<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/NCT03287414</url>
  </required_header>
  <id_info>
    <org_study_id>CVAY736X2207</org_study_id>
    <secondary_id>2017 002667 17</secondary_id>
    <nct_id>NCT03287414</nct_id>
  </id_info>
  <brief_title>Study of Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of VAY736 in Patients With Idiopathic Pulmonary Fibrosis</brief_title>
  <official_title>A Subject-, Investigator-, and Sponsor-blinded, Randomized, Placebo-controlled, Multicenter Study to Investigate Efficacy, Safety, and Tolerability of VAY736 in Patients With Idiopathic Pulmonary Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</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>
      The purpose of this study was to investigate the safety, tolerability and efficacy of VAY736&#xD;
      as potential therapy for the treatment of idiopathic pulmonary fibrosis (IPF).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was an exploratory (non-confirmatory) randomized, patient-, investigator-, sponsor-&#xD;
      blinded, placebo controlled study of VAY736 in IPF patients. This study investigated the&#xD;
      safety and efficacy of 300 mg VAY736 administered subcutaneously (s.c.) every 4 weeks for 48&#xD;
      weeks.&#xD;
&#xD;
      Participants were randomized in a 1:1 ratio on top of local standard of care (SOC), to&#xD;
      receive VAY736 or placebo. Randomized subjects entered the treatment epoch (for up to 48&#xD;
      weeks), followed by two follow-up epochs: the PK/safety follow-up epoch and the PD/safety&#xD;
      follow-up epoch. The PK/safety follow-up epoch lasted for 20 weeks. When the PK/safety&#xD;
      follow-up epoch was completed, participants in the placebo arm were discharged from the&#xD;
      study; but participants in the active arm (those who had received VAY736) continued into the&#xD;
      PD/safety follow-up epoch. Participants in the PD/safety follow-up epoch were followed until&#xD;
      B-cell recovery (in the peripheral blood), defined as: B cells &gt;=50/μL or B cells &gt;= 80% of&#xD;
      baseline (whichever occurred first). If a participant had not recovered his/her B-cells after&#xD;
      a period of 2 years from the last dose of VAY736, then this participant was discharged from&#xD;
      the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor decision&#xD;
  </why_stopped>
  <start_date type="Actual">December 20, 2017</start_date>
  <completion_date type="Actual">February 14, 2022</completion_date>
  <primary_completion_date type="Actual">November 25, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Forced Vital Capacity (FVC).</measure>
    <time_frame>From baseline up to 48 weeks post first dose of study treatment</time_frame>
    <description>FVC was defined as the maximum amount of air that an individual was able to forcibly exhale from his / her lungs after taking the deepest breath they could. Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With All-cause Mortality Events</measure>
    <time_frame>Up to 48 weeks post first dose of study treatment</time_frame>
    <description>All-cause mortality events were defined as deaths due to any cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Survival Idiopathic Pulmonary Fibrosis (IPF) -Related Mortality Events</measure>
    <time_frame>Up to 48 weeks post first dose of study treatment</time_frame>
    <description>IPF-related mortality events were defined as deaths due to IPF related cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Progression-free Survival (PFS) Events</measure>
    <time_frame>Up to 48 weeks post first dose of study treatment</time_frame>
    <description>PFS events were divided into: 1) PFS1 events including progression (relative reduction in FVC ≥ 10%) or death due to all causes, and 2) PFS2 events including progression (relative reduction in FVC ≥ 10%) or death due to IPF-related causes. Kaplan-Meier estimates of the percentage of participants with the event of interest (PFS1 events or PFS2 events) along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Disease Progression Events</measure>
    <time_frame>Up to 48 weeks post first dose of study treatment</time_frame>
    <description>The following disease progression events were considered: a) relative reduction in FVC ≥ 10%; b) relative reduction in Diffusing Capacity of the Lungs (DLCO) ≥ 15%; c) absolute reduction in Six Minute Walk Distance (6MWD) ≥ 50 m. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Composite Events</measure>
    <time_frame>Up to 48 weeks post first dose of study treatment</time_frame>
    <description>Composite events were defined as: 1) death (all-cause mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 1); and 2) Death (IPF-related mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 2). Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Diffusing Capacity of the Lungs</measure>
    <time_frame>From baseline up to 48 weeks post first dose of study treatment</time_frame>
    <description>DLCO is a measurement to assess the lungs' ability to transfer gas from inspired air to the bloodstream. DLCO was determined according to ATS guidelines. Change from baseline to end of treatment epoch (48 weeks of treatment) in diffusing capacity of the lung for carbon monoxide (DLCO) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement.&#xD;
Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in 6-minute Walk Distance (6MWD)</measure>
    <time_frame>From baseline up to 48 weeks post first dose of study treatment</time_frame>
    <description>A standardized 6-minute walk test (6MWT) was performed in accordance with the guidelines of the American Thoracic Society 2002. The distance walked in six minutes (6MWD) was recorded. Change from baseline to end of treatment epoch (48 weeks of treatment) in 6MWD was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Distance Saturation Product</measure>
    <time_frame>From baseline up to 48 weeks post first dose of study treatment</time_frame>
    <description>Distance saturation product is the product of distance walked and lowest oxygen saturation during the 6-min walk test. Change from baseline to end of treatment epoch (48 weeks of treatment) in distance saturation product was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Resting Oxygen Saturation Level (on Room Air)</measure>
    <time_frame>From baseline up to 48 weeks post first dose of study treatment</time_frame>
    <description>Change from baseline to end of treatment epoch (48 weeks of treatment) in resting oxygen saturation (on room air) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Positive Serum Anti-VAY736 Antibodies</measure>
    <time_frame>Day 1, 29, 85, 169, 253 and 337</time_frame>
    <description>Number of participants with positive serum anti-VAY736 antibodies. A bridging ELISA method that is designed to detect the presence of anti-VAY736 antibodies in human serum was used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ctrough of VAY736 From the Serum Concentration-time Data</measure>
    <time_frame>At pre-dose on Day 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 and 337</time_frame>
    <description>The lowest serum concentration of VAY736 observed during a dosing interval at steady state (Ctrough) was determined</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Idiopathic Pulmonary Fibrosis</condition>
  <arm_group>
    <arm_group_label>VAY736</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>VAY736</intervention_name>
    <description>300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks</description>
    <arm_group_label>VAY736</arm_group_label>
    <other_name>Ianalumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo administered subcutaneously every 4 weeks for 48 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of Care (SoC)</intervention_name>
    <description>Background standard-of-care treatment for IPF: nintedanib, pirfenidone, or no background therapy</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>VAY736</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A diagnosis of definite or probable IPF within 5 years of the screening visit&#xD;
&#xD;
          -  Forced Vital Capacity (FVC) 40-90% predicted (inclusive)&#xD;
&#xD;
          -  Diffusing Capacity of the Lungs (DLCO), corrected for hemoglobin, 25-79% predicted&#xD;
             (inclusive)&#xD;
&#xD;
          -  Forced Expiratory Volume in first second (FEV1)/FVC &gt;70%&#xD;
&#xD;
          -  Unlikely to die from cause other than IPF within the next 3 years, in the opinion of&#xD;
             the investigator&#xD;
&#xD;
          -  Unlikely to undergo lung transplantation during this trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Emphysema &gt; fibrosis on screening high-resolution computed tomography (must be&#xD;
             confirmed by central reader)&#xD;
&#xD;
          -  History of major organ, hematopoietic stem cell or bone marrow transplant&#xD;
&#xD;
          -  Clinically diagnosed acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) or&#xD;
             other significant clinical worsening within 3 months of randomization&#xD;
&#xD;
          -  New York Heart Association (NYHA) class III/IV Congestive Heart Failure (CHF),&#xD;
             Ejection Fraction (EF) &lt;25%&#xD;
&#xD;
          -  Current smoker&#xD;
&#xD;
          -  Prior use of any B-cell depleting therapy (e.g., rituximab, ofatumumab, or other&#xD;
             anti-CD20 mAb, anti-CD40, anti-CD19,anti-CD22 mAb, anti-CD52 mAb, or anti-BAFF mAb)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294-0007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 2T9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Coswig</city>
        <zip>01640</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dublin</city>
        <zip>D04</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Forli</city>
        <state>FC</state>
        <zip>47100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Modena</city>
        <state>MO</state>
        <zip>41124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Siena</city>
        <state>SI</state>
        <zip>53100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cambridge</city>
        <state>Cambridgeshire</state>
        <zip>CB23 3RE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>High Heaton</city>
        <state>Newcastle Upon Tyne</state>
        <zip>NE7 7DN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Germany</country>
    <country>Ireland</country>
    <country>Italy</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>France</country>
  </removed_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <results_first_submitted>February 13, 2023</results_first_submitted>
  <results_first_submitted_qc>February 13, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 10, 2023</results_first_posted>
  <disposition_first_submitted>October 26, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>October 26, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">October 28, 2021</disposition_first_posted>
  <last_update_submitted>February 13, 2023</last_update_submitted>
  <last_update_submitted_qc>February 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>idiopathic pulmonary fibrosis</keyword>
  <keyword>VAY736</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Fibrosis</mesh_term>
    <mesh_term>Idiopathic Pulmonary Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </patient_data>
  <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>March 23, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT03287414/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>August 6, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT03287414/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted across 16 centers in 6 countries.</recruitment_details>
      <pre_assignment_details>A total of 142 participants were screened of which 30 participants were randomized. 1 participant in the VAY736 arm did not receive treatment as the patient withdrew consent before first dosing. Treatment epoch (duration of up to 48 weeks) was followed by: i) PK/safety follow-up epoch with duration of 20 weeks, and ii) PD/safety follow-up (only for participants who had received VAY736) until participants met pre-specified criteria for B-Cell recover or up to 2 years from the last dose of VAY736.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>VAY736</title>
          <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Treatment Epoch</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study terminated by sponsor</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject/Guardian decision</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Discontinued early with reason &quot;other&quot; selected</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>PK/Safety Follow-up Epoch</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>PD/Safety Follow-up Epoch</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject/Guardian decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline characteristics are provided for all participants who received at least one dose of any study drug</population>
      <group_list>
        <group group_id="B1">
          <title>VAY736</title>
          <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="13"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="29"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69.7" spread="9.30"/>
                    <measurement group_id="B2" value="68.3" spread="8.15"/>
                    <measurement group_id="B3" value="68.9" spread="8.55"/>
                  </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 group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Forced Vital Capacity (FVC).</title>
        <description>FVC was defined as the maximum amount of air that an individual was able to forcibly exhale from his / her lungs after taking the deepest breath they could. Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
        <time_frame>From baseline up to 48 weeks post first dose of study treatment</time_frame>
        <population>Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>VAY736</title>
            <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Forced Vital Capacity (FVC).</title>
          <description>FVC was defined as the maximum amount of air that an individual was able to forcibly exhale from his / her lungs after taking the deepest breath they could. Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
          <population>Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.</population>
          <units>Liter (L)</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.039" spread="0.1116"/>
                    <measurement group_id="O2" value="-0.023" spread="0.0773"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3248</p_value>
            <p_value_desc>1-sided p-values were obtained using MMRM Model.</p_value_desc>
            <method>MMRM</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>0.063</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.1379</dispersion_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.115</ci_lower_limit>
            <ci_upper_limit>0.241</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With All-cause Mortality Events</title>
        <description>All-cause mortality events were defined as deaths due to any cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
        <time_frame>Up to 48 weeks post first dose of study treatment</time_frame>
        <population>PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.</population>
        <group_list>
          <group group_id="O1">
            <title>VAY736</title>
            <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With All-cause Mortality Events</title>
          <description>All-cause mortality events were defined as deaths due to any cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
          <population>PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>80% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.3" lower_limit="2.39" upper_limit="26.92"/>
                    <measurement group_id="O2" value="0" lower_limit="NA" upper_limit="NA">NA: Not estimable because no events occurred within this group</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.868</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Survival Idiopathic Pulmonary Fibrosis (IPF) -Related Mortality Events</title>
        <description>IPF-related mortality events were defined as deaths due to IPF related cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
        <time_frame>Up to 48 weeks post first dose of study treatment</time_frame>
        <population>PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.</population>
        <group_list>
          <group group_id="O1">
            <title>VAY736</title>
            <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Survival Idiopathic Pulmonary Fibrosis (IPF) -Related Mortality Events</title>
          <description>IPF-related mortality events were defined as deaths due to IPF related cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
          <population>PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>80% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="NA" upper_limit="NA">NA: Not estimable because no events occurred within this group</measurement>
                    <measurement group_id="O2" value="0" lower_limit="NA" upper_limit="NA">NA: Not estimable because no events occurred within this group</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Progression-free Survival (PFS) Events</title>
        <description>PFS events were divided into: 1) PFS1 events including progression (relative reduction in FVC ≥ 10%) or death due to all causes, and 2) PFS2 events including progression (relative reduction in FVC ≥ 10%) or death due to IPF-related causes. Kaplan-Meier estimates of the percentage of participants with the event of interest (PFS1 events or PFS2 events) along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
        <time_frame>Up to 48 weeks post first dose of study treatment</time_frame>
        <population>PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.</population>
        <group_list>
          <group group_id="O1">
            <title>VAY736</title>
            <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Progression-free Survival (PFS) Events</title>
          <description>PFS events were divided into: 1) PFS1 events including progression (relative reduction in FVC ≥ 10%) or death due to all causes, and 2) PFS2 events including progression (relative reduction in FVC ≥ 10%) or death due to IPF-related causes. Kaplan-Meier estimates of the percentage of participants with the event of interest (PFS1 events or PFS2 events) along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
          <population>PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>80% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PFS1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.0" lower_limit="38.22" upper_limit="84.20"/>
                    <measurement group_id="O2" value="31.9" lower_limit="18.04" upper_limit="52.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PFS2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.1" lower_limit="33.44" upper_limit="82.86"/>
                    <measurement group_id="O2" value="31.9" lower_limit="18.04" upper_limit="52.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>PFS1</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.921</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>2.6</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.1</ci_lower_limit>
            <ci_upper_limit>6.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>PFS2</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.863</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>2.2</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.9</ci_lower_limit>
            <ci_upper_limit>5.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Disease Progression Events</title>
        <description>The following disease progression events were considered: a) relative reduction in FVC ≥ 10%; b) relative reduction in Diffusing Capacity of the Lungs (DLCO) ≥ 15%; c) absolute reduction in Six Minute Walk Distance (6MWD) ≥ 50 m. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
        <time_frame>Up to 48 weeks post first dose of study treatment</time_frame>
        <population>PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.</population>
        <group_list>
          <group group_id="O1">
            <title>VAY736</title>
            <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Disease Progression Events</title>
          <description>The following disease progression events were considered: a) relative reduction in FVC ≥ 10%; b) relative reduction in Diffusing Capacity of the Lungs (DLCO) ≥ 15%; c) absolute reduction in Six Minute Walk Distance (6MWD) ≥ 50 m. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
          <population>PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>80% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>FVC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.1" lower_limit="33.44" upper_limit="82.86"/>
                    <measurement group_id="O2" value="31.9" lower_limit="18.04" upper_limit="52.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DLCO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73.8" lower_limit="46.56" upper_limit="94.24"/>
                    <measurement group_id="O2" value="56.1" lower_limit="38.65" upper_limit="75.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6MWD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.3" lower_limit="19.96" upper_limit="64.88"/>
                    <measurement group_id="O2" value="75.0" lower_limit="58.52" upper_limit="88.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>FVC</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.863</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>2.2</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.9</ci_lower_limit>
            <ci_upper_limit>5.6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>DLCO</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.457</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.9</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.4</ci_lower_limit>
            <ci_upper_limit>2.0</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6MWD</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.019</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.3</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.1</ci_lower_limit>
            <ci_upper_limit>0.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Composite Events</title>
        <description>Composite events were defined as: 1) death (all-cause mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 1); and 2) Death (IPF-related mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 2). Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
        <time_frame>Up to 48 weeks post first dose of study treatment</time_frame>
        <population>PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.</population>
        <group_list>
          <group group_id="O1">
            <title>VAY736</title>
            <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Composite Events</title>
          <description>Composite events were defined as: 1) death (all-cause mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 1); and 2) Death (IPF-related mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 2). Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.</description>
          <population>PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>80% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Composite Endpoint 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.0" lower_limit="63.86" upper_limit="93.29"/>
                    <measurement group_id="O2" value="66.3" lower_limit="50.84" upper_limit="81.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Composite Endpoint 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.2" lower_limit="61.07" upper_limit="92.70"/>
                    <measurement group_id="O2" value="66.3" lower_limit="50.84" upper_limit="81.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Composite Endpoint 1</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.611</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.1</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.6</ci_lower_limit>
            <ci_upper_limit>2.0</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Composite Endpoint 2</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.549</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.1</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.6</ci_lower_limit>
            <ci_upper_limit>1.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Diffusing Capacity of the Lungs</title>
        <description>DLCO is a measurement to assess the lungs' ability to transfer gas from inspired air to the bloodstream. DLCO was determined according to ATS guidelines. Change from baseline to end of treatment epoch (48 weeks of treatment) in diffusing capacity of the lung for carbon monoxide (DLCO) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement.&#xD;
Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
        <time_frame>From baseline up to 48 weeks post first dose of study treatment</time_frame>
        <population>Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>VAY736</title>
            <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Diffusing Capacity of the Lungs</title>
          <description>DLCO is a measurement to assess the lungs' ability to transfer gas from inspired air to the bloodstream. DLCO was determined according to ATS guidelines. Change from baseline to end of treatment epoch (48 weeks of treatment) in diffusing capacity of the lung for carbon monoxide (DLCO) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement.&#xD;
Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
          <population>Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.</population>
          <units>mililiter/minute/millimeter Mercury</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.954" spread="1.0816"/>
                    <measurement group_id="O2" value="-1.033" spread="0.7244"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.7576</p_value>
            <p_value_desc>1-sided p-values were obtained using MMRM Model.</p_value_desc>
            <method>MMRM</method>
            <param_type>Least Squares of the Mean</param_type>
            <param_value>-0.920</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.3109</dispersion_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.615</ci_lower_limit>
            <ci_upper_limit>0.774</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in 6-minute Walk Distance (6MWD)</title>
        <description>A standardized 6-minute walk test (6MWT) was performed in accordance with the guidelines of the American Thoracic Society 2002. The distance walked in six minutes (6MWD) was recorded. Change from baseline to end of treatment epoch (48 weeks of treatment) in 6MWD was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
        <time_frame>From baseline up to 48 weeks post first dose of study treatment</time_frame>
        <population>Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>VAY736</title>
            <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in 6-minute Walk Distance (6MWD)</title>
          <description>A standardized 6-minute walk test (6MWT) was performed in accordance with the guidelines of the American Thoracic Society 2002. The distance walked in six minutes (6MWD) was recorded. Change from baseline to end of treatment epoch (48 weeks of treatment) in 6MWD was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
          <population>Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.</population>
          <units>Meter (m)</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.743" spread="53.5268"/>
                    <measurement group_id="O2" value="-12.479" spread="28.9400"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3018</p_value>
            <p_value_desc>1-sided p-values were obtained using MMRM Model.</p_value_desc>
            <method>MMRM</method>
            <param_type>Least Squares of the Mean</param_type>
            <param_value>32.222</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>61.8632</dispersion_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-47.572</ci_lower_limit>
            <ci_upper_limit>112.015</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Distance Saturation Product</title>
        <description>Distance saturation product is the product of distance walked and lowest oxygen saturation during the 6-min walk test. Change from baseline to end of treatment epoch (48 weeks of treatment) in distance saturation product was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
        <time_frame>From baseline up to 48 weeks post first dose of study treatment</time_frame>
        <population>Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>VAY736</title>
            <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Distance Saturation Product</title>
          <description>Distance saturation product is the product of distance walked and lowest oxygen saturation during the 6-min walk test. Change from baseline to end of treatment epoch (48 weeks of treatment) in distance saturation product was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
          <population>Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.</population>
          <units>Meter% (m%)</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.746" spread="52.2985"/>
                    <measurement group_id="O2" value="-19.420" spread="28.3755"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3140</p_value>
            <p_value_desc>1-sided p-values were obtained using MMRM Model.</p_value_desc>
            <method>MMRM</method>
            <param_type>Least Squares of the Mean</param_type>
            <param_value>29.166</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>60.0143</dispersion_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-48.220</ci_lower_limit>
            <ci_upper_limit>106.553</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Resting Oxygen Saturation Level (on Room Air)</title>
        <description>Change from baseline to end of treatment epoch (48 weeks of treatment) in resting oxygen saturation (on room air) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
        <time_frame>From baseline up to 48 weeks post first dose of study treatment</time_frame>
        <population>Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>VAY736</title>
            <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Resting Oxygen Saturation Level (on Room Air)</title>
          <description>Change from baseline to end of treatment epoch (48 weeks of treatment) in resting oxygen saturation (on room air) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.</description>
          <population>Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.</population>
          <units>Percentage (%)</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.117" spread="1.0179"/>
                    <measurement group_id="O2" value="-1.887" spread="0.9415"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1269</p_value>
            <p_value_desc>1-sided p-values were obtained using MMRM Model.</p_value_desc>
            <method>MMRM</method>
            <param_type>Least Squares of the mean</param_type>
            <param_value>1.770</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.5422</dispersion_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.219</ci_lower_limit>
            <ci_upper_limit>3.759</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Positive Serum Anti-VAY736 Antibodies</title>
        <description>Number of participants with positive serum anti-VAY736 antibodies. A bridging ELISA method that is designed to detect the presence of anti-VAY736 antibodies in human serum was used.</description>
        <time_frame>Day 1, 29, 85, 169, 253 and 337</time_frame>
        <population>Immunogenicity (IG) analysis set including all participants with at least one available valid (i.e. not flagged for exclusion) IG concentration measurement, who received any study drug and with no protocol deviations that impact on IG data.</population>
        <group_list>
          <group group_id="O1">
            <title>VAY736</title>
            <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Positive Serum Anti-VAY736 Antibodies</title>
          <description>Number of participants with positive serum anti-VAY736 antibodies. A bridging ELISA method that is designed to detect the presence of anti-VAY736 antibodies in human serum was used.</description>
          <population>Immunogenicity (IG) analysis set including all participants with at least one available valid (i.e. not flagged for exclusion) IG concentration measurement, who received any study drug and with no protocol deviations that impact on IG data.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29</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>Day 85</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>Day 169</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 253</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 337</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>Secondary</type>
        <title>Ctrough of VAY736 From the Serum Concentration-time Data</title>
        <description>The lowest serum concentration of VAY736 observed during a dosing interval at steady state (Ctrough) was determined</description>
        <time_frame>At pre-dose on Day 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 and 337</time_frame>
        <population>Overall number of participants analyzed represents the Pharmacokinetic (PK) analysis set including all participants with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement who received at least one dose of VAY736 and with no protocol deviations that impact on PK data. The number of participants analyzed in each row represents the number of participants with a valid value in the corresponding time point.</population>
        <group_list>
          <group group_id="O1">
            <title>VAY736</title>
            <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Ctrough of VAY736 From the Serum Concentration-time Data</title>
          <description>The lowest serum concentration of VAY736 observed during a dosing interval at steady state (Ctrough) was determined</description>
          <population>Overall number of participants analyzed represents the Pharmacokinetic (PK) analysis set including all participants with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement who received at least one dose of VAY736 and with no protocol deviations that impact on PK data. The number of participants analyzed in each row represents the number of participants with a valid value in the corresponding time point.</population>
          <units>nanogram (ng) / mililiter (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="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="676.79" spread="499.931"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="779.89" spread="645.363"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 85</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="786.63" spread="501.225"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 113</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="771.88" spread="623.268"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 141</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="1316.05" spread="877.240"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 169</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1019.00" spread="587.097"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 197</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="985.50" spread="495.652"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 225</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="1271.10" spread="863.055"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 253</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="998.57" spread="947.343"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 281</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="705.00" spread="997.021"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 309</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="827.40" spread="678.836"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 337</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="688.50" spread="1172.124"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From baseline up to end of study, assessed up to approximately 2.4 years</time_frame>
      <desc>Safety analyses were performed in the safety set including all participants who received at least one dose of any study drug</desc>
      <group_list>
        <group group_id="E1">
          <title>VAY736</title>
          <description>Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy</description>
        </group>
        <group group_id="E3">
          <title>Total</title>
          <description>Total</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (25.0)</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="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic valve incompetence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Retinal vein occlusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Idiopathic pulmonary fibrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Vasculitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (25.0)</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="13" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="28" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Eosinophilia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic valve incompetence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Arteriosclerosis coronary artery</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Eustachian tube dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Corneal degeneration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Ocular hyperaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Enteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Frequent bowel movements</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Injection site bruising</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Injection site dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Injection site inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Injection site pruritus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Injection site rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Injection site warmth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Facial bones fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Heat stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Injection related reaction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Sunburn</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Antinuclear antibody increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood parathyroid hormone decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood potassium increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood triglycerides increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood urine present</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Escherichia test positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Glucose urine present</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Mean cell volume increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Monocyte count increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Neutrophil count increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Protein urine present</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Urine albumin/creatinine ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Urine analysis abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Urine protein/creatinine ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Vitamin D deficiency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Limb discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dysplastic naevus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Keratoacanthoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Carotid artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Cervical radiculopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Cognitive disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Idiopathic pulmonary fibrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dermatitis atopic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Drug eruption</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Keloid scar</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Photosensitivity reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Rash erythematous</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Skin lesion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
      <email>novartis.email@novartis.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/NCT03287414
org study id: CVAY736X2207
secondary id: 2017 002667 17
nct id: NCT03287414
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study was to investigate the safety, tolerability and efficacy of VAY736
      as potential therapy for the treatment of idiopathic pulmonary fibrosis (IPF).
This was an exploratory (non-confirmatory) randomized, patient-, investigator-, sponsor-
      blinded, placebo controlled study of VAY736 in IPF patients. This study investigated the
      safety and efficacy of 300 mg VAY736 administered subcutaneously (s.c.) every 4 weeks for 48
      weeks.

      Participants were randomized in a 1:1 ratio on top of local standard of care (SOC), to
      receive VAY736 or placebo. Randomized subjects entered the treatment epoch (for up to 48
      weeks), followed by two follow-up epochs: the PK/safety follow-up epoch and the PD/safety
      follow-up epoch. The PK/safety follow-up epoch lasted for 20 weeks. When the PK/safety
      follow-up epoch was completed, participants in the placebo arm were discharged from the
      study; but participants in the active arm (those who had received VAY736) continued into the
      PD/safety follow-up epoch. Participants in the PD/safety follow-up epoch were followed until
      B-cell recovery (in the peripheral blood), defined as: B cells >=50/μL or B cells >= 80% of
      baseline (whichever occurred first). If a participant had not recovered his/her B-cells after
      a period of 2 years from the last dose of VAY736, then this participant was discharged from
      the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Forced Vital Capacity (FVC).
time frame: From baseline up to 48 weeks post first dose of study treatment
description: FVC was defined as the maximum amount of air that an individual was able to forcibly exhale from his / her lungs after taking the deepest breath they could. Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
measure: Percentage of Participants With All-cause Mortality Events
time frame: Up to 48 weeks post first dose of study treatment
description: All-cause mortality events were defined as deaths due to any cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.
measure: Percentage of Participants With Survival Idiopathic Pulmonary Fibrosis (IPF) -Related Mortality Events
time frame: Up to 48 weeks post first dose of study treatment
description: IPF-related mortality events were defined as deaths due to IPF related cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.
measure: Percentage of Participants With Progression-free Survival (PFS) Events
time frame: Up to 48 weeks post first dose of study treatment
description: PFS events were divided into: 1) PFS1 events including progression (relative reduction in FVC ≥ 10%) or death due to all causes, and 2) PFS2 events including progression (relative reduction in FVC ≥ 10%) or death due to IPF-related causes. Kaplan-Meier estimates of the percentage of participants with the event of interest (PFS1 events or PFS2 events) along with 80% two-sided confidence intervals using Greenwood's formula are provided.
measure: Percentage of Participants With Disease Progression Events
time frame: Up to 48 weeks post first dose of study treatment
description: The following disease progression events were considered: a) relative reduction in FVC ≥ 10%; b) relative reduction in Diffusing Capacity of the Lungs (DLCO) ≥ 15%; c) absolute reduction in Six Minute Walk Distance (6MWD) ≥ 50 m. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.
measure: Percentage of Participants With Composite Events
time frame: Up to 48 weeks post first dose of study treatment
description: Composite events were defined as: 1) death (all-cause mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 1); and 2) Death (IPF-related mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 2). Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.
measure: Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Diffusing Capacity of the Lungs
time frame: From baseline up to 48 weeks post first dose of study treatment
description: DLCO is a measurement to assess the lungs' ability to transfer gas from inspired air to the bloodstream. DLCO was determined according to ATS guidelines. Change from baseline to end of treatment epoch (48 weeks of treatment) in diffusing capacity of the lung for carbon monoxide (DLCO) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement.
Baseline was defined as the last available assessment pre-dose before or on randomization date.
measure: Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in 6-minute Walk Distance (6MWD)
time frame: From baseline up to 48 weeks post first dose of study treatment
description: A standardized 6-minute walk test (6MWT) was performed in accordance with the guidelines of the American Thoracic Society 2002. The distance walked in six minutes (6MWD) was recorded. Change from baseline to end of treatment epoch (48 weeks of treatment) in 6MWD was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
measure: Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Distance Saturation Product
time frame: From baseline up to 48 weeks post first dose of study treatment
description: Distance saturation product is the product of distance walked and lowest oxygen saturation during the 6-min walk test. Change from baseline to end of treatment epoch (48 weeks of treatment) in distance saturation product was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
measure: Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Resting Oxygen Saturation Level (on Room Air)
time frame: From baseline up to 48 weeks post first dose of study treatment
description: Change from baseline to end of treatment epoch (48 weeks of treatment) in resting oxygen saturation (on room air) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
measure: Number of Participants With Positive Serum Anti-VAY736 Antibodies
time frame: Day 1, 29, 85, 169, 253 and 337
description: Number of participants with positive serum anti-VAY736 antibodies. A bridging ELISA method that is designed to detect the presence of anti-VAY736 antibodies in human serum was used.
measure: Ctrough of VAY736 From the Serum Concentration-time Data
time frame: At pre-dose on Day 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 and 337
description: The lowest serum concentration of VAY736 observed during a dosing interval at steady state (Ctrough) was determined
arm group label: VAY736
arm group type: Experimental
description: Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy
intervention type: Drug
intervention name: VAY736
description: 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks
arm group label: VAY736
other name: Ianalumab
intervention type: Drug
intervention name: Placebo
description: Placebo administered subcutaneously every 4 weeks for 48 weeks
arm group label: Placebo
intervention type: Drug
intervention name: Standard of Care (SoC)
description: Background standard-of-care treatment for IPF: nintedanib, pirfenidone, or no background therapy
arm group label: Placebo
arm group label: VAY736
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
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country: Canada
country: Germany
country: Ireland
country: Italy
country: United Kingdom
country: United States
country: France
responsible party type: Sponsor
mesh term: Pulmonary Fibrosis
mesh term: Idiopathic Pulmonary Fibrosis
mesh term: Fibrosis
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 