<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/NCT01731990</url>
  </required_header>
  <id_info>
    <org_study_id>CACZ885M2201</org_study_id>
    <secondary_id>2012-001427-12</secondary_id>
    <nct_id>NCT01731990</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability and Efficacy of ACZ885 on Leg Artery Structure in Patients With Peripheral Artery Disease</brief_title>
  <official_title>A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability and Effects on Arterial Structure and Function of ACZ885 in Patients With Intermittent Claudication.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</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>
      This study was designed to assess the safety, tolerability and efficacy of ACZ885 on the leg&#xD;
      artery structure and physical activity in patients with atherosclerotic peripheral artery&#xD;
      disease and leg pain from walking.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study got terminated based on result from primary endpoint analysis&#xD;
  </why_stopped>
  <start_date type="Actual">October 30, 2012</start_date>
  <completion_date type="Actual">August 4, 2016</completion_date>
  <primary_completion_date type="Actual">August 4, 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Vessel Wall Area Ratio of 12 Months to Baseline</measure>
    <time_frame>Baseline, 12 months post-dose</time_frame>
    <description>Peripheral artery wall area (superficial femoral artery) measured using Magnetic Resonance Imaging (MRI) cross-section slices. Mean vessel wall area (mm^2) was derived by converting total plaque volume (TPV) (mL) of the vessel to mm^3 by multiplying by 1000, dividing by the number of slices used for the volume calculation, and dividing by the thickness of a slice (3 mm). Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, the treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Adverse Events in 12 Months</measure>
    <time_frame>Baseline to 12 months post-dose</time_frame>
    <description>Summary statistics on adverse event is reported. It is categorized as number of patients in total adverse events (non serious and serious AEs), serious adverse event, death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Amyloid A (SAA) Level Ratio of 12 Months to Baseline</measure>
    <time_frame>Baseline, 12 months post-dose</time_frame>
    <description>Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High Sensitivity C-reactive Protein (hsCRP) Ratio of 12 Months to Baseline</measure>
    <time_frame>Baseline, 12 months post-dose</time_frame>
    <description>Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Peripheral Artery Disease</condition>
  <arm_group>
    <arm_group_label>Canakinumab (ACZ885)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Canakinumab (ACZ885)</intervention_name>
    <description>Dosage form: solution for injection Strength: 150 mg/1 mL Mode of administration: subcutaneous use.</description>
    <arm_group_label>Canakinumab (ACZ885)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo of Canakinumab</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Must have a signed informed consent form.&#xD;
&#xD;
          -  Must be between the ages of 18 and 85&#xD;
&#xD;
          -  Must experience leg pain associated with walking and have an ankle brachial index&#xD;
             between 0.40 and 0.9&#xD;
&#xD;
          -  Must be on stable aspirin and statin doses for at least 6 weeks&#xD;
&#xD;
          -  Blood pressure within ranges specified in the protocol&#xD;
&#xD;
          -  Able to communicate well with the Investigator and understand and comply with the&#xD;
             study procedures&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Recent use of any other experimental drugs&#xD;
&#xD;
          -  Pregnant or nursing women&#xD;
&#xD;
          -  Women of child bearing potential unless willing to use contraception as detailed in&#xD;
             the protocol&#xD;
&#xD;
          -  Cannot walk 15 meters (50 feet)&#xD;
&#xD;
          -  People on restricted medications as listed in the protocol&#xD;
&#xD;
          -  Any open or non-healing wounds with 3 months of study start or infection within 2&#xD;
             weeks or study start&#xD;
&#xD;
          -  Significant heart disease&#xD;
&#xD;
          -  Uncontrolled diabetes&#xD;
&#xD;
          -  Significant kidney or liver disease&#xD;
&#xD;
          -  Live vaccinations within 3 months of study start&#xD;
&#xD;
          -  History of untreated tuberculosis or active tuberculosis (TB)&#xD;
&#xD;
          -  Patients with metal in their body (excluded due to MRI scan) as detailed in the&#xD;
             protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85302</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lutherville</city>
        <state>Maryland</state>
        <zip>21093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hamburg</city>
        <zip>20099</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hamburg</city>
        <zip>22559</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Mainz</city>
        <zip>55116</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>München</city>
        <zip>80336</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Amman</city>
        <zip>11941</zip>
        <country>Jordan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Jordan</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=162</url>
    <description>A Plain Language Trial Summary is available on novartisclinicaltrials.com</description>
  </link>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>November 18, 2012</study_first_submitted>
  <study_first_submitted_qc>November 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2012</study_first_posted>
  <results_first_submitted>July 21, 2017</results_first_submitted>
  <results_first_submitted_qc>July 21, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">August 22, 2017</results_first_posted>
  <last_update_submitted>December 9, 2020</last_update_submitted>
  <last_update_submitted_qc>December 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Peripheral artery disease</keyword>
  <keyword>Intermittent claudication</keyword>
  <keyword>magnetic resonance imaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Arterial Disease</mesh_term>
    <mesh_term>Intermittent Claudication</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 38 patients were enrolled into the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Canakinumab (ACZ885)</title>
          <description>Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18">&quot;Started&quot; indicates Safety and Pharmacodynamics set .</participants>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol deviation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>safety analysis set: All patients that received any study drug were included in the safety analysis set</population>
      <group_list>
        <group group_id="B1">
          <title>Canakinumab (ACZ885)</title>
          <description>Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
            <count group_id="B2" value="20"/>
            <count group_id="B3" value="38"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66.0" spread="8.64"/>
                    <measurement group_id="B2" value="63.5" spread="7.98"/>
                    <measurement group_id="B3" value="64.7" spread="8.29"/>
                  </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="4"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Vessel Wall Area Ratio of 12 Months to Baseline</title>
        <description>Peripheral artery wall area (superficial femoral artery) measured using Magnetic Resonance Imaging (MRI) cross-section slices. Mean vessel wall area (mm^2) was derived by converting total plaque volume (TPV) (mL) of the vessel to mm^3 by multiplying by 1000, dividing by the number of slices used for the volume calculation, and dividing by the thickness of a slice (3 mm). Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, the treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.</description>
        <time_frame>Baseline, 12 months post-dose</time_frame>
        <population>The pharmacodynamics (PD) analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Patients who underwent iliac/femoral stenting were removed from all data points that occurred after this procedure in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Canakinumab (ACZ885)</title>
            <description>Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Vessel Wall Area Ratio of 12 Months to Baseline</title>
          <description>Peripheral artery wall area (superficial femoral artery) measured using Magnetic Resonance Imaging (MRI) cross-section slices. Mean vessel wall area (mm^2) was derived by converting total plaque volume (TPV) (mL) of the vessel to mm^3 by multiplying by 1000, dividing by the number of slices used for the volume calculation, and dividing by the thickness of a slice (3 mm). Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, the treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.</description>
          <population>The pharmacodynamics (PD) analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Patients who underwent iliac/femoral stenting were removed from all data points that occurred after this procedure in the analysis.</population>
          <units>Ratio</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.05" spread="0.03"/>
                    <measurement group_id="O2" value="0.99" spread="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.284</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Treatment effect for ratio to placebo</param_type>
            <param_value>1.06</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.97</ci_lower_limit>
            <ci_upper_limit>1.15</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Adverse Events in 12 Months</title>
        <description>Summary statistics on adverse event is reported. It is categorized as number of patients in total adverse events (non serious and serious AEs), serious adverse event, death.</description>
        <time_frame>Baseline to 12 months post-dose</time_frame>
        <population>All patients that received any study drug were included in the safety analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Canakinumab (ACZ885)</title>
            <description>Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Adverse Events in 12 Months</title>
          <description>Summary statistics on adverse event is reported. It is categorized as number of patients in total adverse events (non serious and serious AEs), serious adverse event, death.</description>
          <population>All patients that received any study drug were included in the safety analysis set.</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="18"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total Adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious Adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Amyloid A (SAA) Level Ratio of 12 Months to Baseline</title>
        <description>Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.</description>
        <time_frame>Baseline, 12 months post-dose</time_frame>
        <population>The PD analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Patients with baseline and 12 month data are included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Canakinumab (ACZ885)</title>
            <description>Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Amyloid A (SAA) Level Ratio of 12 Months to Baseline</title>
          <description>Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.</description>
          <population>The PD analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Patients with baseline and 12 month data are included in this analysis.</population>
          <units>Ratio</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.62" spread="0.12"/>
                    <measurement group_id="O2" value="0.79" spread="0.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>High Sensitivity C-reactive Protein (hsCRP) Ratio of 12 Months to Baseline</title>
        <description>Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.</description>
        <time_frame>Baseline, 12 months post-dose</time_frame>
        <population>The PD analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Patients with baseline and 12 month data are included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Canakinumab (ACZ885)</title>
            <description>Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months</description>
          </group>
        </group_list>
        <measure>
          <title>High Sensitivity C-reactive Protein (hsCRP) Ratio of 12 Months to Baseline</title>
          <description>Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.</description>
          <population>The PD analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Patients with baseline and 12 month data are included in this analysis.</population>
          <units>Ratio</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.62" spread="0.14"/>
                    <measurement group_id="O2" value="0.83" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Canakinumab (ACZ885)</title>
          <description>Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.1)</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="10" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Atrioventricular block</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Atrioventricular block complete</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Mesenteric arterial occlusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Mesenteric arteriosclerosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abscess limb</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Groin abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Helicobacter gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pulmonary vascular disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral arterial occlusive disease</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Peripheral artery occlusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Peripheral vascular disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (19.1)</default_vocab>
        <default_assessment>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="16" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Plasma cell disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Atrioventricular block first degree</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Cerumen impaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Deafness unilateral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Goitre</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Diverticulum</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Erosive oesophagitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Gingival bleeding</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hiatus hernia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Large intestine polyp</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Oesophageal mucosa erythema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Oesophageal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pancreatic cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Drug intolerance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Feeling cold</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Conjunctivitis viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Escherichia urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Tinea pedis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Tooth abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Vulvovaginal mycotic infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Excoriation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Muscle strain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Soft tissue injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood triglycerides increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Oesophagogastroduodenoscopy abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypochloraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Intervertebral disc degeneration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Plantar fasciitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Areflexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dizziness postural</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Muscle contractions involuntary</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Polyuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Renal artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Renal cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Genital pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Prostatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pulmonary mass</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Drug eruption</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Eczema asteatotic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyperkeratosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Lichen nitidus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nail discolouration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Photosensitivity reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Skin lesion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Skin plaque</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic aneurysm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Aortic thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Intermittent claudication</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Peripheral arterial occlusive disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Peripheral ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </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 terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Study was terminated after the third interim analysis based on result from primary outcome analysis.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
    </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/NCT01731990
org study id: CACZ885M2201
secondary id: 2012-001427-12
nct id: NCT01731990
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study was designed to assess the safety, tolerability and efficacy of ACZ885 on the leg
      artery structure and physical activity in patients with atherosclerotic peripheral artery
      disease and leg pain from walking.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean Vessel Wall Area Ratio of 12 Months to Baseline
time frame: Baseline, 12 months post-dose
description: Peripheral artery wall area (superficial femoral artery) measured using Magnetic Resonance Imaging (MRI) cross-section slices. Mean vessel wall area (mm^2) was derived by converting total plaque volume (TPV) (mL) of the vessel to mm^3 by multiplying by 1000, dividing by the number of slices used for the volume calculation, and dividing by the thickness of a slice (3 mm). Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, the treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.
measure: Number of Patients With Adverse Events in 12 Months
time frame: Baseline to 12 months post-dose
description: Summary statistics on adverse event is reported. It is categorized as number of patients in total adverse events (non serious and serious AEs), serious adverse event, death.
measure: Serum Amyloid A (SAA) Level Ratio of 12 Months to Baseline
time frame: Baseline, 12 months post-dose
description: Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.
measure: High Sensitivity C-reactive Protein (hsCRP) Ratio of 12 Months to Baseline
time frame: Baseline, 12 months post-dose
description: Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.
arm group label: Canakinumab (ACZ885)
arm group type: Experimental
description: Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months
arm group label: Placebo
arm group type: Placebo Comparator
description: Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months
intervention type: Drug
intervention name: Canakinumab (ACZ885)
description: Dosage form: solution for injection Strength: 150 mg/1 mL Mode of administration: subcutaneous use.
arm group label: Canakinumab (ACZ885)
intervention type: Drug
intervention name: Placebo
description: Matching placebo of Canakinumab
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: Germany
country: Jordan
country: United States
url: https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=162
description: A Plain Language Trial Summary is available on novartisclinicaltrials.com
responsible party type: Sponsor
mesh term: Peripheral Arterial Disease
mesh term: Intermittent Claudication
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study was terminated after the third interim analysis based on result from primary outcome analysis.
point of contact: 