<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/NCT04426890</url>
  </required_header>
  <id_info>
    <org_study_id>CT-P39 3.1</org_study_id>
    <secondary_id>2020-000952-36</secondary_id>
    <nct_id>NCT04426890</nct_id>
  </id_info>
  <brief_title>To Compare Efficacy and Safety of CT-P39 and EU-approved Xolair in Patients With Chronic Spontaneous Urticaria</brief_title>
  <acronym>omalizumab</acronym>
  <official_title>A Double-blind, Randomized, Active-controlled, Parallel Group, Phase 3 Study to Compare Efficacy and Safety of CT-P39 and Xolair in Patients With Chronic Spontaneous Urticaria Who Remain Symptomatic Despite H1 Antihistamine Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celltrion</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Celltrion</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Double-blind, Randomized, Active-controlled, Parallel Group, Phase 3 Study to Compare&#xD;
      Efficacy and Safety of CT-P39 and Xolair in Patients with Chronic Spontaneous Urticaria Who&#xD;
      Remain Symptomatic despite H1 antihistamine Treatment&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CT-P39, containing the active ingredient omalizumab, is a recombinant humanized monoclonal&#xD;
      antibody that is being developed and manufactured as a proposed biosimilar to Xolair&#xD;
      (omalizumab) by the Sponsor. CT-P39 is identical to Xolair with respect to concentration and&#xD;
      presentation. The 150 mg of drug product (CT-P39) will have the same pharmaceutical form and&#xD;
      strength as 150 mg Xolair (in a prefilled syringe [PFS] for subcutaneous injection) and is&#xD;
      intended to have a similar quality profile compared with Xolair.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 9, 2020</start_date>
  <completion_date type="Actual">April 27, 2023</completion_date>
  <primary_completion_date type="Actual">October 21, 2022</primary_completion_date>
  <phase>Phase 3</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>Demonstrate the equivalence of efficacy</measure>
    <time_frame>Change from baseline in Weekly Itch Severity Score(ISS7) at Week 12</time_frame>
    <description>CT-P39 to EU-approved Xolair at a dose of 300 mg</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluate the relative potency CT-P39 compared to EU-approved Xolair</measure>
    <time_frame>Change from baseline in Weekly Itch Severity Score(ISS7) at Week 12</time_frame>
    <description>The relative potency of CT-P39 to the Xolair is defined as the dose of CT-P39 that produces the same biological response as one unit of the dose of the Xolair. The biological response will be estimated by the change from baseline in Weekly Itch Severity Score(ISS7) at Week 12. Since the 2 treatments will be compared at the same 2-dose levels (300 mg and 150 mg), a 4 point assay will be used to calculate the relative potency and its CI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dose response in terms of efficacy [Weekly Itch Severity Score(ISS7)]</measure>
    <time_frame>Week 8 and 24</time_frame>
    <description>The ISS will be recorded on scale of 0 (none) to 3 (severe) points. The daily ISS is the average of the morning and evening scores and the ISS7 is the sum of the daily ISS over 7 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose response in terms of efficacy [Urticaria Activity Score(UAS)]</measure>
    <time_frame>Week 8, 12, and 24</time_frame>
    <description>The UAS will be calculated as the sum of the ISS and the HSS. The sum of the scores represents disease severity on a scale from 0 (minimum) to 6 (maximum)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose response in terms of efficacy [Hives Severity Score(HSS)]</measure>
    <time_frame>Week 8, 12, and 24</time_frame>
    <description>The HSS, defined by number of hives, will be counted twice daily on a scale of 0 (none) to 3 (intense) points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose response in terms of efficacy [Angioedema-free days]</measure>
    <time_frame>Week 4 to 12</time_frame>
    <description>Percentage of patients with angioedema-free days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the pharmacokinetics (PK)</measure>
    <time_frame>prior to scheduled study drug administration at Week 0, 4, 8, 12, 16, 20 and 40(End-of-Study, EOS)</time_frame>
    <description>Trough serum concentration (Ctrough) of omalizumab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Assessment [Dermatology Life Quality Index (DLQI)]</measure>
    <time_frame>Week 0, 12 and 24</time_frame>
    <description>Change from baseline in the overall Dermatology Life Quality Index (DLQI) score. Patients will rate their dermatology symptoms as well as the impact of their skin condition on various aspect of their lives. Each question is scored from 0 (not at all) to 3 (very much). Overall score, on scale of 0 to 30.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Assessments [Chronic Urticaria Quality of Life Questionnaire (CU-Q2OL)]</measure>
    <time_frame>Week 0, 12 and 24</time_frame>
    <description>Change from baseline in the overall Chronic Urticaria Quality of Life Questionnaire (CU-Q2OL) score. Patients will rate their CSU symptoms and the impact of their CSU on various aspects of their lives. Each question is scored from 1 (not at all) to 5 (extremely), and overall raw score, on a scale of 23 to 115</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety assessment</measure>
    <time_frame>Up to Week 40(End-of-Study, EOS)</time_frame>
    <description>The summary of Adverse Events (including Serious Adverse Events)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety assessment</measure>
    <time_frame>Week 0, 12, 24 and 40(End-of-Study, EOS)</time_frame>
    <description>Immunogenicity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety assessment</measure>
    <time_frame>Week 0, 4, 8, 12, 16, 20, 24 and 40(End-of-Study, EOS)</time_frame>
    <description>Total IgE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety assessment</measure>
    <time_frame>Week 0, 4, 8, 12, 16, 20, 24 and 40(End-of-Study, EOS)</time_frame>
    <description>Free IgE</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">634</enrollment>
  <condition>Chronic Spontaneous Urticaria</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>300 mg of CT-P39 as SC injections via PFS</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>300 mg of EU-approved Xolair as SC injections via PFS</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2-1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>300 mg of CT-P39 as SC injections via PFS</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2-2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>300 mg of EU-approved Xolair as SC injections via PFS</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment period 1: 150 mg of CT-P39&#xD;
Treatment period 2: 300 mg of CT-P39</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 4</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Treatment period 1: 150 mg of EU-approved Xolair&#xD;
Treatment period 2: 300 mg of EU-approved Xolair</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CT-P39</intervention_name>
    <description>Prefilled syringe (PFS) of 1 mL solution</description>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_label>Arm 2-1</arm_group_label>
    <arm_group_label>Arm 3</arm_group_label>
    <other_name>Omalizumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>EU-approved Xolair</intervention_name>
    <description>Prefilled syringe (PFS) of 1 mL solution</description>
    <arm_group_label>Arm 2</arm_group_label>
    <arm_group_label>Arm 2-2</arm_group_label>
    <arm_group_label>Arm 4</arm_group_label>
    <other_name>Omalizumab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with CSU&#xD;
&#xD;
          -  Diagnosed as CSU refractory to H1-antihistamine&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic urticaria with clearly defined underlying etiology&#xD;
&#xD;
          -  Clinically significant allergic reaction and/or hypersensitivity to any component of&#xD;
             omalizumab&#xD;
&#xD;
          -  History of anaphylactic shock&#xD;
&#xD;
          -  History of and/or concomitant immune complex disease (including Type III&#xD;
             hypersensitivity)&#xD;
&#xD;
          -  Parasitic diseases or colonization on stool evaluation for ova and parasites&#xD;
&#xD;
          -  Unable to receive background therapy with protocol-defined antihistamines or&#xD;
             contraindicated to epinephrine&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MinJi Ma</last_name>
    <role>Study Chair</role>
    <affiliation>Celltrion, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Klinika Ambroziak ESTEDERM</name>
      <address>
        <city>Warszawa</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 19, 2023</last_update_submitted>
  <last_update_submitted_qc>June 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic Spontaneous Urticaria</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urticaria</mesh_term>
    <mesh_term>Chronic Urticaria</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Omalizumab</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04426890
org study id: CT-P39 3.1
secondary id: 2020-000952-36
nct id: NCT04426890
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
A Double-blind, Randomized, Active-controlled, Parallel Group, Phase 3 Study to Compare
      Efficacy and Safety of CT-P39 and Xolair in Patients with Chronic Spontaneous Urticaria Who
      Remain Symptomatic despite H1 antihistamine Treatment
CT-P39, containing the active ingredient omalizumab, is a recombinant humanized monoclonal
      antibody that is being developed and manufactured as a proposed biosimilar to Xolair
      (omalizumab) by the Sponsor. CT-P39 is identical to Xolair with respect to concentration and
      presentation. The 150 mg of drug product (CT-P39) will have the same pharmaceutical form and
      strength as 150 mg Xolair (in a prefilled syringe [PFS] for subcutaneous injection) and is
      intended to have a similar quality profile compared with Xolair.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Demonstrate the equivalence of efficacy
time frame: Change from baseline in Weekly Itch Severity Score(ISS7) at Week 12
description: CT-P39 to EU-approved Xolair at a dose of 300 mg
measure: Evaluate the relative potency CT-P39 compared to EU-approved Xolair
time frame: Change from baseline in Weekly Itch Severity Score(ISS7) at Week 12
description: The relative potency of CT-P39 to the Xolair is defined as the dose of CT-P39 that produces the same biological response as one unit of the dose of the Xolair. The biological response will be estimated by the change from baseline in Weekly Itch Severity Score(ISS7) at Week 12. Since the 2 treatments will be compared at the same 2-dose levels (300 mg and 150 mg), a 4 point assay will be used to calculate the relative potency and its CI.
measure: Dose response in terms of efficacy [Weekly Itch Severity Score(ISS7)]
time frame: Week 8 and 24
description: The ISS will be recorded on scale of 0 (none) to 3 (severe) points. The daily ISS is the average of the morning and evening scores and the ISS7 is the sum of the daily ISS over 7 days
measure: Dose response in terms of efficacy [Urticaria Activity Score(UAS)]
time frame: Week 8, 12, and 24
description: The UAS will be calculated as the sum of the ISS and the HSS. The sum of the scores represents disease severity on a scale from 0 (minimum) to 6 (maximum)
measure: Dose response in terms of efficacy [Hives Severity Score(HSS)]
time frame: Week 8, 12, and 24
description: The HSS, defined by number of hives, will be counted twice daily on a scale of 0 (none) to 3 (intense) points
measure: Dose response in terms of efficacy [Angioedema-free days]
time frame: Week 4 to 12
description: Percentage of patients with angioedema-free days
measure: Evaluate the pharmacokinetics (PK)
time frame: prior to scheduled study drug administration at Week 0, 4, 8, 12, 16, 20 and 40(End-of-Study, EOS)
description: Trough serum concentration (Ctrough) of omalizumab
measure: Quality of Life Assessment [Dermatology Life Quality Index (DLQI)]
time frame: Week 0, 12 and 24
description: Change from baseline in the overall Dermatology Life Quality Index (DLQI) score. Patients will rate their dermatology symptoms as well as the impact of their skin condition on various aspect of their lives. Each question is scored from 0 (not at all) to 3 (very much). Overall score, on scale of 0 to 30.
measure: Quality of Life Assessments [Chronic Urticaria Quality of Life Questionnaire (CU-Q2OL)]
time frame: Week 0, 12 and 24
description: Change from baseline in the overall Chronic Urticaria Quality of Life Questionnaire (CU-Q2OL) score. Patients will rate their CSU symptoms and the impact of their CSU on various aspects of their lives. Each question is scored from 1 (not at all) to 5 (extremely), and overall raw score, on a scale of 23 to 115
measure: Safety assessment
time frame: Up to Week 40(End-of-Study, EOS)
description: The summary of Adverse Events (including Serious Adverse Events)
measure: Safety assessment
time frame: Week 0, 12, 24 and 40(End-of-Study, EOS)
description: Immunogenicity
measure: Safety assessment
time frame: Week 0, 4, 8, 12, 16, 20, 24 and 40(End-of-Study, EOS)
description: Total IgE
measure: Safety assessment
time frame: Week 0, 4, 8, 12, 16, 20, 24 and 40(End-of-Study, EOS)
description: Free IgE
arm group label: Arm 1
arm group type: Experimental
description: 300 mg of CT-P39 as SC injections via PFS
arm group label: Arm 2
arm group type: Active Comparator
description: 300 mg of EU-approved Xolair as SC injections via PFS
arm group label: Arm 2-1
arm group type: Experimental
description: 300 mg of CT-P39 as SC injections via PFS
arm group label: Arm 2-2
arm group type: Active Comparator
description: 300 mg of EU-approved Xolair as SC injections via PFS
arm group label: Arm 3
arm group type: Experimental
description: Treatment period 1: 150 mg of CT-P39
Treatment period 2: 300 mg of CT-P39
arm group label: Arm 4
arm group type: Active Comparator
description: Treatment period 1: 150 mg of EU-approved Xolair
Treatment period 2: 300 mg of EU-approved Xolair
intervention type: Biological
intervention name: CT-P39
description: Prefilled syringe (PFS) of 1 mL solution
arm group label: Arm 1
arm group label: Arm 2-1
arm group label: Arm 3
other name: Omalizumab
intervention type: Biological
intervention name: EU-approved Xolair
description: Prefilled syringe (PFS) of 1 mL solution
arm group label: Arm 2
arm group label: Arm 2-2
arm group label: Arm 4
other name: Omalizumab
criteria: 
gender: All
minimum age: 12 Years
maximum age: 75 Years
healthy volunteers: No
last name: MinJi Ma
role: Study Chair
affiliation: Celltrion, Inc.
facility: 
country: Poland
responsible party type: Sponsor
mesh term: Urticaria
mesh term: Chronic Urticaria
mesh term: Omalizumab
mesh term: Antibodies, Monoclonal