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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Rhinosinusitis Without Nasal Polyps
• Intervention / Treatment: Drug: Brensocatib; Drug: Mometasone furoate nasal spray (MFNS); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 288
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Mar del Plata, Argentina, B7602DCK
    • ARG002
  • Mendoza, Argentina, 5500
    • ARG014
  • Mendoza, Argentina, M5500CCG
    • ARG003
  • Rosario, Argentina, S2002KDT
    • ARG016
  • Santa Fe, Argentina, 3000
    • ARG008
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina, B1900BNN
      • ARG015
    • La Plata, Buenos Aires, Argentina, B1900
      • ARG001
    • Lobos, Buenos Aires, Argentina, B7240AAN
      • ARG006
  • Ciudad Autónoma de BuenosAires
    • Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina, C1121ABE
      • ARG005
    • Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina, C1414
      • ARG012
    • Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina, C1425
      • ARG011
    • Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina, C1426ABP
      • ARG017
  • Mendoza Province
    • San Rafael, Mendoza Province, Argentina, M5600IBJ
      • ARG013
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2013DBS
      • ARG007
    • Rosario, Santa Fe Province, Argentina, S2013DTC
      • ARG010
    • Rosario, Santa Fe Province, Argentina, S2013
      • ARG004
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, T4000AXL
      • ARG009
• Australia
  • Queensland
    • Herston, Queensland, Australia, 4029
      • AUS001
  • Western Australia
    • Spearwood, Western Australia, Australia, 6163
      • AUS002
• Belgium
  • Erpent, Belgium, 5101
    • BEL002
  • Woluwe-Saint-Lambert, Belgium, 1200
    • BEL003
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • BEL001
• Bulgaria
  • Plovdiv, Bulgaria, 4001
    • BGR003
  • Stara Zagora, Bulgaria, 6000
    • BGR006
  • Sofia-Grad
    • Sofia, Sofia-Grad, Bulgaria, 1606
      • BGR005
• Canada
  • Québec, Canada, G1V 4W2
    • CAN002
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • CAN003
  • Ontario
    • London, Ontario, Canada, N6A 4V2
      • CAN006
    • Toronto, Ontario, Canada, M5G 1X5
      • CAN007
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • CAN005
    • Québec, Quebec, Canada, G1S 4L8
      • CAN001
• Czechia
  • Nový Hradec Králové, Czechia, 500 05
    • CZE005
  • Prague, Czechia, 140 59
    • CZE004
  • Olomoucký kraj
    • Olomouc, Olomoucký kraj, Czechia, 779 00
      • CZE002
  • Pardubický kraj
    • Pardubice, Pardubický kraj, Czechia, 532 03
      • CZE003
• Denmark
  • Capital
    • Hillerød, Capital, Denmark, 3400
      • DNK004
    • København Ø, Capital, Denmark, 2100
      • DNK001
  • Central Jutland
    • Aarhus C, Central Jutland, Denmark, 8000
      • DNK003
  • Zeeland
    • Køge, Zeeland, Denmark, 4600
      • DNK002
• France
  • Bas-Rhin
    • Strasbourg, Bas-Rhin, France, 67200
      • FRA002
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France, 13010
      • FRA003
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44000
      • FRA001
  • Vendée
    • La Roche-sur-Yon, Vendée, France, 85925
      • FRA004
• Germany
  • Berlin, Germany, 10117
    • GER007
  • Dresden, Germany, 01307
    • GER001
  • Hesse
    • Wiesbaden, Hesse, Germany, 65183
      • GER004
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • GER009
    • Mittweida, Saxony, Germany, 09648
      • GER003
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23562
      • GER008
  • Thuringia
    • Jena, Thuringia, Germany, 07747
      • GER005
• Hungary
  • Baranya
    • Pécs, Baranya, Hungary, 7621
      • HUN003
• Italy
  • Lombardy
    • Rozzano, Lombardy, Italy, 20089
      • ITA001
  • Sardinia
    • Sassari, Sardinia, Italy, 07100
      • ITA002
  • Tuscany
    • Pisa, Tuscany, Italy, 56124
      • ITA003
• Poland
  • Warsaw, Poland, 04-141
    • POL008
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 60-309
      • POL002
    • Poznan, Greater Poland Voivodeship, Poland, 60-693
      • POL010
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 30-033
      • POL005
    • Wieliczka, Lesser Poland Voivodeship, Poland, 32-020
      • POL007
  • Lower Silesian Voivodeship
    • Wroclaw, Lower Silesian Voivodeship, Poland, 52-416
      • POL009
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-954
      • POL003
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 00-189
      • POL001
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-276
      • POL004
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-611
      • POL006
• Portugal
  • Aveiro, Portugal, 3814-501
    • PRT004
  • Braga, Portugal, 4710
    • PRT002
  • Braga District
    • Guimarães, Braga District, Portugal, 4835-044
      • PRT001
  • Lisbon District
    • Lisbon, Lisbon District, Portugal, 1349-019
      • PRT003
  • Porto District
    • Senhora da Hora, Porto District, Portugal, 4464-513
      • PRT005
• Spain
  • Seville, Spain, 41009
    • ESP001
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • ESP003
  • Cádiz
    • Jerez de la Frontera, Cádiz, Spain, 11407
      • ESP002
  • Málaga
    • Málaga, Málaga, Spain, 29009
      • ESP004
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
      • USA034
  • California
    • Roseville, California, United States, 95661
      • USA002
    • Upland, California, United States, 91786
      • USA006
  • Florida
    • Boca Raton, Florida, United States, 33487
      • USA016
    • Hollywood, Florida, United States, 33024
      • USA019
    • Miami, Florida, United States, 33135
      • USA001
    • Tampa, Florida, United States, 33613
      • USA009
  • Illinois
    • Chicago, Illinois, United States, 60611
      • USA031
    • Chicago, Illinois, United States, 60612
      • USA021
  • Indiana
    • New Albany, Indiana, United States, 47150
      • USA003
  • Louisiana
    • Mandeville, Louisiana, United States, 70471
      • USA035
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • USA026
  • Missouri
    • Columbia, Missouri, United States, 65212
      • USA011
    • St Louis, Missouri, United States, 63141
      • USA024
  • New York
    • New York, New York, United States, 10016
      • USA033
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74132
      • USA028
    • Tulsa, Oklahoma, United States, 74136
      • USA004
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • USA015
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • USA023
    • North Charleston, South Carolina, United States, 29406
      • USA022
  • Texas
    • Dallas, Texas, United States, 75231
      • USA025
    • Fredericksburg, Texas, United States, 78624
      • USA037
    • Houston, Texas, United States, 77030
      • USA018
    • Houston, Texas, United States, 77022
      • USA029
    • San Antonio, Texas, United States, 78258
      • USA030
    • Tomball, Texas, United States, 77375
      • USA038
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • USA005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brensocatib 40 mg; 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.	Drug: Brensocatib; Film-coated tablet.; Other Names: INS1007; Drug: Mometasone furoate nasal spray (MFNS); Nasal spray suspension.
Experimental: Brensocatib 10 mg; 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.	Drug: Brensocatib; Film-coated tablet.; Other Names: INS1007; Drug: Mometasone furoate nasal spray (MFNS); Nasal spray suspension.
Placebo Comparator: Placebo; 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.	Drug: Mometasone furoate nasal spray (MFNS); Nasal spray suspension.; Drug: Placebo; Film-coated tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline to the 28-day Average of Daily Sinus Total Symptom Score (sTSS) at Week 24	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Percentage of Sinus (Maxillary and Ethmoid) Opacification as Measured by Volumetry at 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.	Baseline and Week 24
Change From Baseline in Modified Lund-MacKay (LMK) Computed Tomography (CT) Score at Week 24		Baseline and Week 24
Change From Baseline to the 28-day Average of Daily Nasal Congestion Score (NCS) at Week 24		Baseline and Week 24
Change From Baseline to the 28-day Average of Daily Peak Nasal Inspiratory Flow (PNIF) at Week 24		Baseline and Week 24
Change From Baseline in Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24		Baseline and Week 24
Plasma Concentration of Brensocatib		Pre-dose and at multiple timepoints post-dose up to Week 24
Percentage of Participants who Experienced at Least One Adverse Event (AE)	Determination of the safety and tolerability of brensocatib compared with placebo.	Up to 28 weeks
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 24		Baseline up to Week 24

Collaborators and Investigators

• Sponsor: Insmed Incorporated

Publications and helpful links

Helpful Links

• Prescreening tool

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Actual): September 30, 2025
• Study Completion (Actual): October 30, 2025

Study Registration Dates

• First Submitted: August 22, 2023
• First Submitted That Met QC Criteria: August 22, 2023
• First Posted (Actual): August 28, 2023

Study Record Updates

• Last Update Posted (Actual): November 10, 2025
• Last Update Submitted That Met QC Criteria: November 7, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: CRSsNP
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Nose Diseases; Otorhinolaryngologic Diseases; Rhinitis; Paranasal Sinus Diseases; Rhinosinusitis; Polyps; Nasal Polyps; Sinusitis; Anti-Inflammatory Agents; Dermatologic Agents; Anti-Allergic Agents; brensocatib
• Other Study ID Numbers: INS1007-221; 2022-502481-24-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No