<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/NCT04465409</url>
  </required_header>
  <id_info>
    <org_study_id>CMG-PRT-002-Rev6</org_study_id>
    <nct_id>NCT04465409</nct_id>
  </id_info>
  <brief_title>Evaluation of Safety and Efficacy of Intrastromal Implantation of CorVision® Bioengineered Corneal Inlay for Correction of Presbyopia.</brief_title>
  <acronym>CorVision</acronym>
  <official_title>Evaluation of Safety and Efficacy of Intrastromal Implantation of CorVision® Bioengineered Corneal Inlay for Correction of Presbyopia.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>LinkoCare Life Sciences AB</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>LinkoCare Life Sciences AB</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>
      This clinical investigation is a prospective, multicentre, non-comparative case series to&#xD;
      assess safety and efficacy of CorVision® bioengineered corneal inlay for improving&#xD;
      uncorrected near vision in presbyopic subjects.&#xD;
&#xD;
      In this study a sterile medical grade collagen-based bioengineered corneal inlay&#xD;
      (CorVision®), which closely mimics the human corneal tissue, will be tested as a natural&#xD;
      microlens for correction of near vision in presbyopic patients. The primary endpoint for this&#xD;
      study is to further determine the safety of the inlay and the secondary endpoint is to&#xD;
      determine the efficacy of the inlay to improve uncorrected near vision.&#xD;
&#xD;
      CorVision® implantation will be done via a minimally invasive laser-assisted intra-stromal&#xD;
      surgery. Besides important information concerning details of the surgical method and&#xD;
      postoperative care, tolerance of the device and possible adverse events will be reported&#xD;
      along with several clinical parameters to be measured preoperatively and postoperatively. The&#xD;
      study will consist of 110 subjects receiving the inlay to be included within a recruitment&#xD;
      period of 18 months at multiple clinical sites. All subjects will be followed for minimum&#xD;
      12-months postoperatively. Postoperative evaluations are scheduled at 1 week, 1, 3, 6, and 12&#xD;
      months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Upon signing of informed consent and study inclusion, both eyes will be screened to determine&#xD;
      which eye is dominant and to ensure that the non-dominant eye meets the visual acuity,&#xD;
      refraction, and other inclusion criteria. In this investigation, the monovision concept will&#xD;
      be utilized, e.g. CorVision® will be implanted in the non-dominant eye to improve near vision&#xD;
      and the dominant eye is left intact or corrected by a standard refractive surgery to&#xD;
      emmetropia. In brief, subjects will undergo laser corneal surgery on their non-dominant eye&#xD;
      to create an anterior stromal pocket into which the investigational device will be implanted.&#xD;
      Combined antibiotic - steroid eye drops will be instilled for 4 weeks post-implantation.&#xD;
&#xD;
      The investigational treatment does not introduce foreign cells into the patient, requires&#xD;
      only a short course of local immunosuppression (4 weeks compared to 12 months or longer for&#xD;
      some other treatment options), and is reversible as the investigational device can be removed&#xD;
      later if required. Moreover, should serious intra-operative or post-operative complications&#xD;
      arise during or following implantation of the investigational device that cannot be treated&#xD;
      with medications (for example thinning or clouding of the cornea), the CorVision® device can&#xD;
      be removed and the patient can undergo standard-of-care for complications after laser&#xD;
      surgery.&#xD;
&#xD;
      Following implantation of the CorVision®, postoperative eye examinations will be conducted at&#xD;
      1 week, 1 month, then at month 3, 6, and 12 and outside of these standard examination times&#xD;
      on an as-needed basis at any time. Examinations will include corneal tomography, central&#xD;
      corneal thickness, slit lamp corneal transparency, keratometry, anterior segment optical&#xD;
      coherence tomography, and general ophthalmic examination including tear break up time,&#xD;
      refraction, uncorrected and corrected distance, intermediate and near visual acuity, and in&#xD;
      some eyes aberrometer measurements, defocus curve or contrast sensitivity.&#xD;
&#xD;
      The proof-of-concept and feasibility to implant CorVision® by standard surgical methods such&#xD;
      as a femto-second assisted pocket surgery and postoperative treatment and assessment protocol&#xD;
      for this new medical device have already been developed via prior pre-clinical evaluations&#xD;
      and some pilot clinical studies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 25, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2023</completion_date>
  <primary_completion_date type="Actual">September 25, 2022</primary_completion_date>
  <phase>N/A</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>Safety outcome</measure>
    <time_frame>6 months</time_frame>
    <description>The primary safety endpoint is defined such that a rejection leading to implant removal should occur in no more than 3% of implanted eyes. The implant rejection is defined as a clinical situation when the implanted eye has decreased central corneal clarity and decreased implant clarity, corneal vascularization inside of laser created pocket and inflammation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy outcome</measure>
    <time_frame>6 months</time_frame>
    <description>The primary efficacy endpoint is that more than 65% of the eyes should have an uncorrected near visual acuity (UNVA) of 0.3 logMAR or better at 6 months postoperatively.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">110</enrollment>
  <condition>Presbyopia</condition>
  <arm_group>
    <arm_group_label>Presbyopic adults</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Presbyopic adults, male or female between 40-65 years of age who need from +1.25 D to +3.50 D of reading addition in the non-dominant eye to improve near visual acuity by at least one line or more.&#xD;
In this investigation, CorVision® will be implanted in the non-dominant eye to improve near vision and the dominant eye is left intact or corrected by a standard refractive surgery to emmetropia. In brief, subjects will undergo laser corneal surgery on their non-dominant eye to create an anterior stromal pocket into which the investigational device will be implanted.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Intrastromal implantation of CorVision bioengineered corneal inlay for correction of presbyopia.</intervention_name>
    <description>Presbyopia is an age-related progressive loss of crystalline lens accommodation power resulting in the decreased ability to see near objects. CorVision® is a tissue-mimetic device primarily intended to be used as a corneal inlay in the management of presbyopia and low hypermetropia. The inlay is inserted into the patient's cornea via a minimally invasive laser pocket procedure to modify corneal surface topography and corneal optical performance.</description>
    <arm_group_label>Presbyopic adults</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed and dated informed consent&#xD;
&#xD;
          -  Presbyopic adults, Male or female between 40-65 years of age who need from +1.25 D to&#xD;
             +3.50 D of reading addition in the non- dominant eye to improve near visual acuity by&#xD;
             at least one line or more.&#xD;
&#xD;
          -  Manifest refraction spherical equivalent (MRSE) between -0.75 and +1.50 D with ≤1.5 D&#xD;
             of refractive cylinder in the non-dominant eye.&#xD;
&#xD;
          -  Stable refraction, i.e. MSRE within 0.50 D over prior 12 months in the non-dominant&#xD;
             eye.&#xD;
&#xD;
          -  Corrected distance visual acuity CDVA ≥ 0.7 in the dominant and non-dominant eye&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Anterior segment pathology in the non-dominant eye.&#xD;
&#xD;
          -  Signs or symptoms of clinically significant cataracts in the non-dominant eye.&#xD;
&#xD;
          -  Residual, recurrent, active ocular or uncontrolled eyelid disease, or any corneal&#xD;
             abnormality (including endothelial dystrophy, recurrent corneal erosion, etc.) in the&#xD;
             nondominant eye.&#xD;
&#xD;
          -  Visually significant macular pathology&#xD;
&#xD;
          -  Central corneal thickness &lt;470 microns in either eye and corneal curvature ≥ 50D&#xD;
&#xD;
          -  Corneal ectasia, keratoconus or form frust keratoconus&#xD;
&#xD;
          -  Clinically significant dry eye disease&#xD;
&#xD;
          -  Any prior ocular surgery in the non-dominant eye.&#xD;
&#xD;
          -  History of herpes zoster or herpes simplex keratitis in the non-dominant eye.&#xD;
&#xD;
          -  Inability of patient to understand the study procedures and thus inability to give&#xD;
             informed consent.&#xD;
&#xD;
          -  Participation in another clinical study within the last 3 months&#xD;
&#xD;
          -  Already included once in this study (can only be included for one treated eye).&#xD;
&#xD;
          -  General history judged by the investigator to be incompatible with the study (e.g.,&#xD;
             life-&#xD;
&#xD;
          -  threatening patient condition, other condition where postoperative follow-up may be&#xD;
             difficult).&#xD;
&#xD;
          -  known uncontrolled diabetes or other neuro-degenerative disorder (as corneal nerves&#xD;
             can be affected leading to impaired wound healing)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Katerina Klimesova, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Gemini Eye Clinics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Gemini Eye Clinics</name>
      <address>
        <city>Zlín</city>
        <zip>760 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>March 8, 2023</last_update_submitted>
  <last_update_submitted_qc>March 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>presbyopia</keyword>
  <keyword>bioengineered corneal inlay</keyword>
  <keyword>femto second laser</keyword>
  <keyword>intrastromal implantation</keyword>
  <keyword>biocompatible</keyword>
  <keyword>medical device</keyword>
  <keyword>sterile</keyword>
  <keyword>medical grade</keyword>
  <keyword>natural</keyword>
  <keyword>refractive error</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Presbyopia</mesh_term>
  </condition_browse>
  <!-- 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/NCT04465409
org study id: CMG-PRT-002-Rev6
nct id: NCT04465409
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This clinical investigation is a prospective, multicentre, non-comparative case series to
      assess safety and efficacy of CorVision® bioengineered corneal inlay for improving
      uncorrected near vision in presbyopic subjects.

      In this study a sterile medical grade collagen-based bioengineered corneal inlay
      (CorVision®), which closely mimics the human corneal tissue, will be tested as a natural
      microlens for correction of near vision in presbyopic patients. The primary endpoint for this
      study is to further determine the safety of the inlay and the secondary endpoint is to
      determine the efficacy of the inlay to improve uncorrected near vision.

      CorVision® implantation will be done via a minimally invasive laser-assisted intra-stromal
      surgery. Besides important information concerning details of the surgical method and
      postoperative care, tolerance of the device and possible adverse events will be reported
      along with several clinical parameters to be measured preoperatively and postoperatively. The
      study will consist of 110 subjects receiving the inlay to be included within a recruitment
      period of 18 months at multiple clinical sites. All subjects will be followed for minimum
      12-months postoperatively. Postoperative evaluations are scheduled at 1 week, 1, 3, 6, and 12
      months.
Upon signing of informed consent and study inclusion, both eyes will be screened to determine
      which eye is dominant and to ensure that the non-dominant eye meets the visual acuity,
      refraction, and other inclusion criteria. In this investigation, the monovision concept will
      be utilized, e.g. CorVision® will be implanted in the non-dominant eye to improve near vision
      and the dominant eye is left intact or corrected by a standard refractive surgery to
      emmetropia. In brief, subjects will undergo laser corneal surgery on their non-dominant eye
      to create an anterior stromal pocket into which the investigational device will be implanted.
      Combined antibiotic - steroid eye drops will be instilled for 4 weeks post-implantation.

      The investigational treatment does not introduce foreign cells into the patient, requires
      only a short course of local immunosuppression (4 weeks compared to 12 months or longer for
      some other treatment options), and is reversible as the investigational device can be removed
      later if required. Moreover, should serious intra-operative or post-operative complications
      arise during or following implantation of the investigational device that cannot be treated
      with medications (for example thinning or clouding of the cornea), the CorVision® device can
      be removed and the patient can undergo standard-of-care for complications after laser
      surgery.

      Following implantation of the CorVision®, postoperative eye examinations will be conducted at
      1 week, 1 month, then at month 3, 6, and 12 and outside of these standard examination times
      on an as-needed basis at any time. Examinations will include corneal tomography, central
      corneal thickness, slit lamp corneal transparency, keratometry, anterior segment optical
      coherence tomography, and general ophthalmic examination including tear break up time,
      refraction, uncorrected and corrected distance, intermediate and near visual acuity, and in
      some eyes aberrometer measurements, defocus curve or contrast sensitivity.

      The proof-of-concept and feasibility to implant CorVision® by standard surgical methods such
      as a femto-second assisted pocket surgery and postoperative treatment and assessment protocol
      for this new medical device have already been developed via prior pre-clinical evaluations
      and some pilot clinical studies.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety outcome
time frame: 6 months
description: The primary safety endpoint is defined such that a rejection leading to implant removal should occur in no more than 3% of implanted eyes. The implant rejection is defined as a clinical situation when the implanted eye has decreased central corneal clarity and decreased implant clarity, corneal vascularization inside of laser created pocket and inflammation.
measure: Efficacy outcome
time frame: 6 months
description: The primary efficacy endpoint is that more than 65% of the eyes should have an uncorrected near visual acuity (UNVA) of 0.3 logMAR or better at 6 months postoperatively.
arm group label: Presbyopic adults
arm group type: Experimental
description: Presbyopic adults, male or female between 40-65 years of age who need from +1.25 D to +3.50 D of reading addition in the non-dominant eye to improve near visual acuity by at least one line or more.
In this investigation, CorVision® will be implanted in the non-dominant eye to improve near vision and the dominant eye is left intact or corrected by a standard refractive surgery to emmetropia. In brief, subjects will undergo laser corneal surgery on their non-dominant eye to create an anterior stromal pocket into which the investigational device will be implanted.
intervention type: Device
intervention name: Intrastromal implantation of CorVision bioengineered corneal inlay for correction of presbyopia.
description: Presbyopia is an age-related progressive loss of crystalline lens accommodation power resulting in the decreased ability to see near objects. CorVision® is a tissue-mimetic device primarily intended to be used as a corneal inlay in the management of presbyopia and low hypermetropia. The inlay is inserted into the patient's cornea via a minimally invasive laser pocket procedure to modify corneal surface topography and corneal optical performance.
arm group label: Presbyopic adults
criteria: 
gender: All
minimum age: 40 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Katerina Klimesova, MD
role: Principal Investigator
affiliation: Gemini Eye Clinics
facility: 
country: Czechia
responsible party type: Sponsor
mesh term: Presbyopia