xml: <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/NCT06025032</url>
    </required_header>
    <id_info>
      <org_study_id>HG20501</org_study_id>
      <nct_id>NCT06025032</nct_id>
    </id_info>
    <brief_title>A Study in Subjects With Otoferlin Mutation-related Hearing Loss Using RNA Base-eDiting Therapy</brief_title>
    <acronym>SOUND</acronym>
    <official_title>An Open-label, Multiple-cohort, Dose-finding, Investigator-initiated Trial to Evaluate the Safety, Tolerability, and Efficacy of HG205 RNA Base-Editing Therapy in Subjects With OTOF-p.Q829X Mutation-associated Hearing Loss</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>HuidaGene Therapeutics Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Eye &amp; ENT Hospital of Fudan University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>HuidaGene Therapeutics Co., Ltd.</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of the study is to determine whether HG205 as CRISPR/Cas13 RNA base-editing&#xD;
        therapy is safe and effective for the treatment of hearing loss caused by p.Q829X mutation in&#xD;
        OTOF gene.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 30, 2023</start_date>
    <completion_date type="Anticipated">April 28, 2030</completion_date>
    <primary_completion_date type="Anticipated">June 30, 2025</primary_completion_date>
    <phase>Early 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>Incidence of otological and systemic adverse events</measure>
      <time_frame>26 weeks</time_frame>
      <description>Number of AE(Adverse events),SAE(Serious Adverse Events),DLT(Dose Limiting Toxicities)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in ABR(Auditory Brainstem Response) intensity threshold (decibels normal hearing level [dB nHL])</measure>
      <time_frame>26 weeks</time_frame>
      <description>ABR intensity threshold (decibels normal hearing level [dB nHL]) measurement</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in hearing performance by behavioral audiometry with pure-tone audiometry</measure>
      <time_frame>26 weeks</time_frame>
      <description>Behavioral audiometry and pure-tone audiometry measurement</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">6</enrollment>
    <condition>Congenital Hearing Loss</condition>
    <arm_group>
      <arm_group_label>HG205</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Method of Administration: Once Unilateral intracochlear injection/subject; The duration of the study for each subject includes a screening period, enrollment visit, treatment visit, a 26-week follow-up period, and a 5-year long-term safety follow-up after the injection</description>
    </arm_group>
    <intervention>
      <intervention_type>Genetic</intervention_type>
      <intervention_name>HG205</intervention_name>
      <description>The study will enroll up to 2 cohorts, evaluating a starting dose plus a higher or lower dose</description>
      <arm_group_label>HG205</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male or females between 1 and 16 years of age at the time the subject/parent/legal&#xD;
               guardian signs the informed consent form.&#xD;
  &#xD;
            -  Willing to adhere to the protocol as evidenced by written informed consent or parental&#xD;
               permission and subject assent.&#xD;
  &#xD;
            -  Molecular diagnosis of biallelic mutations in the OTOF gene with at least one mutation&#xD;
               being p.Q829X through collected blood samples at screening;&#xD;
  &#xD;
            -  Based on auditory brainstem response (ABR), clinically diagnosed sensorineural hearing&#xD;
               loss (SNHL) with the following hearing thresholds: severe (65 dB ≤ hearing threshold &lt;&#xD;
               80 dB) or profound (80 dB ≤ hearing threshold &lt; 95 dB) or complete (hearing threshold&#xD;
               ≥ 95 dB) hearing loss in both ears.&#xD;
  &#xD;
            -  Acceptable hematology, clinical chemistry, and urine laboratory parameters.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pre-existing other hearing-loss conditions that would preclude the planned surgery or&#xD;
               interfere with the interpretation of study endpoints or complications of surgery.&#xD;
  &#xD;
            -  Presence of cochlear implants in the study ear.&#xD;
  &#xD;
            -  Complicating systemic diseases or clinically significant abnormal baseline laboratory&#xD;
               values.&#xD;
  &#xD;
            -  Complicating systemic diseases would include those in which the disease itself, or the&#xD;
               treatment for the disease, can alter hearing function.&#xD;
  &#xD;
            -  Prior participation in clinical study with an investigational drug within the past six&#xD;
               months.&#xD;
  &#xD;
            -  Prior gene therapy treatments.&#xD;
  &#xD;
            -  Any condition which leads the investigator to believe that the participant cannot&#xD;
               comply with the protocol requirements or that may place the participant at an&#xD;
               unacceptable risk for participation.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Year</minimum_age>
      <maximum_age>16 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Study Director</last_name>
      <role>Study Director</role>
      <affiliation>HuidaGene Therapeutics Co., Ltd.</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Study Director</last_name>
      <phone>+86 021-25076143</phone>
      <email>HG20501@huidagene.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Eye &amp; ENT Hospital of Fudan University</name>
        <address>
          <city>Shanghai</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Yilai Shu, MD,PhD</last_name>
        <phone>+86 021-64377134</phone>
      </contact>
      <investigator>
        <last_name>Yilai Shu, MD,PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Congenital hearing loss</keyword>
    <keyword>OTOF</keyword>
    <keyword>Q829X</keyword>
    <keyword>HG205</keyword>
    <keyword>CRISPR</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hearing Loss</mesh_term>
      <mesh_term>Deafness</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06025032
  org study id: HG20501
  nct id: NCT06025032
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of the study is to determine whether HG205 as CRISPR/Cas13 RNA base-editing
        therapy is safe and effective for the treatment of hearing loss caused by p.Q829X mutation in
        OTOF gene.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of otological and systemic adverse events
  time frame: 26 weeks
  description: Number of AE(Adverse events),SAE(Serious Adverse Events),DLT(Dose Limiting Toxicities)
  measure: Change from baseline in ABR(Auditory Brainstem Response) intensity threshold (decibels normal hearing level [dB nHL])
  time frame: 26 weeks
  description: ABR intensity threshold (decibels normal hearing level [dB nHL]) measurement
  measure: Change from baseline in hearing performance by behavioral audiometry with pure-tone audiometry
  time frame: 26 weeks
  description: Behavioral audiometry and pure-tone audiometry measurement
  arm group label: HG205
  arm group type: Experimental
  description: Method of Administration: Once Unilateral intracochlear injection/subject; The duration of the study for each subject includes a screening period, enrollment visit, treatment visit, a 26-week follow-up period, and a 5-year long-term safety follow-up after the injection
  intervention type: Genetic
  intervention name: HG205
  description: The study will enroll up to 2 cohorts, evaluating a starting dose plus a higher or lower dose
  arm group label: HG205
  criteria: 
  gender: All
  minimum age: 1 Year
  maximum age: 16 Years
  healthy volunteers: No
  last name: Study Director
  role: Study Director
  affiliation: HuidaGene Therapeutics Co., Ltd.
  last name: Study Director
  phone: +86 021-25076143
  email: HG20501@huidagene.com
  facility: 
  contact: 
  investigator: 
  country: China
  responsible party type: Sponsor
  mesh term: Hearing Loss
  mesh term: Deafness
  sharing ipd: No