<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/NCT03290560</url>
  </required_header>
  <id_info>
    <org_study_id>DM199-2017-001</org_study_id>
    <nct_id>NCT03290560</nct_id>
  </id_info>
  <brief_title>Evaluation to Assess Safety and Tolerability of DM199 in Subjects With Acute Ischemic Stroke</brief_title>
  <acronym>ReMEDy1</acronym>
  <official_title>A Randomized, Double-blind, Placebo-controlled Phase II Multi-Center Evaluation to Assess the Safety and Tolerability of DM199 Administered Intravenously and Subcutaneously in Subjects With Acute Ischemic Stroke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>DiaMedica Therapeutics Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>DiaMedica Therapeutics Inc</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase II study to assess the safety and tolerability of DM199 in acute ischemic&#xD;
      stroke patients. The study will be randomized, placebo controlled at multiple centers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 19, 2018</start_date>
  <completion_date type="Actual">January 23, 2020</completion_date>
  <primary_completion_date type="Actual">January 23, 2020</primary_completion_date>
  <phase>Phase 2</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.3</measure>
    <time_frame>90 Days</time_frame>
    <description>Assessed by total number and severity of all treatment-related adverse events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline to Day 90 of NIH Stroke Scale.</measure>
    <time_frame>90 Days</time_frame>
    <description>Assessed by a reduction in points from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline to Day 90 of Barthel Index.</measure>
    <time_frame>90 Days</time_frame>
    <description>Assessed by an increase in points from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline to Day 90 of Modified Rankin Scale.</measure>
    <time_frame>90 Days</time_frame>
    <description>Assessed by a reduction in points from baseline.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">92</enrollment>
  <condition>Acute Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>Recombinant human tissue kallikrein</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single IV infusion of 1 microgram/kg followed by 8 subcutaneous injections of 3 microgram/kg occurring every 72 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A single IV infusion of 1 microgram/kg followed by 8 subcutaneous injections of 3 microgram/kg occurring every 72 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Recombinant human tissue kallikrein</intervention_name>
    <description>Recombinant human tissue kallikrein</description>
    <arm_group_label>Recombinant human tissue kallikrein</arm_group_label>
    <other_name>DM199</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo Comparator: Phosphate buffered saline</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is &gt;/= 18 years of age&#xD;
&#xD;
          2. Subject has been diagnosed with acute ischemic stroke with onset ≤ 24 hours from&#xD;
             enrollment.&#xD;
&#xD;
          3. Subject has NIH stroke score (NIHSS) ≥ 6 and ≤ 25.&#xD;
&#xD;
          4. Subject or legally authorized representative is willing and able to sign written&#xD;
             informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject is currently prescribed angiotensin-converting-enzyme inhibitors (ACEi) and is&#xD;
             unable or unwilling to convert to another antihypertensive pharmacological treatment&#xD;
             during the active treatment period (+5 days) of the study.&#xD;
&#xD;
          2. Subject has a history of significant allergic diathesis such as urticaria, angioedema&#xD;
             or anaphylaxis.&#xD;
&#xD;
          3. Subjects with current malignancy or active malignancy ≤ 3 years prior to enrollment&#xD;
             except basal cell or squamous cell carcinoma of the skin or in situ cervical cancer&#xD;
             that has undergone potentially curative therapy and at least six months have elapsed&#xD;
             since the procedure.&#xD;
&#xD;
          4. Subject has a history of clinically significant acute bacterial, viral, or fungal&#xD;
             systemic infections in the last four weeks prior to enrollment.&#xD;
&#xD;
          5. Subject has clinical or laboratory evidence of an active infection at the time of&#xD;
             enrollment.&#xD;
&#xD;
          6. Subject has known alpha 1-antitrypsin deficiency (α1-antitrypsin deficiency).&#xD;
&#xD;
          7. Subject has a known diagnosis of human immunodeficiency virus (HIV), hepatitis B&#xD;
             surface antigen (HBsAg), or anti-hepatitis C virus (Anti-HCV) at screening.&#xD;
&#xD;
          8. Subject is pregnant or nursing.&#xD;
&#xD;
          9. Subject is male or female of childbearing potential, is participating in heterosexual&#xD;
             sexual activity that could lead to pregnancy, and is unable or unwilling to practice&#xD;
             medically effective contraception during the study.&#xD;
&#xD;
         10. Subject is participating in any other investigational device or other drug study ≤ 4&#xD;
             weeks or 5 half-lives of the investigational product, whichever is longer.&#xD;
&#xD;
         11. Subject does not have sufficient venous access for infusion of study treatment or&#xD;
             blood sampling.&#xD;
&#xD;
         12. In the opinion of the Investigator, subject is unlikely to be followed for the&#xD;
             duration of t the study.&#xD;
&#xD;
         13. Subject is unable or unwilling to comply with protocol requirements, including&#xD;
             assessments, tests, and follow-up visits.&#xD;
&#xD;
         14. Subject has any other medical condition which in the opinion of the Investigator will&#xD;
             make participation medically unsafe or interfere with the study results.&#xD;
&#xD;
         15. Pre-stroke Modified Rankin Scale ≥4&#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>Bruce Campbell</last_name>
    <role>Principal Investigator</role>
    <affiliation>Melbourne Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lismore Base Hospital</name>
      <address>
        <city>Lismore</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liverpool Hospital</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Hunter Hospital</name>
      <address>
        <city>New Lambton Heights</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane and Women's Hospital</name>
      <address>
        <city>Herston</city>
        <state>Queensland</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Alexandria Hospital</name>
      <address>
        <city>Woolloongabba</city>
        <state>Queensland</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alfred Health</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Melbourne Hospital</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunshine Hospital</name>
      <address>
        <city>St Albans</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fiona Stanley Hospital</name>
      <address>
        <city>Murdoch</city>
        <state>Western Australia</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital</name>
      <address>
        <city>Adelaide</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ballarat Health Services</name>
      <address>
        <city>Ballarat</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Box Hill Hospital</name>
      <address>
        <city>Box Hill</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>March 17, 2022</last_update_submitted>
  <last_update_submitted_qc>March 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 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>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kallikreins</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 20, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT03290560/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03290560
org study id: DM199-2017-001
nct id: NCT03290560
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a Phase II study to assess the safety and tolerability of DM199 in acute ischemic
      stroke patients. The study will be randomized, placebo controlled at multiple centers.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.3
time frame: 90 Days
description: Assessed by total number and severity of all treatment-related adverse events.
measure: Changes from baseline to Day 90 of NIH Stroke Scale.
time frame: 90 Days
description: Assessed by a reduction in points from baseline.
measure: Changes from baseline to Day 90 of Barthel Index.
time frame: 90 Days
description: Assessed by an increase in points from baseline.
measure: Changes from baseline to Day 90 of Modified Rankin Scale.
time frame: 90 Days
description: Assessed by a reduction in points from baseline.
arm group label: Recombinant human tissue kallikrein
arm group type: Experimental
description: A single IV infusion of 1 microgram/kg followed by 8 subcutaneous injections of 3 microgram/kg occurring every 72 hours.
arm group label: Placebo
arm group type: Placebo Comparator
description: A single IV infusion of 1 microgram/kg followed by 8 subcutaneous injections of 3 microgram/kg occurring every 72 hours.
intervention type: Drug
intervention name: Recombinant human tissue kallikrein
description: Recombinant human tissue kallikrein
arm group label: Recombinant human tissue kallikrein
other name: DM199
intervention type: Other
intervention name: Placebo
description: Placebo Comparator: Phosphate buffered saline
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bruce Campbell
role: Principal Investigator
affiliation: Melbourne Health
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Cerebral Infarction
mesh term: Ischemia
mesh term: Kallikreins
sharing ipd: Undecided
provided document: 