <last_update_submitted_qc>November 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>IRCCS San Raffaele</investigator_affiliation>
    <investigator_full_name>Alessandro Aiuti</investigator_full_name>
    <investigator_title>Dr</investigator_title>
  </responsible_party>
  <keyword>Beta Thalassaemia</keyword>
  <keyword>previously GSK2696277</keyword>
  <keyword>Lentiviral vector</keyword>
  <keyword>TIGET-BTHAL</keyword>
  <keyword>Gene therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thalassemia</mesh_term>
    <mesh_term>beta-Thalassemia</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/NCT03275051
org study id: 207757
secondary id: 2017-001366-14
nct id: NCT03275051
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
OTL-300 is a gene therapy drug product consisting of autologous hematopoietic stem/progenitor
      cluster of differentiation (CD) 34+ cells genetically modified with a lentiviral vector
      (GLOBE) encoding the human beta globin gene. The TIGET-BTHAL is a phase I/II study evaluating
      safety and efficacy of OTL-300 in subjects with transfusion dependent beta-thalassemia for
      two years post gene-therapy. Subjects with rare disease who have undergone gene therapy are
      followed for efficacy and possible delayed adverse events. Thus, this study is designed to
      follow patients who have received gene therapy on TIGET-BTHAL for an additional six years
      (for a total of eight years).
allocation: N/A
intervention model: Single Group Assignment
intervention model description: No study treatment will be administered in this study. Subjects who have received treatment with OTL-300 in and completed study TIGET-BTHAL will be included in this study.
primary purpose: Other
masking: None (Open Label)
masking description: No study treatment will be administered.
measure: Number of subjects with absence of abnormal clonal proliferation (ACP)
time frame: Up to 6 years
description: Clonal proliferation describes the selection and reproduction of only one type of cell.
measure: Number of subjects with Polyclonal engraftment
time frame: Up to 6 years
description: Integration site analysis will be performed on different hematopoietic lineages from peripheral blood and/or bone marrow. Polyclonality of hematopoiesis is defined as >1000 unique integration sites retrieved at specified time points. The number of subjects with polyclonality of hematopoiesis will be estimated.
measure: Number of subjects with reduction in red blood cells (RBC) transfusion volume
time frame: Up to 6 years
measure: Number of subjects with reduction in transfusion rate up to transfusion independence
time frame: Up to 6 years
measure: Number of subjects with transfusion independence
time frame: Up to 6 years
description: Transfusion independence is defined as <= 1 transfusion in the previous 6 months.
measure: Hemoglobin (Hb) levels in subjects achieving transfusion independence
time frame: Up to 6 years
measure: Number of subjects with sustained engraftment of genetically corrected cells
time frame: Up to 6 years
description: Engraftment will be assessed by vector-specific quantitative polymerase chain reaction (PCR) on bone marrow. Sustained engraftment is defined as >=0.15 vector copy number (VCN)/genome in bone marrow erythroid cells.
measure: Number of subjects with overall survival
time frame: Up to 6 years
description: The number of subjects alive over all the trial.
measure: Number of subjects with adverse events (AEs), serious AEs (SAEs)
time frame: Up to 6 years
measure: Clinical chemistry laboratory parameters as a measure of safety
time frame: Up to 6 years
measure: Hematology laboratory parameters as a measure of safety
time frame: Up to 6 years
measure: Urinalysis as a measure of safety
time frame: Up to 6 years
measure: Occurrence of viral infections as a measure of safety
time frame: Up to 6 years
description: Microbiological laboratory tests will be performed to analyze the presence of hepatitis C virus ribonucleic acid (RNA), hepatitis B virus RNA, hepatitis B surface antigen, human T cell lymphotropic virus type 1-2 antibodies. Molecular tests will be performed for human immunodeficiency virus in peripheral blood or plasma.
measure: Screening for occurrence of antibodies against viruses and toxoplasma as a measure of safety
time frame: Up to 6 years
description: Immunological laboratory tests will be performed to analyze antibodies to Epstein-Barr virus, cytomegalovirus, herpes simplex virus 1-2, varicella zoster virus, toxoplasma.
measure: Functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) scores
time frame: Up to 6 years
measure: Short-Form-36 (SF-36) scores
time frame: Up to 6 years
description: Impact of disease on overall QoL in adults will be measured using the SF-36.
measure: Pediatric Quality of Life (PedsQL) questionnaire scores
time frame: Up to 6 years
description: The PedsQL 4.0 generic core scale will be used to measure QoL in pediatric subjects.
measure: Evaluation of growth in pediatric subjects
time frame: Up to 6 years
description: Growth will be assessed by changes in height versus national growth charts and predicted genetic height.
measure: Assessment of hormonal levels in pediatric subjects
time frame: Up to 6 years
measure: Changes in puberty status as assessed by clinical examination
time frame: Up to 6 years
measure: Changes in puberty status as assessed by Tanner scale (TS)
time frame: Up to 6 years
description: Puberty will be assessed using TS.
measure: Changes in puberty status as assessed by general questioning
time frame: Up to 6 years
arm group label: All subjects
arm group type: Experimental
description: Subjects who have received treatment with OTL-300 in and completed study TIGET-BTHAL will be included in this study. Subjects received OTL-300 injection administered intraosseously in TIGET-BTHAL study. No study treatment will be administered in this study (207757).
intervention type: Other
intervention name: Safety and Efficacy assessments
description: Safety and efficacy assessment of OTL-300 in subjects with transfusion dependent beta-thalassemia will be performed.
arm group label: All subjects
criteria: 
gender: All
minimum age: 3 Years
maximum age: N/A
healthy volunteers: No
last name: Orchard Clinical Trials
role: Principal Investigator
affiliation: Ospedale San Raffaele- Telething Institute for Gene Therapy (SR-TIGET)
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: IRCCS San Raffaele
investigator full name: Alessandro Aiuti
investigator title: Dr
mesh term: Thalassemia
mesh term: beta-Thalassemia