<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/NCT04460105</url>
  </required_header>
  <id_info>
    <org_study_id>TAK-743-1002</org_study_id>
    <nct_id>NCT04460105</nct_id>
  </id_info>
  <brief_title>Lanadelumab in Participants Hospitalized With COVID-19 Pneumonia</brief_title>
  <official_title>A Phase 1b, Randomized, Double-blind, Single and Repeat Dosing Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab When Added to Standard-of-Care in Subjects Hospitalized With COVID-19 Pneumonia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shire</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Takeda Development Center Americas, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety, pharmacokinetic and pharmacodynamics of&#xD;
      lanadelumab administered by intravenous (IV) infusion when added to standard-of-care (SoC) in&#xD;
      adults hospitalized with COVID-19 pneumonia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study consists of two cohorts (Cohort 1 [Single-dose Cohort], and Cohort 2 [Repeat-dose&#xD;
      Cohort]). Up to approximately 24 participants will be enrolled in this study, in which up to&#xD;
      12 participants may be enrolled into Cohort 1. However, Cohort 1 will be closed upon&#xD;
      implementation of Amendment 2. Approximately 12 participants will be enrolled in Cohort 2.&#xD;
      Participants will be randomized in 3:1 ratio (9 lanadelumab: 3 placebo) in each Cohort.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study was withdrawn due to challenges in site recruitment and lack of patient enrollment&#xD;
  </why_stopped>
  <start_date type="Anticipated">October 31, 2020</start_date>
  <completion_date type="Anticipated">January 27, 2021</completion_date>
  <primary_completion_date type="Anticipated">January 27, 2021</primary_completion_date>
  <phase>Phase 1</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Treatment emergent adverse events (TEAEs)</measure>
    <time_frame>From start of study drug administration to follow-up (up to Day 29)</time_frame>
    <description>Treatment-emergent adverse events are defined as Adverse events (AEs) with onset at the time of or following the start of treatment with study medication, or medical conditions present prior to the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose: results in death, is lifethreatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. Number of participants with TEAEs including AESI and SAE will be assessed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab</measure>
    <time_frame>Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 1, 24, 72, 73, 144, 216, 336 hours post-dose</time_frame>
    <description>Pharmacokinetic plasma concentrations of lanadelumab after a single and repeat intravenous (IV) doses will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change from Baseline in Plasma Kallikrein Activity (pKal)</measure>
    <time_frame>Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose</time_frame>
    <description>Percentage change from baseline in pKal activity to assess pharmacodynamics (PD) of lanadelumab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change from Baseline in Cleaved High Molecular Weight Kininogen (cHMWK)</measure>
    <time_frame>Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose</time_frame>
    <description>Percentage change from baseline in cHMWK levels to assess PD of lanadelumab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change from Baseline in Functional C1-Inhibitor (C1-INH)</measure>
    <time_frame>Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose</time_frame>
    <description>Percentage change from baseline in functional C1-INH levels to assess PD of lanadelumab.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>COVID-19 Pneumonia</condition>
  <arm_group>
    <arm_group_label>Lanadelumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive 300 milligram (mg) of lanadelumab intravenous (IV) infusion on Day 1 during Cohort 1 (single dose cohort) and on Day 1 and Day 4 during Cohort 2 (repeat-dose cohort).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive placebo matching IV infusion on Day 1 during Cohort 1 (single dose cohort) and on Day 1 and Day 4 during Cohort 2 (repeat-dose cohort).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lanadelumab</intervention_name>
    <description>Participants will receive 300 mg of lanadelumab IV infusion on Day 1 and Day 4.</description>
    <arm_group_label>Lanadelumab</arm_group_label>
    <other_name>SHP643</other_name>
    <other_name>TAK-743</other_name>
    <other_name>DX-2930</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive placebo matching IV infusion on Day 1 and Day 4.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females 18 years of age or older at the time of signing of the informed&#xD;
             consent form (ICF).&#xD;
&#xD;
          -  Hospitalized with evidence of COVID-19 pneumonia defined as:&#xD;
&#xD;
               1. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection documented&#xD;
                  with polymerase chain reaction (PCR) of any specimen; e.g. respiratory, blood,&#xD;
                  urine, stool, other body fluid&#xD;
&#xD;
               2. Presence of respiratory distress as indicated by peripheral capillary oxygen&#xD;
                  saturation (SpO2) lesser than or equal to (=&lt;) 93 percent (%) on room air or&#xD;
                  respiratory rate greater than or equal to (&gt;=) 30 breaths per minute&#xD;
                  (breaths/min).&#xD;
&#xD;
          -  The participant (or a legally acceptable representative) has provided written informed&#xD;
             consent approved by the institutional review board (IRB)/ independent ethics committee&#xD;
             (IEC) before any study-specific procedures are performed.&#xD;
&#xD;
          -  Agree to adhere to the protocol-defined schedule of treatments, assessments, and&#xD;
             procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Invasive mechanical ventilation (IMV) extracorporeal membrane oxygenation (ECMO) or&#xD;
             with evidence of severe respiratory distress such that IMV/ECMO is imminent within 12&#xD;
             hours of randomization.&#xD;
&#xD;
          -  Where, in the opinion of the investigator, progression to death is imminent and&#xD;
             inevitable within the next 24 hours, irrespective of the provision of treatments.&#xD;
&#xD;
          -  Requiring vasopressor support (use of fluid support is not exclusionary)&#xD;
&#xD;
          -  Known or suspected venous thromboembolism.&#xD;
&#xD;
          -  Known or suspected hypersensitivity to lanadelumab or any of its excipients.&#xD;
&#xD;
          -  Dosing with an investigational drug or exposure to an investigational device within 4&#xD;
             weeks prior to screening.&#xD;
&#xD;
          -  Previous (within 3 months of screening) or current use of immunomodulators (e.g.&#xD;
             methotrexate, azathioprine, 6-mercaptopurine, tumor necrosis factor [TNF] alpha&#xD;
             inhibitor, Janus kinase [JAK] inhibitor, alpha-integrin).&#xD;
&#xD;
          -  Previous (within 3 months of screening) or current use of plasma kallikrein inhibitor&#xD;
             or bradykinin receptor blocker.&#xD;
&#xD;
          -  Use of supplemental oxygen for a medical condition prior to receiving COVID-19&#xD;
             diagnosis.&#xD;
&#xD;
          -  Previously diagnosed with acquired immunodeficiency syndrome (AIDS).&#xD;
&#xD;
          -  Active tuberculosis or clinical suspicion of latent tuberculosis.&#xD;
&#xD;
          -  Any of the following laboratory abnormalities at screening:&#xD;
&#xD;
               1. Hemoglobin &lt;= 8 grams per deciliter (g/dL)&#xD;
&#xD;
               2. White blood cells &lt;= 3000/ microliters (μL)&#xD;
&#xD;
               3. Platelets &lt;= 75,000/μL&#xD;
&#xD;
               4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) &gt;= 3×upper&#xD;
                  limit of normal (ULN); alkaline phosphatase (ALP) &gt;= 3×ULN; or total bilirubin&#xD;
                  greater than (&gt;) 2×ULN (unless the bilirubin elevation is a result of Gilbert's&#xD;
                  syndrome)&#xD;
&#xD;
               5. Creatinine &gt;= 2×ULN&#xD;
&#xD;
          -  Pregnant or breastfeeding.&#xD;
&#xD;
          -  Any significant condition (any surgical or medical condition) that, in the opinion of&#xD;
             the investigator or sponsor, may compromise their safety or compliance, preclude the&#xD;
             successful conduct of the study, or interfere with interpretation of the results (e.g.&#xD;
             significant pre-existing illness or other major comorbidities that the investigator&#xD;
             considers may confound the interpretation of study results).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda Development Center Americas, Inc.</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>October 9, 2020</last_update_submitted>
  <last_update_submitted_qc>October 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Pneumonia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_access_criteria>IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04460105
org study id: TAK-743-1002
nct id: NCT04460105
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the safety, pharmacokinetic and pharmacodynamics of
      lanadelumab administered by intravenous (IV) infusion when added to standard-of-care (SoC) in
      adults hospitalized with COVID-19 pneumonia.
This study consists of two cohorts (Cohort 1 [Single-dose Cohort], and Cohort 2 [Repeat-dose
      Cohort]). Up to approximately 24 participants will be enrolled in this study, in which up to
      12 participants may be enrolled into Cohort 1. However, Cohort 1 will be closed upon
      implementation of Amendment 2. Approximately 12 participants will be enrolled in Cohort 2.
      Participants will be randomized in 3:1 ratio (9 lanadelumab: 3 placebo) in each Cohort.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Number of Participants with Treatment emergent adverse events (TEAEs)
time frame: From start of study drug administration to follow-up (up to Day 29)
description: Treatment-emergent adverse events are defined as Adverse events (AEs) with onset at the time of or following the start of treatment with study medication, or medical conditions present prior to the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose: results in death, is lifethreatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. Number of participants with TEAEs including AESI and SAE will be assessed.
measure: Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab
time frame: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 1, 24, 72, 73, 144, 216, 336 hours post-dose
description: Pharmacokinetic plasma concentrations of lanadelumab after a single and repeat intravenous (IV) doses will be assessed.
measure: Percentage Change from Baseline in Plasma Kallikrein Activity (pKal)
time frame: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose
description: Percentage change from baseline in pKal activity to assess pharmacodynamics (PD) of lanadelumab.
measure: Percentage Change from Baseline in Cleaved High Molecular Weight Kininogen (cHMWK)
time frame: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose
description: Percentage change from baseline in cHMWK levels to assess PD of lanadelumab.
measure: Percentage Change from Baseline in Functional C1-Inhibitor (C1-INH)
time frame: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose
description: Percentage change from baseline in functional C1-INH levels to assess PD of lanadelumab.
arm group label: Lanadelumab
arm group type: Experimental
description: Participants receive 300 milligram (mg) of lanadelumab intravenous (IV) infusion on Day 1 during Cohort 1 (single dose cohort) and on Day 1 and Day 4 during Cohort 2 (repeat-dose cohort).
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive placebo matching IV infusion on Day 1 during Cohort 1 (single dose cohort) and on Day 1 and Day 4 during Cohort 2 (repeat-dose cohort).
intervention type: Drug
intervention name: Lanadelumab
description: Participants will receive 300 mg of lanadelumab IV infusion on Day 1 and Day 4.
arm group label: Lanadelumab
other name: SHP643
other name: TAK-743
other name: DX-2930
intervention type: Other
intervention name: Placebo
description: Participants will receive placebo matching IV infusion on Day 1 and Day 4.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Takeda Development Center Americas, Inc.
country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Pneumonia
sharing ipd: Yes
ipd description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
ipd url: https://vivli.org/ourmember/takeda/