<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/NCT03308045</url>
  </required_header>
  <id_info>
    <org_study_id>EYS606-CT1</org_study_id>
    <nct_id>NCT03308045</nct_id>
  </id_info>
  <brief_title>Evaluation of EYS606 in Patients With Non-infectious Posterior, Intermediate or Panuveitis</brief_title>
  <official_title>A Phase I/II, Open-label, Multicentre, Dose Escalation Study Assessing Safety/Tolerability of pEYS606 When Administered by Electrotransfer (ET) in Ciliary Muscle of Patients With Non-infectious Posterior, Intermediate or Panuveitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eyevensys</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eyevensys</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Primary objective: safety and tolerability&#xD;
&#xD;
      Secondary objectives: additional indicators of long term safety and indicators of clinical&#xD;
      activity&#xD;
&#xD;
      Exploratory objectives: to characterize EYS606 biodistribution, immunogenicity and biomarkers&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The maximum study duration per patient is 51 Weeks (including an up to 3 week screening&#xD;
      period + 48 weeks follow-up after treatment).&#xD;
&#xD;
      The study is conducted in 2 parts. Part 1 is a dose escalation phase which will investigate&#xD;
      three pEYS606 doses levels (lower, intermediate and higher dose) over 3 cohorts. Part 1 of&#xD;
      the study has been completed. Part 2, the extension phase, which is now ongoing will confirm&#xD;
      to safety of the maximum tolerated higher dose from Part 1 and allow a preliminary assessment&#xD;
      of efficacy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 4, 2017</start_date>
  <completion_date type="Actual">June 1, 2021</completion_date>
  <primary_completion_date type="Actual">June 1, 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>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Clinical trial with a single arm</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with treatment emergent adverse events</measure>
    <time_frame>4 weeks</time_frame>
    <description>Assessment of the safety and tolerability of EYS606</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in ocular safety assessments</measure>
    <time_frame>6 months</time_frame>
    <description>Measured as change from baseline in adverse events, concomitant medications, intraocular pressure, electroretinogram, electrocardiogram, vital signs, physical exam and routine labs (blood and urinalysis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in best corrected visual acuity</measure>
    <time_frame>6 months</time_frame>
    <description>Measured as change from baseline eye in best corrected visual acuity using ETDRS scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in anterior chamber cell grade</measure>
    <time_frame>6 months</time_frame>
    <description>Measured as change from baseline in anterior cell grade according to the SUN scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in vitreous haze grade</measure>
    <time_frame>6 months</time_frame>
    <description>Measures as change from baseline in vitreous haze grade according to SUN scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in central retinal thickness</measure>
    <time_frame>6 months</time_frame>
    <description>Measures as change from baseline in central retinal thickness using ocular coherence tomography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in corticosteroid dose</measure>
    <time_frame>6 months</time_frame>
    <description>Measures as change from baseline in prescribed dose of corticosteroids</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Non-infectious Uveitis</condition>
  <arm_group>
    <arm_group_label>pEYS606</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 1 (pEYS606 lower dose); Cohort 2 (pEYS606 intermediate dose); Cohort 3 (pEYS606 higher dose); Extension Cohort (pEYS606 maximum tolerated dose)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pEYS606</intervention_name>
    <description>pEYS606 is a DNA plasmid solution administered by electrotransfection into the ciliary muscle</description>
    <arm_group_label>pEYS606</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient must be 18 years of age or older&#xD;
&#xD;
          -  Both female patients of childbearing potential and male patients able to father a&#xD;
             child must agree to practice at least one effective method of birth control for six&#xD;
             months following administration of study medication. Acceptable methods of birth&#xD;
             control for this study include hormonal contraception (birth control pills, injected&#xD;
             hormones, dermal patch or vaginal ring), intrauterine device, barrier methods&#xD;
             (diaphragm, condom) with spermicide or surgical sterilization (hysterectomy, tubal&#xD;
             ligation or vasectomy). Patients with a hysterectomy or vasectomy (or have a partner&#xD;
             with a hysterectomy or vasectomy) are exempt from using these methods of birth&#xD;
             control.&#xD;
&#xD;
          -  Female patients of childbearing potential must not be pregnant or breast-feeding and&#xD;
             must have a negative urine pregnancy test at baseline and throughout the study.&#xD;
&#xD;
          -  Voluntary written informed consent before performance of any study related procedure&#xD;
             not part of normal medical care, with the understanding that consent may be withdrawn&#xD;
             by the subject at any time without prejudice to future medical care.&#xD;
&#xD;
          -  Patient has only one eligible eye with the following criteria:&#xD;
&#xD;
          -  non-infectious intermediate, posterior, or panuveitis,&#xD;
&#xD;
          -  media clarity, pupillary dilation, and individual cooperation sufficient for adequate&#xD;
             fundus imaging,&#xD;
&#xD;
          -  macular atrophy, AND/OR degenerative macular edema, AND/OR advanced optic neuropathy,&#xD;
             AND/OR macular scar,&#xD;
&#xD;
          -  Patients must maintain regiment of local and/or systemic corticosteroids between&#xD;
             screening and baseline (if applicable).&#xD;
&#xD;
        Visual Criteria - Part 1 (enrolment is Part 1 is completed)&#xD;
&#xD;
        - BCVA of 0.1 (ETDRS of 35) or worse at screening in the treated eye, and BCVA of 0.32 or&#xD;
        higher in the fellow eye.&#xD;
&#xD;
        Key Inclusion Criteria - Part 2 (enrolment in Part 2 is ongoing)&#xD;
&#xD;
          -  BCVA of ≤ 0.63 or 20/32 Snellen but ≥ 0.025 or 20/800 Snellen (equivalent to ≥ 5 and ≤&#xD;
             77 ETDRS letters) in the treated eye&#xD;
&#xD;
          -  Patient must have a diagnosis of non-infectious uveitis of any anatomic subtype&#xD;
&#xD;
          -  Patient must have a history of chronic or recurrent uveitis requiring or having&#xD;
             required treatment with corticosteroids (systemic, periocular or intraocular) and/or&#xD;
             systemic immunosuppressive medication(s) in the 12 months prior to the screening visit&#xD;
&#xD;
          -  At the screening and baseline visits patient must have active uveitis as evidenced by&#xD;
             at least one or more of the following in the study eye:&#xD;
&#xD;
        oActive retinal vasculitis (retinal vascular leakage) oVitreous haze grade ≥ 2+ oAnterior&#xD;
        chamber cell grade ≥ 2+ oMacular edema&#xD;
&#xD;
          -  Patient receiving concomitant topical and/or systemic corticosteroids or allowed&#xD;
             systemic immunosuppressive medications must have maintained the same treatment regimen&#xD;
             (dosage/frequency) for at least 2 weeks prior to the baseline (V1) visit, (if&#xD;
             applicable).&#xD;
&#xD;
          -  Willingness to receive local therapy to treat ocular inflammation in the fellow eye&#xD;
             during the course of the study (if needed).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient has or is suspected to have infectious uveitis or a uveitis masquerade&#xD;
             syndrome.&#xD;
&#xD;
          -  Patient suspected to have tuberculosis, has had a positive test for tuberculosis in&#xD;
             the past or has a positive γ-interferon tuberculosis test at the screening visit.&#xD;
&#xD;
          -  For a patient with a primary diagnosis of idiopathic intermediate uveitis exclusion of&#xD;
             any signs of multiple sclerosis must be demonstrated by an MRI examination of the&#xD;
             brain and orbits with gadolinium prior to the baseline visit.&#xD;
&#xD;
          -  Patient with macular edema as the only evidence of uveitis (e.g. absence of any&#xD;
             vitreous haze or vasculitis) for which a non-uveitic cause of macular edema such as&#xD;
             cataract extraction, age-related macular degeneration, diabetic retinopathy or retinal&#xD;
             vein occlusion cannot be excluded.&#xD;
&#xD;
          -  Patient with media opacity in the study eye that precludes visualization of the fundus&#xD;
             or that is likely to require cataract surgery during the course of the trial.&#xD;
&#xD;
          -  Patient with history of glaucoma filtering surgery (e.g. trabeculectomy or aqueous&#xD;
             shunt implant) or who underwent eye surgery within 3 months in the treated eye.&#xD;
&#xD;
          -  Patient who has uncontrolled intraocular pressure of ≥ 25 mmHg in the study eye at the&#xD;
             screening and baseline visits.&#xD;
&#xD;
          -  Patient with intraocular hypotension (&lt;6 mmHg) that in the opinion of the Investigator&#xD;
             would interfere with the administration of EYS606 or the evaluation of its safety or&#xD;
             efficacy.&#xD;
&#xD;
          -  Patient with history of scleritis, scleral thinning, cicatrizing conjunctival&#xD;
             diseases, severe ocular allergies or other severe ocular surface disease that could&#xD;
             interfere with the administration of EYS606 or the evaluation of its safety or&#xD;
             efficacy.&#xD;
&#xD;
          -  Patient has received Ozurdex® (dexamethasone implant) or other intraocular or&#xD;
             periocular corticosteroids injections within 3 months prior to the baseline visit in&#xD;
             the study eye&#xD;
&#xD;
          -  Patient has received a fluocinolone implant (Retisert®, Illuvien®, YutiqTM) within 12&#xD;
             months prior to the baseline visit in the study eye.&#xD;
&#xD;
          -  Patient has received treatment with a TNFα inhibitor intravitreally in the study eye&#xD;
             within 2 months prior to the baseline visit.&#xD;
&#xD;
          -  Patient has received intravitreal anti-VEGF therapy such as Lucentis® (ranibizumab) or&#xD;
             Avastin® (bevacizumab) or Eylea® (aflibercept) within 2 months prior to the baseline&#xD;
             visit or Beovu® (Brolucizumab) within 3 months prior to the baseline visit in the&#xD;
             study eye.&#xD;
&#xD;
          -  Patient has received intravitreal methotrexate within 2 months prior to the baseline&#xD;
             visit in the study eye.&#xD;
&#xD;
          -  Patient with a history of allergic reaction or intolerance to any routinely used&#xD;
             ophthalmic medicines (e.g. fluorescein dye, topical dilating agents or local&#xD;
             anesthetics) that will be prescribed during the course of the study.&#xD;
&#xD;
          -  Patient with active or uncontrolled underlying systemic autoimmune or inflammatory&#xD;
             disease requiring or likely to require an increase in systemic immunosuppressive&#xD;
             medications or treatment with a biologic agent during the course of the study.&#xD;
&#xD;
          -  Patient has received treatment with an alkylating agent (cyclophosphamide or&#xD;
             chlorambucil) for the management of uveitis or an associated underlying disease.&#xD;
&#xD;
          -  Patient has received treatment with a systemic biologic therapy (e.g. anti-TNFα,&#xD;
             anti-IL-1, anti-IL-6, anti-IL-17, interferon) within 1 month prior to the baseline&#xD;
             visit.&#xD;
&#xD;
          -  Patient has received treatment with Rituximab within 6 months of the baseline visit.&#xD;
&#xD;
          -  Patient with a history of or current evidence of any unstable medical condition (such&#xD;
             as heart disease due to a cardiac conduction abnormality requiring a pacemaker,&#xD;
             neurologic or psychiatric disorders requiring electroconvulsive therapy, acute or&#xD;
             chronic liver diseases, malignancy, severe systemic allergy, etc.) that in the opinion&#xD;
             of the Investigator, would expose the subject to an undue risk of a significant&#xD;
             adverse event or interfere with the administration of EYS606 or the evaluation of its&#xD;
             safety or efficacy during the course of the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Antoine AB BREZIN, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpital Cochin - Paris - France</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Grenoble - Hôpital Michallon</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Cochin</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bristol Eye Hospital</name>
      <address>
        <city>Bristol</city>
        <zip>BS1 2LX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moorfields Eye Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>March 31, 2017</study_first_submitted>
  <study_first_submitted_qc>October 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 12, 2017</study_first_posted>
  <last_update_submitted>March 9, 2022</last_update_submitted>
  <last_update_submitted_qc>March 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>plasmid</keyword>
  <keyword>electrotransfer</keyword>
  <keyword>ciliary muscle</keyword>
  <keyword>uveitis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uveitis</mesh_term>
    <mesh_term>Panuveitis</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/NCT03308045
org study id: EYS606-CT1
nct id: NCT03308045
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Primary objective: safety and tolerability

      Secondary objectives: additional indicators of long term safety and indicators of clinical
      activity

      Exploratory objectives: to characterize EYS606 biodistribution, immunogenicity and biomarkers
The maximum study duration per patient is 51 Weeks (including an up to 3 week screening
      period + 48 weeks follow-up after treatment).

      The study is conducted in 2 parts. Part 1 is a dose escalation phase which will investigate
      three pEYS606 doses levels (lower, intermediate and higher dose) over 3 cohorts. Part 1 of
      the study has been completed. Part 2, the extension phase, which is now ongoing will confirm
      to safety of the maximum tolerated higher dose from Part 1 and allow a preliminary assessment
      of efficacy.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Clinical trial with a single arm
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with treatment emergent adverse events
time frame: 4 weeks
description: Assessment of the safety and tolerability of EYS606
measure: Change from baseline in ocular safety assessments
time frame: 6 months
description: Measured as change from baseline in adverse events, concomitant medications, intraocular pressure, electroretinogram, electrocardiogram, vital signs, physical exam and routine labs (blood and urinalysis)
measure: Improvement in best corrected visual acuity
time frame: 6 months
description: Measured as change from baseline eye in best corrected visual acuity using ETDRS scale
measure: Improvement in anterior chamber cell grade
time frame: 6 months
description: Measured as change from baseline in anterior cell grade according to the SUN scale
measure: Improvement in vitreous haze grade
time frame: 6 months
description: Measures as change from baseline in vitreous haze grade according to SUN scale
measure: Improvement in central retinal thickness
time frame: 6 months
description: Measures as change from baseline in central retinal thickness using ocular coherence tomography
measure: Change in corticosteroid dose
time frame: 6 months
description: Measures as change from baseline in prescribed dose of corticosteroids
arm group label: pEYS606
arm group type: Experimental
description: Cohort 1 (pEYS606 lower dose); Cohort 2 (pEYS606 intermediate dose); Cohort 3 (pEYS606 higher dose); Extension Cohort (pEYS606 maximum tolerated dose)
intervention type: Biological
intervention name: pEYS606
description: pEYS606 is a DNA plasmid solution administered by electrotransfection into the ciliary muscle
arm group label: pEYS606
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Antoine AB BREZIN, MD
role: Principal Investigator
affiliation: Hôpital Cochin - Paris - France
facility: 
facility: 
facility: 
facility: 
country: France
country: United Kingdom
responsible party type: Sponsor
mesh term: Uveitis
mesh term: Panuveitis
sharing ipd: No