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A Study of the Efficacy and Safety of Brensocatib in Participants With Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)

Phase 2
Active, not recruiting
Conditions
Chronic Rhinosinusitis Without Nasal Polyps
Interventions
Registration Number
NCT06013241
Lead Sponsor
Insmed Incorporated
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
288
Inclusion Criteria
  • Participants who have at least a 12-week history before Screening Visit of CRSsNP and confirmed by endoscopy at Visit 1 (Screening).

  • Participants must have a NCS of ≥2 at Visit 1 (Screening Visit) and Visit 2 (Baseline; average score in the week prior to randomization).

  • Participants must have sTSS (nasal congestion [NC], anterior/posterior rhinorrhea, facial pain/pressure) ≥5 at Visit 1 (Screening) and at Visit 2 (Baseline; average score in the week prior to randomization).

  • Participants who have at least 1 of the 3 following features:

    1. Previous sinonasal surgery for CRS, including but not limited to fenestrated endoscopic sinus surgery and balloon sinuplasty.
    2. Received medical treatment with systemic corticosteroids (SCS) to treat symptoms of CRS as defined by any dose and duration within 1 year of Screening Visit or intolerance/contraindication to SCS.
    3. Received a course of antibiotics to treat symptoms of CRS within 1 year before the Screening Visit.
  • Participants who have a blood eosinophil count ≤750 cells/microliter (μL) at Visit 1 (Screening).

  • Participants who have bilateral inflammation of paranasal sinuses in the CT scan performed during Screening and bilateral ethmoid and/or maxillary opacification before randomization as confirmed by the central reader.

  • Participants who have a SNOT-22 score of ≥20 at Visit 1 (Screening) and Visit 2 (Baseline).

  • Participants who have received a stable daily dose regimen of MFNS for at least 4 weeks before Visit 2 (Baseline).

Exclusion Criteria
  • Diagnosis of unilateral or bilateral chronic rhinosinusitis with nasal polyps (CRSwNP).
  • Clinical diagnosis of cystic fibrosis (CF) or primary ciliary dyskinesia.
  • Scheduled sinus surgery at any time during the study.
  • Participants who have had nasal surgery within 4 weeks before Visit 1 (Screening) and during the Screening Period.
  • Significant oral maxillofacial structural abnormalities or severe septal deviation.
  • Participants with radiological suspicion or confirmed invasive fungal rhinosinusitis, odontogenic sinusitis, osteomas, or nasal tumors.
  • Participants with acute change in symptoms consistent with acute rhinosinusitis.
  • Participants with seasonal allergic rhinitis whose symptoms coincide with the treatment period of the study.
  • Participants with moderate to severe atopic dermatitis requiring treatment with high potency topical steroids or topical calcineurin inhibitors or biologics.
  • Clinical diagnosis of Papillon-Lefèvre syndrome.

Note: Other inclusion/exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Brensocatib 40 mgMometasone furoate nasal spray (MFNS)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.
Brensocatib 10 mgMometasone furoate nasal spray (MFNS)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.
PlaceboPlaceboParticipants 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.
Brensocatib 10 mgBrensocatibParticipants 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.
PlaceboMometasone furoate nasal spray (MFNS)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.
Brensocatib 40 mgBrensocatibParticipants 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.
Primary Outcome Measures
NameTimeMethod
Change From Baseline to the 28-day Average of Daily Sinus Total Symptom Score (sTSS) at Week 24Baseline and Week 24
Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Percentage of Sinus (Maxillary and Ethmoid) Opacification as Measured by Volumetry at Week 24Baseline and Week 24

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.

Proportion of Participants Requiring Rescue (Antibiotics, Systemic Corticosteroids [SCS], and/or Nasal Surgery) due to Worsening of any Chronic Rhinosinusitis (CRS) Symptoms up to Week 24Baseline up to Week 24
Change From Baseline to the 28-day Average of Daily Nasal Congestion Score (NCS) at Week 24Baseline and Week 24
Change From Baseline to the 28-day Average of Daily Peak Nasal Inspiratory Flow (PNIF) at Week 24Baseline and Week 24
Change From Baseline in Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24Baseline and Week 24
Plasma Concentration of BrensocatibPre-dose and at multiple timepoints post-dose up to Week 24
Percentage of Participants who Experienced at Least One Adverse Event (AE)Up to 28 weeks

Determination of the safety and tolerability of brensocatib compared with placebo.

Change From Baseline in Modified Lund-MacKay (LMK) Computed Tomography (CT) Score at Week 24Baseline and Week 24

Trial Locations

Locations (100)

USA034

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Tucson, Arizona, United States

USA002

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Roseville, California, United States

USA006

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Upland, California, United States

USA016

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Boca Raton, Florida, United States

USA019

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Hollywood, Florida, United States

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Miami, Florida, United States

USA009

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Tampa, Florida, United States

USA031

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Chicago, Illinois, United States

USA021

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Chicago, Illinois, United States

USA003

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New Albany, Indiana, United States

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USA034
🇺🇸Tucson, Arizona, United States

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