Clinical trial NCT06013241: A Study of the Efficacy and Safety of Brensocatib in Participants With Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Rhinosinusitis Without Nasal Polyps
Keywords: CRSsNP
Lead sponsor: Insmed Incorporated
Sponsor class: INDUSTRY
First posted: 2023-08-28
Enrollment: 288
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline to the 28-day Average of Daily Sinus Total Symptom Score (sTSS) at Week 24
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Change From Baseline in Percentage of Sinus (Maxillary and Ethmoid) Opacification as Measured by Volumetry at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Modified Lund-MacKay (LMK) Computed Tomography (CT) Score at Week 24
timeFrame: Baseline and Week 24
measure: 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
timeFrame: Baseline up to Week 24
measure: Change From Baseline to the 28-day Average of Daily Nasal Congestion Score (NCS) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline to the 28-day Average of Daily Peak Nasal Inspiratory Flow (PNIF) at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24
timeFrame: Baseline and Week 24
measure: Plasma Concentration of Brensocatib
timeFrame: Pre-dose and at multiple timepoints post-dose up to Week 24
measure: Percentage of Participants who Experienced at Least One Adverse Event (AE)
timeFrame: Up to 28 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: USA034
state: Arizona
city: Roseville
country: United States
facility: USA002
state: California
city: Upland
country: United States
facility: USA006
state: California
city: Boca Raton
country: United States
facility: USA016
state: Florida
city: Hollywood
country: United States
facility: USA019
state: Florida
city: Miami
country: United States
facility: USA001
state: Florida
city: Tampa
country: United States
facility: USA009
state: Florida
city: Chicago
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facility: USA031
state: Illinois
city: Chicago
country: United States
facility: USA021
state: Illinois
city: New Albany
country: United States
facility: USA003
state: Indiana
city: Mandeville
country: United States
facility: USA035
state: Louisiana
city: Baltimore
country: United States
facility: USA026
state: Maryland
city: Columbia
country: United States
facility: USA011
state: Missouri
city: Saint Louis
country: United States
facility: USA024
state: Missouri
city: New York
country: United States
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state: New York
city: Tulsa
country: United States
facility: USA028
state: Oklahoma
city: Tulsa
country: United States
facility: USA004
state: Oklahoma
city: Hershey
country: United States
facility: USA015
state: Pennsylvania
city: Charleston
country: United States
facility: USA023
state: South Carolina
city: North Charleston
country: United States
facility: USA022
state: South Carolina
city: Dallas
country: United States
facility: USA025
state: Texas
city: Fredericksburg
country: United States
facility: USA037
state: Texas
city: Houston
country: United States
facility: USA029
state: Texas
city: Houston
country: United States
facility: USA018
state: Texas
city: San Antonio
country: United States
facility: USA030
state: Texas
city: Tomball
country: United States
facility: USA038
state: Texas
city: Norfolk
country: United States
facility: USA005
state: Virginia
city: La Plata
country: Argentina
facility: ARG015
state: Buenos Aires
city: La Plata
country: Argentina
facility: ARG001
state: Buenos Aires
city: Lobos
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facility: ARG006
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: ARG005
state: Ciudad Autónoma De BuenosAires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: ARG012
state: Ciudad Autónoma De BuenosAires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: ARG011
state: Ciudad Autónoma De BuenosAires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: ARG017
state: Ciudad Autónoma De BuenosAires
city: San Rafael
country: Argentina
facility: ARG013
state: Mendoza
city: Rosario
country: Argentina
facility: ARG007
state: Santa Fe
city: Rosario
country: Argentina
facility: ARG010
state: Santa Fe
city: Rosario
country: Argentina
facility: ARG004
state: Santa Fe
city: San Miguel De Tucumán
country: Argentina
facility: ARG009
state: Tucumán
city: Mar del Plata
country: Argentina
facility: ARG002
city: Mendoza
country: Argentina
facility: ARG014
city: Mendoza
country: Argentina
facility: ARG003
city: Rosario
country: Argentina
facility: ARG016
city: Santa Fe
country: Argentina
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city: Herston
country: Australia
facility: AUS001
state: Queensland
city: Spearwood
country: Australia
facility: AUS002
state: Western Australia
city: Gent
country: Belgium
facility: BEL001
state: Oost-Vlaanderen
city: Erpent
country: Belgium
facility: BEL002
city: Sint-Lambrechts-Woluwe
country: Belgium
facility: BEL003
city: Sofia
country: Bulgaria
facility: BGR005
state: Sofia-Grad
city: Plovdiv
country: Bulgaria
facility: BGR003
city: Stara Zagora
country: Bulgaria
facility: BGR006
city: Vancouver
country: Canada
facility: CAN003
state: British Columbia
city: London
country: Canada
facility: CAN006
state: Ontario
city: Toronto
country: Canada
facility: CAN007
state: Ontario
city: Montreal
country: Canada
facility: CAN005
state: Quebec
city: Quebec City
country: Canada
facility: CAN001
state: Quebec
city: Quebec
country: Canada
facility: CAN002
city: Olomouc
country: Czechia
facility: CZE002
state: Olomoucký Kraj
city: Pardubice
country: Czechia
facility: CZE003
state: Pardubický Kraj
city: Nový Hradec Králové
country: Czechia
facility: CZE005
city: Prague
country: Czechia
facility: CZE004
city: Hillerød
country: Denmark
facility: DNK004
state: Capital
city: København Ø
country: Denmark
facility: DNK001
state: Capital
city: Aarhus C
country: Denmark
facility: DNK003
state: Central Jutland
city: Køge
country: Denmark
facility: DNK002
state: Zeeland
city: Strasbourg
country: France
facility: FRA002
state: Bas-Rhin
city: Marseille
country: France
facility: FRA003
state: Bouches-du-Rhône
city: Nantes
country: France
facility: FRA001
state: Loire-Atlantique
city: La Roche-sur-Yon
country: France
facility: FRA004
state: Vendée
city: Wiesbaden
country: Germany
facility: GER004
state: Hessen
city: Leipzig
country: Germany
facility: GER009
state: Sachsen
city: Mittweida
country: Germany
facility: GER003
state: Sachsen
city: Lübeck
country: Germany
facility: GER008
state: Schleswig-Holstein
city: Jena
country: Germany
facility: GER005
state: Thüringen
city: Berlin
country: Germany
facility: GER007
city: Dresden
country: Germany
facility: GER001
city: Pécs
country: Hungary
facility: HUN003
state: Baranya
city: Rozzano
country: Italy
facility: ITA001
state: Lombardia
city: Sassari
country: Italy
facility: ITA002
state: Sardegna
city: Pisa
country: Italy
facility: ITA003
state: Toscana
city: Wroclaw
country: Poland
facility: POL009
state: Dolnoslaskie
city: Lublin
country: Poland
facility: POL003
state: Lubelskie
city: Kraków
country: Poland
facility: POL005
state: Malopolskie
city: Wieliczka
country: Poland
facility: POL007
state: Malopolskie
city: Warszawa
country: Poland
facility: POL001
state: Mazowieckie
city: Białystok
country: Poland
facility: POL004
state: Podlaskie
city: Katowice
country: Poland
facility: POL006
state: Slaskie
city: Poznan
country: Poland
facility: POL002
state: Wielkopolskie
city: Poznan
country: Poland
facility: POL010
state: Wielkopolskie
city: Warszawa
country: Poland
facility: POL008
city: Guimarães
country: Portugal
facility: PRT001
state: Braga
city: Lisbon
country: Portugal
facility: PRT003
state: Lisboa
city: Senhora Da Hora
country: Portugal
facility: PRT005
state: Porto
city: Aveiro
country: Portugal
facility: PRT004
city: Braga
country: Portugal
facility: PRT002
city: Santander
country: Spain
facility: ESP003
state: Cantabria
city: Jerez de la Frontera
country: Spain
facility: ESP002
state: Cádiz
city: Malaga
country: Spain
facility: ESP004
state: Málaga
city: Sevilla
country: Spain
facility: ESP001
Study officials:
References: