<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/NCT02264639</url>
  </required_header>
  <id_info>
    <org_study_id>APL-CP0514</org_study_id>
    <nct_id>NCT02264639</nct_id>
  </id_info>
  <brief_title>A Phase I Study to Assess the Safety of Pegcetacoplan (APL-2) as an Add-On to Standard of Care in Subjects With PNH</brief_title>
  <official_title>An Open Label, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of APL-2 as an Add-On to Standard of Care in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Apellis Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Apellis Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</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 will be the initial exploration of pegcetacoplan in patients with PNH. The&#xD;
      assessments of the safety, tolerability, PK, and PD following administration of single and&#xD;
      multiples doses of pegcetacoplan will guide decisions to further develop the drug.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 23, 2015</start_date>
  <completion_date type="Actual">October 22, 2018</completion_date>
  <primary_completion_date type="Actual">October 22, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase</measure>
    <time_frame>From single dose of study drug (Day 1) up to 30 days</time_frame>
    <description>TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase</measure>
    <time_frame>From first dose of study drug up to 30 days after last dose of study drug (Cohorts 1-3: up to 58 days; Cohort 4: up to 759 days).</time_frame>
    <description>TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to CTCAE, v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4</measure>
    <time_frame>Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.</time_frame>
    <description>Assessment of AUC0-t of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach and calculated by the linear-log trapezoidal method. Pegcetacoplan pharmacokinetic (PK) parameters were summarized for Cohort 4 only.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4</measure>
    <time_frame>Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.</time_frame>
    <description>Assessment of Ctrough,max of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach. Pegcetacoplan PK parameters were summarized for Cohort 4 only. Ctrough,max was calculated for both 270 mg/day and 360 mg/day where subjects received both doses. Note: 1 subject in Cohort 4 who was receiving 360 mg/day was granted Sponsor and institutional review board approval to increase the dose further to the equivalent of 440 mg/day and Ctrough,max is also reported for this dose.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Paroxysmal Nocturnal Hemoglobinuria (PNH)</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>First Dose 25mg, Repeated Dose 5 mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>First Dose 50 mg, Repeated Dose 30 mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Repeated Dose 180 mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Repeated Dose 270 mg/day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegcetacoplan</intervention_name>
    <description>Complement (C3) Inhibitor</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
    <other_name>APL-2</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or Female&#xD;
&#xD;
          -  At least 18 years of age&#xD;
&#xD;
          -  Weigh &gt;55 kg&#xD;
&#xD;
          -  Diagnosed with PNH&#xD;
&#xD;
          -  On treatment with eculizumab (Soliris®) for at least 3 months&#xD;
&#xD;
          -  Hb &lt; 10 g/dL at screening OR have received at least one transfusion within 12 months&#xD;
             prior to screening&#xD;
&#xD;
          -  Platelet count of &gt;30,000/mm3&#xD;
&#xD;
          -  Absolute neutrophil count &gt; 500/mm3&#xD;
&#xD;
          -  Women of child-bearing potential (WOCBP) must have a negative pregnancy test at&#xD;
             screening and must agree to use protocol defined methods of contraception for the&#xD;
             duration of the study (see below)&#xD;
&#xD;
          -  Males with female partners of child bearing potential must agree to use protocol&#xD;
             defined methods of contraception (see below) and agree to refrain from donating sperm&#xD;
             for the duration of the study&#xD;
&#xD;
          -  Willing and able to give informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active bacterial infection&#xD;
&#xD;
          -  Known infection with hepatitis B, C or HIV&#xD;
&#xD;
          -  Hereditary complement deficiency&#xD;
&#xD;
          -  History of bone marrow transplantation&#xD;
&#xD;
          -  Participation in any other investigational drug trial or exposure to other&#xD;
             investigational agent, device or procedure within 30 days&#xD;
&#xD;
          -  Evidence of QTcF prolongation defined as &gt; 450 ms for males and &gt; 470 ms for females&#xD;
             at screening&#xD;
&#xD;
          -  Creatinine clearance (CrCl) &lt; 50 mL/min (Cockcroft-Gault formula) at screening&#xD;
&#xD;
          -  Breast-feeding women&#xD;
&#xD;
          -  History of meningococcal disease&#xD;
&#xD;
          -  No vaccination against N. meningitidis types A, C, W, Y and B (administered as two&#xD;
             separate vaccinations), Pneumococcal conjugate vaccine or Pneumococcal polysaccharide&#xD;
             vaccine 23 (PCV13 or PPSV23, respectively) and Haemophilus influenzae Type B (Hib)&#xD;
             vaccination within 2 years prior to Day 1 (Visit 2) dosing.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Federico Grossi, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Apellis Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Southern California Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lakes Research</name>
      <address>
        <city>Miami Lakes</city>
        <state>Florida</state>
        <zip>33014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Lousiville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cure 4 The Kids Foundation</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89135</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>October 8, 2014</study_first_submitted>
  <study_first_submitted_qc>October 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <results_first_submitted>July 31, 2020</results_first_submitted>
  <results_first_submitted_qc>December 14, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 8, 2021</results_first_posted>
  <last_update_submitted>December 14, 2020</last_update_submitted>
  <last_update_submitted_qc>December 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PNH</keyword>
  <keyword>Paroxysmal Nocturnal Hemoglobinuria</keyword>
  <keyword>Complement inhibitor</keyword>
  <keyword>Anemia</keyword>
  <keyword>Hemoglobinuria</keyword>
  <keyword>hematologic diseases</keyword>
  <keyword>extravascular hemolysis (EVH)</keyword>
  <keyword>intravascular hemolysis (IVH)</keyword>
  <keyword>C3 inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemoglobinuria</mesh_term>
    <mesh_term>Hemoglobinuria, Paroxysmal</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 15, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/39/NCT02264639/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 7, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/39/NCT02264639/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Paroxysmal nocturnal hemoglobinuria (PNH) subjects who were still anemic during treatment with eculizumab (Soliris®) were enrolled in this Phase 1, open-label, single- and multiple-ascending dose study to receive treatment with pegcetacoplan (APL-2) as an add-on to standard of care treatment. The study was conducted at 7 sites in the United States.</recruitment_details>
      <pre_assignment_details>Subjects could participate in more than 1 cohort. Overall, 9 unique subjects were evaluated in 4 cohorts, with some subjects participating in &gt;1 cohort. Single-dose phase: 4 unique subjects evaluated (2 each in Cohorts 1 and 2). Multiple-dose phase: 8 unique subjects evaluated, comprising 3 subjects who also participated in single-dose phase (1 in Cohort 1; 2 in Cohort 2) plus a further 5 unique subjects. Each cohort included a 30-day screening phase prior to treatment with pegcetacoplan.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1 Single- and Multiple-dose Phase</title>
          <description>Cohort 1 single-dose phase: Subjects received a single subcutaneous (SC) dose of 25 milligrams (mg) pegcetacoplan on Day 1.&#xD;
Cohort 1 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 5 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2 Single- and Multiple-dose Phase</title>
          <description>Cohort 2 single-dose phase: Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.&#xD;
Cohort 2 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 30 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).</description>
        </group>
        <group group_id="P3">
          <title>Cohort 2 Single-dose Phase, Then Cohorts 2, 3, and 4 Multiple-dose Phase</title>
          <description>Cohort 2 single-dose phase: Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.&#xD;
Cohort 2 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 30 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).&#xD;
Cohort 3 multiple-dose phase: Subjects received 180 mg/day SC dose of pegcetacoplan for 28 days (from Day 1 to Day 28).&#xD;
Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:&#xD;
Part 1: Subjects received daily doses of pegcetacoplan for 28 days.&#xD;
Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.&#xD;
Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.&#xD;
Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.&#xD;
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.</description>
        </group>
        <group group_id="P4">
          <title>Cohorts 3 and 4 Multiple-dose Phase</title>
          <description>Cohort 3 multiple-dose phase: Subjects received 180 mg/day SC dose of pegcetacoplan for 28 days (from Day 1 to Day 28).&#xD;
Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:&#xD;
Part 1: Subjects received daily doses of pegcetacoplan for 28 days.&#xD;
Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.&#xD;
Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.&#xD;
Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.&#xD;
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.</description>
        </group>
        <group group_id="P5">
          <title>Cohort 4 Multiple-dose Phase</title>
          <description>Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:&#xD;
Part 1: Subjects received daily doses of pegcetacoplan for 28 days.&#xD;
Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.&#xD;
Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.&#xD;
Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.&#xD;
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2">Subjects in this arm participated in Cohort 1 only.</participants>
                <participants group_id="P2" count="1">Subject in this arm participated in Cohort 2 only.</participants>
                <participants group_id="P3" count="1">Subject in this arm participated in Cohorts 2, 3 and 4.</participants>
                <participants group_id="P4" count="1">Subject in this arm participated in Cohorts 3 and 4; single-dose phase was not applicable.</participants>
                <participants group_id="P5" count="4">Subjects in this arm participated in Cohort 4 only; single-dose phase was not applicable.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death (after completing single-dose phase)</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by subject (during multiple-dose phase)</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pregnancy (during multiple-dose phase)</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Major Intercurrent Illness (during multiple-dose phase)</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety population included all enrolled subjects who received at least 1 dose of study drug. Total unique participants = 9. Subjects could participate in more than 1 cohort. 1 subject participated in Cohorts 2, 3 and 4, and 1 subject participated in Cohorts 3 and 4.</population>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1 Single- and Multiple-dose Phase</title>
          <description>Cohort 1 single-dose phase: Subjects received a single SC dose of 25 mg pegcetacoplan on Day 1.&#xD;
Cohort 1 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 5 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2 Single- and Multiple-dose Phase</title>
          <description>Cohort 2 single-dose phase: Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.&#xD;
Cohort 2 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 30 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).</description>
        </group>
        <group group_id="B3">
          <title>Cohort 2 Single-dose Phase, Then Cohorts 2, 3, and 4 Multiple-dose Phase</title>
          <description>Cohort 2 single-dose phase: Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.&#xD;
Cohort 2 multiple-dose phase: Following a waiting period of at least 28 days after single dosing, subjects received 30 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).&#xD;
Cohort 3 multiple-dose phase: Subjects received 180 mg/day SC dose of pegcetacoplan for 28 days (from Day 1 to Day 28).&#xD;
Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:&#xD;
Part 1: Subjects received daily doses of pegcetacoplan for 28 days.&#xD;
Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.&#xD;
Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.&#xD;
Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.&#xD;
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.</description>
        </group>
        <group group_id="B4">
          <title>Cohorts 3 and 4 Multiple-dose Phase</title>
          <description>Cohort 3 multiple-dose phase: Subjects received 180 mg/day SC dose of pegcetacoplan for 28 days (from Day 1 to Day 28).&#xD;
Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:&#xD;
Part 1: Subjects received daily doses of pegcetacoplan for 28 days.&#xD;
Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.&#xD;
Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.&#xD;
Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.&#xD;
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.</description>
        </group>
        <group group_id="B5">
          <title>Cohort 4 Multiple-dose Phase</title>
          <description>Cohort 4 multiple-dose phase: Subjects received 270 mg/day SC doses of pegcetacoplan for up to 729 days (from Day 1 up to Day 729). The treatment period consisted of the following:&#xD;
Part 1: Subjects received daily doses of pegcetacoplan for 28 days.&#xD;
Part 2A: On Day 29, subjects who demonstrated clinical benefit from the treatment were automatically entered into Part 2A and continued to receive daily doses of pegcetacoplan until Day 84.&#xD;
Part 2B: If there was ongoing evidence of clinical benefit, subjects who completed Part 2A could enter Part 2B and continue to receive daily doses of pegcetacoplan until Day 364.&#xD;
Part 2C: If there was ongoing evidence of clinical benefit, subjects who completed Part 2B could enter Part 2C and continue to receive daily doses of pegcetacoplan until Day 729.&#xD;
After Day 28 (Part 1), individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.</description>
        </group>
        <group group_id="B6">
          <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="2"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="1"/>
            <count group_id="B4" value="1"/>
            <count group_id="B5" value="4"/>
            <count group_id="B6" value="9"/>
          </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </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="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </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>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase</title>
        <description>TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.</description>
        <time_frame>From single dose of study drug (Day 1) up to 30 days</time_frame>
        <population>The safety population included all enrolled subjects who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 Single-dose Phase</title>
            <description>Subjects received a single SC dose of 25 mg pegcetacoplan on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 Single-dose Phase</title>
            <description>Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase</title>
          <description>TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.</description>
          <population>The safety population included all enrolled subjects who received at least 1 dose of study drug.</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="2"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE at least possibly related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to study drug discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum severity of all TEAEs: mild</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum severity of all TEAEs: moderate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum severity of all TEAEs: severe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase</title>
        <description>TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to CTCAE, v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.</description>
        <time_frame>From first dose of study drug up to 30 days after last dose of study drug (Cohorts 1-3: up to 58 days; Cohort 4: up to 759 days).</time_frame>
        <population>The safety population included all enrolled subjects who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1 Multiple-dose Phase</title>
            <description>Subjects received 5 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2 Multiple-dose Phase</title>
            <description>Subjects received 30 mg/day SC dose of pegcetacoplan for 28 days (from Day 29 to Day 56).</description>
          </group>
          <group group_id="O3">
            <title>Cohort 3 Multiple-dose Phase</title>
            <description>Subjects received 180 mg/day SC dose of pegcetacoplan for 28 days (from Day 1 to Day 28).</description>
          </group>
          <group group_id="O4">
            <title>Cohort 4 Multiple-dose Phase</title>
            <description>Subjects received 270 mg/day SC dose of pegcetacoplan for up to 729 days (from Day 1 up to Day 729).&#xD;
After Day 28, individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase</title>
          <description>TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to CTCAE, v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.</description>
          <population>The safety population included all enrolled subjects who received at least 1 dose of study drug.</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="1"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE at least possibly related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to study drug discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum severity of all TEAEs: mild</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum severity of all TEAEs: moderate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum severity of all TEAEs: severe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum severity of all TEAEs: life-threatening</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4</title>
        <description>Assessment of AUC0-t of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach and calculated by the linear-log trapezoidal method. Pegcetacoplan pharmacokinetic (PK) parameters were summarized for Cohort 4 only.</description>
        <time_frame>Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.</time_frame>
        <population>The PK population was defined as all subjects in the safety population who had at least 1 PK sample drawn with a measurable serum concentration. Results were reported for Cohort 4 only. Due to the small sample size in Cohorts 1 through 3, summaries for continuous data using descriptive statistics were not performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 4 Multiple-dose Phase</title>
            <description>Subjects received 270 mg/day SC dose of pegcetacoplan for up to 729 days (from Day 1 up to Day 729).&#xD;
After Day 28, individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4</title>
          <description>Assessment of AUC0-t of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach and calculated by the linear-log trapezoidal method. Pegcetacoplan pharmacokinetic (PK) parameters were summarized for Cohort 4 only.</description>
          <population>The PK population was defined as all subjects in the safety population who had at least 1 PK sample drawn with a measurable serum concentration. Results were reported for Cohort 4 only. Due to the small sample size in Cohorts 1 through 3, summaries for continuous data using descriptive statistics were not performed.</population>
          <units>micrograms*hour/milliliter (μg*hour/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6,500,000" spread="3,990,000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4</title>
        <description>Assessment of Ctrough,max of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach. Pegcetacoplan PK parameters were summarized for Cohort 4 only. Ctrough,max was calculated for both 270 mg/day and 360 mg/day where subjects received both doses. Note: 1 subject in Cohort 4 who was receiving 360 mg/day was granted Sponsor and institutional review board approval to increase the dose further to the equivalent of 440 mg/day and Ctrough,max is also reported for this dose.</description>
        <time_frame>Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.</time_frame>
        <population>The PK population was defined as all subjects in the safety population who had at least 1 PK sample drawn with a measurable serum concentration. Results were reported for Cohort 4 only. Due to the small sample size in Cohorts 1 through 3, summaries for continuous data using descriptive statistics were not performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 4 Multiple-dose Phase</title>
            <description>Subjects received 270 mg/day SC dose of pegcetacoplan for up to 729 days (from Day 1 up to Day 729).&#xD;
After Day 28, individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4</title>
          <description>Assessment of Ctrough,max of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach. Pegcetacoplan PK parameters were summarized for Cohort 4 only. Ctrough,max was calculated for both 270 mg/day and 360 mg/day where subjects received both doses. Note: 1 subject in Cohort 4 who was receiving 360 mg/day was granted Sponsor and institutional review board approval to increase the dose further to the equivalent of 440 mg/day and Ctrough,max is also reported for this dose.</description>
          <population>The PK population was defined as all subjects in the safety population who had at least 1 PK sample drawn with a measurable serum concentration. Results were reported for Cohort 4 only. Due to the small sample size in Cohorts 1 through 3, summaries for continuous data using descriptive statistics were not performed.</population>
          <units>μg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>270 mg Dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="627" spread="207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>360 mg Dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="543" spread="192"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>440 mg Dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="624" spread="NA">No standard deviation is presented since mean value is derived from a single subject.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>TEAE data is reported from first dose of study drug up to 30 days after last dose of study drug (Cohorts 1 and 2, single-dose phase: up to 30 days; Cohorts 1-3, multiple-dose phase: up to 58 days; Cohort 4, multiple-dose phase: up to 759 days).</time_frame>
      <desc>The safety population included all enrolled subjects who received at least 1 dose of study drug. The 4 cohorts of 12 subjects overall represents 9 unique participants. Subjects could participate in more than 1 cohort. The all-cause mortality table includes the death of 1 subject in Cohort 1, resulting from a serious AE which was not treatment-emergent.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1 Single-dose Phase</title>
          <description>Subjects received a single SC dose of 25 mg pegcetacoplan on Day 1.</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2 Single-dose Phase</title>
          <description>Subjects received a single SC dose of 50 mg pegcetacoplan on Day 1.</description>
        </group>
        <group group_id="E3">
          <title>Cohort 1 Multiple-dose Phase</title>
          <description>Subjects received pegcetacoplan 5 mg/day as SC dose for 28 days (from Day 29 to Day 56).</description>
        </group>
        <group group_id="E4">
          <title>Cohort 2 Multiple-dose Phase</title>
          <description>Subjects received pegcetacoplan 30 mg/day as SC dose for 28 days (from Day 29 to Day 56).</description>
        </group>
        <group group_id="E5">
          <title>Cohort 3 Multiple-dose Phase</title>
          <description>Subjects received pegcetacoplan 180 mg/day as SC dose for 28 days (from Day 1 to Day 28).</description>
        </group>
        <group group_id="E6">
          <title>Cohort 4 Multiple-dose Phase</title>
          <description>Subjects received pegcetacoplan 270 mg/day as SC dose for up to 729 days (from Day 1 up to Day 729).&#xD;
After Day 28, individual subject dose escalation up to a dose of 360 mg/day could occur in subjects who had a sub-optimal hematological response but acceptable tolerability.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Lower gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Portal vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (17.0)</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="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperacusis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Eye irritation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Eye pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="5" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="4" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lip blister</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rectal hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="5" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection-site bruising</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="4" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E6" events="145" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection-site induration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="43" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection-site erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="19" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection-site pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="13" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection-site swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="9" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="8" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection-site pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="7" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Infusion-site bruising</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection-site haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Induration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection-site discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection-site oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection-site warmth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="3" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Excoriation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Serum ferritin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="4" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="3" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Body temperature increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Electrocardiogram abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vitamin B12 decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="7" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="7" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain in jaw</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="11" subjects_affected="5" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Burning sensation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypersomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dysaesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </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="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Polyuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urine odour abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="12" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="9" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="3" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Decubitus ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Generalised erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Onychoclasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash macular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </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>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Apellis Clinical Trial Information Line</name_or_title>
      <organization>Apellis Pharmaceuticals, Inc.</organization>
      <phone>1-833-284-6361</phone>
      <email>clinicaltrials@apellis.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/NCT02264639
org study id: APL-CP0514
nct id: NCT02264639
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will be the initial exploration of pegcetacoplan in patients with PNH. The
      assessments of the safety, tolerability, PK, and PD following administration of single and
      multiples doses of pegcetacoplan will guide decisions to further develop the drug.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase
time frame: From single dose of study drug (Day 1) up to 30 days
description: TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.
measure: Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase
time frame: From first dose of study drug up to 30 days after last dose of study drug (Cohorts 1-3: up to 58 days; Cohort 4: up to 759 days).
description: TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to CTCAE, v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.
measure: Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4
time frame: Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.
description: Assessment of AUC0-t of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach and calculated by the linear-log trapezoidal method. Pegcetacoplan pharmacokinetic (PK) parameters were summarized for Cohort 4 only.
measure: Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4
time frame: Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.
description: Assessment of Ctrough,max of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach. Pegcetacoplan PK parameters were summarized for Cohort 4 only. Ctrough,max was calculated for both 270 mg/day and 360 mg/day where subjects received both doses. Note: 1 subject in Cohort 4 who was receiving 360 mg/day was granted Sponsor and institutional review board approval to increase the dose further to the equivalent of 440 mg/day and Ctrough,max is also reported for this dose.
arm group label: Cohort 1
arm group type: Experimental
description: First Dose 25mg, Repeated Dose 5 mg/day
arm group label: Cohort 2
arm group type: Experimental
description: First Dose 50 mg, Repeated Dose 30 mg/day
arm group label: Cohort 3
arm group type: Experimental
description: Repeated Dose 180 mg/day
arm group label: Cohort 4
arm group type: Experimental
description: Repeated Dose 270 mg/day
intervention type: Drug
intervention name: Pegcetacoplan
description: Complement (C3) Inhibitor
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
other name: APL-2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Federico Grossi, MD, PhD
role: Study Director
affiliation: Apellis Pharmaceuticals, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hemoglobinuria
mesh term: Hemoglobinuria, Paroxysmal
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 