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/NCT05966493</url>
    </required_header>
    <id_info>
      <org_study_id>AMB-01-006</org_study_id>
      <nct_id>NCT05966493</nct_id>
    </id_info>
    <brief_title>A Study to Evaluate the Safety and Efficacy of NEXAGON® (Lufepirsen Ophthalmic Gel) in Subjects With PCED</brief_title>
    <acronym>NEXPEDE-1</acronym>
    <official_title>A Randomized, Multicenter, Double-Masked, Vehicle-Controlled Phase 2/3 Study to Evaluate the Safety and Efficacy of NEXAGON® (Lufepirsen Ophthalmic Gel) in Subjects With Persistent Corneal Epithelial Defects (NEXPEDE-1)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Amber Ophthalmics, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Amber Ophthalmics, 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 study is to evaluate the safety and efficacy of NEXAGON® (lufepirsen ophthalmic gel)&#xD;
        (NEXAGON) in subjects with persistent corneal epithelial defects (PCED). The objectives of&#xD;
        the study are to evaluate the safety and efficacy of NEXAGON in this population.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study is a randomized, multicenter, double-masked, vehicle-controlled study to evaluate&#xD;
        the safety and efficacy of NEXAGON (lufepirsen ophthalmic gel) in subjects with persistent&#xD;
        corneal epithelial defects (PCED). The study will enroll subjects who will complete a&#xD;
        Screening Period, Treatment Period (up to 8 weeks) and Follow-up Period (4 weeks). Those&#xD;
        subjects whose defect has not re-epithelialized by the completion of the Treatment Period or&#xD;
        who achieved re-epithelialization but failed to maintain re-epithelialization for 28 days&#xD;
        after treatment completion (durability) are eligible to enter the NEXAGON Open-label&#xD;
        Treatment Period for an additional 8 weeks.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">July 2023</start_date>
    <completion_date type="Anticipated">October 2024</completion_date>
    <primary_completion_date type="Anticipated">October 2024</primary_completion_date>
    <phase>Phase 2/Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Achieve Corneal Re-epithelialization Including Durability (CRC)</measure>
      <time_frame>End of Study: 28 Days after achieving re-epithelialization</time_frame>
      <description>The proportion of subjects achieving corneal re-epithelialization that is maintained for a minimum of 28 days, based on assessment of corneal fluorescein staining images of the PCED by a Central Reading Center (CRC).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Achieve Corneal Re-epithelialization Including Durability (Investigator)</measure>
      <time_frame>End of Study: 28 Days after achieving re-epithelialization</time_frame>
      <description>The proportion of subjects achieving corneal re-epithelialization that is maintained for a minimum of 28 days, based on assessment of corneal fluorescein staining of the PCED by the Investigator</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Achieve Corneal Re-epithelialization (CRC)</measure>
      <time_frame>Weeks 1, 2, 3, 4, 5, 6, 7, 8</time_frame>
      <description>The proportion of subjects achieving corneal re-epithelialization, based on assessment of corneal fluorescein staining images of the PCED by a CRC.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Achieve Corneal Re-epithelialization (Investigator)</measure>
      <time_frame>Weeks 1, 2, 3, 4, 5, 6, 7, 8</time_frame>
      <description>The proportion of subjects achieving corneal re-epithelialization based on assessment of corneal fluorescein staining images of the PCED by Investigator.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Dose Administrations Required to Achieve Corneal Re-epithelialization (CRC)</measure>
      <time_frame>Weeks 1, 2, 3, 4, 5, 6, 7, 8</time_frame>
      <description>The number of dose administrations subjects required to achieve corneal re-epithelialization that is maintained for a minimum of 28 days after completing treatment, based on assessment of corneal fluorescein staining images of the PCED by a CRC.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Dose Administrations Required to Achieve Corneal Re-epithelialization (Investigator)</measure>
      <time_frame>Weeks 4, 5, 6, 7, 8</time_frame>
      <description>The number of dose administrations subjects required to achieve corneal re-epithelialization that is maintained for a minimum of 28 days after completing treatment, based on assessment of corneal fluorescein staining images of the PCED by Investigator.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to Corneal Re-epithelialization (CRC)</measure>
      <time_frame>Weeks 1, 2, 3, 4, 5, 6, 7, 8</time_frame>
      <description>The time (in days) to corneal re-epithelialization, defined as the time from randomization to the time of corneal re-epithelialization based on assessment of corneal fluorescein staining images of the PCED by a CRC.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to Corneal Re-epithelialization (Investigator)</measure>
      <time_frame>Weeks 1, 2, 3, 4, 5, 6, 7, 8</time_frame>
      <description>The time (in days) to corneal re-epithelialization, defined as the time from randomization to the time of corneal re-epithelialization based on assessment of corneal fluorescein staining images of the PCED by Investigator.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ocular Pain Assessment Survey</measure>
      <time_frame>End of Study: Week 9, 10, 11, or 12</time_frame>
      <description>The mean change from baseline (CFB) in ocular pain based on Ocular Pain Assessment Survey (OPAS).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of visual health status indices by the administration of the NEI Visual Function Questionnaire (NEI-VFQ-25).</measure>
      <time_frame>End of Study: Week 9, 10, 11, or 12</time_frame>
      <description>Assess the change from baseline in the subject's visual health status using the NEI-VFQ-25 (0-100, higher scores representing a better status).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Visual Acuity Assessment</measure>
      <time_frame>End of Study: Week 9, 10, 11, or 12</time_frame>
      <description>The mean CFB in Best Corrected Distance Visual Acuity (BCDVA).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Visual Acuity Improvement</measure>
      <time_frame>End of Study: Week 9, 10, 11, or 12</time_frame>
      <description>The proportion of subjects who achieve a 15 letter (ETDRS) gain in BCDVA.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Open-label Treatment Period</measure>
      <time_frame>Open-label Day 1</time_frame>
      <description>The proportion of subjects requiring open-label treatment during the Treatment Period.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Achieve Corneal Re-epithelialization in Open-label Treatment Period</measure>
      <time_frame>End of Study: 28 Days after achieving re-epithelialization</time_frame>
      <description>The proportion of subjects in the Open-Label Treatment Period that achieve re-epithelialization of the corneal epithelial defect that remains durable for a minimum of 28 days based on the CRC assessment on images.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Persistent Corneal Epithelial Defect</condition>
    <arm_group>
      <arm_group_label>NEXAGON® (lufepirsen ophthalmic gel) High Dose Concentration</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Lufepirsen (High dose concentration) applied topically weekly for 4 to 8 weeks.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>NEXAGON® (lufepirsen ophthalmic gel) Low Dose Concentration</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Lufepirsen (Low dose concentration) applied topically weekly for 4 to 8 weeks.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>NEXAGON Vehicle (ophthalmic gel)</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Vehicle applied topically weekly for 4 to 8 weeks.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>lufepirsen</intervention_name>
      <description>Lufepirsen is an unmodified connexin43 antisense oligonucleotide.</description>
      <arm_group_label>NEXAGON® (lufepirsen ophthalmic gel) High Dose Concentration</arm_group_label>
      <arm_group_label>NEXAGON® (lufepirsen ophthalmic gel) Low Dose Concentration</arm_group_label>
      <other_name>NEXAGON®</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Vehicle</intervention_name>
      <description>Matching vehicle without lufepirsen.</description>
      <arm_group_label>NEXAGON Vehicle (ophthalmic gel)</arm_group_label>
      <other_name>Placebo</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Have a PCED that is at least 2 weeks in duration and refractory to one or more&#xD;
               conventional non-surgical standard of care (SOC) treatments&#xD;
  &#xD;
            2. Have no clinical evidence of improvement in the PCED within 2 weeks prior to&#xD;
               randomization despite the use of non-surgical SOC treatment&#xD;
  &#xD;
            3. PCED measures at least 2 mm along the largest diameter&#xD;
  &#xD;
            4. Subject must provide written informed consent (or assent)&#xD;
  &#xD;
            5. Subjects with childbearing potential must be 1-year postmenopausal, surgically&#xD;
               sterilized, or have a negative urine pregnancy test&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Have a known ocular infection that is deemed to be active requiring therapeutic&#xD;
               intervention&#xD;
  &#xD;
            2. Present with a corneal surface defect in either eye that is directly attributed to an&#xD;
               infectious etiology (bacterial, viral, fungal and/or protozoal) that has not fully&#xD;
               resolved and/or treatment has not been completed&#xD;
  &#xD;
            3. Present with evidence of corneal ulceration/melting involving the posterior third of&#xD;
               the stroma and/or perforation in either eye&#xD;
  &#xD;
            4. Have a blepharitis or meibomian gland disease in the study eye that in the opinion of&#xD;
               the Investigator is deemed to be clinically relevant and/or active&#xD;
  &#xD;
            5. Have a history of a full thickness keratoplasty, &gt; 1 Descemet membrane endothelial&#xD;
               keratoplasty (DMEK) or Descemet's stripping endothelial keratoplasty (DSEK) procedure&#xD;
  &#xD;
            6. Have a history of ocular surgery or any ocular procedure(s) not meeting the designated&#xD;
               washout time&#xD;
  &#xD;
            7. Have any other ocular disease requiring topical ocular medication in the affected eye&#xD;
  &#xD;
            8. A Schirmer I test result (without anesthesia) of ≤ 3 mm/5 minutes in the study eye&#xD;
  &#xD;
            9. Have a presence or history of any ocular or systemic disorder or condition that, in&#xD;
               the judgement of the Investigator, might hinder the efficacy of the study treatment or&#xD;
               its evaluation, could possibly interfere with the interpretation of study results, or&#xD;
               could be incompatible with the study visit schedule or conduct&#xD;
  &#xD;
           10. Have a known hypersensitivity to one of the components of the study or procedural&#xD;
               medications (e.g., NEXAGON, fluorescein)&#xD;
  &#xD;
           11. Participated in an interventional clinical drug or device trial within 28 days prior&#xD;
               to Day 1&#xD;
  &#xD;
           12. Use of the medications presented in the protocol that are prohibited in the study.&#xD;
  &#xD;
           13. Use of Oxervate within 30 days of study enrollment.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>2 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>President and CSO, PharmD</last_name>
      <phone>858-663-1500</phone>
      <email>clinical@amberophthalmics.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Principal Investigator</name>
        <address>
          <city>Pasadena</city>
          <state>California</state>
          <zip>91107</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Study Coordinator</last_name>
        <phone>626-793-3625</phone>
        <phone_ext>0</phone_ext>
      </contact>
    </location>
    <location>
      <facility>
        <name>Principal Investigator</name>
        <address>
          <city>Torrance</city>
          <state>California</state>
          <zip>90505</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Study Coordinator</last_name>
        <phone>310-602-5640</phone>
        <email>tstudy1@wgea.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Principal Investigator</name>
        <address>
          <city>Grand Junction</city>
          <state>Colorado</state>
          <zip>81501</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Study Coordinator</last_name>
        <phone>970-205-9555</phone>
        <email>Chris.Bosch@iconeyecare.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Principal Investigator</name>
        <address>
          <city>Atlanta</city>
          <state>Georgia</state>
          <zip>30339</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Study Coordinator</last_name>
        <phone>404-351-2220</phone>
      </contact>
    </location>
    <location>
      <facility>
        <name>Principal Investigator</name>
        <address>
          <city>Nashville</city>
          <state>Tennessee</state>
          <zip>37215</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Study Coordinator</last_name>
        <phone>615-327-4015</phone>
      </contact>
    </location>
    <location>
      <facility>
        <name>Principal Investigator</name>
        <address>
          <city>San Antonio</city>
          <state>Texas</state>
          <zip>78238</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Study Coordinator</last_name>
        <phone>210-226-6169</phone>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>June 20, 2023</study_first_submitted>
    <study_first_submitted_qc>July 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 21, 2023</last_update_submitted>
    <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>PCED</keyword>
    <keyword>Corneal Defect</keyword>
    <keyword>PED</keyword>
    <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/NCT05966493
  org study id: AMB-01-006
  nct id: NCT05966493
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This study is to evaluate the safety and efficacy of NEXAGON® (lufepirsen ophthalmic gel)
        (NEXAGON) in subjects with persistent corneal epithelial defects (PCED). The objectives of
        the study are to evaluate the safety and efficacy of NEXAGON in this population.
  This study is a randomized, multicenter, double-masked, vehicle-controlled study to evaluate
        the safety and efficacy of NEXAGON (lufepirsen ophthalmic gel) in subjects with persistent
        corneal epithelial defects (PCED). The study will enroll subjects who will complete a
        Screening Period, Treatment Period (up to 8 weeks) and Follow-up Period (4 weeks). Those
        subjects whose defect has not re-epithelialized by the completion of the Treatment Period or
        who achieved re-epithelialization but failed to maintain re-epithelialization for 28 days
        after treatment completion (durability) are eligible to enter the NEXAGON Open-label
        Treatment Period for an additional 8 weeks.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Achieve Corneal Re-epithelialization Including Durability (CRC)
  time frame: End of Study: 28 Days after achieving re-epithelialization
  description: The proportion of subjects achieving corneal re-epithelialization that is maintained for a minimum of 28 days, based on assessment of corneal fluorescein staining images of the PCED by a Central Reading Center (CRC).
  measure: Achieve Corneal Re-epithelialization Including Durability (Investigator)
  time frame: End of Study: 28 Days after achieving re-epithelialization
  description: The proportion of subjects achieving corneal re-epithelialization that is maintained for a minimum of 28 days, based on assessment of corneal fluorescein staining of the PCED by the Investigator
  measure: Achieve Corneal Re-epithelialization (CRC)
  time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8
  description: The proportion of subjects achieving corneal re-epithelialization, based on assessment of corneal fluorescein staining images of the PCED by a CRC.
  measure: Achieve Corneal Re-epithelialization (Investigator)
  time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8
  description: The proportion of subjects achieving corneal re-epithelialization based on assessment of corneal fluorescein staining images of the PCED by Investigator.
  measure: Number of Dose Administrations Required to Achieve Corneal Re-epithelialization (CRC)
  time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8
  description: The number of dose administrations subjects required to achieve corneal re-epithelialization that is maintained for a minimum of 28 days after completing treatment, based on assessment of corneal fluorescein staining images of the PCED by a CRC.
  measure: Number of Dose Administrations Required to Achieve Corneal Re-epithelialization (Investigator)
  time frame: Weeks 4, 5, 6, 7, 8
  description: The number of dose administrations subjects required to achieve corneal re-epithelialization that is maintained for a minimum of 28 days after completing treatment, based on assessment of corneal fluorescein staining images of the PCED by Investigator.
  measure: Time to Corneal Re-epithelialization (CRC)
  time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8
  description: The time (in days) to corneal re-epithelialization, defined as the time from randomization to the time of corneal re-epithelialization based on assessment of corneal fluorescein staining images of the PCED by a CRC.
  measure: Time to Corneal Re-epithelialization (Investigator)
  time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8
  description: The time (in days) to corneal re-epithelialization, defined as the time from randomization to the time of corneal re-epithelialization based on assessment of corneal fluorescein staining images of the PCED by Investigator.
  measure: Ocular Pain Assessment Survey
  time frame: End of Study: Week 9, 10, 11, or 12
  description: The mean change from baseline (CFB) in ocular pain based on Ocular Pain Assessment Survey (OPAS).
  measure: Assessment of visual health status indices by the administration of the NEI Visual Function Questionnaire (NEI-VFQ-25).
  time frame: End of Study: Week 9, 10, 11, or 12
  description: Assess the change from baseline in the subject's visual health status using the NEI-VFQ-25 (0-100, higher scores representing a better status).
  measure: Visual Acuity Assessment
  time frame: End of Study: Week 9, 10, 11, or 12
  description: The mean CFB in Best Corrected Distance Visual Acuity (BCDVA).
  measure: Visual Acuity Improvement
  time frame: End of Study: Week 9, 10, 11, or 12
  description: The proportion of subjects who achieve a 15 letter (ETDRS) gain in BCDVA.
  measure: Open-label Treatment Period
  time frame: Open-label Day 1
  description: The proportion of subjects requiring open-label treatment during the Treatment Period.
  measure: Achieve Corneal Re-epithelialization in Open-label Treatment Period
  time frame: End of Study: 28 Days after achieving re-epithelialization
  description: The proportion of subjects in the Open-Label Treatment Period that achieve re-epithelialization of the corneal epithelial defect that remains durable for a minimum of 28 days based on the CRC assessment on images.
  arm group label: NEXAGON® (lufepirsen ophthalmic gel) High Dose Concentration
  arm group type: Experimental
  description: Lufepirsen (High dose concentration) applied topically weekly for 4 to 8 weeks.
  arm group label: NEXAGON® (lufepirsen ophthalmic gel) Low Dose Concentration
  arm group type: Experimental
  description: Lufepirsen (Low dose concentration) applied topically weekly for 4 to 8 weeks.
  arm group label: NEXAGON Vehicle (ophthalmic gel)
  arm group type: Placebo Comparator
  description: Vehicle applied topically weekly for 4 to 8 weeks.
  intervention type: Drug
  intervention name: lufepirsen
  description: Lufepirsen is an unmodified connexin43 antisense oligonucleotide.
  arm group label: NEXAGON® (lufepirsen ophthalmic gel) High Dose Concentration
  arm group label: NEXAGON® (lufepirsen ophthalmic gel) Low Dose Concentration
  other name: NEXAGON®
  intervention type: Drug
  intervention name: Vehicle
  description: Matching vehicle without lufepirsen.
  arm group label: NEXAGON Vehicle (ophthalmic gel)
  other name: Placebo
  criteria: 
  gender: All
  minimum age: 2 Years
  maximum age: N/A
  healthy volunteers: No
  last name: President and CSO, PharmD
  phone: 858-663-1500
  email: clinical@amberophthalmics.com
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Sponsor
  sharing ipd: No