<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/NCT02994407</url>
  </required_header>
  <id_info>
    <org_study_id>NN7170-4213</org_study_id>
    <secondary_id>U1111-1183-5111</secondary_id>
    <secondary_id>2016-002396-99</secondary_id>
    <secondary_id>JapicCTI-173683</secondary_id>
    <nct_id>NCT02994407</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, and Pharmacokinetics Study of Turoctocog Alfa Pegol Injected Under the Skin in Patients With Haemophilia A</brief_title>
  <acronym>alleviate 1</acronym>
  <official_title>Safety, Tolerability, and Pharmacokinetics Study of Single and Multiple Subcutaneous Doses of Turoctocog Alfa Pegol in Patients With Haemophilia A</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novo Nordisk A/S</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novo Nordisk A/S</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>
      The trial is conducted in Asia, Europe and North America. The aim of the study is to evaluate&#xD;
      the safety of administration under the skin of turoctocog alfa pegol (SC N8-GP) in patients&#xD;
      with severe haemophilia A.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 30, 2017</start_date>
  <completion_date type="Actual">October 15, 2018</completion_date>
  <primary_completion_date type="Actual">October 15, 2018</primary_completion_date>
  <phase>Phase 1</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>Number of adverse events</measure>
    <time_frame>Day 0-Day 28</time_frame>
    <description>Count and % of Adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of FVIII inhibitors above or equal to 0.6 BU</measure>
    <time_frame>Day 0-Day 28</time_frame>
    <description>Count of presence of inhibitors</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the activity time curve from 0 to infinity</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the activity time curve from 0 to t</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the activity time curve from 0 to last</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax- time to maximal FVIII activity</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin -the minimal FVIII activity</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmin - time to minimal FVIII activity</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css, min - the minimum FVIII activity at steady state</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css, max - the maximal FVIII activity at steady state</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css - the mean FVIII activity at steady state</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Racc - accumulation ratio</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t½ - terminal half-life</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL - total plasma clearance of drug after intravenous administration</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz -apparent volume of distribution during terminal phase</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vss - apparent volume of distribution during steady state</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRT - mean residence time</measure>
    <time_frame>0-144 hours</time_frame>
    <description>Calculated based on plasma FVIII activity measured in blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Injection site reactions</measure>
    <time_frame>Day 0 - day 28</time_frame>
    <description>Count of reactions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of treatment requiring bleeding episodes</measure>
    <time_frame>Day 0 - day 120</time_frame>
    <description>Count of episodes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of FVIII</measure>
    <time_frame>Day 0 - day 120</time_frame>
    <description>Measured in IU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Coagulation parameters, fibrinogen</measure>
    <time_frame>Day 0, day 7</time_frame>
    <description>Measured in g/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Coagulation parameters, antithrombin</measure>
    <time_frame>Day 0, day 7</time_frame>
    <description>Measured in %</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Coagulation parameters, international normalised ratio</measure>
    <time_frame>Day 0, day 7</time_frame>
    <description>Measured in INR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Coagulation parameters, activated partial thromboplastin time</measure>
    <time_frame>Day 0, day 7</time_frame>
    <description>Measured in sec.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Coagulation parameters, von Willebrand Factor</measure>
    <time_frame>Day 0, day 7</time_frame>
    <description>Measured in %</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Congenital Bleeding Disorder</condition>
  <condition>Haemophilia A</condition>
  <arm_group>
    <arm_group_label>N8-GP s.c.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>turoctocog alfa pegol</intervention_name>
    <description>Part A: Participants will receive a single dose of turoctocog alfa pegol, administered subcutaneously (under the skin), at a dose of 12.5, 25 or 50 U/kg.&#xD;
Part B: Participants will receive a daily dose of turoctocog alfa pegol, as identified in Part A, as a subcutaneous (under the skin) injection for a period of 3 months.</description>
    <arm_group_label>N8-GP s.c.</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male, age above or equal to 18 years at the time of signing informed consent,(part A).&#xD;
&#xD;
          -  Male, age above or equal to 12 years at the time of signing informed consent,(part B).&#xD;
&#xD;
          -  Diagnosis of congenital haemophilia A based on medical records (FVIII activity &lt;1%).&#xD;
&#xD;
          -  History of more than 150 exposure days to any FVIII containing products.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous participation in this trial. Participation is defined as signed informed&#xD;
             consent.&#xD;
&#xD;
        (Patients who have completed part A are allowed to also participate in part B. If so, a&#xD;
        separate informed consent covering part B must be signed.)&#xD;
&#xD;
          -  Immune compromised patients due to human immunodeficiency virus (HIV) infection&#xD;
             (defined as viral load greater than or equal to 400.000 copies/mL and/or cluster of&#xD;
             differentiation 4+ (CD4+) lymphocyte count less than or equal to 200/μL performed at&#xD;
             screening or defined by medical records no older than 6 months)&#xD;
&#xD;
          -  Any history of FVIII inhibitors (defined by medical records within 8 years of&#xD;
             randomisation)&#xD;
&#xD;
          -  Inhibitors to FVIII (greater than or equal to 0.6 Bethesda unit (BU)) at screening,&#xD;
             measured by Nijmegen modified Bethesda method at central laboratory.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32827</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>East Lansing</city>
        <state>Michigan</state>
        <zip>48823</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425-0001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Innsbruck</city>
        <zip>A 6020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Nantes Cedex 1</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>10249</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Duisburg</city>
        <zip>47051</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Homburg</city>
        <zip>66421</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Shinjuku-ku, Tokyo</city>
        <zip>160 0023</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Tokyo</city>
        <zip>167-0035</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Belgrade</city>
        <zip>11070</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Novi Sad</city>
        <zip>21000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>France</country>
    <country>Germany</country>
    <country>Japan</country>
    <country>Serbia</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <last_update_submitted>January 31, 2020</last_update_submitted>
  <last_update_submitted_qc>January 31, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2020</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>Hemostatic Disorders</mesh_term>
    <mesh_term>Hemophilia A</mesh_term>
    <mesh_term>Blood Coagulation Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>According to the Novo Nordisk disclosure commitment on novonordisk-trials.com</ipd_description>
  </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/NCT02994407
org study id: NN7170-4213
secondary id: U1111-1183-5111
secondary id: 2016-002396-99
secondary id: JapicCTI-173683
nct id: NCT02994407
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The trial is conducted in Asia, Europe and North America. The aim of the study is to evaluate
      the safety of administration under the skin of turoctocog alfa pegol (SC N8-GP) in patients
      with severe haemophilia A.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of adverse events
time frame: Day 0-Day 28
description: Count and % of Adverse events
measure: Cmax
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: Incidence of FVIII inhibitors above or equal to 0.6 BU
time frame: Day 0-Day 28
description: Count of presence of inhibitors
measure: Area under the activity time curve from 0 to infinity
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: Area under the activity time curve from 0 to t
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: Area under the activity time curve from 0 to last
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: tmax- time to maximal FVIII activity
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: Cmin -the minimal FVIII activity
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: tmin - time to minimal FVIII activity
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: Css, min - the minimum FVIII activity at steady state
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: Css, max - the maximal FVIII activity at steady state
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: Css - the mean FVIII activity at steady state
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: Racc - accumulation ratio
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: t½ - terminal half-life
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: CL - total plasma clearance of drug after intravenous administration
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: Vz -apparent volume of distribution during terminal phase
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: Vss - apparent volume of distribution during steady state
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: MRT - mean residence time
time frame: 0-144 hours
description: Calculated based on plasma FVIII activity measured in blood.
measure: Injection site reactions
time frame: Day 0 - day 28
description: Count of reactions
measure: Number of treatment requiring bleeding episodes
time frame: Day 0 - day 120
description: Count of episodes
measure: Consumption of FVIII
time frame: Day 0 - day 120
description: Measured in IU
measure: Change in Coagulation parameters, fibrinogen
time frame: Day 0, day 7
description: Measured in g/L
measure: Change in Coagulation parameters, antithrombin
time frame: Day 0, day 7
description: Measured in %
measure: Change in Coagulation parameters, international normalised ratio
time frame: Day 0, day 7
description: Measured in INR
measure: Change in Coagulation parameters, activated partial thromboplastin time
time frame: Day 0, day 7
description: Measured in sec.
measure: Change in Coagulation parameters, von Willebrand Factor
time frame: Day 0, day 7
description: Measured in %
arm group label: N8-GP s.c.
arm group type: Experimental
intervention type: Drug
intervention name: turoctocog alfa pegol
description: Part A: Participants will receive a single dose of turoctocog alfa pegol, administered subcutaneously (under the skin), at a dose of 12.5, 25 or 50 U/kg.
Part B: Participants will receive a daily dose of turoctocog alfa pegol, as identified in Part A, as a subcutaneous (under the skin) injection for a period of 3 months.
arm group label: N8-GP s.c.
criteria: 
gender: Male
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
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facility: 
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country: Austria
country: France
country: Germany
country: Japan
country: Serbia
country: United States
responsible party type: Sponsor
mesh term: Hemostatic Disorders
mesh term: Hemophilia A
mesh term: Blood Coagulation Disorders
sharing ipd: Yes
ipd description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com