<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/NCT04483440</url>
  </required_header>
  <id_info>
    <org_study_id>4D-110-CP-0001</org_study_id>
    <nct_id>NCT04483440</nct_id>
  </id_info>
  <brief_title>Dose Escalation Study of Intravitreal 4D-110 in Patients With Choroideremia</brief_title>
  <official_title>Phase 1 Open-Label, Dose-Escalation Study of the Safety, Tolerability and Preliminary Efficacy of Intravitreal 4D-110 in Patients With Choroideremia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>4D Molecular Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>4D Molecular Therapeutics</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>
      This study will evaluate safety, tolerability, and preliminary efficacy of a single&#xD;
      intravitreal (IVT) injection of a recombinant adeno-associated virus (AAV) gene therapy,&#xD;
      4D-110, in male patients with genetically-confirmed Choroideremia (CHM).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, Phase 1 study to evaluate safety and tolerability as well as&#xD;
      preliminary efficacy of a single IVT injection of 4D-110 at two dose levels in male patients&#xD;
      with genetically-confirmed CHM.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 2, 2020</start_date>
  <completion_date type="Anticipated">June 2027</completion_date>
  <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Each dose escalation cohort will initially recruit up to 3 patients to receive a single uniocular intravitreal injection of 4D-110 in a standard 3+3 design. The cohort will be expanded in the event of a dose limiting toxicity (DLT). Once the maximum tolerated dose (MTD)/maximum feasible dose (MFD) has been identified, up to 3 additional patients may be enrolled at that dose level to provide additional safety information.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency and severity of ocular and systemic adverse events (AEs)</measure>
    <time_frame>24 months</time_frame>
    <description>Frequency and severity of ocular and systemic AEs including clinically significant changes in ocular evaluations, systemic examinations and laboratory testing.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Choroideremia</condition>
  <arm_group>
    <arm_group_label>4D-110 Dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4D-110 IVT injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4D-110 Dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4D-110 IVT injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>4D-110</intervention_name>
    <description>4D-110 drug product developed for gene therapy which comprises an AAV capsid variant (4D-R100) carrying a transgene encoding a codon-optimized human CHM gene.</description>
    <arm_group_label>4D-110 Dose 1</arm_group_label>
    <arm_group_label>4D-110 Dose 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of CHM defined as a pathogenic mutation in the CHM gene, confirmed by&#xD;
             genetic testing&#xD;
&#xD;
          -  Both eyes must have ≥ 34 ETDRS letters (~20/200)&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Clinically significant, active ocular or peri-ocular infection or inflammation in the&#xD;
             study eye&#xD;
&#xD;
          -  Patient has previously received any AAV treatment&#xD;
&#xD;
          -  Ocular conditions or ocular media opacity in either eye that would preclude the&#xD;
             planned treatment (i.e. IVT injection) or interfere with the interpretation of study&#xD;
             endpoints (e.g. significant lens opacity)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Schonmei Lee, MD</last_name>
    <role>Study Director</role>
    <affiliation>4D Molecular Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Retina Foundation of the Southwest</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75251</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moran Eye Center, University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>January 18, 2023</last_update_submitted>
  <last_update_submitted_qc>January 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CHM</keyword>
  <keyword>transgene</keyword>
  <keyword>gene therapy</keyword>
  <keyword>AAV</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Choroideremia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04483440
org study id: 4D-110-CP-0001
nct id: NCT04483440
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate safety, tolerability, and preliminary efficacy of a single
      intravitreal (IVT) injection of a recombinant adeno-associated virus (AAV) gene therapy,
      4D-110, in male patients with genetically-confirmed Choroideremia (CHM).
This is an open-label, Phase 1 study to evaluate safety and tolerability as well as
      preliminary efficacy of a single IVT injection of 4D-110 at two dose levels in male patients
      with genetically-confirmed CHM.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Each dose escalation cohort will initially recruit up to 3 patients to receive a single uniocular intravitreal injection of 4D-110 in a standard 3+3 design. The cohort will be expanded in the event of a dose limiting toxicity (DLT). Once the maximum tolerated dose (MTD)/maximum feasible dose (MFD) has been identified, up to 3 additional patients may be enrolled at that dose level to provide additional safety information.
primary purpose: Treatment
masking: None (Open Label)
measure: Frequency and severity of ocular and systemic adverse events (AEs)
time frame: 24 months
description: Frequency and severity of ocular and systemic AEs including clinically significant changes in ocular evaluations, systemic examinations and laboratory testing.
arm group label: 4D-110 Dose 1
arm group type: Experimental
description: 4D-110 IVT injection
arm group label: 4D-110 Dose 2
arm group type: Experimental
description: 4D-110 IVT injection
intervention type: Biological
intervention name: 4D-110
description: 4D-110 drug product developed for gene therapy which comprises an AAV capsid variant (4D-R100) carrying a transgene encoding a codon-optimized human CHM gene.
arm group label: 4D-110 Dose 1
arm group label: 4D-110 Dose 2
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Schonmei Lee, MD
role: Study Director
affiliation: 4D Molecular Therapeutics
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Choroideremia
sharing ipd: No