<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/NCT02222545</url>
  </required_header>
  <id_info>
    <org_study_id>OMS721-TMA-001</org_study_id>
    <secondary_id>2014-001032-11</secondary_id>
    <nct_id>NCT02222545</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy Study of OMS721 in Patients With Thrombotic Microangiopathies</brief_title>
  <official_title>A Phase 2, Uncontrolled, Three-Stage, Dose-Escalation Cohort Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Clinical Activity of OMS721 in Adults With Thrombotic Microangiopathies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Omeros Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Omeros Corporation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the safety, efficacy, pharmacokinetics (PK),&#xD;
      pharmacodynamics (PD), and immunogenicity of OMS721 in patients with thrombotic&#xD;
      microangiopathies (TMA).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2, uncontrolled, 3-stage, ascending-dose-escalation study in patients with 1&#xD;
      of 3 forms of TMA: atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenia&#xD;
      (TTP), and hematopoietic stem cell transplant - associated TMA (HSCT-associated TMA). In&#xD;
      Stage 1 of the study, OMS721 was administered to 3 cohorts, with dose escalation by cohort to&#xD;
      identify the optimal dosing regimen. In Stage 2, the dose selected in the first stage was&#xD;
      administered to expanded cohorts of patients with distinct etiologies (aHUS alone in 1 cohort&#xD;
      and TTP or HSCT-TMA in the other cohort). Patients completing Stage 2 were eligible for&#xD;
      continued treatment in Stage 3 if they tolerated OMS721 treatment and derived clinical&#xD;
      benefit. Enrollment in the study has been completed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2, 2014</start_date>
  <completion_date type="Actual">August 11, 2020</completion_date>
  <primary_completion_date type="Actual">January 30, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</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>Assess the safety and tolerability of multiple-dose administration of OMS721 in subjects with TMA</measure>
    <time_frame>4 to 24 weeks</time_frame>
    <description>Incidence of Adverse Events, vital signs, ECG, and clinical laboratory tests</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluate the response rate to OMS721 in patients with HSCT-TMA</measure>
    <time_frame>4 to 24 weeks</time_frame>
    <description>Improvement in TMA laboratory markers of platelet count and lactate dehydrogenase (LDH) and improvement in clinical status</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate the following in patients with HSCT-TMA treated with OMS721: 100-day survival</measure>
    <time_frame>Study Day 1 to 100 days later</time_frame>
    <description>Vital status</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the following in patients with HSCT-TMA treated with OMS721: Overall survival</measure>
    <time_frame>Study Day 1 to up to 2 years following first dose of OMS721</time_frame>
    <description>Vital status</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the following in patients with HSCT-TMA treated with OMS721: Duration of response</measure>
    <time_frame>Study Day 1 to up to 2 years following first dose of OMS721</time_frame>
    <description>Number of days from the first response date to the first relapse date</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the following in patients with HSCT-TMA treated with OMS721: Freedom from platelet transfusion</measure>
    <time_frame>Study Day -14 to 4 weeks following the last platelet transfusion</time_frame>
    <description>Absence of platelet transfusions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the following in patients with HSCT-TMA treated with OMS721: Freedom from red blood cell (RBC) transfusion</measure>
    <time_frame>Study Day -14 to 4 weeks following the last RBC transfusion</time_frame>
    <description>Absence of RBC transfusions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the following in patients with HSCT-TMA treated with OMS721: Change from baseline in platelet count, LDH, haptoglobin, hemoglobin (Hgb), creatinine</measure>
    <time_frame>Study Day 1 to up to 2 years following the first dose of OMS721</time_frame>
    <description>Platelet count, LDH, haptoglobin, Hgb, creatinine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the following in patients with HSCT-TMA, aHUS, and TTP: Pharmacokinetics (PK) of multiple-dose administration of OMS721</measure>
    <time_frame>Pre-dose and up to 204 days post-dose</time_frame>
    <description>PK parameters including maximum concentration, time to maximum concentration, elimination half-life, area under time-concentration curve, clearance, and volume of distribution</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the following in patients with HSCT-TMA, aHUS, and TTP: Pharmacodynamics (PD) of multiple-dose administration of OMS721 in subjects with TMA</measure>
    <time_frame>Pre-dose and up to 204 days post-dose</time_frame>
    <description>PD measure in inhibition of ex vivo lectin pathway activation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the following in patients with HSCT-TMA, aHUS, and TTP: Immunogenicity of multiple-dose administration of OMS721 in subjects with TMA</measure>
    <time_frame>Pre-dose and up to 204 days post-dose</time_frame>
    <description>Presence of ADA response</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>Thrombotic Microangiopathies</condition>
  <arm_group>
    <arm_group_label>OMS721 low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of OMS721 at a low dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OMS721 medium dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of OMS721 at a medium dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OMS721 high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of OMS721 at a high dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>OMS721</intervention_name>
    <arm_group_label>OMS721 high dose</arm_group_label>
    <arm_group_label>OMS721 low dose</arm_group_label>
    <arm_group_label>OMS721 medium dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Are at least age 18 at screening (Visit 1)&#xD;
&#xD;
          2. Have a diagnosis of primary aHUS, persistent HSCT-associated TMA or TTP&#xD;
&#xD;
          3. No clinically apparent alternative explanation for thrombocytopenia and anemia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Had eculizumab therapy within three months prior to screening&#xD;
&#xD;
          2. Have STEC-HUS&#xD;
&#xD;
          3. Have a positive direct Coombs test&#xD;
&#xD;
          4. Have an active systemic bacterial or fungal infection requiring antimicrobial therapy&#xD;
             (prophylactic antimicrobial therapy administered as standard of care is allowed)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Liege</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>PokFuLam</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Sha Tin</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Bergamo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Vilnius</city>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Selangor</city>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Christchurch</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Katowice</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Krakow</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Warsaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Łódź</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Bangkok</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Pathum Thani</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omeros Investigational Site</name>
      <address>
        <city>Pathumwan</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Bulgaria</country>
    <country>Hong Kong</country>
    <country>Italy</country>
    <country>Lithuania</country>
    <country>Malaysia</country>
    <country>New Zealand</country>
    <country>Poland</country>
    <country>Singapore</country>
    <country>Taiwan</country>
    <country>Thailand</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <last_update_submitted>July 1, 2021</last_update_submitted>
  <last_update_submitted_qc>July 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TMA, aHUS, HSCT-associated TMA, TTP</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vascular Diseases</mesh_term>
    <mesh_term>Thrombotic Microangiopathies</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>August 4, 2023</submitted>
    <returned>August 29, 2023</returned>
  </pending_results>
  <!-- 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/NCT02222545
org study id: OMS721-TMA-001
secondary id: 2014-001032-11
nct id: NCT02222545
lead sponsor: 
has dmc: Yes
The purpose of this study is to assess the safety, efficacy, pharmacokinetics (PK),
      pharmacodynamics (PD), and immunogenicity of OMS721 in patients with thrombotic
      microangiopathies (TMA).
This is a Phase 2, uncontrolled, 3-stage, ascending-dose-escalation study in patients with 1
      of 3 forms of TMA: atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenia
      (TTP), and hematopoietic stem cell transplant - associated TMA (HSCT-associated TMA). In
      Stage 1 of the study, OMS721 was administered to 3 cohorts, with dose escalation by cohort to
      identify the optimal dosing regimen. In Stage 2, the dose selected in the first stage was
      administered to expanded cohorts of patients with distinct etiologies (aHUS alone in 1 cohort
      and TTP or HSCT-TMA in the other cohort). Patients completing Stage 2 were eligible for
      continued treatment in Stage 3 if they tolerated OMS721 treatment and derived clinical
      benefit. Enrollment in the study has been completed.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Assess the safety and tolerability of multiple-dose administration of OMS721 in subjects with TMA
time frame: 4 to 24 weeks
description: Incidence of Adverse Events, vital signs, ECG, and clinical laboratory tests
measure: Evaluate the response rate to OMS721 in patients with HSCT-TMA
time frame: 4 to 24 weeks
description: Improvement in TMA laboratory markers of platelet count and lactate dehydrogenase (LDH) and improvement in clinical status
measure: Evaluate the following in patients with HSCT-TMA treated with OMS721: 100-day survival
time frame: Study Day 1 to 100 days later
description: Vital status
measure: Evaluate the following in patients with HSCT-TMA treated with OMS721: Overall survival
time frame: Study Day 1 to up to 2 years following first dose of OMS721
description: Vital status
measure: Evaluate the following in patients with HSCT-TMA treated with OMS721: Duration of response
time frame: Study Day 1 to up to 2 years following first dose of OMS721
description: Number of days from the first response date to the first relapse date
measure: Evaluate the following in patients with HSCT-TMA treated with OMS721: Freedom from platelet transfusion
time frame: Study Day -14 to 4 weeks following the last platelet transfusion
description: Absence of platelet transfusions
measure: Evaluate the following in patients with HSCT-TMA treated with OMS721: Freedom from red blood cell (RBC) transfusion
time frame: Study Day -14 to 4 weeks following the last RBC transfusion
description: Absence of RBC transfusions
measure: Evaluate the following in patients with HSCT-TMA treated with OMS721: Change from baseline in platelet count, LDH, haptoglobin, hemoglobin (Hgb), creatinine
time frame: Study Day 1 to up to 2 years following the first dose of OMS721
description: Platelet count, LDH, haptoglobin, Hgb, creatinine
measure: Evaluate the following in patients with HSCT-TMA, aHUS, and TTP: Pharmacokinetics (PK) of multiple-dose administration of OMS721
time frame: Pre-dose and up to 204 days post-dose
description: PK parameters including maximum concentration, time to maximum concentration, elimination half-life, area under time-concentration curve, clearance, and volume of distribution
measure: Evaluate the following in patients with HSCT-TMA, aHUS, and TTP: Pharmacodynamics (PD) of multiple-dose administration of OMS721 in subjects with TMA
time frame: Pre-dose and up to 204 days post-dose
description: PD measure in inhibition of ex vivo lectin pathway activation
measure: Evaluate the following in patients with HSCT-TMA, aHUS, and TTP: Immunogenicity of multiple-dose administration of OMS721 in subjects with TMA
time frame: Pre-dose and up to 204 days post-dose
description: Presence of ADA response
arm group label: OMS721 low dose
arm group type: Experimental
description: Administration of OMS721 at a low dose
arm group label: OMS721 medium dose
arm group type: Experimental
description: Administration of OMS721 at a medium dose
arm group label: OMS721 high dose
arm group type: Experimental
description: Administration of OMS721 at a high dose
intervention type: Biological
intervention name: OMS721
arm group label: OMS721 high dose
arm group label: OMS721 low dose
arm group label: OMS721 medium dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Belgium
country: Bulgaria
country: Hong Kong
country: Italy
country: Lithuania
country: Malaysia
country: New Zealand
country: Poland
country: Singapore
country: Taiwan
country: Thailand
country: United States
responsible party type: Sponsor
mesh term: Vascular Diseases
mesh term: Thrombotic Microangiopathies
submitted: August 4, 2023
returned: August 29, 2023