<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/NCT02999984</url>
  </required_header>
  <id_info>
    <org_study_id>OTL-101-4</org_study_id>
    <nct_id>NCT02999984</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of the Cryopreserved Formulation of OTL-101 in Subjects With ADA-SCID</brief_title>
  <official_title>Efficacy and Safety of Cryopreserved Formulation of Autologous CD34+ Hematopoietic Stem Cells Transduced Ex Vivo With Elongation Factor 1 Alpha Shortened (EFS) Lentiviral Vector Encoding for Human ADA Gene in Subjects With Severe Combined Immunodeficiency Due to ADA Deficiency</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>California Institute for Regenerative Medicine (CIRM)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Orchard Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, Los Angeles</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective, non-randomized, single-cohort, longitudinal, single-center, clinical&#xD;
      study designed to assess the efficacy and safety of a cryopreserved formulation of OTL-101&#xD;
      (autologous CD34+ hematopoietic stem/progenitor cells transduced ex vivo with EFS (Elongation&#xD;
      Factor 1α Short form) Lentiviral Vector (LV) encoding for the human ADA gene) administered to&#xD;
      ADA-SCID subjects between the ages of 30 days and 17 years of age, who are not eligible for&#xD;
      an Human Leukocyte Antigen (HLA) matched sibling/family donor and meeting the&#xD;
      inclusion/exclusion criteria. The OTL-101 product is infused after a minimal interval of at&#xD;
      least 24 hours following the completion of reduced intensity conditioning. For subjects who&#xD;
      successfully receive the OTL-101 product, pegademase bovine (PEG-ADA) Enzyme Replacement&#xD;
      Therapy (ERT) is discontinued at Day+30 (-3/+15) after the transplant. After their discharge&#xD;
      from hospital, the subjects will be seen at regular intervals to review their history,&#xD;
      perform examinations and draw blood samples to assess immunity and safety.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 16, 2016</start_date>
  <completion_date type="Actual">September 26, 2019</completion_date>
  <primary_completion_date type="Actual">October 11, 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Percentage of Participants With Treatment Efficacy After Treatment With OTL 101 (6 Months)</measure>
    <time_frame>6 months</time_frame>
    <description>Efficacy of OTL-101 treatment at 6 months post OTL-101 infusion based on the following parameters and thresholds:&#xD;
ADA enzyme activity in erythrocytes above baseline/pretreatment level (i.e., &gt;0 units). ADA enzyme activity is measured to assess the amount of functional gene product produced from the normal ADA transgene delivered by EFS-ADA LV.&#xD;
Absolute CD3+ T cell counts ≥200 cells/μL. Increase in CD3+ T cell counts is a marker of immune reconstitution.&#xD;
Granulocyte samples positive for vector sequences by quantitative Polymerase Chain Reaction (PCR) (≥1/10,000 cells). Vector copy number (VCN) in the Peripheral Blood (PB) Granulocytes fraction that was T cell depleted, is a surrogate for amount of engrafted genetically modified Hematopoietic stem cell (HSC) that are producing granulocytes every 3-5 days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)</measure>
    <time_frame>12 Months</time_frame>
    <description>Overall survival is defined as the percentage of subjects alive at 12 months post- treatment with cryopreserved OTL-101.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)</measure>
    <time_frame>12 Months</time_frame>
    <description>Event-free survival is defined as the percentage of subjects alive with no &quot;event&quot;, an &quot;event&quot; being the resumption of PEG-ADA ERT or the need for a rescue allogeneic Hematopoietic Stem Cell Transplant (HSCT), or death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)</measure>
    <time_frame>24 months</time_frame>
    <description>OS is defined as the percentage of subjects alive at 24 months post- treatment with cryopreserved OTL-101.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)</measure>
    <time_frame>24 months</time_frame>
    <description>Event-free survival is defined as the percentage of subjects alive with no &quot;event&quot;, an &quot;event&quot; being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in CD3+ T Cell Counts (2 Years)</measure>
    <time_frame>24 months</time_frame>
    <description>Immune reconstitution was assessed by change in CD3+ T Cell counts over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe Infections Excluding First 3 Months After Treatment</measure>
    <time_frame>24 months</time_frame>
    <description>The infections of interest in this study were severe infections or opportunistic infectious episodes, defined as infections requiring hospitalization or prolonging hospitalization and/or documented infections by opportunistic pathogens. Infections that took place in the first 3 months of follow-up post treatment were excluded from calculations to avoid possible bias introduced in the data by the effects of conditioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Quality of Life Measures (2 Years)</measure>
    <time_frame>24 months</time_frame>
    <description>Assessment of quality of life was measured by the Lansky Performance Status Scale. The maximum score on the Lansky Performance Scale is 100 - the child is fully active and able to carry on normal activity with no special care needed. The minimum score is 10 - the child is completely disabled, not even passive play. The scores at baseline (pre-treatment with OTL-101) and scores at Month 24 post-treatment with OTL-101 were compared to establish if there were any changes in the child's score in this timeframe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Who Stopped Immunoglobulin Replacement Therapy (IgRT) (2 Years)</measure>
    <time_frame>24 months</time_frame>
    <description>Use of immunoglobulin replacement therapies prior to and after gene therapy were monitored. Indications for considering the discontinuation of immunoglobulin replacement therapy included: absolute CD4+ &gt;200, absolute B cell &gt;100/μl, IgA or IgM &gt; lower limit of normal for age or gene marking &gt;1% detectable in B cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Cessation of IgRT for Those Who Stopped (2 Years)</measure>
    <time_frame>24 months</time_frame>
    <description>Use of immunoglobulin replacement therapies prior to and after gene therapy were monitored. For subjects who stopped IgRT during the study, the time of cessation was recorded.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Severe Combined Immunodeficiency Due to ADA Deficiency</condition>
  <arm_group>
    <arm_group_label>Gene Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101)</intervention_name>
    <description>autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101) are infused intravenously</description>
    <arm_group_label>Gene Therapy</arm_group_label>
    <other_name>OTL-101</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>busulfan</intervention_name>
    <description>Busulfan is used for non-myeloablative conditioning</description>
    <arm_group_label>Gene Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PEG-ADA ERT</intervention_name>
    <description>PEG-ADA ERT is discontinued at Day +30 (-3/+15 days) after successful engraftment</description>
    <arm_group_label>Gene Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of written informed consent prior to any study related procedures. In this&#xD;
             study consent must be provided by the parents/legal guardians and, where applicable&#xD;
             according to local laws, a signed assent from the child,&#xD;
&#xD;
          2. Subjects ≥30 days and &lt;18 years of age,&#xD;
&#xD;
          3. With a diagnosis of ADA-SCID based on:&#xD;
&#xD;
             Evidence of ADA deficiency, defined as:&#xD;
&#xD;
             i. Decreased ADA enzymatic activity in erythrocytes, leukocytes, skin fibroblasts, or&#xD;
             in cultured fetal cells to levels consistent with ADA-SCID as determined by the&#xD;
             reference laboratory, or ii. Identified mutations in ADA alleles consistent with a&#xD;
             severe reduction in ADA activity,&#xD;
&#xD;
             Evidence of ADA-SCID based on either:&#xD;
&#xD;
             i. Family history of a first order relative with ADA deficiency and clinical and&#xD;
             laboratory evidence of severe immunologic deficiency, or ii. Evidence of severe&#xD;
             immunologic deficiency in subjects prior to the institution of immune restorative&#xD;
             therapy, based on&#xD;
&#xD;
               -  Lymphopenia (absolute lymphocyte count (ALC) &lt;400 cells/µL) OR absence or low&#xD;
                  number of T cells (absolute CD3+ count &lt; 300 cells/µL), or&#xD;
&#xD;
               -  Severely decreased T lymphocyte blastogenic responses to phytohemagglutinin&#xD;
                  (either &lt;10% of lower limit of normal controls for the diagnostic laboratory, or&#xD;
                  &lt;10% of the response of the normal control of the day, or stimulation index &lt;10),&#xD;
                  or&#xD;
&#xD;
               -  Identification of SCID by neonatal screening revealing low T cell Receptor&#xD;
                  Excision Circle (TREC) levels.&#xD;
&#xD;
          4. Ineligible for matched family allogeneic Bone Marrow (BM) transplantation, defined as&#xD;
             the absence of a medically eligible HLA-identical sibling or family donor, with normal&#xD;
             immune function, who could serve as an allogeneic bone marrow donor.&#xD;
&#xD;
          5. Females of child-bearing age will be required to provide a negative pregnancy test 30&#xD;
             days prior to Visit 2.&#xD;
&#xD;
          6. Subjects and their parents/legal guardians must be willing and able to comply with&#xD;
             study restrictions and to remain at the clinic for the required duration during the&#xD;
             study period and willing to return to the clinic for the follow up evaluation as&#xD;
             specified in the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Ineligible for autologous Hematopoietic Stem Cell Transplantation (HSCT) as per&#xD;
             clinical site criteria.&#xD;
&#xD;
          2. Other conditions which in the opinion of the Principal Investigator and/or Co&#xD;
             Investigators, contraindicate the harvest of bone marrow, the administration of&#xD;
             Busulfan and the infusion of transduced cells, or which indicate an inability of the&#xD;
             subject or subject's parent/legal guardian to comply with the protocol.&#xD;
&#xD;
          3. Hematologic abnormality, defined as:&#xD;
&#xD;
               -  Anemia (Hb &lt;8.0 g/dl).&#xD;
&#xD;
               -  Neutropenia (ANC &lt;500/mm3). Note: ANC &lt;500 with absence of myelodysplastic&#xD;
                  syndrome on bone marrow aspirate and biopsy and normal marrow cytogenetics are&#xD;
                  acceptable for eligibility.&#xD;
&#xD;
               -  Thrombocytopenia (platelet count &lt;50,000/mm3, at any age).&#xD;
&#xD;
               -  Prothrombin time or international normalized ratio (INR) and partial&#xD;
                  thromboplastin time (PTT) &gt;2 x upper limit of normal (ULN) (subjects with a&#xD;
                  correctable deficiency controlled on medication will not be excluded).&#xD;
&#xD;
               -  Cytogenetic abnormalities on peripheral blood or bone marrow or amniotic fluid&#xD;
                  (if available).&#xD;
&#xD;
               -  Prior allogeneic HSCT with cytoreductive conditioning.&#xD;
&#xD;
          4. Pulmonary abnormality, defined as:&#xD;
&#xD;
               -  Resting O2 saturation by pulse oximetry &lt;90% on room air.&#xD;
&#xD;
               -  Chest X-ray indicating active or progressive pulmonary disease. Note: Chest X ray&#xD;
                  indicating residual signs of treated pneumonitis is acceptable for eligibility.&#xD;
&#xD;
          5. Cardiac abnormality, defined as:&#xD;
&#xD;
               -  Abnormal ECG indicating cardiac pathology.&#xD;
&#xD;
               -  Uncorrected congenital cardiac malformation with clinical symptoms.&#xD;
&#xD;
               -  Active cardiac disease, including clinical evidence of congestive heart failure,&#xD;
                  cyanosis, hypotension.&#xD;
&#xD;
               -  Poor cardiac function as evidenced by left ventricular ejection fraction &lt;40% on&#xD;
                  echocardiogram.&#xD;
&#xD;
          6. Neurologic abnormality, defined as:&#xD;
&#xD;
               -  Significant neurologic abnormality revealed by examination.&#xD;
&#xD;
               -  Uncontrolled seizure disorder.&#xD;
&#xD;
          7. Renal abnormality, defined as:&#xD;
&#xD;
               -  Renal insufficiency: serum creatinine ≥1.2 mg/dl (106 µmol/L), or ≥3+&#xD;
                  proteinuria.&#xD;
&#xD;
               -  Abnormal serum sodium, potassium, calcium, magnesium or phosphate levels at &gt;2 x&#xD;
                  ULN.&#xD;
&#xD;
          8. Hepatic/gastrointestinal abnormality, defined as:&#xD;
&#xD;
               -  Serum transaminases &gt;5 x ULN.&#xD;
&#xD;
               -  Serum bilirubin &gt;2 x ULN.&#xD;
&#xD;
               -  Serum glucose &gt;1.5 x ULN.&#xD;
&#xD;
          9. Oncologic disease, defined as:&#xD;
&#xD;
               -  Evidence of active malignant disease other than dermatofibrosarcoma protuberans&#xD;
                  (DFSP).&#xD;
&#xD;
               -  Evidence of DFSP expected to require anti-neoplastic therapy within the 5 years&#xD;
                  following the infusion of genetically corrected cells (if anti-neoplastic therapy&#xD;
                  has been completed, a subject with a history of DFSP can be included).&#xD;
&#xD;
               -  Evidence of DFSP expected to be life limiting within the 5 years following the&#xD;
                  infusion of genetically corrected cells.&#xD;
&#xD;
         10. Known sensitivity to Busulfan.&#xD;
&#xD;
         11. Confirmation of an infectious disease by deoxyribonucleic acid (DNA) Polymerase chain&#xD;
             reaction (PCR) positive at time of screening assessment for the following:&#xD;
&#xD;
               -  HIV-1,&#xD;
&#xD;
               -  Hepatitis B,&#xD;
&#xD;
               -  Parvovirus B19.&#xD;
&#xD;
         12. The subject is pregnant or has a major congenital anomaly.&#xD;
&#xD;
         13. Is likely to require treatment during the study with drugs that are not permitted by&#xD;
             the study protocol.&#xD;
&#xD;
         14. The subject has previously received another form of gene therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Days</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Donald B. Kohn, MD</last_name>
    <role>Study Director</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944341/</url>
    <description>Pre-clinical activity and safety data</description>
  </link>
  <reference>
    <citation>Carbonaro DA, Zhang L, Jin X, Montiel-Equihua C, Geiger S, Carmo M, Cooper A, Fairbanks L, Kaufman ML, Sebire NJ, Hollis RP, Blundell MP, Senadheera S, Fu PY, Sahaghian A, Chan RY, Wang X, Cornetta K, Thrasher AJ, Kohn DB, Gaspar HB. Preclinical demonstration of lentiviral vector-mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency. Mol Ther. 2014 Mar;22(3):607-622. doi: 10.1038/mt.2013.265. Epub 2013 Nov 20.</citation>
    <PMID>24256635</PMID>
  </reference>
  <reference>
    <citation>Kohn DB, Booth C, Shaw KL, Xu-Bayford J, Garabedian E, Trevisan V, Carbonaro-Sarracino DA, Soni K, Terrazas D, Snell K, Ikeda A, Leon-Rico D, Moore TB, Buckland KF, Shah AJ, Gilmour KC, De Oliveira S, Rivat C, Crooks GM, Izotova N, Tse J, Adams S, Shupien S, Ricketts H, Davila A, Uzowuru C, Icreverzi A, Barman P, Campo Fernandez B, Hollis RP, Coronel M, Yu A, Chun KM, Casas CE, Zhang R, Arduini S, Lynn F, Kudari M, Spezzi A, Zahn M, Heimke R, Labik I, Parrott R, Buckley RH, Reeves L, Cornetta K, Sokolic R, Hershfield M, Schmidt M, Candotti F, Malech HL, Thrasher AJ, Gaspar HB. Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency. N Engl J Med. 2021 May 27;384(21):2002-2013. doi: 10.1056/NEJMoa2027675. Epub 2021 May 11.</citation>
    <PMID>33974366</PMID>
  </reference>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <results_first_submitted>April 26, 2022</results_first_submitted>
  <results_first_submitted_qc>June 29, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">July 22, 2022</results_first_posted>
  <disposition_first_submitted>January 24, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>January 24, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">February 5, 2020</disposition_first_posted>
  <last_update_submitted>August 1, 2022</last_update_submitted>
  <last_update_submitted_qc>August 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Los Angeles</investigator_affiliation>
    <investigator_full_name>Donald B. Kohn, M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>gene therapy</keyword>
  <keyword>hematopoietic and progenitor cells</keyword>
  <keyword>lentiviral vector</keyword>
  <keyword>ADA-SCID</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Severe Combined Immunodeficiency</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Busulfan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 28, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/84/NCT02999984/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 25, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/84/NCT02999984/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Gene Therapy</title>
          <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Treatment Failure</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Gene Therapy</title>
          <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Afro-American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Treatment Efficacy After Treatment With OTL 101 (6 Months)</title>
        <description>Efficacy of OTL-101 treatment at 6 months post OTL-101 infusion based on the following parameters and thresholds:&#xD;
ADA enzyme activity in erythrocytes above baseline/pretreatment level (i.e., &gt;0 units). ADA enzyme activity is measured to assess the amount of functional gene product produced from the normal ADA transgene delivered by EFS-ADA LV.&#xD;
Absolute CD3+ T cell counts ≥200 cells/μL. Increase in CD3+ T cell counts is a marker of immune reconstitution.&#xD;
Granulocyte samples positive for vector sequences by quantitative Polymerase Chain Reaction (PCR) (≥1/10,000 cells). Vector copy number (VCN) in the Peripheral Blood (PB) Granulocytes fraction that was T cell depleted, is a surrogate for amount of engrafted genetically modified Hematopoietic stem cell (HSC) that are producing granulocytes every 3-5 days.</description>
        <time_frame>6 months</time_frame>
        <population>The efficacy population was a modified intent-to-treat population and consisted of all evaluable subjects at 6-month post-treatment with OTL-101.&#xD;
For outcome measure &quot;% of subjects with CD3+ T-cell count &gt;=200 cells/μL&quot;, only 9 subjects were evaluable as data was not available for 1 subject.</population>
        <group_list>
          <group group_id="O1">
            <title>Gene Therapy</title>
            <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Treatment Efficacy After Treatment With OTL 101 (6 Months)</title>
          <description>Efficacy of OTL-101 treatment at 6 months post OTL-101 infusion based on the following parameters and thresholds:&#xD;
ADA enzyme activity in erythrocytes above baseline/pretreatment level (i.e., &gt;0 units). ADA enzyme activity is measured to assess the amount of functional gene product produced from the normal ADA transgene delivered by EFS-ADA LV.&#xD;
Absolute CD3+ T cell counts ≥200 cells/μL. Increase in CD3+ T cell counts is a marker of immune reconstitution.&#xD;
Granulocyte samples positive for vector sequences by quantitative Polymerase Chain Reaction (PCR) (≥1/10,000 cells). Vector copy number (VCN) in the Peripheral Blood (PB) Granulocytes fraction that was T cell depleted, is a surrogate for amount of engrafted genetically modified Hematopoietic stem cell (HSC) that are producing granulocytes every 3-5 days.</description>
          <population>The efficacy population was a modified intent-to-treat population and consisted of all evaluable subjects at 6-month post-treatment with OTL-101.&#xD;
For outcome measure &quot;% of subjects with CD3+ T-cell count &gt;=200 cells/μL&quot;, only 9 subjects were evaluable as data was not available for 1 subject.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>% of subjects with an increase from baseline in RBC ADA activity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% of subjects with CD3+ T-cell count &gt;=200 cells/μL</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% of subjects with detectable gene-marked granulocytes by quantitative PCR &gt;=1/10,000 cells</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)</title>
        <description>Overall survival is defined as the percentage of subjects alive at 12 months post- treatment with cryopreserved OTL-101.</description>
        <time_frame>12 Months</time_frame>
        <population>The efficacy population was a modified intent-to-treat population and consisted of all subjects treated with OTL-101 within this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Gene Therapy</title>
            <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)</title>
          <description>Overall survival is defined as the percentage of subjects alive at 12 months post- treatment with cryopreserved OTL-101.</description>
          <population>The efficacy population was a modified intent-to-treat population and consisted of all subjects treated with OTL-101 within this study.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="66.37" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)</title>
        <description>Event-free survival is defined as the percentage of subjects alive with no &quot;event&quot;, an &quot;event&quot; being the resumption of PEG-ADA ERT or the need for a rescue allogeneic Hematopoietic Stem Cell Transplant (HSCT), or death.</description>
        <time_frame>12 Months</time_frame>
        <population>The efficacy population was a modified intent-to-treat population and consisted of all subjects treated with OTL-101 within this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Gene Therapy</title>
            <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
          </group>
        </group_list>
        <measure>
          <title>Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)</title>
          <description>Event-free survival is defined as the percentage of subjects alive with no &quot;event&quot;, an &quot;event&quot; being the resumption of PEG-ADA ERT or the need for a rescue allogeneic Hematopoietic Stem Cell Transplant (HSCT), or death.</description>
          <population>The efficacy population was a modified intent-to-treat population and consisted of all subjects treated with OTL-101 within this study.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Percentage event-free at 12 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.00" lower_limit="55.50" upper_limit="99.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Percentage without reinstitution of PEG-ADA by 12 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.00" lower_limit="55.50" upper_limit="99.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Percentage without rescue HSCT by 12 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="66.37" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)</title>
        <description>OS is defined as the percentage of subjects alive at 24 months post- treatment with cryopreserved OTL-101.</description>
        <time_frame>24 months</time_frame>
        <population>The efficacy population was a modified intent-to-treat population and consisted of all subjects treated with OTL-101 within this study, with the exception of 1 subject who was withdrawn prior to Month 24 timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Gene Therapy</title>
            <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
          </group>
        </group_list>
        <measure>
          <title>OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)</title>
          <description>OS is defined as the percentage of subjects alive at 24 months post- treatment with cryopreserved OTL-101.</description>
          <population>The efficacy population was a modified intent-to-treat population and consisted of all subjects treated with OTL-101 within this study, with the exception of 1 subject who was withdrawn prior to Month 24 timepoint.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="66.37" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)</title>
        <description>Event-free survival is defined as the percentage of subjects alive with no &quot;event&quot;, an &quot;event&quot; being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death.</description>
        <time_frame>24 months</time_frame>
        <population>The efficacy population was a modified intent-to-treat population and consisted of all subjects treated with OTL-101 within this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Gene Therapy</title>
            <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
          </group>
        </group_list>
        <measure>
          <title>EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)</title>
          <description>Event-free survival is defined as the percentage of subjects alive with no &quot;event&quot;, an &quot;event&quot; being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death.</description>
          <population>The efficacy population was a modified intent-to-treat population and consisted of all subjects treated with OTL-101 within this study.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Percentage event-free at 24 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.00" lower_limit="55.50" upper_limit="99.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Percentage without reinstitution of PEG-ADA by 24 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.00" lower_limit="55.50" upper_limit="99.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Percentage without rescue HSCT by 24 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="66.37" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in CD3+ T Cell Counts (2 Years)</title>
        <description>Immune reconstitution was assessed by change in CD3+ T Cell counts over time.</description>
        <time_frame>24 months</time_frame>
        <population>The efficacy population was a modified intent-to-treat population and consisted of all subjects treated with OTL-101 within this study, with the exception of 1 subject who was withdrawn prior to Month 24 timepoint and an additional 1 subject for whom CD3+ T cell count data was not available at the Month 24 timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Gene Therapy</title>
            <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in CD3+ T Cell Counts (2 Years)</title>
          <description>Immune reconstitution was assessed by change in CD3+ T Cell counts over time.</description>
          <population>The efficacy population was a modified intent-to-treat population and consisted of all subjects treated with OTL-101 within this study, with the exception of 1 subject who was withdrawn prior to Month 24 timepoint and an additional 1 subject for whom CD3+ T cell count data was not available at the Month 24 timepoint.</population>
          <units>cells/μL</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="418.5" lower_limit="-332" upper_limit="1976"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Severe Infections Excluding First 3 Months After Treatment</title>
        <description>The infections of interest in this study were severe infections or opportunistic infectious episodes, defined as infections requiring hospitalization or prolonging hospitalization and/or documented infections by opportunistic pathogens. Infections that took place in the first 3 months of follow-up post treatment were excluded from calculations to avoid possible bias introduced in the data by the effects of conditioning.</description>
        <time_frame>24 months</time_frame>
        <population>The efficacy population was a modified intent-to-treat population and consisted of all subjects treated with OTL-101 within this study.</population>
        <group_list>
          <group group_id="O1">
            <title>Gene Therapy</title>
            <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
          </group>
        </group_list>
        <measure>
          <title>Severe Infections Excluding First 3 Months After Treatment</title>
          <description>The infections of interest in this study were severe infections or opportunistic infectious episodes, defined as infections requiring hospitalization or prolonging hospitalization and/or documented infections by opportunistic pathogens. Infections that took place in the first 3 months of follow-up post treatment were excluded from calculations to avoid possible bias introduced in the data by the effects of conditioning.</description>
          <population>The efficacy population was a modified intent-to-treat population and consisted of all subjects treated with OTL-101 within this study.</population>
          <units>Infections per person per year</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Quality of Life Measures (2 Years)</title>
        <description>Assessment of quality of life was measured by the Lansky Performance Status Scale. The maximum score on the Lansky Performance Scale is 100 - the child is fully active and able to carry on normal activity with no special care needed. The minimum score is 10 - the child is completely disabled, not even passive play. The scores at baseline (pre-treatment with OTL-101) and scores at Month 24 post-treatment with OTL-101 were compared to establish if there were any changes in the child's score in this timeframe.</description>
        <time_frame>24 months</time_frame>
        <population>Quality of life data was available for 7/10 subjects at the Month 24 timepoint there only 7 subjects were included in the analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Gene Therapy</title>
            <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Quality of Life Measures (2 Years)</title>
          <description>Assessment of quality of life was measured by the Lansky Performance Status Scale. The maximum score on the Lansky Performance Scale is 100 - the child is fully active and able to carry on normal activity with no special care needed. The minimum score is 10 - the child is completely disabled, not even passive play. The scores at baseline (pre-treatment with OTL-101) and scores at Month 24 post-treatment with OTL-101 were compared to establish if there were any changes in the child's score in this timeframe.</description>
          <population>Quality of life data was available for 7/10 subjects at the Month 24 timepoint there only 7 subjects were included in the analysis for this outcome measure.</population>
          <units>Lansky Performance Score</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients Who Stopped Immunoglobulin Replacement Therapy (IgRT) (2 Years)</title>
        <description>Use of immunoglobulin replacement therapies prior to and after gene therapy were monitored. Indications for considering the discontinuation of immunoglobulin replacement therapy included: absolute CD4+ &gt;200, absolute B cell &gt;100/μl, IgA or IgM &gt; lower limit of normal for age or gene marking &gt;1% detectable in B cells.</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Gene Therapy</title>
            <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Who Stopped Immunoglobulin Replacement Therapy (IgRT) (2 Years)</title>
          <description>Use of immunoglobulin replacement therapies prior to and after gene therapy were monitored. Indications for considering the discontinuation of immunoglobulin replacement therapy included: absolute CD4+ &gt;200, absolute B cell &gt;100/μl, IgA or IgM &gt; lower limit of normal for age or gene marking &gt;1% detectable in B cells.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Cessation of IgRT for Those Who Stopped (2 Years)</title>
        <description>Use of immunoglobulin replacement therapies prior to and after gene therapy were monitored. For subjects who stopped IgRT during the study, the time of cessation was recorded.</description>
        <time_frame>24 months</time_frame>
        <population>IgRT data was available for 7/10 subjects at the Month 24 timepoint there only 7 subjects were included in the analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Gene Therapy</title>
            <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Cessation of IgRT for Those Who Stopped (2 Years)</title>
          <description>Use of immunoglobulin replacement therapies prior to and after gene therapy were monitored. For subjects who stopped IgRT during the study, the time of cessation was recorded.</description>
          <population>IgRT data was available for 7/10 subjects at the Month 24 timepoint there only 7 subjects were included in the analysis for this outcome measure.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" lower_limit="9" upper_limit="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 2-years post-treatment with OTL-101.</time_frame>
      <desc>The safety population consisted of all subjects treated with OTL-101 within this study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Gene Therapy</title>
          <description>Infusion of autologous cryopreserved CD34+ cells genetically modified by the EF1αS-ADA (EFS-ADA) lentiviral vector (LV)&#xD;
Busulfan: Busulfan is used for non-myeloablative conditioning&#xD;
Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day 30 +/- 3 days from date of infusion of OTL-101.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Bronchiolitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 20.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="19" subjects_affected="10" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="17" subjects_affected="10" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="8" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Monocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Cerumen impaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye discharge</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Eye pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Retching</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>H1N1 influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Respiratory syncytial virus infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tinea infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Human rhinovirus test positive</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Haematocrit decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Mean cell haemoglobin concentration decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Mean cell haemoglobin decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Mean cell volume decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis diaper</sub_title>
                <counts group_id="E1" events="9" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Skin lesion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Miliaria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Seborrhoeic dermatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Sinus operation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Orchard Medical Information</name_or_title>
      <organization>Orchard Therapeutics (Europe) Ltd</organization>
      <phone>+44 (0) 203 808 8286</phone>
      <email>medinfo@orchard-tx.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02999984
org study id: OTL-101-4
nct id: NCT02999984
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
This is a prospective, non-randomized, single-cohort, longitudinal, single-center, clinical
      study designed to assess the efficacy and safety of a cryopreserved formulation of OTL-101
      (autologous CD34+ hematopoietic stem/progenitor cells transduced ex vivo with EFS (Elongation
      Factor 1α Short form) Lentiviral Vector (LV) encoding for the human ADA gene) administered to
      ADA-SCID subjects between the ages of 30 days and 17 years of age, who are not eligible for
      an Human Leukocyte Antigen (HLA) matched sibling/family donor and meeting the
      inclusion/exclusion criteria. The OTL-101 product is infused after a minimal interval of at
      least 24 hours following the completion of reduced intensity conditioning. For subjects who
      successfully receive the OTL-101 product, pegademase bovine (PEG-ADA) Enzyme Replacement
      Therapy (ERT) is discontinued at Day+30 (-3/+15) after the transplant. After their discharge
      from hospital, the subjects will be seen at regular intervals to review their history,
      perform examinations and draw blood samples to assess immunity and safety.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Treatment Efficacy After Treatment With OTL 101 (6 Months)
time frame: 6 months
description: Efficacy of OTL-101 treatment at 6 months post OTL-101 infusion based on the following parameters and thresholds:
ADA enzyme activity in erythrocytes above baseline/pretreatment level (i.e., >0 units). ADA enzyme activity is measured to assess the amount of functional gene product produced from the normal ADA transgene delivered by EFS-ADA LV.
Absolute CD3+ T cell counts ≥200 cells/μL. Increase in CD3+ T cell counts is a marker of immune reconstitution.
Granulocyte samples positive for vector sequences by quantitative Polymerase Chain Reaction (PCR) (≥1/10,000 cells). Vector copy number (VCN) in the Peripheral Blood (PB) Granulocytes fraction that was T cell depleted, is a surrogate for amount of engrafted genetically modified Hematopoietic stem cell (HSC) that are producing granulocytes every 3-5 days.
measure: Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)
time frame: 12 Months
description: Overall survival is defined as the percentage of subjects alive at 12 months post- treatment with cryopreserved OTL-101.
measure: Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)
time frame: 12 Months
description: Event-free survival is defined as the percentage of subjects alive with no "event", an "event" being the resumption of PEG-ADA ERT or the need for a rescue allogeneic Hematopoietic Stem Cell Transplant (HSCT), or death.
measure: OS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)
time frame: 24 months
description: OS is defined as the percentage of subjects alive at 24 months post- treatment with cryopreserved OTL-101.
measure: EvFS of Subjects Treated With Investigational Medicinal Product (IMP) (2 Years)
time frame: 24 months
description: Event-free survival is defined as the percentage of subjects alive with no "event", an "event" being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death.
measure: Change From Baseline in CD3+ T Cell Counts (2 Years)
time frame: 24 months
description: Immune reconstitution was assessed by change in CD3+ T Cell counts over time.
measure: Severe Infections Excluding First 3 Months After Treatment
time frame: 24 months
description: The infections of interest in this study were severe infections or opportunistic infectious episodes, defined as infections requiring hospitalization or prolonging hospitalization and/or documented infections by opportunistic pathogens. Infections that took place in the first 3 months of follow-up post treatment were excluded from calculations to avoid possible bias introduced in the data by the effects of conditioning.
measure: Change From Baseline in Quality of Life Measures (2 Years)
time frame: 24 months
description: Assessment of quality of life was measured by the Lansky Performance Status Scale. The maximum score on the Lansky Performance Scale is 100 - the child is fully active and able to carry on normal activity with no special care needed. The minimum score is 10 - the child is completely disabled, not even passive play. The scores at baseline (pre-treatment with OTL-101) and scores at Month 24 post-treatment with OTL-101 were compared to establish if there were any changes in the child's score in this timeframe.
measure: Percentage of Patients Who Stopped Immunoglobulin Replacement Therapy (IgRT) (2 Years)
time frame: 24 months
description: Use of immunoglobulin replacement therapies prior to and after gene therapy were monitored. Indications for considering the discontinuation of immunoglobulin replacement therapy included: absolute CD4+ >200, absolute B cell >100/μl, IgA or IgM > lower limit of normal for age or gene marking >1% detectable in B cells.
measure: Time to Cessation of IgRT for Those Who Stopped (2 Years)
time frame: 24 months
description: Use of immunoglobulin replacement therapies prior to and after gene therapy were monitored. For subjects who stopped IgRT during the study, the time of cessation was recorded.
arm group label: Gene Therapy
arm group type: Experimental
description: Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells
intervention type: Genetic
intervention name: Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101)
description: autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101) are infused intravenously
arm group label: Gene Therapy
other name: OTL-101
intervention type: Drug
intervention name: busulfan
description: Busulfan is used for non-myeloablative conditioning
arm group label: Gene Therapy
intervention type: Drug
intervention name: PEG-ADA ERT
description: PEG-ADA ERT is discontinued at Day +30 (-3/+15 days) after successful engraftment
arm group label: Gene Therapy
criteria: 
gender: All
minimum age: 30 Days
maximum age: 17 Years
healthy volunteers: No
last name: Donald B. Kohn, MD
role: Study Director
affiliation: University of California, Los Angeles
facility: 
country: United States
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944341/
description: Pre-clinical activity and safety data
citation: Carbonaro DA, Zhang L, Jin X, Montiel-Equihua C, Geiger S, Carmo M, Cooper A, Fairbanks L, Kaufman ML, Sebire NJ, Hollis RP, Blundell MP, Senadheera S, Fu PY, Sahaghian A, Chan RY, Wang X, Cornetta K, Thrasher AJ, Kohn DB, Gaspar HB. Preclinical demonstration of lentiviral vector-mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency. Mol Ther. 2014 Mar;22(3):607-622. doi: 10.1038/mt.2013.265. Epub 2013 Nov 20.
PMID: 24256635
citation: Kohn DB, Booth C, Shaw KL, Xu-Bayford J, Garabedian E, Trevisan V, Carbonaro-Sarracino DA, Soni K, Terrazas D, Snell K, Ikeda A, Leon-Rico D, Moore TB, Buckland KF, Shah AJ, Gilmour KC, De Oliveira S, Rivat C, Crooks GM, Izotova N, Tse J, Adams S, Shupien S, Ricketts H, Davila A, Uzowuru C, Icreverzi A, Barman P, Campo Fernandez B, Hollis RP, Coronel M, Yu A, Chun KM, Casas CE, Zhang R, Arduini S, Lynn F, Kudari M, Spezzi A, Zahn M, Heimke R, Labik I, Parrott R, Buckley RH, Reeves L, Cornetta K, Sokolic R, Hershfield M, Schmidt M, Candotti F, Malech HL, Thrasher AJ, Gaspar HB. Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency. N Engl J Med. 2021 May 27;384(21):2002-2013. doi: 10.1056/NEJMoa2027675. Epub 2021 May 11.
PMID: 33974366
responsible party type: Principal Investigator
investigator affiliation: University of California, Los Angeles
investigator full name: Donald B. Kohn, M.D.
investigator title: Principal Investigator
mesh term: Severe Combined Immunodeficiency
mesh term: Immunologic Deficiency Syndromes
mesh term: Busulfan
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 