<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/NCT03030183</url>
  </required_header>
  <id_info>
    <org_study_id>RA101495-01.203</org_study_id>
    <nct_id>NCT03030183</nct_id>
  </id_info>
  <brief_title>Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495) to Treat PNH Patients Who Have an Inadequate Response to Eculizumab</brief_title>
  <official_title>A Phase 2 Multicenter, Open-Label, Uncontrolled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria Who Have an Inadequate Response to Eculizumab</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ra Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>UCB Pharma</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate the safety and efficacy of RA101495 in patients with&#xD;
      paroxysmal nocturnal hemoglobinuria (PNH) who have an inadequate response to eculizumab.&#xD;
      Patients will be treated with RA101495 for 12 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 17, 2017</start_date>
  <completion_date type="Actual">March 28, 2018</completion_date>
  <primary_completion_date type="Actual">March 28, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Levels.</measure>
    <time_frame>Through Week 12 of the study</time_frame>
    <description>Change-from-baseline through Week 12 in serum lactate dehydrogenase (LDH) levels</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change-from-baseline Bilirubin Values</measure>
    <time_frame>Through week 12</time_frame>
    <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change-from-baseline Total Hemoglobin Values</measure>
    <time_frame>Through week 12</time_frame>
    <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change-from-baseline Free Hemoglobin Values</measure>
    <time_frame>Through week 12</time_frame>
    <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change-from-baseline Haptoglobin Values</measure>
    <time_frame>Through week 12</time_frame>
    <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change-from-baseline Reticulocyte Values</measure>
    <time_frame>Through week 12</time_frame>
    <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change-from-baseline Hemoglobinuria Values</measure>
    <time_frame>Through week 12</time_frame>
    <description>Changes from baseline at each of the scheduled postbaseline time-points Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10. Where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Paroxysmal Nocturnal Hemoglobinuria (PNH)</condition>
  <arm_group>
    <arm_group_label>Zilucoplan (RA101495)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive RA101495 at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zilucoplan (RA101495)</intervention_name>
    <description>0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC</description>
    <arm_group_label>Zilucoplan (RA101495)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of PNH by flow cytometry&#xD;
&#xD;
          -  Inadequate response to eculizumab defined as having received eculizumab for at least 6&#xD;
             months plus a documented LDH level ≥ 1.5 x the upper limit of normal (ULN) and/or the&#xD;
             presence of a known C5 mutation conferring resistance to eculizumab&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of meningococcal disease&#xD;
&#xD;
          -  Current systemic infection or suspicion of active bacterial infection&#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>Dr. Anita Hill</last_name>
    <role>Study Chair</role>
    <affiliation>St James' Institute of Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Manhasset</city>
        <state>New York</state>
        <zip>11030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://learningcenter.ehaweb.org/eha/2018/stockholm/214782/anita.hill.ra101495.a.subcutaneously-administered.peptide.inhibitor.of.html?f=menu=14*media=3*speaker=664274</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <results_first_submitted>August 13, 2019</results_first_submitted>
  <results_first_submitted_qc>February 25, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">February 26, 2020</results_first_posted>
  <last_update_submitted>July 26, 2022</last_update_submitted>
  <last_update_submitted_qc>July 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PNH</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>January 17, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03030183/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>September 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03030183/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Zilucoplan (RA101495)</title>
          <description>Subjects will receive zilucoplan (RA101495) at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC&#xD;
Zilucoplan (RA101495): 0. 3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Zilucoplan (RA101495)</title>
          <description>Subjects will receive zilucoplan (RA101495) at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC&#xD;
Zilucoplan (RA101495): 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35.3" spread="16.3"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </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_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="109.67" spread="13.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="176.20" spread="7.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35.72" spread="7.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Levels.</title>
        <description>Change-from-baseline through Week 12 in serum lactate dehydrogenase (LDH) levels</description>
        <time_frame>Through Week 12 of the study</time_frame>
        <population>Efficacy Evaluable</population>
        <group_list>
          <group group_id="O1">
            <title>Zilucoplan (RA101495)</title>
            <description>Subjects will receive zilucoplan (RA101495) at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC&#xD;
Zilucoplan (RA101495): 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Levels.</title>
          <description>Change-from-baseline through Week 12 in serum lactate dehydrogenase (LDH) levels</description>
          <population>Efficacy Evaluable</population>
          <units>U/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.3" spread="128.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change-from-baseline Bilirubin Values</title>
        <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
        <time_frame>Through week 12</time_frame>
        <population>Efficacy Evaluable</population>
        <group_list>
          <group group_id="O1">
            <title>Zilucoplan (RA101495)</title>
            <description>Subjects will receive zilucoplan (RA101495) at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC&#xD;
Zilucoplan (RA101495): 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Change-from-baseline Bilirubin Values</title>
          <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
          <population>Efficacy Evaluable</population>
          <units>umol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.3" spread="5.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.7" spread="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.3" spread="7.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.7" spread="17.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.3" spread="12.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.7" spread="14.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" spread="6.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change-from-baseline Total Hemoglobin Values</title>
        <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
        <time_frame>Through week 12</time_frame>
        <population>Efficacy Evaluable</population>
        <group_list>
          <group group_id="O1">
            <title>Zilucoplan (RA101495)</title>
            <description>Subjects will receive zilucoplan (RA101495) at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC&#xD;
Zilucoplan (RA101495): 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Change-from-baseline Total Hemoglobin Values</title>
          <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
          <population>Efficacy Evaluable</population>
          <units>g/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7" spread="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3" spread="3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.3" spread="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change-from-baseline Free Hemoglobin Values</title>
        <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
        <time_frame>Through week 12</time_frame>
        <population>Efficacy Evaluable</population>
        <group_list>
          <group group_id="O1">
            <title>Zilucoplan (RA101495)</title>
            <description>Subjects will receive zilucoplan (RA101495) at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC&#xD;
Zilucoplan (RA101495): 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Change-from-baseline Free Hemoglobin Values</title>
          <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
          <population>Efficacy Evaluable</population>
          <units>mg/dL</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</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="-145.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</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="-140.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</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="-147.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</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="-138.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</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="-147.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</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="-148.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</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="-143.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</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="-144.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change-from-baseline Haptoglobin Values</title>
        <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
        <time_frame>Through week 12</time_frame>
        <population>Efficacy Evaluable</population>
        <group_list>
          <group group_id="O1">
            <title>Zilucoplan (RA101495)</title>
            <description>Subjects will receive zilucoplan (RA101495) at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC&#xD;
Zilucoplan (RA101495): 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Change-from-baseline Haptoglobin Values</title>
          <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
          <population>Efficacy Evaluable</population>
          <units>g/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.133" spread="0.231"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change-from-baseline Reticulocyte Values</title>
        <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
        <time_frame>Through week 12</time_frame>
        <population>Efficacy Evaluable</population>
        <group_list>
          <group group_id="O1">
            <title>Zilucoplan (RA101495)</title>
            <description>Subjects will receive zilucoplan (RA101495) at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC&#xD;
Zilucoplan (RA101495): 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Change-from-baseline Reticulocyte Values</title>
          <description>Changes from baseline at each of the scheduled postbaseline time-points</description>
          <population>Efficacy Evaluable</population>
          <units>10^12 cells/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0190" spread="0.0382"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0090" spread="0.0052"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0430" spread="0.0327"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0477" spread="0.0499"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0310" spread="0.0157"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0253" spread="0.0248"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0350" spread="0.0350"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0190" spread="0.0092"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change-from-baseline Hemoglobinuria Values</title>
        <description>Changes from baseline at each of the scheduled postbaseline time-points Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10. Where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria.</description>
        <time_frame>Through week 12</time_frame>
        <population>Efficacy Evaluable</population>
        <group_list>
          <group group_id="O1">
            <title>Zilucoplan (RA101495)</title>
            <description>Subjects will receive zilucoplan (RA101495) at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC&#xD;
Zilucoplan (RA101495): 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Change-from-baseline Hemoglobinuria Values</title>
          <description>Changes from baseline at each of the scheduled postbaseline time-points Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10. Where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria.</description>
          <population>Efficacy Evaluable</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</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="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</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="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Through week 12 of the Study</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Zilucoplan (RA101495)</title>
          <description>Subjects will receive zilucoplan (RA101495) at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC&#xD;
Zilucoplan (RA101495): 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haemoglobinuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </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 the Principal Investigator and the Sponsor (or its agents) that restricts the PI's right to discuss or publish trial results after the trial is completed. Disclosure agreements are negotiated separately with each PI</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Sponsor Ra Pharmaceutical, Inc</name_or_title>
      <organization>Ra Pharmaceutical, Inc</organization>
      <phone>1 617 401 4060</phone>
      <email>trials@rapharma.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/NCT03030183
org study id: RA101495-01.203
nct id: NCT03030183
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of the study is to evaluate the safety and efficacy of RA101495 in patients with
      paroxysmal nocturnal hemoglobinuria (PNH) who have an inadequate response to eculizumab.
      Patients will be treated with RA101495 for 12 weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Levels.
time frame: Through Week 12 of the study
description: Change-from-baseline through Week 12 in serum lactate dehydrogenase (LDH) levels
measure: Change-from-baseline Bilirubin Values
time frame: Through week 12
description: Changes from baseline at each of the scheduled postbaseline time-points
measure: Change-from-baseline Total Hemoglobin Values
time frame: Through week 12
description: Changes from baseline at each of the scheduled postbaseline time-points
measure: Change-from-baseline Free Hemoglobin Values
time frame: Through week 12
description: Changes from baseline at each of the scheduled postbaseline time-points
measure: Change-from-baseline Haptoglobin Values
time frame: Through week 12
description: Changes from baseline at each of the scheduled postbaseline time-points
measure: Change-from-baseline Reticulocyte Values
time frame: Through week 12
description: Changes from baseline at each of the scheduled postbaseline time-points
measure: Change-from-baseline Hemoglobinuria Values
time frame: Through week 12
description: Changes from baseline at each of the scheduled postbaseline time-points Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10. Where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria.
arm group label: Zilucoplan (RA101495)
arm group type: Experimental
description: Subjects will receive RA101495 at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
intervention type: Drug
intervention name: Zilucoplan (RA101495)
description: 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
arm group label: Zilucoplan (RA101495)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dr. Anita Hill
role: Study Chair
affiliation: St James' Institute of Oncology
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://learningcenter.ehaweb.org/eha/2018/stockholm/214782/anita.hill.ra101495.a.subcutaneously-administered.peptide.inhibitor.of.html?f=menu=14*media=3*speaker=664274
description: Related Info
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: 