xml: <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/NCT06042478</url>
    </required_header>
    <id_info>
      <org_study_id>CLOU064A2304</org_study_id>
      <secondary_id>2022-000518-32</secondary_id>
      <nct_id>NCT06042478</nct_id>
    </id_info>
    <brief_title>52 Weeks Double-blind, Double-dummy, Randomized Placebo-controlled Trial to Evaluate Safety, Efficacy and Tolerability of Remibrutinib in Comparison to Placebo With Omalizumab as Active Control in Adult Patients With CSU and Inadequate Response to H1-antihistamine.</brief_title>
    <official_title>A Global, Multicenter, Randomized, Double-blind, Double-dummy, Parallel-group, Phase 3b Study to Assess the Efficacy, Safety, and Tolerability of Remibrutinib 25 mg b.i.d. in Comparison to Placebo With Omalizumab 300 mg Every 4 Weeks as Active Control Over 52 Weeks in Adult Patients With Chronic Spontaneous Urticaria Inadequately Controlled by Second-generation H1-antihistamines</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>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this trial is to assess the efficacy, safety and tolerability of remibrutinib&#xD;
        (LOU064) 25 milligrams (mg) twice a day (b.i.d.) over placebo for 24 weeks and in comparison&#xD;
        to omalizumab 300 mg every 4 weeks (q4w) for 52 weeks in participants with chronic&#xD;
        spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines (H1-AH).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study consists of three periods, and the total study duration is up to 72 weeks.&#xD;
        Approximately 468 adult participants with CSU are expected to be randomized in the study.&#xD;
  &#xD;
        Screening period: A screening period of up to 4 weeks will allow for the assessment of&#xD;
        eligibility, determination of baseline disease activity and wash-out of prohibited&#xD;
        medications.&#xD;
  &#xD;
        Treatment period:&#xD;
  &#xD;
        The treatment period will be double-dummy and double-blind, with placebo injections matching&#xD;
        omalizumab 300 mg s.c. given to participants in the remibrutinib arm and placebo tablets&#xD;
        matching remibrutinib 25 mg given to participants in the omalizumab arm (double-dummy).&#xD;
  &#xD;
        At the randomization visit, eligible participants will be randomized to one of four treatment&#xD;
        arms.&#xD;
  &#xD;
        Follow-up period:&#xD;
  &#xD;
        There will be a 16-week, treatment-free, safety follow-up period (for participants who do not&#xD;
        roll-over to the extension study).&#xD;
  &#xD;
        All participants will be on a stable, local label-approved standard dose of a&#xD;
        second-generation H1-AH (&quot;background therapy&quot;) throughout the entire study (starting a&#xD;
        minimum of 7 days prior to randomization until the end of the study). In addition, to treat&#xD;
        unbearable symptoms of CSU flare-ups, participants will be allowed to use a different&#xD;
        second-generation H1-AH on an as-needed basis (&quot;rescue therapy&quot;).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 24, 2023</start_date>
    <completion_date type="Anticipated">June 23, 2026</completion_date>
    <primary_completion_date type="Anticipated">August 15, 2025</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>
      <intervention_model_description>At the randomization visit, eligible participants will be randomized to one of four treatment arms in a 2:1:1:2 ratio:&#xD;
  Remibrutinib 25 mg b.i.d. arm: participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks&#xD;
  Placebo to remibrutinib arm: participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w.&#xD;
  Placebo to omalizumab arm: participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d.&#xD;
  Omalizumab 300 mg every 4 weeks arm: participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Absolute change from baseline in UAS7</measure>
      <time_frame>Week 12</time_frame>
      <description>The UAS7 is the sum of the HSS7 score and the ISS7 score. The possible range of the weekly UAS7 score is 0 - 42 (highest activity).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Achievement of UAS7=0 (yes/no)</measure>
      <time_frame>Week 12</time_frame>
      <description>Complete UAS7 response is UAS7 = 0</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score</measure>
      <time_frame>Week 12</time_frame>
      <description>The severity of the itch will be recorded by the participant twice daily in their eDiary, on a scale of 0 (none) to 3 (severe). A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 - 21.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score</measure>
      <time_frame>Week 12</time_frame>
      <description>The hives (wheals) severity score, defined by number of hives, will be recorded by the participant twice daily in their eDiary, on a scale of 0 (none) to 3 (&gt; 12 hives/12 hours). A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 - 21.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Occurrence of treatment-emergent adverse events and serious adverse events (SAEs)</measure>
      <time_frame>up to 68 weeks</time_frame>
      <description>To demonstrate the safety and tolerability of remibrutinib (25 mg b.i.d.)</description>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">468</enrollment>
    <condition>Chronic Spontaneous Urticaria</condition>
    <arm_group>
      <arm_group_label>Remibrutinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo to remibrutinib</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo to omalizumab</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Omalizumab</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Remibrutinib</intervention_name>
      <description>Active treatment</description>
      <arm_group_label>Remibrutinib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo to remibrutinib</intervention_name>
      <description>Placebo followed by active treatment</description>
      <arm_group_label>Placebo to remibrutinib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo to omalizumab</intervention_name>
      <description>Placebo followed by active comparator</description>
      <arm_group_label>Placebo to omalizumab</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Omalizumab</intervention_name>
      <description>Active comparator</description>
      <arm_group_label>Omalizumab</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male and female adult participants ≥18 years of age at the time of signing the&#xD;
               informed consent.&#xD;
  &#xD;
            -  CSU duration for ≥ 6 months prior to screening.&#xD;
  &#xD;
            -  Diagnosis of CSU inadequately controlled by second generation H1-AH at the time of&#xD;
               randomization, defined as:&#xD;
  &#xD;
            -  The presence of itch and hives for ≥6 consecutive weeks prior to screening, despite&#xD;
               the use of second-generation H1-AH during this time period.&#xD;
  &#xD;
            -  UAS7 score (range 0-42) ≥16, ISS7 score (range 0-21) ≥ 6 and HSS7 score (range 0- 21)&#xD;
               ≥ 6 during the 7 days prior to randomization (Day 1).&#xD;
  &#xD;
            -  Documentation of hives within three months before randomization.&#xD;
  &#xD;
            -  Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration&#xD;
               of the study and adhere to the study protocol.&#xD;
  &#xD;
            -  Participants must not have had more than one missing UPDD entry (either morning or&#xD;
               evening) in the 7 days prior to randomization (Day 1).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Prior exposure to ligelizumab, omalizumab and other biologics with any effect in CSU,&#xD;
               including anti-IgE therapies.&#xD;
  &#xD;
            -  Significant bleeding risk or coagulation disorders.&#xD;
  &#xD;
            -  History of gastrointestinal bleeding.&#xD;
  &#xD;
            -  Requirement for anti-platelet or anti-coagulant medication.&#xD;
  &#xD;
            -  History or current hepatic disease.&#xD;
  &#xD;
            -  Evidence of clinically significant cardiovascular, neurological, psychiatric,&#xD;
               pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders,&#xD;
               gastrointestinal disease or immunodeficiency that, in the investigator's opinion,&#xD;
               would compromise the safety of the participant, interfere with the interpretation of&#xD;
               the study results or otherwise preclude participation or protocol adherence of the&#xD;
               participant.&#xD;
  &#xD;
            -  Evidence of helminthic parasitic infection as evidenced by stools being positive for a&#xD;
               pathogenic organism according to local guidelines.&#xD;
  &#xD;
            -  Documented history of anaphylaxis.&#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>Novartis Pharmaceuticals</last_name>
      <role>Study Director</role>
      <affiliation>Novartis Pharmaceuticals</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Novartis Pharmaceuticals</last_name>
      <phone>+41613241111</phone>
      <email>novartis.email@novartis.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Novartis Pharmaceuticals</last_name>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 7, 2023</study_first_submitted>
    <study_first_submitted_qc>September 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 14, 2023</last_update_submitted>
    <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>CSU</keyword>
    <keyword>urticaria</keyword>
    <keyword>LOU064</keyword>
    <keyword>omalizumab</keyword>
    <keyword>remibrutinib</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>
      <mesh_term>Remibrutinib</mesh_term>
    </intervention_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>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06042478
  org study id: CLOU064A2304
  secondary id: 2022-000518-32
  nct id: NCT06042478
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this trial is to assess the efficacy, safety and tolerability of remibrutinib
        (LOU064) 25 milligrams (mg) twice a day (b.i.d.) over placebo for 24 weeks and in comparison
        to omalizumab 300 mg every 4 weeks (q4w) for 52 weeks in participants with chronic
        spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines (H1-AH).
  The study consists of three periods, and the total study duration is up to 72 weeks.
        Approximately 468 adult participants with CSU are expected to be randomized in the study.
  
        Screening period: A screening period of up to 4 weeks will allow for the assessment of
        eligibility, determination of baseline disease activity and wash-out of prohibited
        medications.
  
        Treatment period:
  
        The treatment period will be double-dummy and double-blind, with placebo injections matching
        omalizumab 300 mg s.c. given to participants in the remibrutinib arm and placebo tablets
        matching remibrutinib 25 mg given to participants in the omalizumab arm (double-dummy).
  
        At the randomization visit, eligible participants will be randomized to one of four treatment
        arms.
  
        Follow-up period:
  
        There will be a 16-week, treatment-free, safety follow-up period (for participants who do not
        roll-over to the extension study).
  
        All participants will be on a stable, local label-approved standard dose of a
        second-generation H1-AH ("background therapy") throughout the entire study (starting a
        minimum of 7 days prior to randomization until the end of the study). In addition, to treat
        unbearable symptoms of CSU flare-ups, participants will be allowed to use a different
        second-generation H1-AH on an as-needed basis ("rescue therapy").
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: At the randomization visit, eligible participants will be randomized to one of four treatment arms in a 2:1:1:2 ratio:
  Remibrutinib 25 mg b.i.d. arm: participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks
  Placebo to remibrutinib arm: participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w.
  Placebo to omalizumab arm: participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d.
  Omalizumab 300 mg every 4 weeks arm: participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.
  primary purpose: Treatment
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Absolute change from baseline in UAS7
  time frame: Week 12
  description: The UAS7 is the sum of the HSS7 score and the ISS7 score. The possible range of the weekly UAS7 score is 0 - 42 (highest activity).
  measure: Achievement of UAS7=0 (yes/no)
  time frame: Week 12
  description: Complete UAS7 response is UAS7 = 0
  measure: Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score
  time frame: Week 12
  description: The severity of the itch will be recorded by the participant twice daily in their eDiary, on a scale of 0 (none) to 3 (severe). A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 - 21.
  measure: Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score
  time frame: Week 12
  description: The hives (wheals) severity score, defined by number of hives, will be recorded by the participant twice daily in their eDiary, on a scale of 0 (none) to 3 (> 12 hives/12 hours). A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 - 21.
  measure: Occurrence of treatment-emergent adverse events and serious adverse events (SAEs)
  time frame: up to 68 weeks
  description: To demonstrate the safety and tolerability of remibrutinib (25 mg b.i.d.)
  arm group label: Remibrutinib
  arm group type: Experimental
  description: Participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks.
  arm group label: Placebo to remibrutinib
  arm group type: Placebo Comparator
  description: Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w.
  arm group label: Placebo to omalizumab
  arm group type: Placebo Comparator
  description: Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d.
  arm group label: Omalizumab
  arm group type: Active Comparator
  description: participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.
  intervention type: Drug
  intervention name: Remibrutinib
  description: Active treatment
  arm group label: Remibrutinib
  intervention type: Drug
  intervention name: Placebo to remibrutinib
  description: Placebo followed by active treatment
  arm group label: Placebo to remibrutinib
  intervention type: Drug
  intervention name: Placebo to omalizumab
  description: Placebo followed by active comparator
  arm group label: Placebo to omalizumab
  intervention type: Drug
  intervention name: Omalizumab
  description: Active comparator
  arm group label: Omalizumab
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Novartis Pharmaceuticals
  role: Study Director
  affiliation: Novartis Pharmaceuticals
  last name: Novartis Pharmaceuticals
  phone: +41613241111
  email: novartis.email@novartis.com
  last name: Novartis Pharmaceuticals
  responsible party type: Sponsor
  mesh term: Urticaria
  mesh term: Chronic Urticaria
  mesh term: Omalizumab
  mesh term: Antibodies, Monoclonal
  mesh term: Remibrutinib
  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