<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/NCT03790852</url>
  </required_header>
  <id_info>
    <org_study_id>KSI-CL-101</org_study_id>
    <nct_id>NCT03790852</nct_id>
  </id_info>
  <brief_title>Exploratory Study to Investigate the Bioactivity, Ocular and Systemic Safety, Tolerability, and Pharmacokinetics Following Single and Multiple Intravitreal Administrations of KSI-301 in Subjects With wAMD, DME and RVO</brief_title>
  <official_title>A Phase 1/1b Open Label, Multi-center Exploratory Study to Investigate the Bioactivity, Ocular and Systemic Safety, Tolerability, and Pharmacokinetics Following Single and Multiple Intravitreal Administrations of KSI-301 in Subjects With Wet Age-Related Macular Degeneration (wAMD), Diabetic Macular Edema (DME) and Retinal Vein Occlusion (RVO)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kodiak Sciences Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kodiak Sciences Inc</source>
  <oversight_info>
    <has_dmc>No</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 Phase 1b open-label study to assess the bioactivity, ocular and systemic safety,&#xD;
      tolerability, and pharmacokinetics of repeated injections of KSI-301 at two dose levels: 2.5&#xD;
      mg and 5 mg&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    All patients past planned primary endpoint; decision by Sponsor to wind down open-label&#xD;
    follow-up activities.&#xD;
  </why_stopped>
  <start_date type="Actual">December 26, 2018</start_date>
  <completion_date type="Actual">June 9, 2022</completion_date>
  <primary_completion_date type="Actual">June 2, 2021</primary_completion_date>
  <phase>Phase 1</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of ocular (study eye) and systemic adverse events</measure>
    <time_frame>Week 72</time_frame>
  </primary_outcome>
  <other_outcome>
    <measure>Mean change in central retinal thickness on optical coherence tomography</measure>
    <time_frame>Baseline, Week 72</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Mean change in best corrected visual acuity</measure>
    <time_frame>Baseline, Week 72</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">121</enrollment>
  <condition>Wet Age-related Macular Degeneration</condition>
  <condition>Retinal Vein Occlusion</condition>
  <condition>Diabetic Macular Edema</condition>
  <arm_group>
    <arm_group_label>KSI-301 2.5 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KSI-301 2.5 mg, 3 monthly initiating doses, with subsequent doses per protocol-specified retreatment criteria</description>
  </arm_group>
  <arm_group>
    <arm_group_label>KSI-301 5 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KSI-301 5 mg, 3 monthly initiating doses, with subsequent doses per protocol-specified retreatment criteria</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KSI-301</intervention_name>
    <description>Intravitreal injection</description>
    <arm_group_label>KSI-301 2.5 mg</arm_group_label>
    <arm_group_label>KSI-301 5 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Wet AMD Cohort&#xD;
&#xD;
          1. Treatment naïve wet age-related macular degeneration involving the fovea.&#xD;
&#xD;
          2. A lesion area &lt;30 mm2 (12 disc areas) of any lesion type.&#xD;
&#xD;
          3. BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the&#xD;
             study eye.&#xD;
&#xD;
          4. Decrease in vision in the study eye determined by the investigator to be primarily the&#xD;
             result of wAMD.&#xD;
&#xD;
        DME Cohort&#xD;
&#xD;
          1. Treatment naïve diabetic macular edema.&#xD;
&#xD;
          2. BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the&#xD;
             study eye.&#xD;
&#xD;
          3. Central subfield thickness (CST) of ≥ 300 microns on SD-OCT (Heidelberg Spectralis or&#xD;
             equivalent).&#xD;
&#xD;
          4. Decrease in vision in the study eye determined by the investigator to be primarily the&#xD;
             result of DME.&#xD;
&#xD;
        RVO Cohort&#xD;
&#xD;
          1. Treatment naïve retinal vein occlusion with macular edema and secondary visual&#xD;
             impairment.&#xD;
&#xD;
          2. BCVA ETDRS letter score ≤ 78 and ≥ 23 (-20/25 to -20/320 Snellen equivalent) in the&#xD;
             study eye.&#xD;
&#xD;
          3. Central subfield thickness (CST) of ≥ 300 microns on SD-OCT (Heidelberg Spectralis or&#xD;
             equivalent).&#xD;
&#xD;
          4. Branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) are&#xD;
             both eligible.&#xD;
&#xD;
          5. Decrease in vision in the study eye determined by the investigator to be primarily the&#xD;
             result of macular edema secondary to RVO.&#xD;
&#xD;
        General Inclusion Criteria&#xD;
&#xD;
          -  Adults ≥ 21 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Wet AMD Cohort:&#xD;
&#xD;
          1. Choroidal neovascularization due to causes other than age-related macular degeneration&#xD;
             in the study eye.&#xD;
&#xD;
          2. Geographic atrophy and/or subretinal fibrosis involving the fovea of the study eye.&#xD;
&#xD;
          3. Prior intravitreal anti-VEGF therapy in the study eye.&#xD;
&#xD;
        DME Cohort:&#xD;
&#xD;
          1. Initial diagnosis of DME of more than 6 months from screening in the study eye.&#xD;
&#xD;
          2. Hard exudates in the fovea.&#xD;
&#xD;
          3. Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant&#xD;
             (dexamethasone or triamcinolone) in the study eye.&#xD;
&#xD;
          4. Moderate or dense vitreous hemorrhage preventing clear. visualization of the macula or&#xD;
             optic disc in the study eye.&#xD;
&#xD;
          5. Fibrovascular proliferation or tractional retinal detachment in the posterior pole in&#xD;
             the study eye. If traction is present outside the posterior pole, it should be&#xD;
             considered not at risk of increasing and threatening the macula with the use of&#xD;
             anti-VEGF injections, in the investigator's judgement.&#xD;
&#xD;
        RVO Cohort:&#xD;
&#xD;
          1. Initial diagnosis of RVO of more than 4 months from screening in the study eye.&#xD;
&#xD;
          2. Active retinal or iris neovascularization in the study eye.&#xD;
&#xD;
          3. Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant&#xD;
             (dexamethasone or triamcinolone) in the study eye.&#xD;
&#xD;
        For all phase 1b subjects:&#xD;
&#xD;
          1. Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment&#xD;
             with antiglaucoma medication) in the study eye.&#xD;
&#xD;
          2. History of retinal detachment or treatment or surgery for retinal detachment in the&#xD;
             study eye.&#xD;
&#xD;
          3. Any history of uveitis in either eye.&#xD;
&#xD;
          4. Significant media opacities, including visually significant cataract, in the study eye&#xD;
             that might interfere with visual acuity assessments, optical coherence tomography,&#xD;
             fundus photography, or with examination of the eye for assessment of safety.&#xD;
&#xD;
          5. Prior vitrectomy surgery in the study eye.&#xD;
&#xD;
          6. Active retinal disease other than the conditions under investigation.&#xD;
&#xD;
          7. Active ocular or periocular infection or inflammation in either eye.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jason Ehrlich, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Kodiak Sciences Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Retinal Research Institute, LLC</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85053</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Vitreous Associates Medical Group</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northern California Retina Vitreous Associates</name>
      <address>
        <city>Mountain View</city>
        <state>California</state>
        <zip>94040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Byers Eye Institute at Stanford</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Vitreous Associates of Florida</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33711</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sierra Eye Associates</name>
      <address>
        <city>Reno</city>
        <state>Nevada</state>
        <zip>89502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mid Atlantic Retina</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Research Institute of Texas</name>
      <address>
        <city>Abilene</city>
        <state>Texas</state>
        <zip>79606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Clinical Research</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78750</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Texas</name>
      <address>
        <city>Bellaire</city>
        <state>Texas</state>
        <zip>77401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Texas Woodlands</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77384</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>December 27, 2018</study_first_submitted>
  <study_first_submitted_qc>December 31, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>DME</keyword>
  <keyword>wAMD</keyword>
  <keyword>RVO</keyword>
  <keyword>KSI-301</keyword>
  <keyword>Kodiak</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Degeneration</mesh_term>
    <mesh_term>Macular Edema</mesh_term>
    <mesh_term>Retinal Vein Occlusion</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/NCT03790852
org study id: KSI-CL-101
nct id: NCT03790852
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1b open-label study to assess the bioactivity, ocular and systemic safety,
      tolerability, and pharmacokinetics of repeated injections of KSI-301 at two dose levels: 2.5
      mg and 5 mg
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of ocular (study eye) and systemic adverse events
time frame: Week 72
measure: Mean change in central retinal thickness on optical coherence tomography
time frame: Baseline, Week 72
measure: Mean change in best corrected visual acuity
time frame: Baseline, Week 72
arm group label: KSI-301 2.5 mg
arm group type: Experimental
description: KSI-301 2.5 mg, 3 monthly initiating doses, with subsequent doses per protocol-specified retreatment criteria
arm group label: KSI-301 5 mg
arm group type: Experimental
description: KSI-301 5 mg, 3 monthly initiating doses, with subsequent doses per protocol-specified retreatment criteria
intervention type: Drug
intervention name: KSI-301
description: Intravitreal injection
arm group label: KSI-301 2.5 mg
arm group label: KSI-301 5 mg
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Jason Ehrlich, MD, PhD
role: Study Director
affiliation: Kodiak Sciences Inc
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: Macular Edema
mesh term: Retinal Vein Occlusion