A Study to Assess the Efficacy, Safety, and Tolerability of Brensocatib in Participants With Non-Cystic Fibrosis Bronchiectasis

Non-Cystic Fibrosis Bronchiectasis Clinical Trial

— ASPEN  

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of Brensocatib Administered Once Daily for 52 Weeks in Subjects With Non-Cystic Fibrosis Bronchiectasis - The ASPEN Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04594369
• Other study ID #: INS1007-301
• Secondary ID: 2020-003688-25
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 1, 2020
• Est. completion date: March 22, 2024

Study information

• Verified date: March 2024
• Source: Insmed Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the effect of brensocatib at 10 mg and 25 mg compared with placebo on the rate of pulmonary exacerbations (PEs) over the 52-week treatment period.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1767
• Est. completion date: March 22, 2024
• Est. primary completion date: March 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Provide their signed study informed consent to participate. a. Adolescent participants must have signed study assent form to participate, and the adolescent's parent or legal guardian must have provided signed informed consent for the adolescent to participate.

2. Clinical history consistent with non-cystic fibrosis bronchiectasis (NCFBE) (cough, chronic sputum production and/or recurrent respiratory infections) that is confirmed by chest computerized tomography (CT) scan.

3. At least 2 PEs defined by need for antibiotic prescription by a physician for the signs and symptoms of respiratory infections in the past 12 months before the Screening Visit. a. Adolescent participants are required to have at least 1 pulmonary exacerbation in the prior 12 months.

4. Women must be postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, or using highly effective contraception (ie, methods that can achieve a failure rate <1% per year when used consistently and correctly) from Day 1 to at least 90 days after the last dose.

5. Male participants with female partners of childbearing potential must be using effective contraception from Day 1 to at least 90 days after the last dose.

6. Male participants with pregnant or non-pregnant women of child-bearing potential partners must use condoms to avoid potential exposure to the embryo/fetus.

Exclusion Criteria:

1. A primary diagnosis of chronic obstructive pulmonary disease (COPD) or asthma as judged by the Investigator.

2. Bronchiectasis due to cystic fibrosis.

3. Current smokers as defined per Centers for Disease Control (CDC).

4. Known or suspected immunodeficiency disorder, including history of invasive opportunistic infections.

5. Known history of human immunodeficiency virus (HIV) infection.

6. Currently being treated for nontuberculous mycobacteria (NTM) lung infection, allergic bronchopulmonary aspergillosis, or tuberculosis (TB).

7. Active and current symptomatic infection by 2019 corona virus disease (COVID-19).

8. Inability to follow the procedures of the study (eg, due to language problems or psychological disorders).

9. Receiving medications or therapy that are prohibited as concomitant medications.

10. Previously participated in a clinical trial for brensocatib.

11. Received any live attenuated vaccine within 4 weeks prior to the first administration of brensocatib.

12. Suffering an exacerbation 4 weeks before Screening or during the Screening period.

13. Adult participants only: Have compliance issues with completion of electronic diary entries during the Screening Period and in the opinion of the Investigator, compliance is unlikely to improve during the study.

14. Participated in any other interventional clinical studies within 3 months before Screening Visit.

15. History of alcohol or drug abuse within 6 months prior to the Screening Visit.

16. Is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study.

17. Known history of hypersensitivity to brensocatib or any of its excipients.

Related Conditions & MeSH terms

• Bronchiectasis
• Fibrosis
• Non-Cystic Fibrosis Bronchiectasis

Intervention

Drug:
• Brensocatib 10 mg
Oral tablet.
• Brensocatib 25 mg
Oral tablet.
• Placebo
Brensocatib-matching oral tablet.

Locations

Country	Name	City	State
Argentina	ARG027	Bahia Blanca	Buenos Aires
Argentina	ARG001	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	ARG002	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	ARG012	Ciudad Autónoma de Buenos Aires	Ciudad Autónoma De BuenosAires
Argentina	ARG018	Ciudad Autónoma de Buenos Aires	Ciudad Autónoma De BuenosAires
Argentina	ARG021	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	ARG022	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	ARG003	Ciudad Autónoma de BuenosAires	Buenos Aires
Argentina	ARG004	Ciudad Autónoma de BuenosAires	Buenos Aires
Argentina	ARG005	Córdoba
Argentina	ARG006	la Plata	Buenos Aires
Argentina	ARG013	Mar del Plata	Buenos Aires
Argentina	ARG017	Mar Del Plata	Buenos Aires
Argentina	ARG007	Mendoza
Argentina	ARG026	Recoleta	Ciudad Autónoma De BuenosAires
Argentina	ARG023	Río Cuarto	Córdoba
Argentina	ARG010	Rosario	Santa Fe
Argentina	ARG011	Rosario
Argentina	ARG015	San Miguel De Tucumán	Tucumán
Argentina	ARG025	San Miguel de Tucumán	Tucumán
Argentina	ARG019	Santa Fe
Argentina	ARG009	Villa Vatteone	Buenos Aires
Argentina	ARG014	Vistalba	Mendoza
Australia	AUS011	Adelaide	South Australia
Australia	AUS017	Bedford Park	South Australia
Australia	AUS002	Box Hill	Victoria
Australia	AUS012	Cairns North	Queensland
Australia	AUS001	Chermside	Queensland
Australia	AUS014	Clayton	Victoria
Australia	AUS003	Concord
Australia	AUS010	Greenslopes	Queensland
Australia	AUS013	Kogarah	New South Wales
Australia	AUS018	Murdoch	Western Australia
Australia	AUS005	Nedlands	Western Australia
Australia	AUS008	New Lambton Heights	New South Wales
Australia	AUS022	North Adelaide	South Australia
Australia	AUS006	South Brisbane	Queensland
Australia	AUS019	South Brisbane	Queensland
Australia	AUS015	Spearwood
Australia	AUS007	Westmead	New South Wales
Australia	AUS009	Woodville South	South Australia
Austria	AUT002	Linz
Belgium	BEL002	Gent	Oost-Vlaanderen
Belgium	BEL009	Gent	Oost-Vlaanderen
Belgium	BEL001	Leuven
Belgium	BEL007	Liège
Belgium	BEL003	Mechelen
Belgium	BEL004	Roeselare	West-Vlaanderen
Belgium	BEL008	Sint-Niklaas
Brazil	BRA001	Blumenau	Santa Catarina
Brazil	BRA003	Botucatu
Brazil	BRA009	Passo Fundo	Rio Grande Do Sul
Brazil	BRA005	Porto Alegre	Rio Grande Do Sul
Brazil	BRA006	Santo André	São Paulo
Brazil	BRA004	São Bernardo do Campo
Brazil	BRA011	São Paulo
Bulgaria	BGR005	Blagoevgrad
Bulgaria	BGR006	Gabrovo
Bulgaria	BGR014	Kozloduy
Bulgaria	BGR015	Lovech
Bulgaria	BGR007	Montana
Bulgaria	BGR018	Pazardzhik
Bulgaria	BGR019	Pleven
Bulgaria	BGR004	Plovdiv
Bulgaria	BGR008	Ruse
Bulgaria	BGR017	Sliven
Bulgaria	BGR002	Sofia	Sofia-Grad
Bulgaria	BGR009	Sofia	Sofia-Grad
Bulgaria	BGR010	Sofia
Bulgaria	BGR011	Sofia	Sofia-Grad
Bulgaria	BGR012	Veliko Tarnovo
Bulgaria	BGR013	Vidin
Bulgaria	BGR016	Vratsa
Canada	CAN002	Montreal	Quebec
Canada	CAN004	Toronto	Ontario
Chile	CHL005	Curicó	Maule
Chile	CHL001	Providencia	Región-MetropolitanadeSantiago
Chile	CHL002	Providencia	Región-MetropolitanadeSantiago
Chile	CHL008	Providencia	Región-MetropolitanadeSantiago
Chile	CHL004	Quillota
Chile	CHL010	Talca	Maule
Chile	CHL007	Valdivia	Los Ríos
Colombia	COL001	Bogotá	Distrito Capital De Bogotá
Colombia	COL002	Bogota DC
Colombia	COL003	Cali	Valle Del Cauca
Colombia	COL005	Floridablanca	Santander
Colombia	COL004	Santiago de Cali
Colombia	COL006	Zipaquira	Cundinamarca
Denmark	DNK003	Aalborg
Denmark	DNK007	Aarhus
Denmark	DNK008	Copenhagen O	Capital
Denmark	DNK004	Hellerup
Denmark	DNK001	Hvidovre	Capital
Denmark	DNK005	Odense C	South Denmark
Denmark	DNK002	Roskilde
Denmark	DNK006	Vejle	South Denmark
France	FRA004	Amiens cedex 1
France	FRA011	Creteil
France	FRA005	Montpellier	Hérault
France	FRA003	Nantes
France	FRA009	Nice
France	FRA010	Paris
France	FRA002	Strasbourg	Bas-Rhin
France	FRA006	Toulouse
Germany	DEU002	Berlin
Germany	DEU006	Berlin
Germany	DEU011	Berlin
Germany	DEU019	Berlin
Germany	DEU014	Dresden
Germany	DEU013	Essen	Nordrhein-Westfalen
Germany	DEU021	Frankfurt
Germany	DEU008	Frankfurt am Main	Hessen
Germany	DEU020	Geesthacht	Schleswig-Holstein
Germany	DEU016	Halle	Sachsen-Anhalt
Germany	DEU015	Hannover
Germany	DEU031	Hannover	Niedersachsen
Germany	DEU009	Heidelberg	Baden-Württemberg
Germany	DEU003	Leipzig	Sachsen
Germany	DEU023	Mainz
Germany	DEU005	Marburg	Hessen
Germany	DEU029	Muenster
Germany	DEU025	München	Bayern
Germany	DEU027	Potsdam	Brandenburg
Greece	GRC003	Alexandroupoli	Evros
Greece	GRC007	Herakleion
Greece	GRC006	Thessaloniki
Hungary	HUN005	Tatabánya	Komárom-Esztergom
Ireland	IRL002	Dublin
Ireland	IRL003	Dublin
Ireland	IRL001	Limerick
Israel	ISR001	Ashkelon
Israel	ISR010	Beer Sheva
Israel	ISR008	Haifa
Israel	ISR002	Jerusalem
Israel	ISR006	Jerusalem
Israel	ISR009	Kefar-Sava
Israel	ISR011	Petach Tikva
Israel	ISR007	Ramat Gan
Israel	ISR003	Rehovot
Israel	ISR004	Zerifin
Italy	ITA010	Bologna	Emilia-Romagna
Italy	ITA008	Ferrara	Emilia-Romagna
Italy	ITA003	Milano
Italy	ITA006	Milano	Lombardia
Italy	ITA012	Milano	Lombardia
Italy	ITA001	Palermo
Italy	ITA007	Pavia
Italy	ITA002	Reggio Emilia	Emilia-Romagna
Italy	ITA009	Roma
Italy	ITA011	Rozzano	Lombardia
Italy	ITA004	Siena	Toscana
Japan	JPN012	Chuo-ku	Niigata
Japan	JPN027	Fukuoka-Shi	Hukuoka
Japan	JPN030	Fukuoka-shi
Japan	JPN003	Hamamatsu-Shi
Japan	JPN023	Iizuka-Shi	Hukuoka
Japan	JPN020	Kasama-Shi	Ibaraki
Japan	JPN004	Kita Kyushu-shi
Japan	JPN007	Kiyose	Tokyo
Japan	JPN009	Kobe-City	Hyôgo
Japan	JPN005	Koshi shi	Kumamoto
Japan	JPN015	Matsue	Simane
Japan	JPN016	Matsue-shi
Japan	JPN008	Matsusaka-shi	Mie
Japan	JPN010	Meguro-ku
Japan	JPN013	Nagasaki-Shi	Nagasaki
Japan	JPN001	Naka-gun	Ibaraki
Japan	JPN014	Ota-Ku	Tokyo
Japan	JPN034	Sendai-shi	Miyagi
Japan	JPN019	Shimonoseki-Shi	Yamaguti
Japan	JPN006	Shinagawa-ku	Tokyo
Japan	JPN017	Shinagawa-ku	Tokyo
Japan	JPN002	Shinjuku-ku	Tokyo
Japan	JPN032	Shinjuku-ku	Tokyo
Japan	JPN022	Takamatsu-Shi	Kagawa
Japan	JPN031	Toon-Shi	Ehime
Japan	JPN029	Toyoake	Aiti
Japan	JPN018	Toyonaka-shi
Japan	JPN011	Tsu	Mie
Japan	JPN028	Yokohama-Shi Konan-Ku	Kanagawa
Korea, Republic of	KOR015	Ansan-si	Gyeonggido
Korea, Republic of	KOR008	Bucheon-si	Gyeonggido
Korea, Republic of	KOR004	Incheon
Korea, Republic of	KOR007	Seongnam-si	Gyeonggido
Korea, Republic of	KOR003	Seoul	Seoul Teugbyeolsi
Korea, Republic of	KOR005	Seoul
Korea, Republic of	KOR009	Seoul
Korea, Republic of	KOR010	Seoul
Korea, Republic of	KOR011	Seoul
Korea, Republic of	KOR012	Seoul
Korea, Republic of	KOR013	Seoul
Latvia	LVA002	Daugavpils	Daugavpils Aprinkis
Latvia	LVA005	Jurmala
Malaysia	MYS003	Kota Bahru
Malaysia	MYS001	Kuala Lumpur	WilayahPersekutuan KualaLumpur
Malaysia	MYS005	Kuala Lumpur
Malaysia	MYS004	Kuantan	Pahang
Mexico	MEX006	Durango
Mexico	MEX004	Guadalajara	Jalisco
Mexico	MEX005	Guadalajara	Jalisco
Mexico	MEX007	Guadalajara	Jalisco
Mexico	MEX008	Guadalajara	Jalisco
Mexico	MEX001	Monterrey
Mexico	MEX003	Monterrey	Nuevo León
Mexico	MEX002	Oaxaca
Netherlands	NLD001	Alkmaar	Noord-Holland
Netherlands	NLD002	Amsterdam	Noord-Holland
Netherlands	NLD003	Arnhem	Gelderland
Netherlands	NLD006	Rotterdam
New Zealand	NZL003	Auckland
New Zealand	NZL008	Auckland
New Zealand	NZL005	Christchurch	South Island
New Zealand	NZL001	Dunedin	South Island
New Zealand	NZL002	Hamilton	Waikato
New Zealand	NZL009	Hastings	Hawkes's Bay
New Zealand	NZL006	Otahuhu	Auckland
New Zealand	NZL011	Paraparaumu	Wellington
New Zealand	NZL007	Tauranga
New Zealand	NZL010	Wellington
Peru	PER005	Chancay
Peru	PER001	Lima
Peru	PER002	Lima
Peru	PER003	Lima
Peru	PER006	Piura
Poland	POL005	Bialystok
Poland	POL006	Bielsko Biala
Poland	POL016	Katowice
Poland	POL015	Kielce
Poland	POL017	Krakow
Poland	POL018	Ksawerow
Poland	POL012	Ostrowiec Swietokrzyski	Swietokrzyskie
Poland	POL008	Rabka-Zdroj
Poland	POL011	Rzeszów
Poland	POL010	Siedlce
Poland	POL007	Sosnowiec
Poland	POL001	Sucha Beskidzka
Poland	POL014	Szczecin
Poland	POL009	Tarnow
Portugal	PRT005	Aveiro
Portugal	PRT009	Braga
Portugal	PRT006	Guarda
Portugal	PRT002	Guimaraes
Portugal	PRT003	Lisboa
Serbia	SRB001	Belgrade
Serbia	SRB003	Belgrade
Serbia	SRB007	Nis
Serbia	SRB014	Sombor
Serbia	SRB010	Uzice
Slovakia	SVK002	Bardejov
Slovakia	SVK003	Spisská Nová Ves
Spain	ESP013	Badalona	Barcelona
Spain	ESP003	Barcelona
Spain	ESP016	Barcelona
Spain	ESP001	Girona
Spain	ESP006	L´Hospitalet de Llobregat
Spain	ESP002	Madrid
Spain	ESP007	Madrid
Spain	ESP008	Oviedo	Asturias
Spain	ESP011	Pamplona	Navarra
Spain	ESP015	Pozuelo de Alarcon	Madrid
Spain	ESP012	Santander	Cantabria
Spain	ESP009	Santiago de Compostela	A Coruña
Taiwan	TWN001	Kaohsiung
Taiwan	TWN002	Kaohsiung
Taiwan	TWN003	Kaohsiung City
Taiwan	TWN005	New Taipei City
Taiwan	TWN004	Taipei
Taiwan	TWN007	Taipei
Taiwan	TWN006	Taipei City
Thailand	THA003	Khon Kaen
Thailand	THA002	Muang	Nonthaburi
Thailand	THA004	Nakhonnayok	Nakhon Nayok
Turkey	TUR010	Ankara
Turkey	TUR011	Ankara
Turkey	TUR006	Atakum	Samsun
Turkey	TUR003	Canakkale
Turkey	TUR004	Izmir
Turkey	TUR008	Izmir
Turkey	TUR009	Kocaeli
Turkey	TUR005	Konya
Turkey	TUR001	Mersin
Ukraine	UKR012	Dnipro
Ukraine	UKR009	Ivano-Frankivsk
Ukraine	UKR001	Kharkiv	Kharkivs'ka Oblast
Ukraine	UKR007	Kherson	Khersons'ka Oblast
Ukraine	UKR004	Kyiv
Ukraine	UKR008	Kyiv
Ukraine	UKR003	Odesa
Ukraine	UKR005	Poltava	Poltavs'ka Oblast
Ukraine	UKR010	Vinnytsia
United Kingdom	GBR006	Birmingham
United Kingdom	GBR016	Bradford	Yorkshire
United Kingdom	GBR001	Cambridge	Cambridgeshire
United Kingdom	GBR002	Chertsey
United Kingdom	GBR007	Dundee
United Kingdom	GBR015	Exeter	Devon
United Kingdom	GBR004	Liverpool
United Kingdom	GBR013	Llandough, Penarth	Vale Of Glamorgan, The
United Kingdom	GBR009	London
United Kingdom	GBR008	Manchester
United Kingdom	GBR011	Manchester
United Kingdom	GBR003	Newcastle upon Tyne
United Kingdom	GBR017	Norwich	Norfolk
United Kingdom	GBR012	Salford
United Kingdom	GBR018	Southampton
United Kingdom	GBR010	Swansea
United States	USA012	Atlanta	Georgia
United States	USA053	Augusta	Georgia
United States	USA003	Baltimore	Maryland
United States	USA013	Birmingham	Alabama
United States	USA079	Boston	Massachusetts
United States	USA005	Charleston	South Carolina
United States	USA006	Chesterfield	Missouri
United States	USA073	Chicago	Illinois
United States	USA067	Cincinnati	Ohio
United States	USA015	Clearwater	Florida
United States	USA093	Cleveland	Ohio
United States	USA080	Conway	Arkansas
United States	USA097	Dallas	Texas
United States	USA075	Denver	Colorado
United States	USA038	DuBois	Pennsylvania
United States	USA017	Farmington	Connecticut
United States	USA041	Franklin	Tennessee
United States	USA104	Fresno	California
United States	USA076	Gainesville	Florida
United States	USA033	Gastonia	North Carolina
United States	USA115	Hammond	Indiana
United States	USA096	Huntersville	North Carolina
United States	USA063	Iowa City	Iowa
United States	USA082	Jacksonville	Florida
United States	USA031	Kansas City	Kansas
United States	USA039	Kissimmee	Florida
United States	USA072	Leesburg	Florida
United States	USA110	Lincoln	Nebraska
United States	USA044	Little Rock	Arkansas
United States	USA055	Los Angeles	California
United States	USA061	Maywood	Illinois
United States	USA050	McKinney	Texas
United States	USA037	Miami	Florida
United States	USA019	Miami Lakes	Florida
United States	USA049	Naples	Florida
United States	USA109	Nashville	Tennessee
United States	USA066	New Hyde Park	New York
United States	USA020	New Orleans	Louisiana
United States	USA051	New Orleans	Louisiana
United States	USA021	New York	New York
United States	USA085	New York	New York
United States	USA029	Newport Beach	California
United States	USA102	Northridge	California
United States	USA052	Orlando	Florida
United States	USA022	Palm Springs	California
United States	USA046	Philadelphia	Pennsylvania
United States	USA103	Plantation	Florida
United States	USA023	Portland	Oregon
United States	USA010	Rochester	Minnesota
United States	USA036	Rock Hill	South Carolina
United States	USA024	Sacramento	California
United States	USA059	Saint Louis	Missouri
United States	USA074	Saint Petersburg	Florida
United States	USA089	Saint Petersburg	Florida
United States	USA011	San Antonio	Texas
United States	USA035	San Diego	California
United States	USA078	Santa Barbara	California
United States	USA084	Sarasota	Florida
United States	USA064	Springfield	Massachusetts
United States	USA120	Tampa	Florida
United States	USA065	Toms River	New Jersey
United States	USA002	Tyler	Texas
United States	USA088	Vancouver	Washington
United States	USA027	Ventura	California
United States	USA001	Washington	District of Columbia
United States	USA034	Williamsburg	Virginia
United States	USA026	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Insmed Incorporated

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Denmark,  France,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Peru,  Poland,  Portugal,  Serbia,  Slovakia,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Adjudicated Pulmonary Exacerbations (PEs)		52 Weeks
Secondary	Time to First Adjudicated Pulmonary Exacerbation (PE)		52 Weeks
Secondary	Percentage of Participants who are Pulmonary Exacerbation (PE) Free		52 Weeks
Secondary	Change From Baseline in Postbronchodilator Forced Expiratory Volume in 1 Second (FEV1)		Baseline, at Week 52
Secondary	Rate of Severe Adjudicated Pulmonary Exacerbations (PEs)		52 Weeks
Secondary	Change from Baseline to Week 52 in Quality of Life Questionnaire - Bronchiectasis (QOL-B) Respiratory Symptoms Domain Score in Adult Participants		Baseline to Week 52
Secondary	Number of Participants who Experience at Least one Treatment-Emergent Adverse Events (TEAEs)		56 Weeks
Secondary	Plasma Concentration of Brensocatib at Select Time Points		Pre-dose and post-dose at multiple time points up to Week 52