<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/NCT03780972</url>
  </required_header>
  <id_info>
    <org_study_id>ONL1204-RRD-001</org_study_id>
    <nct_id>NCT03780972</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety and Tolerability of ONL1204 in Patients With Macula-off, Rhegmatogenous Retinal Detachment</brief_title>
  <official_title>A Phase 1 Open-Label, Dose Escalation Study to Assess the Safety and Tolerability of Intravitreal ONL1204 in Patients With Macula-off, Rhegmatogenous Retinal Detachment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ONL Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ONL Therapeutics</source>
  <oversight_info>
    <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 this study is to evaluate the safety and tolerability of ONL1204 in&#xD;
      participants with Macula-off, Rhegmatogenous Retinal Detachment (RRD). RRD is an acute and&#xD;
      serious vision threatening condition in which a tear in the retina, typically resulting from&#xD;
      a vitreous detachment, allows liquid to accumulate under the retina, detaching the&#xD;
      photoreceptor (PR) layer of the retina from the retinal pigment epithelium (RPE). As the RPE&#xD;
      is the principal source of nutritional support for the PR layer, the photoreceptors begin a&#xD;
      cascade of inflammation and cell death. Photoreceptor cell death is the primary mechanism of&#xD;
      vision loss after retinal detachment.&#xD;
&#xD;
      ONL1204 is a first-in-class inhibitor of Fragment Apoptosis Stimulator receptor&#xD;
      (Fas)-mediated cell death. ONL1204 has demonstrated protection of multiple retinal cell types&#xD;
      in numerous preclinical models of acute ocular injury. This will be a first-in-human (FIH)&#xD;
      study to evaluate safety and tolerability of a single-dose of ONL1204 in participants with&#xD;
      macula-off RRD. The standard of care for surgical repair of macula-off RRD is reattachment&#xD;
      surgery within 7 days of the macula detaching. Participants in this study will receive a&#xD;
      single intravitreal injection upon diagnosis and enrollment in the study, followed by&#xD;
      standard of care surgery. The surgery includes vitrectomy, a procedure that removes the bulk&#xD;
      of drug remaining in the vitreous.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 21, 2019</start_date>
  <completion_date type="Actual">August 24, 2022</completion_date>
  <primary_completion_date type="Actual">August 24, 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Vital sign-systolic and diastolic blood pressure</measure>
    <time_frame>24 weeks</time_frame>
    <description>Systolic and diastolic blood pressure in mmHg</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital sign-heart rate</measure>
    <time_frame>24 weeks</time_frame>
    <description>Heart rate in beats per minute</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Best corrected visual acuity</measure>
    <time_frame>24 weeks</time_frame>
    <description>ETDRS chart (number of letters read)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Intraocular pressure</measure>
    <time_frame>24 weeks</time_frame>
    <description>Intraocular pressure in mmHg</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Slit lamp biomicroscopy</measure>
    <time_frame>24 weeks</time_frame>
    <description>Slit lamp biomicroscopy (using US FDA clinical grading scale 0-4; 0=normal, 4=very severe changes)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete blood count</measure>
    <time_frame>24 weeks</time_frame>
    <description>White blood cells with differential, hemoglobin, hematocrit and platelet count</description>
  </primary_outcome>
  <other_outcome>
    <measure>Exploratory outcome-ONL1204 concentration</measure>
    <time_frame>24 weeks</time_frame>
    <description>Measurement of ONL1204 in plasma (ng/ml) after drug administration</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Rhegmatogenous Retinal Detachment - Macula Off</condition>
  <arm_group>
    <arm_group_label>Cohort 1 Dose A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2 Dose B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3 Dose C</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 3</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4 Dose D</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 4</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ONL1204</intervention_name>
    <description>Administration of ONL1204 - inhibitor of Fas(CD95) signaling by intravitreal injection</description>
    <arm_group_label>Cohort 1 Dose A</arm_group_label>
    <arm_group_label>Cohort 2 Dose B</arm_group_label>
    <arm_group_label>Cohort 3 Dose C</arm_group_label>
    <arm_group_label>Cohort 4 Dose D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Intravitreal Injection</intervention_name>
    <description>Injection of study drug into the eye</description>
    <arm_group_label>Cohort 1 Dose A</arm_group_label>
    <arm_group_label>Cohort 2 Dose B</arm_group_label>
    <arm_group_label>Cohort 3 Dose C</arm_group_label>
    <arm_group_label>Cohort 4 Dose D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Collection of ocular fluids</intervention_name>
    <description>vitreous and aqueous fluid collection by a tap and during vitrectomy</description>
    <arm_group_label>Cohort 1 Dose A</arm_group_label>
    <arm_group_label>Cohort 2 Dose B</arm_group_label>
    <arm_group_label>Cohort 3 Dose C</arm_group_label>
    <arm_group_label>Cohort 4 Dose D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females, ≥ 18 to 80 years old&#xD;
&#xD;
          2. Able to give informed consent and comply with all study visits and procedures&#xD;
&#xD;
          3. Patients who:&#xD;
&#xD;
               1. Present between 1 week (7 days) and 4 weeks (28 days) of a macula-off RRD (based&#xD;
                  on patient-reported history of loss of central vision)&#xD;
&#xD;
               2. For whom standard retinal reattachment surgery by means of a pars plana&#xD;
                  vitrectomy (with or without scleral buckle) and gas tamponade is indicated, and&#xD;
&#xD;
               3. In the opinion of the investigator, can safely undergo all study procedures.&#xD;
&#xD;
          4. Best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity of&#xD;
             20/100 to hand motion in the study eye&#xD;
&#xD;
          5. Best corrected ETDRS visual acuity in the fellow eye of 20/60 or better&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of giant retinal tear defined as greater than 3 clock hours or other type of&#xD;
             complex retinal detachment in the study eye&#xD;
&#xD;
          2. Presence of vitreous hemorrhage in the study eye&#xD;
&#xD;
          3. Presence of ocular or periocular infection or intraocular inflammation in either eye&#xD;
&#xD;
          4. Intraocular Pressure &gt; 22 mmHg in the study eye&#xD;
&#xD;
          5. Any other significant ocular disease in the study eye including media opacity that, in&#xD;
             the opinion of the investigator, would preclude a visual acuity of at least 20/25&#xD;
             following successful vitrectomy or limit adequate visibility of the retina&#xD;
&#xD;
          6. Any other ocular pathology in the study eye requiring treatment with topical&#xD;
             ophthalmic drops or intravitreal injection&#xD;
&#xD;
          7. History of previous ocular surgery in the study eye other than uncomplicated cataract&#xD;
             surgery with posterior chamber intraocular lens and intact posterior capsule (which&#xD;
             must have occurred at least 6 months prior to the baseline visit)&#xD;
&#xD;
          8. Participation in other clinical trials or use of any other investigational drugs or&#xD;
             devices within 3 months prior to study participation&#xD;
&#xD;
          9. Females who are pregnant or lactating and women of childbearing potential who are not&#xD;
             using adequate contraceptive precautions (e.g., intrauterine device, oral&#xD;
             contraceptives, barrier method, or other contraception deemed adequate by the&#xD;
             investigator)&#xD;
&#xD;
         10. Known retinopathy, known hepatic disease (or history of significant chronic liver&#xD;
             disease), or known renal disease. Patients with diabetes and no known retinopathy may&#xD;
             be enrolled&#xD;
&#xD;
         11. History of uncontrolled hypertension&#xD;
&#xD;
         12. History of stroke, transient ischemic attack, or major cardiac surgery within 3 months&#xD;
             prior to study, or current treatment for systemic infection&#xD;
&#xD;
         13. Any ocular or systemic condition that in the opinion of the investigator could&#xD;
             compromise the safety of the patient, or may interfere with the safety and&#xD;
             tolerability assessments or study procedures of the trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matthew Simunovic, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Save Sight Institute, Sydney Eye Hospital, Australia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Save Sight Institute, Sydney Eye Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3002</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queensland Eye Institute</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Eye Rearch Australia</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>VIC 3002</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>December 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>October 7, 2022</last_update_submitted>
  <last_update_submitted_qc>October 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Retinal Detachment</mesh_term>
    <mesh_term>Dissociative Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>May 31, 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/NCT03780972
org study id: ONL1204-RRD-001
nct id: NCT03780972
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the safety and tolerability of ONL1204 in
      participants with Macula-off, Rhegmatogenous Retinal Detachment (RRD). RRD is an acute and
      serious vision threatening condition in which a tear in the retina, typically resulting from
      a vitreous detachment, allows liquid to accumulate under the retina, detaching the
      photoreceptor (PR) layer of the retina from the retinal pigment epithelium (RPE). As the RPE
      is the principal source of nutritional support for the PR layer, the photoreceptors begin a
      cascade of inflammation and cell death. Photoreceptor cell death is the primary mechanism of
      vision loss after retinal detachment.

      ONL1204 is a first-in-class inhibitor of Fragment Apoptosis Stimulator receptor
      (Fas)-mediated cell death. ONL1204 has demonstrated protection of multiple retinal cell types
      in numerous preclinical models of acute ocular injury. This will be a first-in-human (FIH)
      study to evaluate safety and tolerability of a single-dose of ONL1204 in participants with
      macula-off RRD. The standard of care for surgical repair of macula-off RRD is reattachment
      surgery within 7 days of the macula detaching. Participants in this study will receive a
      single intravitreal injection upon diagnosis and enrollment in the study, followed by
      standard of care surgery. The surgery includes vitrectomy, a procedure that removes the bulk
      of drug remaining in the vitreous.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Vital sign-systolic and diastolic blood pressure
time frame: 24 weeks
description: Systolic and diastolic blood pressure in mmHg
measure: Vital sign-heart rate
time frame: 24 weeks
description: Heart rate in beats per minute
measure: Best corrected visual acuity
time frame: 24 weeks
description: ETDRS chart (number of letters read)
measure: Intraocular pressure
time frame: 24 weeks
description: Intraocular pressure in mmHg
measure: Slit lamp biomicroscopy
time frame: 24 weeks
description: Slit lamp biomicroscopy (using US FDA clinical grading scale 0-4; 0=normal, 4=very severe changes)
measure: Complete blood count
time frame: 24 weeks
description: White blood cells with differential, hemoglobin, hematocrit and platelet count
measure: Exploratory outcome-ONL1204 concentration
time frame: 24 weeks
description: Measurement of ONL1204 in plasma (ng/ml) after drug administration
arm group label: Cohort 1 Dose A
arm group type: Active Comparator
description: Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 1
arm group label: Cohort 2 Dose B
arm group type: Active Comparator
description: Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 2
arm group label: Cohort 3 Dose C
arm group type: Active Comparator
description: Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 3
arm group label: Cohort 4 Dose D
arm group type: Active Comparator
description: Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 4
intervention type: Drug
intervention name: ONL1204
description: Administration of ONL1204 - inhibitor of Fas(CD95) signaling by intravitreal injection
arm group label: Cohort 1 Dose A
arm group label: Cohort 2 Dose B
arm group label: Cohort 3 Dose C
arm group label: Cohort 4 Dose D
intervention type: Procedure
intervention name: Intravitreal Injection
description: Injection of study drug into the eye
arm group label: Cohort 1 Dose A
arm group label: Cohort 2 Dose B
arm group label: Cohort 3 Dose C
arm group label: Cohort 4 Dose D
intervention type: Procedure
intervention name: Collection of ocular fluids
description: vitreous and aqueous fluid collection by a tap and during vitrectomy
arm group label: Cohort 1 Dose A
arm group label: Cohort 2 Dose B
arm group label: Cohort 3 Dose C
arm group label: Cohort 4 Dose D
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Matthew Simunovic, M.D.
role: Principal Investigator
affiliation: Save Sight Institute, Sydney Eye Hospital, Australia
facility: 
facility: 
facility: 
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Retinal Detachment
mesh term: Dissociative Disorders
sharing ipd: No
submitted: May 31, 2023