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/NCT06013241</url>
    </required_header>
    <id_info>
      <org_study_id>INS1007-221</org_study_id>
      <secondary_id>2022-502481-24-00</secondary_id>
      <nct_id>NCT06013241</nct_id>
    </id_info>
    <brief_title>A Study of the Efficacy and Safety of Brensocatib in Participants With Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)</brief_title>
    <acronym>BiRCh</acronym>
    <official_title>A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of the Efficacy and Safety of Brensocatib in Participants With Chronic Rhinosinusitis Without Nasal Polyps - The BiRCh Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Insmed Incorporated</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Insmed Incorporated</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 primary purpose of the study is to evaluate the efficacy of brensocatib at 10 and 40&#xD;
        milligrams (mg) once daily (QD) compared with placebo in improving clinical symptoms of&#xD;
        CRSsNP.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 29, 2023</start_date>
    <completion_date type="Anticipated">September 25, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 29, 2025</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 the 28-day Average of Daily Sinus Total Symptom Score (sTSS) at Week 24</measure>
      <time_frame>Baseline and Week 24</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change From Baseline in Percentage of Sinus (Maxillary and Ethmoid) Opacification as Measured by Volumetry at Week 24</measure>
      <time_frame>Baseline and Week 24</time_frame>
      <description>The computed tomography (CT) scan performed during Screening (considered as Baseline) and at Week 24 will be used for the volumetric assessment of maxillary and ethmoid sinus opacification.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change From Baseline in Modified Lund-MacKay (LMK) Computed Tomography (CT) Score at Week 24</measure>
      <time_frame>Baseline and Week 24</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Participant Status Indicator Assessed as Percentage of Participants Requiring Rescue (Antibiotics, Systemic Corticosteroids [SCS], and/or Nasal Surgery) due to Worsening of any Chronic Rhinosinusitis (CRS) Symptoms</measure>
      <time_frame>Baseline to Week 24</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change From Baseline to the 28-day Average of Daily Nasal Congestion Score (NCS) at Week 24</measure>
      <time_frame>Baseline and Week 24</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change From Baseline to the 28-day Average of Daily Peak Nasal Inspiratory Flow (PNIF) at Week 24</measure>
      <time_frame>Baseline and Week 24</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change From Baseline in Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24</measure>
      <time_frame>Baseline and Week 24</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma Concentration of Brensocatib</measure>
      <time_frame>Pre-dose and at multiple timepoints post-dose up to Week 24</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of Participants who Experienced at Least One Adverse Event (AE)</measure>
      <time_frame>Up to 28 weeks</time_frame>
      <description>Determination of the safety and tolerability of brensocatib compared with placebo.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">270</enrollment>
    <condition>Chronic Rhinosinusitis Without Nasal Polyps</condition>
    <arm_group>
      <arm_group_label>Brensocatib 40 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive brensocatib 40 mg tablet, orally, QD for 24 weeks along with mometasone furoate nasal spray (MFNS) by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Brensocatib 10 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive brensocatib 10 mg tablet, orally, QD for 24 weeks along with MFNS by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Participants will receive a brensocatib-matching placebo tablet, orally, QD for 24 weeks along with MFNS by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Brensocatib</intervention_name>
      <description>Film-coated tablet.</description>
      <arm_group_label>Brensocatib 10 mg</arm_group_label>
      <arm_group_label>Brensocatib 40 mg</arm_group_label>
      <other_name>INS1007</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Film-coated tablet.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Mometasone furoate nasal spray (MFNS)</intervention_name>
      <description>Nasal spray suspension.</description>
      <arm_group_label>Brensocatib 10 mg</arm_group_label>
      <arm_group_label>Brensocatib 40 mg</arm_group_label>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Participants who have at least a 12-week history before Screening Visit of CRSsNP and&#xD;
               confirmed by endoscopy at Visit 1 (Screening).&#xD;
  &#xD;
            -  Participants must have a NCS of ≥2 at Visit 1 (Screening Visit) and Visit 2 (weekly&#xD;
               average score).&#xD;
  &#xD;
            -  Participants must have sTSS (nasal congestion [NC], anterior/posterior rhinorrhea,&#xD;
               facial pain/pressure) ≥5 at Visit 1 (Screening) and at Visit 2 (Baseline) (average&#xD;
               score in the week prior to randomization).&#xD;
  &#xD;
            -  Participants who have at least 1 of the 3 following features:&#xD;
  &#xD;
                 1. Previous sinonasal surgery for CRS, including but not limited to fenestrated&#xD;
                    endoscopic sinus surgery and balloon sinuplasty.&#xD;
  &#xD;
                 2. Received medical treatment with systemic corticosteroids (SCS) to treat symptoms&#xD;
                    of CRS as defined by any dose and duration within 1 year of Screening Visit or&#xD;
                    intolerance/contraindication to SCS.&#xD;
  &#xD;
                 3. Received a course of antibiotics to treat symptoms of CRS within 1 year before&#xD;
                    the Screening Visit.&#xD;
  &#xD;
            -  Participants who have a blood eosinophil count ≤750 cells/microliter (μL) at Visit 1&#xD;
               (Screening).&#xD;
  &#xD;
            -  Participants who have bilateral inflammation of paranasal sinuses in the CT scan&#xD;
               performed during Screening and bilateral ethmoid and/or maxillary opacification before&#xD;
               randomization as confirmed by the central reader.&#xD;
  &#xD;
            -  Participants who have a SNOT-22 score of ≥20 at Visit 1 (Screening) and Visit 2&#xD;
               (Baseline).&#xD;
  &#xD;
            -  Participants who have received a stable daily dose regimen of MFNS for at least 4&#xD;
               weeks before Visit 2 (Baseline).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Diagnosis of unilateral or bilateral chronic rhinosinusitis with nasal polyps&#xD;
               (CRSwNP).&#xD;
  &#xD;
            -  Clinical diagnosis of cystic fibrosis (CF) or primary ciliary dyskinesia.&#xD;
  &#xD;
            -  Scheduled sinus surgery at any time during the study.&#xD;
  &#xD;
            -  Participants who have had nasal surgery within 4 weeks of Visit 1 (Screening) and&#xD;
               during the Screening Period.&#xD;
  &#xD;
            -  Significant oral maxillofacial structural abnormalities or severe septal deviation.&#xD;
  &#xD;
            -  Participants with radiological suspicion or confirmed invasive fungal rhinosinusitis,&#xD;
               odontogenic sinusitis, osteomas, or nasal tumors.&#xD;
  &#xD;
            -  Participants with acute change in symptoms consistent with acute rhinosinusitis.&#xD;
  &#xD;
            -  Participants with seasonal allergic rhinitis whose symptoms coincide with the&#xD;
               treatment period of the study.&#xD;
  &#xD;
            -  Participants with moderate to severe atopic dermatitis requiring treatment with high&#xD;
               potency topical steroids or topical calcineurin inhibitors or biologics.&#xD;
  &#xD;
            -  Clinical diagnosis of Papillon-Lefèvre syndrome. Note: Other inclusion/exclusion&#xD;
               criteria may apply.&#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_contact>
      <last_name>Insmed Medical Information</last_name>
      <phone>1-844-446-7633</phone>
      <email>medicalinformation@insmed.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>CRSsNP</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Sinusitis</mesh_term>
      <mesh_term>Nasal Polyps</mesh_term>
      <mesh_term>Polyps</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Mometasone Furoate</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT06013241
  org study id: INS1007-221
  secondary id: 2022-502481-24-00
  nct id: NCT06013241
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The primary purpose of the study is to evaluate the efficacy of brensocatib at 10 and 40
        milligrams (mg) once daily (QD) compared with placebo in improving clinical symptoms of
        CRSsNP.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Change From Baseline to the 28-day Average of Daily Sinus Total Symptom Score (sTSS) at Week 24
  time frame: Baseline and Week 24
  measure: Change From Baseline in Percentage of Sinus (Maxillary and Ethmoid) Opacification as Measured by Volumetry at Week 24
  time frame: Baseline and Week 24
  description: The computed tomography (CT) scan performed during Screening (considered as Baseline) and at Week 24 will be used for the volumetric assessment of maxillary and ethmoid sinus opacification.
  measure: Change From Baseline in Modified Lund-MacKay (LMK) Computed Tomography (CT) Score at Week 24
  time frame: Baseline and Week 24
  measure: Participant Status Indicator Assessed as Percentage of Participants Requiring Rescue (Antibiotics, Systemic Corticosteroids [SCS], and/or Nasal Surgery) due to Worsening of any Chronic Rhinosinusitis (CRS) Symptoms
  time frame: Baseline to Week 24
  measure: Change From Baseline to the 28-day Average of Daily Nasal Congestion Score (NCS) at Week 24
  time frame: Baseline and Week 24
  measure: Change From Baseline to the 28-day Average of Daily Peak Nasal Inspiratory Flow (PNIF) at Week 24
  time frame: Baseline and Week 24
  measure: Change From Baseline in Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24
  time frame: Baseline and Week 24
  measure: Plasma Concentration of Brensocatib
  time frame: Pre-dose and at multiple timepoints post-dose up to Week 24
  measure: Percentage of Participants who Experienced at Least One Adverse Event (AE)
  time frame: Up to 28 weeks
  description: Determination of the safety and tolerability of brensocatib compared with placebo.
  arm group label: Brensocatib 40 mg
  arm group type: Experimental
  description: Participants will receive brensocatib 40 mg tablet, orally, QD for 24 weeks along with mometasone furoate nasal spray (MFNS) by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance.
  arm group label: Brensocatib 10 mg
  arm group type: Experimental
  description: Participants will receive brensocatib 10 mg tablet, orally, QD for 24 weeks along with MFNS by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Participants will receive a brensocatib-matching placebo tablet, orally, QD for 24 weeks along with MFNS by nasal route as background therapy at a stable dose according to the Investigator's discretion and local guidance.
  intervention type: Drug
  intervention name: Brensocatib
  description: Film-coated tablet.
  arm group label: Brensocatib 10 mg
  arm group label: Brensocatib 40 mg
  other name: INS1007
  intervention type: Drug
  intervention name: Placebo
  description: Film-coated tablet.
  arm group label: Placebo
  intervention type: Drug
  intervention name: Mometasone furoate nasal spray (MFNS)
  description: Nasal spray suspension.
  arm group label: Brensocatib 10 mg
  arm group label: Brensocatib 40 mg
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Insmed Medical Information
  phone: 1-844-446-7633
  email: medicalinformation@insmed.com
  responsible party type: Sponsor
  mesh term: Sinusitis
  mesh term: Nasal Polyps
  mesh term: Polyps
  mesh term: Mometasone Furoate
  sharing ipd: No