<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/NCT02193113</url>
  </required_header>
  <id_info>
    <org_study_id>KVD001-001</org_study_id>
    <nct_id>NCT02193113</nct_id>
  </id_info>
  <brief_title>A Phase I Single Ascending Dose Study of the Intravitreal Plasma Kallikrein Inhibitor KVD001 in Subjects With DME</brief_title>
  <official_title>An Open Label, Single Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacodynamics of a Novel Intravitreal Plasma Kallikrein Inhibitor in Subjects With Central Involved Diabetic Macular Edema and Reduced Vision</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>KalVista Pharmaceuticals, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Juvenile Diabetes Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>KalVista Pharmaceuticals, Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1 study to investigate the safety, tolerability of the novel plasma&#xD;
      kallikrein inhibitor, KVD001 in subjects with diabetic macular edema. The study is the first&#xD;
      step to investigate the hypothesis that plasma kallikrein plays an important role in the&#xD;
      disease process behind diabetic macular edema in many patients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The plasma kallikrein-kinin system has long been recognized as a key player in inflammatory&#xD;
      processes, capillary leakage and angiogenesis in various organs. Recent work suggests that&#xD;
      plasma kallikrein is central to the pathogenesis of Diabetic Macular Edema (DME) and that&#xD;
      activation of the enzyme contributes to the excessive retinal vascular permeability leading&#xD;
      to DME. Among different persons with DME, plasma kallikrein contributes both independently in&#xD;
      some, and in association with Vascular Endothelial Growth Factor (VEGF) in others. However,&#xD;
      the effect of plasma kallikrein appears to be independent of VEGF. Thus, growing scientific&#xD;
      evidence points to plasma kallikrein inhibitors as an exciting potential new therapeutic&#xD;
      opportunity directed at a novel VEGF-independent pathway that may reduce retinal vascular&#xD;
      permeability and treat DME, in patients whose disease process is, at least in part, driven by&#xD;
      the plasma kallikrein pathway.&#xD;
&#xD;
      This is an open label, single ascending dose study to investigate the safety, tolerability&#xD;
      and pharmacodynamics of a novel plasma kallikrein inhibitor administered by intravitreal&#xD;
      (IVT) injection in subjects with central involved diabetic macular edema and reduced vision.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 18, 2014</start_date>
  <completion_date type="Actual">June 4, 2015</completion_date>
  <primary_completion_date type="Actual">June 4, 2015</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with Adverse Events as a measure of safety and tolerability</measure>
    <time_frame>56 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measurement of KVD001 plasma levels over time following intravitreal injection (with calculation of Tmax, Cmax, AUC and t1/2)</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Corrected Visual Acuity as measured by ETDRS EVA</measure>
    <time_frame>56 days</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in retinal thickness from baseline</measure>
    <time_frame>84 days</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Diabetic Macular Edema</condition>
  <arm_group>
    <arm_group_label>KVD001 Injection Dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single 100 microliters (uL) intravitreal injection of KVD001 Injection Dose 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>KVD001 Injection Dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single 100uL intravitreal injection KVD001 injection Dose 2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>KVD001 Injection Dose 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single 100uL intravitreal injection of KVD001 injection Dose 3</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KVD001 Injection</intervention_name>
    <description>A novel plasma kallikrein inhibitor</description>
    <arm_group_label>KVD001 Injection Dose 1</arm_group_label>
    <arm_group_label>KVD001 Injection Dose 2</arm_group_label>
    <arm_group_label>KVD001 Injection Dose 3</arm_group_label>
    <other_name>KVD001</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female adult subjects 18 years of age and older&#xD;
&#xD;
          2. Confirmed diagnosis of Type I or Type II diabetes mellitus&#xD;
&#xD;
          3. Best corrected visual acuity, using Early Treatment Diabetic Retinopathy Study (ETDRS)&#xD;
             electronic visual acuity (EVA) testing, of between 20/40 and 20/400 (Snellen&#xD;
             equivalent) in the study eye&#xD;
&#xD;
          4. Fellow eye acuity 20/80 or better measured as above with no expectation of requirement&#xD;
             for anti-VEGF treatment in fellow eye within 2 months of study drug administration&#xD;
&#xD;
          5. Presence of central involved DME in the study eye defined as Optical Coherence&#xD;
             Tomography (OCT) Central Subfold Thickness (CST) ≥305 µm in women and ≥320 µm in men&#xD;
             in the study eye&#xD;
&#xD;
          6. Subjects who fulfil one of the following criteria:&#xD;
&#xD;
               1. Subjects who have not previously received an anti-VEGF treatment and who, in the&#xD;
                  view of the Investigator, can have initiation of anti-VEGF treatment in the study&#xD;
                  eye deferred for at least 2 months following the date of anticipated study drug&#xD;
                  administration&#xD;
&#xD;
               2. Subjects who are receiving regular anti-VEGF intravitreal injections who:&#xD;
&#xD;
                    -  Have received at least 3 intravitreal injections of an anti-VEGF treatment&#xD;
                       within the last 5 months (study drug administration will be at least 6 weeks&#xD;
                       after the most recent intravitreal administration of anti-VEGF) and&#xD;
&#xD;
                    -  In the view of the Investigator, can have continuation of anti-VEGF&#xD;
                       treatment in the study eye deferred for at least 2 months following the date&#xD;
                       of anticipated study drug administration&#xD;
&#xD;
               3. Subjects who have received anti-VEGF in the past (&gt;3 months prior to study&#xD;
                  inclusion) but are not actively receiving treatment and who in the view of the&#xD;
                  Investigator, can have resumption of anti-VEGF or alternative treatment in the&#xD;
                  study eye deferred for at least 2 months following anticipated study drug&#xD;
                  administration&#xD;
&#xD;
          7. Subjects, who in the view of the Investigator, are not expected to require panretinal&#xD;
             laser photocoagulation or intravitreal steroids or intraocular surgery in the study&#xD;
             eye for at least 2 months following anticipated study drug administration&#xD;
&#xD;
          8. No prior treatment with panretinal photocoagulation or intravitreal steroid in the&#xD;
             study eye within the previous 3 months&#xD;
&#xD;
          9. No prior treatment with systemic corticosteroids or systemic anti-VEGF therapy within&#xD;
             the previous 3 months&#xD;
&#xD;
         10. Study participant voluntarily agrees to participate in this study and signs the&#xD;
             Institutional Review Board (IRB) approved informed consent prior to performing any&#xD;
             procedure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Females who are pregnant or lactating, or expecting to become pregnant during the&#xD;
             course of the study&#xD;
&#xD;
          2. Poorly controlled diabetes mellitus&#xD;
&#xD;
          3. Uncontrolled hypertension&#xD;
&#xD;
          4. Significant co-existing disease&#xD;
&#xD;
          5. Participation in an investigational intervention clinical study within 2 months prior&#xD;
             to study inclusion&#xD;
&#xD;
          6. History of alcohol and/or drug abuse in the last 2 years&#xD;
&#xD;
          7. Men not willing to use appropriate birth control methods&#xD;
&#xD;
          8. Media clarity or pupillary dilation inadequate to obtain reasonable quality OCT and/or&#xD;
             fundus image&#xD;
&#xD;
          9. Subjects employed by the Sponsor or in any relationship of dependence with the Sponsor&#xD;
             and/or Investigator&#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>Jennifer Sun, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Joslin Diabetes Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David Boyer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Retina-Vitreous Associates Medical Group</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Victor Gonzalez, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Valley Retina Institute, PA</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Raj Maturi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Midwest Eye Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jack Wells, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Palmetto Retina Center</affiliation>
  </overall_official>
  <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>Raj K. Maturi, MD PC</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46290</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beetham Eye Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Palmetto Retina Center</name>
      <address>
        <city>West Columbia</city>
        <state>South Carolina</state>
        <zip>29169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Valley Retina Institute, PA</name>
      <address>
        <city>McAllen</city>
        <state>Texas</state>
        <zip>78503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.kalvista.com</url>
    <description>Sponsor's Website (KalVista Pharmaceuticals)</description>
  </link>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>July 9, 2014</study_first_submitted>
  <study_first_submitted_qc>July 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 17, 2014</study_first_posted>
  <last_update_submitted>March 1, 2017</last_update_submitted>
  <last_update_submitted_qc>March 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetic Macular Edema</keyword>
  <keyword>DME</keyword>
  <keyword>Plasma Kallikrein inhibitor</keyword>
  <keyword>KVD001</keyword>
  <keyword>KVD001-001</keyword>
  <keyword>Intravitreal</keyword>
  <keyword>IVT</keyword>
  <keyword>Diabetes mellitus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Edema</mesh_term>
    <mesh_term>Edema</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/NCT02193113
org study id: KVD001-001
nct id: NCT02193113
lead sponsor: 
collaborator: 
has dmc: Yes
This is a Phase 1 study to investigate the safety, tolerability of the novel plasma
      kallikrein inhibitor, KVD001 in subjects with diabetic macular edema. The study is the first
      step to investigate the hypothesis that plasma kallikrein plays an important role in the
      disease process behind diabetic macular edema in many patients
The plasma kallikrein-kinin system has long been recognized as a key player in inflammatory
      processes, capillary leakage and angiogenesis in various organs. Recent work suggests that
      plasma kallikrein is central to the pathogenesis of Diabetic Macular Edema (DME) and that
      activation of the enzyme contributes to the excessive retinal vascular permeability leading
      to DME. Among different persons with DME, plasma kallikrein contributes both independently in
      some, and in association with Vascular Endothelial Growth Factor (VEGF) in others. However,
      the effect of plasma kallikrein appears to be independent of VEGF. Thus, growing scientific
      evidence points to plasma kallikrein inhibitors as an exciting potential new therapeutic
      opportunity directed at a novel VEGF-independent pathway that may reduce retinal vascular
      permeability and treat DME, in patients whose disease process is, at least in part, driven by
      the plasma kallikrein pathway.

      This is an open label, single ascending dose study to investigate the safety, tolerability
      and pharmacodynamics of a novel plasma kallikrein inhibitor administered by intravitreal
      (IVT) injection in subjects with central involved diabetic macular edema and reduced vision.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with Adverse Events as a measure of safety and tolerability
time frame: 56 days
measure: Measurement of KVD001 plasma levels over time following intravitreal injection (with calculation of Tmax, Cmax, AUC and t1/2)
time frame: 28 days
measure: Best Corrected Visual Acuity as measured by ETDRS EVA
time frame: 56 days
measure: Change in retinal thickness from baseline
time frame: 84 days
arm group label: KVD001 Injection Dose 1
arm group type: Experimental
description: Single 100 microliters (uL) intravitreal injection of KVD001 Injection Dose 1
arm group label: KVD001 Injection Dose 2
arm group type: Experimental
description: Single 100uL intravitreal injection KVD001 injection Dose 2
arm group label: KVD001 Injection Dose 3
arm group type: Experimental
description: Single 100uL intravitreal injection of KVD001 injection Dose 3
intervention type: Drug
intervention name: KVD001 Injection
description: A novel plasma kallikrein inhibitor
arm group label: KVD001 Injection Dose 1
arm group label: KVD001 Injection Dose 2
arm group label: KVD001 Injection Dose 3
other name: KVD001
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jennifer Sun, MD, MPH
role: Principal Investigator
affiliation: Joslin Diabetes Center
last name: David Boyer, MD
role: Principal Investigator
affiliation: Retina-Vitreous Associates Medical Group
last name: Victor Gonzalez, MD
role: Principal Investigator
affiliation: Valley Retina Institute, PA
last name: Raj Maturi, MD
role: Principal Investigator
affiliation: Midwest Eye Institute
last name: Jack Wells, MD
role: Principal Investigator
affiliation: Palmetto Retina Center
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.kalvista.com
description: Sponsor's Website (KalVista Pharmaceuticals)
responsible party type: Sponsor
mesh term: Macular Edema
mesh term: Edema
sharing ipd: No