<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/NCT03749135</url>
  </required_header>
  <id_info>
    <org_study_id>D-001-01</org_study_id>
    <secondary_id>2017-004458-41</secondary_id>
    <nct_id>NCT03749135</nct_id>
  </id_info>
  <brief_title>Dupilumab in Chronic Spontaneous Urticaria</brief_title>
  <acronym>DUPICSU</acronym>
  <official_title>A Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-concept Phase 2, 16-week Treatment Study With a 16 Week Follow-up Period to Assess the Efficacy and Safety of Dupilumab (Anti-IL4Ra) in Adult Patients With Chronic Spontaneous Urticaria Despite H1-antihistamine Treatment.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Charite University, Berlin, Germany</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Proinnovera GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Charite University, Berlin, Germany</source>
  <oversight_info>
    <has_dmc>No</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>
      The purpose of this study is to assess the efficacy in reducing disease activity and safety&#xD;
      of Dupilumab in adult patients with chronic spontaneous urticaria (CSU) who are symptomatic&#xD;
      despite H1-antihistamine treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Treatment with Dupilumab has been shown to reduce clinically significant exacerbations and to&#xD;
      improve skin symptom control as well as quality of life in moderate to severe atopic&#xD;
      dermatitis patients and in moderate to severe asthma patients. It has been approval by&#xD;
      European Medicines Agency (EMA) for the treatment of atopic dermatitis patients in September&#xD;
      2017.&#xD;
&#xD;
      Dupilumab is a novel monoclonal antibody that inhibits interleukin-4 (IL-4) and&#xD;
      interleukin-13 (IL-13) signaling and was previously found to be effective in atopic&#xD;
      dermatitis and asthma. Considering that CSU and atopic diseases share many common features&#xD;
      (e.g. key pathogenic role of mast cells and immunoglobulin E (IgE), itch is a dominant&#xD;
      symptom, Th2 dominance), it is reasonable to expect that Dupilumab is beneficial in CSU.&#xD;
&#xD;
      These results suggest that Dupilumab may provide an effective treatment option for patients&#xD;
      with insufficient treatment responses to H1-antihistamines exhibiting wheal and flare type&#xD;
      skin reactions.&#xD;
&#xD;
      The gold standard treatment of CSU consists of administration of antihistamines. In more than&#xD;
      50% of the patients, symptoms persist with standard dosing of antihistamines. In&#xD;
      antihistamine-refractory patients with chronic spontaneous urticaria, the currently only&#xD;
      licensed treatment is omalizumab, a monoclonal anti-IgE antibody. In 2014, omalizumab has&#xD;
      been licensed for add-on therapy in CSU patients who still have symptoms despite&#xD;
      standard-dosed antihistamine treatment. There is, however, still a great medical need for&#xD;
      additional treatment options, as 20-40% of patients are still without effective therapy.&#xD;
      These patients have no other licensed treatment option and can only be treated off-label with&#xD;
      therapeutics with several known safety risks such as Cyclosporine A.&#xD;
&#xD;
      Dupilumab has excellent potential to provide symptom control in CSU. This study will provide&#xD;
      additional valuable insights into the therapeutic potential of Dupilumab in improving quality&#xD;
      of life in these patients, in addition to managing CSU symptoms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 12, 2018</start_date>
  <completion_date type="Actual">July 7, 2021</completion_date>
  <primary_completion_date type="Actual">July 7, 2021</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>
    <intervention_model_description>This is a Phase 2a multicenter, randomized, double blind, placebo controlled, parallel group, two-arm, proof-of-concept investigator-initiated trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>randomized, double blind, placebo controlled</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Urticaria activity score over 7 days (UAS7)</measure>
    <time_frame>Change from 7 days prior to baseline (Visit (V) 1) to 7 days prior to week 16 (V9)</time_frame>
    <description>0-42 Points total range over 7 days, higher values equal more disease activity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Itch severity score (ISS7; 0 - no pruritus; 21 - most severe pruritus), hive severity score (HSS7; 0 - no hives; 21 - max. hive severity)</measure>
    <time_frame>Change from 7 days prior to baseline (Visit (V) 1) to 7 days prior to week 16 (V9)</time_frame>
    <description>Disease activity scores</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global assessment for disease activity</measure>
    <time_frame>Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)</time_frame>
    <description>Global assessment for disease activity(physician and patient) by visual analogue scale (VAS; 0 - no pain; 10 - max. amount of pain)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>urticaria control test (UCT; 16 - complete disease control; 0 - strong symptoms), dermatological quality of life (DLQI; 0 - no impairment; 30 - max. impairment), chronic urticaria quality of life (Cu2-QoL; 23 - no impairment; 115 - max. impairment)</measure>
    <time_frame>Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)</time_frame>
    <description>Disease specific quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responder rates (regarding disease activity and quality of live (QoL))</measure>
    <time_frame>Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)</time_frame>
    <description>Responder rates (regarding disease activity and quality of live (QoL))</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rate of angioedema burdened days angioedema activity score (AAS; 0 - lowest disease activity; 15 - highest disease activity) angioedema quality of life (AE-Qol; 0 - no impairment; 100 - worst impairment)</measure>
    <time_frame>Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]</time_frame>
    <description>For patients with concomitant angioedema</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue medication use</measure>
    <time_frame>Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]</time_frame>
    <description>Frequency of of how often rescue medication is used</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Chronic Spontaneous Urticaria</condition>
  <condition>Recurrent Angioedema</condition>
  <arm_group>
    <arm_group_label>Dupilumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dupilumab (anti-IL4Ra), s.c. administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Comparator</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>matching Placebo, s.c. administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dupilumab</intervention_name>
    <description>anti-IL4-Receptor alpha</description>
    <arm_group_label>Dupilumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo Comparator</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Diagnosis: chronic spontaneous urticaria (defined as ongoing disease)&#xD;
&#xD;
          1. Patient is informed about study procedures and medications and has given written&#xD;
             informed consent before any assessment.&#xD;
&#xD;
          2. Patient is able to communicate with the investigator, understands and complies with&#xD;
             the requirements of the study.&#xD;
&#xD;
          3. Male or Female&#xD;
&#xD;
          4. Patient is 18-75 years of age&#xD;
&#xD;
          5. Patient is diagnosed with moderate to severe CSU and refractory to standard of care&#xD;
             treatment at the time of randomization, as defined by the following:&#xD;
&#xD;
               1. The presence of itch and hives for more than 6 consecutive weeks at any time&#xD;
                  prior to enrollment despite current use of H1 antihistamine&#xD;
&#xD;
               2. Urticaria activity score UAS7 score (range 0-42) equal or more than 16, 7 days&#xD;
                  prior to randomization (Day 1)&#xD;
&#xD;
               3. CSU diagnosis for 6 months&#xD;
&#xD;
          6. Willing and able to complete a daily symptom diary for the duration of the study and&#xD;
             adhere to the study visit schedules.&#xD;
&#xD;
          7. Patients must not have more than one missing diary entry in the 7 days prior to&#xD;
             randomization. Re-screening may be considered.&#xD;
&#xD;
          8. Women of childbearing potential have to agree to use an acceptable form of&#xD;
             contraception (as determined by the site investigator) and have to continue its use&#xD;
             for the duration of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients whose urticaria is solely due to inducible urticaria.&#xD;
&#xD;
          2. Other diseases with symptoms of urticaria or angioedema, including urticarial&#xD;
             vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and&#xD;
             hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency)&#xD;
&#xD;
          3. Any other active skin disease associated with chronic itching that might confound the&#xD;
             study evaluations and results (e.g., atopic dermatitis, bullous pemphigoid, dermatitis&#xD;
             herpetiformis, etc.)&#xD;
&#xD;
          4. Patients who have received concomitant prohibited medication within the last 3 months&#xD;
             prior to screening&#xD;
&#xD;
               -  Anti-IgE therapy (e.g. omalizumab)&#xD;
&#xD;
               -  Routine (daily or every other day during 5 or more consecutive days) doses of&#xD;
                  systemic corticosteroids or other immunosuppressants&#xD;
&#xD;
               -  Intravenous immunoglobulins&#xD;
&#xD;
               -  Biological therapy&#xD;
&#xD;
               -  Systemic immunosuppressants&#xD;
&#xD;
               -  Live/attenuated vaccines&#xD;
&#xD;
               -  Other investigational drug&#xD;
&#xD;
          5. History of anaphylactic shock&#xD;
&#xD;
          6. Active helminthic parasite infection or treatment of helminthic parasites within 6&#xD;
             months of screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marcus Maurer, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Charite University, Berlin, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universitätsklinikum Giessen und Marburg</name>
      <address>
        <city>Marburg</city>
        <state>Hessen</state>
        <zip>35043</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hautklinik Universitätsklinikum Münster</name>
      <address>
        <city>Münster</city>
        <state>NRW, Germany</state>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hautklinik der Universitätsmedizin Mainz Clinical Research Center</name>
      <address>
        <city>Mainz</city>
        <state>Rheinland-Pfalz, Germany</state>
        <zip>55101</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Carl Gustav Carus</name>
      <address>
        <city>Dresden</city>
        <state>Sachsen</state>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Leipzig, Klinik für Dermatologie, Venerologie und Allergologie</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charite University, Berlin, Germany</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>July 12, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>February 1, 2022</last_update_submitted>
  <last_update_submitted_qc>February 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Charite University, Berlin, Germany</investigator_affiliation>
    <investigator_full_name>Marcus Maurer</investigator_full_name>
    <investigator_title>Research Director Prof. Dr. med. Marcus Maurer</investigator_title>
  </responsible_party>
  <keyword>hives</keyword>
  <keyword>itch</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Angioedema</mesh_term>
    <mesh_term>Urticaria</mesh_term>
    <mesh_term>Chronic Urticaria</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03749135
org study id: D-001-01
secondary id: 2017-004458-41
nct id: NCT03749135
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this study is to assess the efficacy in reducing disease activity and safety
      of Dupilumab in adult patients with chronic spontaneous urticaria (CSU) who are symptomatic
      despite H1-antihistamine treatment.
Treatment with Dupilumab has been shown to reduce clinically significant exacerbations and to
      improve skin symptom control as well as quality of life in moderate to severe atopic
      dermatitis patients and in moderate to severe asthma patients. It has been approval by
      European Medicines Agency (EMA) for the treatment of atopic dermatitis patients in September
      2017.

      Dupilumab is a novel monoclonal antibody that inhibits interleukin-4 (IL-4) and
      interleukin-13 (IL-13) signaling and was previously found to be effective in atopic
      dermatitis and asthma. Considering that CSU and atopic diseases share many common features
      (e.g. key pathogenic role of mast cells and immunoglobulin E (IgE), itch is a dominant
      symptom, Th2 dominance), it is reasonable to expect that Dupilumab is beneficial in CSU.

      These results suggest that Dupilumab may provide an effective treatment option for patients
      with insufficient treatment responses to H1-antihistamines exhibiting wheal and flare type
      skin reactions.

      The gold standard treatment of CSU consists of administration of antihistamines. In more than
      50% of the patients, symptoms persist with standard dosing of antihistamines. In
      antihistamine-refractory patients with chronic spontaneous urticaria, the currently only
      licensed treatment is omalizumab, a monoclonal anti-IgE antibody. In 2014, omalizumab has
      been licensed for add-on therapy in CSU patients who still have symptoms despite
      standard-dosed antihistamine treatment. There is, however, still a great medical need for
      additional treatment options, as 20-40% of patients are still without effective therapy.
      These patients have no other licensed treatment option and can only be treated off-label with
      therapeutics with several known safety risks such as Cyclosporine A.

      Dupilumab has excellent potential to provide symptom control in CSU. This study will provide
      additional valuable insights into the therapeutic potential of Dupilumab in improving quality
      of life in these patients, in addition to managing CSU symptoms.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a Phase 2a multicenter, randomized, double blind, placebo controlled, parallel group, two-arm, proof-of-concept investigator-initiated trial
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: randomized, double blind, placebo controlled
measure: Urticaria activity score over 7 days (UAS7)
time frame: Change from 7 days prior to baseline (Visit (V) 1) to 7 days prior to week 16 (V9)
description: 0-42 Points total range over 7 days, higher values equal more disease activity
measure: Itch severity score (ISS7; 0 - no pruritus; 21 - most severe pruritus), hive severity score (HSS7; 0 - no hives; 21 - max. hive severity)
time frame: Change from 7 days prior to baseline (Visit (V) 1) to 7 days prior to week 16 (V9)
description: Disease activity scores
measure: Global assessment for disease activity
time frame: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)
description: Global assessment for disease activity(physician and patient) by visual analogue scale (VAS; 0 - no pain; 10 - max. amount of pain)
measure: urticaria control test (UCT; 16 - complete disease control; 0 - strong symptoms), dermatological quality of life (DLQI; 0 - no impairment; 30 - max. impairment), chronic urticaria quality of life (Cu2-QoL; 23 - no impairment; 115 - max. impairment)
time frame: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)
description: Disease specific quality of life
measure: Responder rates (regarding disease activity and quality of live (QoL))
time frame: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)
description: Responder rates (regarding disease activity and quality of live (QoL))
measure: rate of angioedema burdened days angioedema activity score (AAS; 0 - lowest disease activity; 15 - highest disease activity) angioedema quality of life (AE-Qol; 0 - no impairment; 100 - worst impairment)
time frame: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]
description: For patients with concomitant angioedema
measure: Rescue medication use
time frame: Change from 7 days prior to baseline (V1) to 7 days prior to week 16 (V9)]
description: Frequency of of how often rescue medication is used
arm group label: Dupilumab
arm group type: Active Comparator
description: Dupilumab (anti-IL4Ra), s.c. administration
arm group label: Placebo Comparator
arm group type: Placebo Comparator
description: matching Placebo, s.c. administration
intervention type: Drug
intervention name: Dupilumab
description: anti-IL4-Receptor alpha
arm group label: Dupilumab
intervention type: Drug
intervention name: Placebo
description: Placebo
arm group label: Placebo Comparator
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Marcus Maurer, Prof.
role: Principal Investigator
affiliation: Charite University, Berlin, Germany
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Charite University, Berlin, Germany
investigator full name: Marcus Maurer
investigator title: Research Director Prof. Dr. med. Marcus Maurer
mesh term: Angioedema
mesh term: Urticaria
mesh term: Chronic Urticaria
sharing ipd: No