<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/NCT02247739</url>
  </required_header>
  <id_info>
    <org_study_id>C1 3201</org_study_id>
    <nct_id>NCT02247739</nct_id>
  </id_info>
  <brief_title>A Phase 2 HAE Prophylaxis Study With Recombinant Human C1 Inhibitor</brief_title>
  <official_title>A Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Period Crossover Study to Evaluate the Efficacy and Safety of Recombinant Human C1 Inhibitor in the Prophylaxis of Angioedema Attacks in Patients With Hereditary Angioedema (HAE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pharming Technologies B.V.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pharming Technologies B.V.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      To evaluate the efficacy of recombinant human C1 inhibitor (rhC1INH) in the prophylaxis of&#xD;
      angioedema attacks in patients with HAE&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
      To evaluate the safety and immunogenicity of recombinant human C1 inhibitor (rhC1INH) in the&#xD;
      prophylaxis of angioedema attacks in patients with HAE&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Design:&#xD;
&#xD;
      This is a multi-center, randomized, double-blind, placebo-controlled, 3-period crossover&#xD;
      study of rhC1INH in prophylaxis of angioedema attacks in patients with HAE.&#xD;
&#xD;
      Medical screening (clinical and laboratory parameters) will be performed and patient medical&#xD;
      history specific to HAE attacks will be collected to assess eligibility. Each patient will&#xD;
      receive three 4 week periods of treatment twice weekly.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</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>Crossover Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of HAE Attacks</measure>
    <time_frame>28 days</time_frame>
    <description>Average number of HAE attacks normalized to a 28 day period</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>20 weeks</time_frame>
    <description>Number of participants that experienced Treatment Emergent Adverse Events observed in safety population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving at Least 50% Reduction in Number of Attacks</measure>
    <time_frame>28 days</time_frame>
    <description>Percentage of participants achieving at least 50% reduction in the number of attacks normalized to a 28-day period as compared to the placebo treatment period</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Immunogenicity</measure>
    <time_frame>20 weeks</time_frame>
    <description>Number of participants analyzed for neutralizing C1INH-specific antibodies and neutralizing rhC1INH-specific antibodies after confirmed anti-C1INH and anti rhC1INH IgM or IgG antibodies</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Hereditary Angioedema</condition>
  <arm_group>
    <arm_group_label>rhC1INH twice weekly</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>rhC1INH administered twice weekly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>rhC1INH once weekly</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>rhC1INH administered once weekly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (Saline) twice weekly</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (Saline) administered twice weekly</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Recombinant human C1 inhibitor</intervention_name>
    <arm_group_label>rhC1INH once weekly</arm_group_label>
    <arm_group_label>rhC1INH twice weekly</arm_group_label>
    <other_name>rhC1INH</other_name>
    <other_name>Ruconest</other_name>
    <other_name>Conestat alfa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo (Saline) twice weekly</arm_group_label>
    <other_name>Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients fulfilling the following criteria at Screening are eligible for participation in&#xD;
        the study:&#xD;
&#xD;
          1. Age 13 years or older&#xD;
&#xD;
          2. Laboratory confirmed diagnosis of HAE&#xD;
&#xD;
          3. A history of frequent HAE attacks (at least 4 attacks per month across a minimum of 3&#xD;
             consecutive months).&#xD;
&#xD;
          4. Female patients of childbearing potential who are sexually active must be willing to&#xD;
             use an acceptable form of contraception.&#xD;
&#xD;
          5. Provided written informed consent (and written assent for minors)&#xD;
&#xD;
          6. Willingness and ability to comply with all protocol procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients who meet any of the following criteria at Screening are to be excluded from study&#xD;
        participation:&#xD;
&#xD;
          1. Patients with medical history of allergy to rabbits or rabbit-derived products&#xD;
             (including rhC1INH)&#xD;
&#xD;
          2. Diagnosis of acquired angioedema (AAE)&#xD;
&#xD;
          3. Patients who are pregnant, or breastfeeding, or are currently intending to become&#xD;
             pregnant&#xD;
&#xD;
          4. Treatment with any investigational drug in the past 30 days&#xD;
&#xD;
          5. Patients with any condition or treatment that, in the opinion of the Investigator,&#xD;
             might interfere with the evaluation of study objectives&#xD;
&#xD;
          6. Patients currently treated with angiotensin-converting enzyme (ACE) inhibitors&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of South Florida Asthma, Allergy and Immunology Clinical Research Unit</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida, Asthma, Allergy &amp; Immunology Clinical Research Unit</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University Division of Allergy and Immunology</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baker Allergy, Asthma and Dermatology Research Center</name>
      <address>
        <city>Lake Oswego</city>
        <state>Oregon</state>
        <zip>97035</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ottawa Allergy Research Corp</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1G6C6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Faculty Hospital by St. Anna Brno, Department of clinical Immunology and Allergology</name>
      <address>
        <city>Brno</city>
        <zip>65691</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Luigi Sacco Di Milano</name>
      <address>
        <city>Milan</city>
        <zip>20157</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PHI University Clinic of Dermatology</name>
      <address>
        <city>Skopje</city>
        <zip>1000</zip>
        <country>Macedonia, The Former Yugoslav Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SC Centrul Clinic Mediquest SRL</name>
      <address>
        <city>Sângeorgiu de Mureş</city>
        <state>Mures</state>
        <zip>547530</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center Serbia</name>
      <address>
        <city>Belgrade</city>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Italy</country>
    <country>Macedonia, The Former Yugoslav Republic of</country>
    <country>Romania</country>
    <country>Serbia</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
    <country>Netherlands</country>
  </removed_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <results_first_submitted>July 26, 2017</results_first_submitted>
  <results_first_submitted_qc>November 7, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 8, 2017</results_first_posted>
  <last_update_submitted>November 7, 2017</last_update_submitted>
  <last_update_submitted_qc>November 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HAE</keyword>
  <keyword>Hereditary Angioedema</keyword>
  <keyword>Prophylaxis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Angioedema</mesh_term>
    <mesh_term>Angioedemas, Hereditary</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Complement C1 Inhibitor Protein</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment Sequence A</title>
          <description>rhC1INH twice weekly / rhC1INH once weekly / saline</description>
        </group>
        <group group_id="P2">
          <title>Treatments Sequence B</title>
          <description>rhC1INH once weekly / rhC1INH twice weekly / Saline</description>
        </group>
        <group group_id="P3">
          <title>Treatment Sequesce C</title>
          <description>Saline / rhC1INH once weekly / rhC1INH twice weekly</description>
        </group>
        <group group_id="P4">
          <title>Treatment Sequence D</title>
          <description>Saline / rhC1INH twice weekly / rhC1INH once weekly</description>
        </group>
        <group group_id="P5">
          <title>Treatment Sequence E</title>
          <description>rhC1INH twice weekly / saline / rhC1INH once weekly</description>
        </group>
        <group group_id="P6">
          <title>Treatment Sequence F</title>
          <description>rhC1INH once weekly / saline / rhC1INH twice weekly</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="5"/>
                <participants group_id="P6" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Population is intention to treat (ITT) population</population>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>All randomized patients</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="32"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46" lower_limit="17" upper_limit="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Czech Republic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Romania</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Macedonia, The Former Yugoslav Republic of</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serbia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Israel</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of HAE Attacks</title>
        <description>Average number of HAE attacks normalized to a 28 day period</description>
        <time_frame>28 days</time_frame>
        <population>Intent-to-Treat (ITT) Population: All patients who were randomized into one of the treatment sequences. The statistical analyses are based on the treatments to which the patient was randomized to receive during that treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>rhC1INH Twice Weekly</title>
            <description>rhC1INH administered twice weekly&#xD;
Recombinant human C1 inhibitor</description>
          </group>
          <group group_id="O2">
            <title>rhC1INH Once Weekly</title>
            <description>rhC1INH administered once weekly&#xD;
Recombinant human C1 inhibitor</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Saline) Twice Weekly</title>
            <description>Placebo (Saline) administered twice weekly&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Number of HAE Attacks</title>
          <description>Average number of HAE attacks normalized to a 28 day period</description>
          <population>Intent-to-Treat (ITT) Population: All patients who were randomized into one of the treatment sequences. The statistical analyses are based on the treatments to which the patient was randomized to receive during that treatment period.</population>
          <units>attacks</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.74" lower_limit="1.8" upper_limit="3.7"/>
                    <measurement group_id="O2" value="4.36" lower_limit="3.1" upper_limit="5.6"/>
                    <measurement group_id="O3" value="7.18" lower_limit="5.8" upper_limit="8.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>Number of participants that experienced Treatment Emergent Adverse Events observed in safety population</description>
        <time_frame>20 weeks</time_frame>
        <population>Safety Population: All patients who received at least a partial injection of study drug. The statistical analyses are based on the actual treatment the patient received.</population>
        <group_list>
          <group group_id="O1">
            <title>rhC1INH Twice Weekly</title>
            <description>rhC1INH administered twice weekly&#xD;
Recombinant human C1 inhibitor</description>
          </group>
          <group group_id="O2">
            <title>rhC1INH Once Weekly</title>
            <description>rhC1INH administered once weekly&#xD;
Recombinant human C1 inhibitor</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Saline) Twice Weekly</title>
            <description>Placebo (Saline) administered twice weekly&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>Number of participants that experienced Treatment Emergent Adverse Events observed in safety population</description>
          <population>Safety Population: All patients who received at least a partial injection of study drug. The statistical analyses are based on the actual treatment the patient received.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="13"/>
                    <measurement group_id="O3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving at Least 50% Reduction in Number of Attacks</title>
        <description>Percentage of participants achieving at least 50% reduction in the number of attacks normalized to a 28-day period as compared to the placebo treatment period</description>
        <time_frame>28 days</time_frame>
        <population>Both the rhC1INH twice weekly treatments and the rhC1INH once weekly treatment periods are compared to the placebo treatment for the safety population. One subject withdrew before receiving any treatment and is excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>rhC1INH Twice Weekly</title>
            <description>rhC1INH administered twice weekly</description>
          </group>
          <group group_id="O2">
            <title>rhC1INH Once Weekly</title>
            <description>rhC1INH administered once weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving at Least 50% Reduction in Number of Attacks</title>
          <description>Percentage of participants achieving at least 50% reduction in the number of attacks normalized to a 28-day period as compared to the placebo treatment period</description>
          <population>Both the rhC1INH twice weekly treatments and the rhC1INH once weekly treatment periods are compared to the placebo treatment for the safety population. One subject withdrew before receiving any treatment and is excluded from the analysis.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74" lower_limit="57" upper_limit="86"/>
                    <measurement group_id="O2" value="42" lower_limit="26" upper_limit="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Immunogenicity</title>
        <description>Number of participants analyzed for neutralizing C1INH-specific antibodies and neutralizing rhC1INH-specific antibodies after confirmed anti-C1INH and anti rhC1INH IgM or IgG antibodies</description>
        <time_frame>20 weeks</time_frame>
        <population>Participants analyzed for Neutralizing antibodies after confirmed testing of anti-C1INH and anti rhC1INH IgM or IgG antibodies. Count of participants displays the number of positives.</population>
        <group_list>
          <group group_id="O1">
            <title>rhC1INH Twice Weekly</title>
            <description>rhC1INH administered twice weekly&#xD;
Recombinant human C1 inhibitor</description>
          </group>
          <group group_id="O2">
            <title>rhC1INH Once Weekly</title>
            <description>rhC1INH administered once weekly&#xD;
Recombinant human C1 inhibitor</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Saline) Twice Weekly</title>
            <description>Placebo (Saline) administered twice weekly&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Immunogenicity</title>
          <description>Number of participants analyzed for neutralizing C1INH-specific antibodies and neutralizing rhC1INH-specific antibodies after confirmed anti-C1INH and anti rhC1INH IgM or IgG antibodies</description>
          <population>Participants analyzed for Neutralizing antibodies after confirmed testing of anti-C1INH and anti rhC1INH IgM or IgG antibodies. Count of participants displays the number of positives.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>20 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>rhC1INH Twice Weekly</title>
          <description>rhC1INH administered twice weekly&#xD;
Recombinant human C1 inhibitor</description>
        </group>
        <group group_id="E2">
          <title>rhC1INH Once Weekly</title>
          <description>rhC1INH administered once weekly&#xD;
Recombinant human C1 inhibitor</description>
        </group>
        <group group_id="E3">
          <title>Placebo (Saline) Twice Weekly</title>
          <description>Placebo (Saline) administered twice weekly&#xD;
Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Phimosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="29"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>VP Clinical Research &amp; Medical Affairs</name_or_title>
      <organization>Pharming Group NV</organization>
      <email>a.relan@pharming.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02247739
org study id: C1 3201
nct id: NCT02247739
lead sponsor: 
has dmc: No
Primary Objective:

      To evaluate the efficacy of recombinant human C1 inhibitor (rhC1INH) in the prophylaxis of
      angioedema attacks in patients with HAE

      Secondary Objective:

      To evaluate the safety and immunogenicity of recombinant human C1 inhibitor (rhC1INH) in the
      prophylaxis of angioedema attacks in patients with HAE
Study Design:

      This is a multi-center, randomized, double-blind, placebo-controlled, 3-period crossover
      study of rhC1INH in prophylaxis of angioedema attacks in patients with HAE.

      Medical screening (clinical and laboratory parameters) will be performed and patient medical
      history specific to HAE attacks will be collected to assess eligibility. Each patient will
      receive three 4 week periods of treatment twice weekly.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of HAE Attacks
time frame: 28 days
description: Average number of HAE attacks normalized to a 28 day period
measure: Number of Participants With Adverse Events
time frame: 20 weeks
description: Number of participants that experienced Treatment Emergent Adverse Events observed in safety population
measure: Percentage of Participants Achieving at Least 50% Reduction in Number of Attacks
time frame: 28 days
description: Percentage of participants achieving at least 50% reduction in the number of attacks normalized to a 28-day period as compared to the placebo treatment period
measure: Immunogenicity
time frame: 20 weeks
description: Number of participants analyzed for neutralizing C1INH-specific antibodies and neutralizing rhC1INH-specific antibodies after confirmed anti-C1INH and anti rhC1INH IgM or IgG antibodies
arm group label: rhC1INH twice weekly
arm group type: Experimental
description: rhC1INH administered twice weekly
arm group label: rhC1INH once weekly
arm group type: Experimental
description: rhC1INH administered once weekly
arm group label: Placebo (Saline) twice weekly
arm group type: Placebo Comparator
description: Placebo (Saline) administered twice weekly
intervention type: Biological
intervention name: Recombinant human C1 inhibitor
arm group label: rhC1INH once weekly
arm group label: rhC1INH twice weekly
other name: rhC1INH
other name: Ruconest
other name: Conestat alfa
intervention type: Other
intervention name: Placebo
arm group label: Placebo (Saline) twice weekly
other name: Saline
criteria: 
gender: All
minimum age: 13 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: Czechia
country: Italy
country: Macedonia, The Former Yugoslav Republic of
country: Romania
country: Serbia
country: United States
country: Czech Republic
country: Netherlands
responsible party type: Sponsor
mesh term: Angioedema
mesh term: Angioedemas, Hereditary
mesh term: Complement C1 Inhibitor Protein
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 