<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/NCT03814408</url>
  </required_header>
  <id_info>
    <org_study_id>RP-L102-0418</org_study_id>
    <nct_id>NCT03814408</nct_id>
  </id_info>
  <brief_title>A Clinical Trial to Evaluate the Safety of RP-L102 in Pediatric Subjects With Fanconi Anemia Subtype A</brief_title>
  <official_title>A Phase I Clinical Trial to Evaluate the Safety of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the FANCA Gene in Pediatric Subjects With Fanconi Anemia Subtype A</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rocket Pharmaceuticals Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rocket Pharmaceuticals Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to assess the therapeutic safety and preliminary efficacy of a&#xD;
      hematopoietic cell-based gene therapy consisting of autologous CD34+ enriched cells&#xD;
      transduced with a lentiviral vector carrying the FANCA gene in subjects with Fanconi anemia&#xD;
      subtype A (FA-A).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a pediatric open-label Phase 1 clinical trial and will include a safety evaluation&#xD;
      and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of&#xD;
      autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene&#xD;
      in subjects with FA-A. CD34+ cells will be transduced ex vivo with the therapeutic lentiviral&#xD;
      vector and infused following transduction, without any prior conditioning. After&#xD;
      transduction, product quality control evaluations will be carried out in aliquots of the&#xD;
      transduced population. Investigational product will be infused via intravenous infusion with&#xD;
      no upper or lower limit; a dose of ≥5 x 105 CD34+ cells/kg body weight will be considered&#xD;
      optimal.&#xD;
&#xD;
      The active agent is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene&#xD;
      and the therapeutic product is subject's autologous HSCs that have been transduced with the&#xD;
      lentiviral vector. The vector contains the functional FANCA gene.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 11, 2019</start_date>
  <completion_date type="Anticipated">March 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>Phase 1</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>Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0</measure>
    <time_frame>3 years</time_frame>
    <description>Evaluation of safety associated with treatment with RP-L102</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102</measure>
    <time_frame>3 years</time_frame>
    <description>Assessment of the percentage of peripheral blood T-cells with DEB-induced chromosomal aberrations that decreases from over or equal to 50% at 0-2 months post-infusion to less than 50% during months 6-36 post-infusion (confirmed in at least 2 determinations conducted in each interval).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phenotypic correction of hematopoietic cells in bone marrow after infusion of RP-L102</measure>
    <time_frame>3 years</time_frame>
    <description>During months 6-36 post-infusion, the survival of bone marrow colony forming units to 10nM MMC increases to over or equal to 10% than values determined at 0-2 months post-infusion. (1 determination is considered valid).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102</measure>
    <time_frame>3 years</time_frame>
    <description>The level of gene marking of the FANCA-LV provirus in total peripheral blood cells is at least 0.1 vector copy number/nucleated cell during months 6-36 post-infusion. (This should be confirmed in at least 2 determinations conducted at different intervals). An increase in the vector copy number/peripheral blood cell is observed from 0-2 months post-infusion to the 3rd year post-infusion. (This should be confirmed in at least 2 determinations conducted in each interval periods).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevention or rescue of bone marrow failure after infusion of RP-L102</measure>
    <time_frame>3 years</time_frame>
    <description>Assessment of the need for treatment of bone marrow failure 6-36 months post-infusion. During the 3rd year post-infusion, peripheral blood parameters: hemoglobin levels, neutrophils, and platelets will be assessed and considered stable if they remain at over or equal to 80% of values determined at pre-treatment evaluation visit or immediately prior to mobilization before the administration of granulocyte-colony stimulating factor.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">2</enrollment>
  <condition>Fanconi Anemia Complementation Group A</condition>
  <arm_group>
    <arm_group_label>RP-L102</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RP-L102 is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RP-L102</intervention_name>
    <description>CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene, PGK-FANCA-WPRE</description>
    <arm_group_label>RP-L102</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Fanconi anemia, as diagnosed by chromosomal fragility assay of cultured T-lymphocytes&#xD;
             in the presence of DEB or a similar DNA-crosslinking agent.&#xD;
&#xD;
          -  Subjects of Fanconi Anemia complementation group A.&#xD;
&#xD;
          -  Minimum age: 1 year and a minimum of 8 kg.&#xD;
&#xD;
          -  Maximum age: 12 years.&#xD;
&#xD;
          -  At least one of the following hematologic parameters below lower limits of normal:&#xD;
&#xD;
               -  Hemoglobin&#xD;
&#xD;
               -  Absolute neutrophils&#xD;
&#xD;
               -  Platelets&#xD;
&#xD;
          -  At least 30 CD34+ cells/μL are determined in one BM aspiration within 3 months prior&#xD;
             to initiation of CD34+ cell collection.&#xD;
&#xD;
          -  If the number of C34+ cells/ μL in BM is in the range of 10-29, PB parameters should&#xD;
             meet two of the three following criteria:&#xD;
&#xD;
               -  Hemoglobin: ≥11g/dL&#xD;
&#xD;
               -  Neutrophils: ≥900 cells/μL&#xD;
&#xD;
               -  Platelets: ≥60,000 cells/μL&#xD;
&#xD;
          -  Provide informed consent in accordance with current legislation.&#xD;
&#xD;
          -  Women of childbearing age must have a negative urine pregnancy test at the baseline&#xD;
             visit and accept the use of an effective contraception method during participation in&#xD;
             the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with an available and medically eligible human leukocyte antigen&#xD;
             (HLA)-identical sibling donor.&#xD;
&#xD;
          -  Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities&#xD;
             predictive of these conditions in BM aspirate analysis. This assessment should be made&#xD;
             by valid studies conducted within the 3 months before the subject commences the stem&#xD;
             cell mobilization/collection procedures of the clinical trial.&#xD;
&#xD;
          -  Subjects with somatic mosaicism associated with stable or improved counts in all PB&#xD;
             cell lineages. (If T-lymphocyte chromosomal fragility analysis indicates potential&#xD;
             mosaicism, a medically significant decrease in at least one blood lineage over time&#xD;
             must be documented to enable eligibility).&#xD;
&#xD;
          -  Lansky performance status ≤60%.&#xD;
&#xD;
          -  Any concomitant disease or condition that, in the opinion of the Principal&#xD;
             Investigator, renders the subject unfit to participate in the study.&#xD;
&#xD;
          -  Pre-existing sensory or motor impairment ≥grade 2 according to the NCI CTCAE v5.0&#xD;
             criteria.&#xD;
&#xD;
          -  Pregnant or breastfeeding women.&#xD;
&#xD;
          -  Hepatic dysfunction as defined by either:&#xD;
&#xD;
               -  Bilirubin &gt;3.0 × upper limit of normal (ULN) or&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) &gt; 5.0 × ULN or&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) &gt; 5.0 × ULN&#xD;
&#xD;
          -  Renal dysfunction requiring either hemodialysis or peritoneal dialysis.&#xD;
&#xD;
          -  Pulmonary dysfunction as defined by either:&#xD;
&#xD;
               -  Need for supplemental oxygen during the prior 2 weeks in absence of acute&#xD;
                  infection.&#xD;
&#xD;
               -  Oxygen saturation by pulse oximetry &lt;90%.&#xD;
&#xD;
          -  Evidence of active metastatic or locoregionally advanced malignancy for which survival&#xD;
             is anticipated to be less than 3 years.&#xD;
&#xD;
          -  Subject is receiving androgens (i.e. danazol, oxymethalone).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Agnieszka Czechowicz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University, Stem Cell Transplantation and Regenerative Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University Institute for Stem Cell Biology and Regenerative Medicine Lucille Packard Children's Hospital, Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>November 23, 2020</last_update_submitted>
  <last_update_submitted_qc>November 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>FANCA, FA-A, Fanconi Anemia Subtype A</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fanconi Syndrome</mesh_term>
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Fanconi Anemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>April 11, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03814408
org study id: RP-L102-0418
nct id: NCT03814408
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The objective of this study is to assess the therapeutic safety and preliminary efficacy of a
      hematopoietic cell-based gene therapy consisting of autologous CD34+ enriched cells
      transduced with a lentiviral vector carrying the FANCA gene in subjects with Fanconi anemia
      subtype A (FA-A).
This is a pediatric open-label Phase 1 clinical trial and will include a safety evaluation
      and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of
      autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene
      in subjects with FA-A. CD34+ cells will be transduced ex vivo with the therapeutic lentiviral
      vector and infused following transduction, without any prior conditioning. After
      transduction, product quality control evaluations will be carried out in aliquots of the
      transduced population. Investigational product will be infused via intravenous infusion with
      no upper or lower limit; a dose of ≥5 x 105 CD34+ cells/kg body weight will be considered
      optimal.

      The active agent is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene
      and the therapeutic product is subject's autologous HSCs that have been transduced with the
      lentiviral vector. The vector contains the functional FANCA gene.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0
time frame: 3 years
description: Evaluation of safety associated with treatment with RP-L102
measure: Phenotypic correction of T-lymphocytes in peripheral blood after infusion of RP-L102
time frame: 3 years
description: Assessment of the percentage of peripheral blood T-cells with DEB-induced chromosomal aberrations that decreases from over or equal to 50% at 0-2 months post-infusion to less than 50% during months 6-36 post-infusion (confirmed in at least 2 determinations conducted in each interval).
measure: Phenotypic correction of hematopoietic cells in bone marrow after infusion of RP-L102
time frame: 3 years
description: During months 6-36 post-infusion, the survival of bone marrow colony forming units to 10nM MMC increases to over or equal to 10% than values determined at 0-2 months post-infusion. (1 determination is considered valid).
measure: Engraftment of gene-corrected hematopoietic cells after infusion of RP-L102
time frame: 3 years
description: The level of gene marking of the FANCA-LV provirus in total peripheral blood cells is at least 0.1 vector copy number/nucleated cell during months 6-36 post-infusion. (This should be confirmed in at least 2 determinations conducted at different intervals). An increase in the vector copy number/peripheral blood cell is observed from 0-2 months post-infusion to the 3rd year post-infusion. (This should be confirmed in at least 2 determinations conducted in each interval periods).
measure: Prevention or rescue of bone marrow failure after infusion of RP-L102
time frame: 3 years
description: Assessment of the need for treatment of bone marrow failure 6-36 months post-infusion. During the 3rd year post-infusion, peripheral blood parameters: hemoglobin levels, neutrophils, and platelets will be assessed and considered stable if they remain at over or equal to 80% of values determined at pre-treatment evaluation visit or immediately prior to mobilization before the administration of granulocyte-colony stimulating factor.
arm group label: RP-L102
arm group type: Experimental
description: RP-L102 is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene
intervention type: Biological
intervention name: RP-L102
description: CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with lentiviral vector carrying the FANCA gene, PGK-FANCA-WPRE
arm group label: RP-L102
criteria: 
gender: All
minimum age: 1 Year
maximum age: 12 Years
healthy volunteers: No
last name: Agnieszka Czechowicz, MD
role: Principal Investigator
affiliation: Stanford University, Stem Cell Transplantation and Regenerative Medicine
facility: 
country: United States
responsible party type: Sponsor
mesh term: Fanconi Syndrome
mesh term: Anemia
mesh term: Fanconi Anemia
sharing ipd: No
submitted: April 11, 2023