<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/NCT04462198</url>
  </required_header>
  <id_info>
    <org_study_id>PTI-505-101</org_study_id>
    <nct_id>NCT04462198</nct_id>
  </id_info>
  <brief_title>Phase I/IIa Study Evaluating Safety and Efficacy of an Intratympanic Dose of PIPE-505 in Subjects With Hearing Loss</brief_title>
  <official_title>A Phase I/IIa, Randomized, Double-Blind, Placebo-Controlled, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Unilateral Intratympanic PIPE-505 in Subjects With Sensorineural Hearing Loss Associated With Speech-in-Noise Impairment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pipeline Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pipeline Therapeutics, 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>
      This is a randomized, double-blind study of PIPE-505, or placebo, in subjects with hearing&#xD;
      loss associated with speech-in-noise impairment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized-controlled, double-blind study of PIPE-505 or placebo given as an&#xD;
      injection one time in subjects with sensorineural hearing loss associated with&#xD;
      speech-in-noise difficulty. Visits to the clinic will occur at baseline, dosing, and days 1,&#xD;
      7, 14, 30, 60 and 90 after treatment. Safety will be assessed by periodic measurement of&#xD;
      vital signs, ear examination, electrocardiogram (ECG), blood laboratory analyses and&#xD;
      occurrence of adverse events (AE). Efficacy will be assessed by periodic audiometry and other&#xD;
      audiological tests.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 15, 2020</start_date>
  <completion_date type="Actual">June 17, 2021</completion_date>
  <primary_completion_date type="Actual">June 17, 2021</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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>The dose preparer and treatment administrator will be unmasked.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Safety: Treatment-Emergent Adverse Events (TEAE)</measure>
    <time_frame>From baseline to 3 months follow up</time_frame>
    <description>Number of participants with TEAEs</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: Area under the curve (AUC)</measure>
    <time_frame>From baseline to 3 months follow up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: t1/2 (half life)</measure>
    <time_frame>From baseline to 3 months follow up</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory: Speech-in-noise assessments</measure>
    <time_frame>1 month, 2 months, and 3 months after drug administration</time_frame>
    <description>Hearing performance in the setting of background noise</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory: Audiogram tests</measure>
    <time_frame>1 month, 2 months, and 3 months after drug administration</time_frame>
    <description>Hearing sensitivity and thresholds with a quiet background</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory: Auditory brainstem potential testing</measure>
    <time_frame>1 month, 2 months, and 3 months after drug administration</time_frame>
    <description>Electrophysiological assessment of auditory nerve and brainstem responses to auditory signals</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Sensorineural Hearing Loss</condition>
  <arm_group>
    <arm_group_label>PIPE-505</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PIPE-505</intervention_name>
    <description>Intratympanic injection</description>
    <arm_group_label>PIPE-505</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Intratympanic injection</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject's primary language is English.&#xD;
&#xD;
          -  Male or female between 18 and 75 years of age, inclusive, at randomization.&#xD;
&#xD;
          -  Diagnosis of bilateral sensorineural hearing loss (SNHL).&#xD;
&#xD;
          -  Normal tympanogram in the ear intended for injection (as defined in protocol) at&#xD;
             Screening.&#xD;
&#xD;
          -  Male or female subjects with reproductive potential agree to comply with&#xD;
             protocol-approved double barrier contraceptive method during and for 3 months after&#xD;
             study drug administration.&#xD;
&#xD;
          -  The subject is in general good medical health with no clinically significant or&#xD;
             relevant abnormalities, including medical history, physical exam, vital signs, ECG,&#xD;
             and laboratory evaluations (hematology, chemistry, and urinalysis) as assessed by the&#xD;
             Investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of chronic otitis externa or media, other chronic middle ear disorders,&#xD;
             barotrauma, Meniere's disease, endolymphatic hydrops, perilymph fistula, herpes zoster&#xD;
             oticus or other infectious etiology of hearing loss.&#xD;
&#xD;
          -  Presence of a genetic, syndromal or developmental auditory disorder or of an&#xD;
             autoimmune or serious neurological disorder that could contribute to auditory loss.&#xD;
&#xD;
          -  Evidence of current conductive hearing loss, mixed hearing loss or otosclerosis.&#xD;
&#xD;
          -  History of auditory loss related to exposure to known high-dose ototoxic drugs; any&#xD;
             prior exposure to platinum-based medications.&#xD;
&#xD;
          -  Otological disorders that would preclude safe tympanic injection.&#xD;
&#xD;
          -  Presence of a cochlear implant.&#xD;
&#xD;
          -  Evidence of bothersome tinnitus as determined by the Investigator.&#xD;
&#xD;
          -  Intratympanic injection within 6 months of randomization.&#xD;
&#xD;
          -  Use of an investigational product or intervention other than a non-interventional&#xD;
             registry study (including vaccine studies) within the greater of 30 days or 5&#xD;
             half-lives (if known) prior to Screening or expected during the study.&#xD;
&#xD;
          -  History of malignancy under current active treatment or considered at substantial risk&#xD;
             for progression or recurrence during the study interval, as determined by the&#xD;
             Investigator. Note, central nervous system neoplasms or head and neck cancer are&#xD;
             excluded from eligibility regardless of treatment status.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephen Huhn, MD</last_name>
    <role>Study Director</role>
    <affiliation>Chief Medical Officer, Pipeline Therapeutics, Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Breathe Clear Institute</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ENT and Allergy Associates of Florida</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33487</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced ENT &amp; Allergy</name>
      <address>
        <city>New Albany</city>
        <state>Indiana</state>
        <zip>47150</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas; Dept of Otolaryngology Head &amp; Neck Surgery</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced ENT &amp; Allergy</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charlotte Eye Ear Nose Throat Associates</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Ear Nose Throat and Associates</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chrysalis Clinical Research</name>
      <address>
        <city>Saint George</city>
        <state>Utah</state>
        <zip>84790</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <disposition_first_submitted>June 7, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>June 7, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">June 10, 2022</disposition_first_posted>
  <last_update_submitted>June 7, 2022</last_update_submitted>
  <last_update_submitted_qc>June 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hearing Loss</keyword>
  <keyword>Cochlear synaptopathy</keyword>
  <keyword>Deafness</keyword>
  <keyword>Speech-in-noise hearing difficulty</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>
    <mesh_term>Hearing Loss, Sensorineural</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT04462198
org study id: PTI-505-101
nct id: NCT04462198
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized, double-blind study of PIPE-505, or placebo, in subjects with hearing
      loss associated with speech-in-noise impairment.
This is a randomized-controlled, double-blind study of PIPE-505 or placebo given as an
      injection one time in subjects with sensorineural hearing loss associated with
      speech-in-noise difficulty. Visits to the clinic will occur at baseline, dosing, and days 1,
      7, 14, 30, 60 and 90 after treatment. Safety will be assessed by periodic measurement of
      vital signs, ear examination, electrocardiogram (ECG), blood laboratory analyses and
      occurrence of adverse events (AE). Efficacy will be assessed by periodic audiometry and other
      audiological tests.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: The dose preparer and treatment administrator will be unmasked.
measure: Safety: Treatment-Emergent Adverse Events (TEAE)
time frame: From baseline to 3 months follow up
description: Number of participants with TEAEs
measure: Pharmacokinetics: Area under the curve (AUC)
time frame: From baseline to 3 months follow up
measure: Pharmacokinetics: t1/2 (half life)
time frame: From baseline to 3 months follow up
measure: Exploratory: Speech-in-noise assessments
time frame: 1 month, 2 months, and 3 months after drug administration
description: Hearing performance in the setting of background noise
measure: Exploratory: Audiogram tests
time frame: 1 month, 2 months, and 3 months after drug administration
description: Hearing sensitivity and thresholds with a quiet background
measure: Exploratory: Auditory brainstem potential testing
time frame: 1 month, 2 months, and 3 months after drug administration
description: Electrophysiological assessment of auditory nerve and brainstem responses to auditory signals
arm group label: PIPE-505
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: PIPE-505
description: Intratympanic injection
arm group label: PIPE-505
intervention type: Drug
intervention name: Placebo
description: Intratympanic injection
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Stephen Huhn, MD
role: Study Director
affiliation: Chief Medical Officer, Pipeline Therapeutics, Inc
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hearing Loss
mesh term: Deafness
mesh term: Hearing Loss, Sensorineural