Study of Efficacy and Safety of QAW039 in Patients With Severe Asthma Inadequately Controlled With Standard of Care Asthma Treatment.

Asthma Clinical Trial

Official title:

A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of QAW039 When Added to Existing Asthma Therapy in Patients With Uncontrolled Severe Asthma.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02563067
• Other study ID #: CQAW039A2314
• Secondary ID: 2015-003172-67
• Status: Completed
• Phase: Phase 3
• Start date: December 3, 2015
• Est. completion date: August 2, 2019

Study information

• Verified date: April 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aimed to determine the efficacy and safety of QAW039 and QAW039 450 mg compared to placebo, when added to GINA (Global Initiative for Asthma) steps 4 and 5 standard-of- care (SoC) asthma therapy (GINA 2016) in the following two populations:

• patient with inadequately controlled severe asthma and high eosinophil counts (eosinophil count at Visit 1 ≥250 cells/ µl) (sub-population)

• patients with inadequately controlled severe asthma (overall study population) Inadequate control is defined as partly controlled or uncontrolled asthma (GINA 2016)

Description:

This study used a randomized, multicenter, double-blind, placebo-controlled parallel-group design in which QAW039 (150 mg and 450 mg) or placebo was added to GINA steps 4 and 5 asthma therapy.

The study included:

• Screening period of up to 2 weeks to assess eligibility;

• Run-in period of approximately 2 weeks and a maximum of 6 weeks on placebo to collect baseline data for efficacy variables and compliance with the Electronic Peak Flow/ eDiary device. Upon completion of the run-in period, all patients who met the eligibility criteria were randomized to one of three treatments: QAW039 150 mg or QAW039 450 mg or placebo once daily in a ratio of 1:1:1.

• Treatment period of 52 weeks (assessment period for all Primary and Secondary Outcome Measures). Clinic visits were scheduled approximately 4 weeks after randomization and then at approximately 8-week intervals during the active-treatment period. Phone calls occurred at specified time points between visits occurring at 8-week intervals. Patients who had successfully completed 52 weeks of treatment in this study were offered an optional participation in a safety study (CQAW039A2315).

• Follow-up period of 4 weeks, investigational and drug-free, following the last dose of study drug. A follow-up visit occurred approximately 4 weeks (i.e., approximately 30 days) following the last dose of study therapy to complete safety assessments and pregnancy testing (if applicable).

The follow-up period applied to all patients except those patients who had entered the optional safety study (CQAW039A2315) directly after the Week 52 study visit

Recruitment information / eligibility

• Status: Completed
• Enrollment: 877
• Est. completion date: August 2, 2019
• Est. primary completion date: July 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent.

• Male and female patients aged =12 years.

• A diagnosis of severe asthma, uncontrolled on GINA 4/5 asthma medication.

• Evidence of airway reversibility or airway hyper- reactivity.

• FEV1 =80% of the predicted normal value for patients aged =18 years; FEV1 of =90% for patients aged 12 to <18 years

• An ACQ score =1.5

• A history of 2 or more asthma exacerbations within the 12 months prior to entering the study.

Exclusion Criteria:

• Use of other investigational drugs within 5 half-lives of study entry, or within 30 days, whichever is longer.

• Subjects who have participated in another trial of QAW039.

• A QTcF (Fridericia) =450 msec (male) or =460 msec (female).

• History of malignancy with the exception of local basal cell carcinoma of the skin.

• Pregnant or nursing (lactating) women.

• Serious co-morbidities.

• Patients on >20 mg of simvastatin, > 40 mg of atorvastatin, >40 mg of pravastatin, or >2 mg of pitavastatin.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• QAW039
QAW039 150 mg once daily
• QAW039
QAW039 450 mg once daily
• Placebo
Placebo once daily

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Berazategui	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires	Ciudad Autonoma De Bs As
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Lanus	Buenos Aires
Argentina	Novartis Investigative Site	Mar del Plata	Buenos Aires
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Ranelagh, Partido De Berazate	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	Santa Fe	Rosario
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Santa Rosa	La Pampa
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Vancouver BC	British Columbia
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Jindrichuv Hradec	Czech Republic
Czechia	Novartis Investigative Site	Karlovy Vary
Czechia	Novartis Investigative Site	Mlada Boleslav
Czechia	Novartis Investigative Site	Plzen-Bory
Czechia	Novartis Investigative Site	Teplice	Czech Republic
Czechia	Novartis Investigative Site	Teplice	CZE
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Thessaloniki	GR
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Coimbatore	Tamil Nadu
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Jaipur	Rajasthan
India	Novartis Investigative Site	Jaipur	Rajasthan
India	Novartis Investigative Site	Lucknow	Uttar Pradesh
India	Novartis Investigative Site	Madurai	Tamil Nadu
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Pune	Maharashtra
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Rehovot
Italy	Novartis Investigative Site	Acquaviva delle Fonti	BA
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Bari	BA
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative Site	Cagliari	Sicilia
Italy	Novartis Investigative Site	Catania	CT
Italy	Novartis Investigative Site	Catanzaro	CZ
Italy	Novartis Investigative Site	Cona	FE
Italy	Novartis Investigative Site	Foggia	FG
Italy	Novartis Investigative Site	Legnago	VR
Italy	Novartis Investigative Site	Messina	ME
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Reggio Emilia
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Salerno
Italy	Novartis Investigative Site	Siena	SI
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Verona	VR
Japan	Novartis Investigative Site	Bunkyo ku	Tokyo
Japan	Novartis Investigative Site	Chikushino-city	Fukuoka
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Hamamatsu-city	Shizuoka
Japan	Novartis Investigative Site	Hiroshima-city	Hiroshima
Japan	Novartis Investigative Site	Kagoshima city	Kagoshima
Japan	Novartis Investigative Site	Kasuga-city	Fukuoka
Japan	Novartis Investigative Site	Kishiwada-city	Osaka
Japan	Novartis Investigative Site	Naka-gun	Ibaraki
Japan	Novartis Investigative Site	Sakaide-city	Kagawa
Japan	Novartis Investigative Site	Setagaya-Ku	Tokyo
Japan	Novartis Investigative Site	Shinagawa-ku	Tokyo
Japan	Novartis Investigative Site	Takamatsu-city	Kagawa
Japan	Novartis Investigative Site	Toshima ku	Tokyo
Japan	Novartis Investigative Site	Yokohama city	Kanagawa
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	El Chouf	LBN
Malaysia	Novartis Investigative Site	Batu Caves
Malaysia	Novartis Investigative Site	Kota Bharu	Kelantan
Malaysia	Novartis Investigative Site	Kuantan	Pahang
Malaysia	Novartis Investigative Site	Taiping	Perak
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Guadalajara Jalisco	Jalisco
Mexico	Novartis Investigative Site	Zapopan	Jalisco
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Arnhem
Netherlands	Novartis Investigative Site	Leeuwarden
Netherlands	Novartis Investigative Site	Leiden
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Izhevsk
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	N.Novgorod
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Sestroretsk
Russian Federation	Novartis Investigative Site	Stavropol
Serbia	Novartis Investigative Site	Belgrade
Serbia	Novartis Investigative Site	Belgrade
Serbia	Novartis Investigative Site	Kragujevac
Slovakia	Novartis Investigative Site	Bardejov	Slovak Republic
Slovakia	Novartis Investigative Site	Bojnice	Slovak Republic
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Dubravka	Bratislava
Slovakia	Novartis Investigative Site	Komarno
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Levice
Slovakia	Novartis Investigative Site	Liptovsky Hradok	Slovak Republic
Slovakia	Novartis Investigative Site	Spisska Nova Ves
Slovakia	Novartis Investigative Site	Vysne Hagy
South Africa	Novartis Investigative Site	Mowbray
South Africa	Novartis Investigative Site	Panorama
South Africa	Novartis Investigative Site	Tygerberg	Cape Town
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Girona
Spain	Novartis Investigative Site	Guadalajara
Spain	Novartis Investigative Site	Jerez	Cadiz
Spain	Novartis Investigative Site	Las Palmas de Gran Canaria
Spain	Novartis Investigative Site	Lugo	Galicia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Palma De Mallorca	Islas Baleares
Spain	Novartis Investigative Site	Sabadell	Cataluña
Spain	Novartis Investigative Site	Santiago de Compostela
Spain	Novartis Investigative Site	Zaragoza
Taiwan	Novartis Investigative Site	Taichung	Taiwan ROC
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taichung
United States	Novartis Investigative Site	Bronx	New York
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Edmond	Oklahoma
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Little Rock	Arkansas
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Overland Park	Kansas
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Plano	Texas
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	San Jose	California
United States	Novartis Investigative Site	Stockton	California
United States	Novartis Investigative Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Czechia,  Greece,  India,  Israel,  Italy,  Japan,  Lebanon,  Malaysia,  Mexico,  Netherlands,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in High Eosinophils Subpopulation	A severe asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours*); or death due to asthma.; A moderate asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours). The high eosinophils subpopulation consists of all patients with blood eosinophil count = 250 cells/µL at baseline.	52 weeks
Primary	Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in Overall Population	A severe asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours*); or death due to asthma.; A moderate asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours).	52 weeks
Secondary	Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score in High Eosinophils Subpopulation	AQLQ is a 32-item instrument administered as a self-assessment. AQLQ+12 is a modified version of AQLQ developed to measure functional impairments of participants aged 12-70 years. It is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Participants were asked to recall their experiences during the last 2 weeks and respond to each question on a 7-point scale (1=severe impairment, 7=no impairment), where higher scores indicated "better quality of life." Overall AQLQ+12 score is the mean of all 32 responses. The high eosinophils subpopulation consists of all patients with blood eosinophil count = 250 cells/µL at baseline.	Baseline, Week 52
Secondary	Change From Baseline to Week 52 in Asthma Control Questionnaire-5 (ACQ-5) Score in High Eosinophils Subpopulation	The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/ limitation) scale. The ACQ-5 score is the average of the individual item scores and ranges from 0 to 6. Higher scores indicates worsening of condition. The high eosinophils subpopulation consists of all patients with blood eosinophil count = 250 cells/µL at baseline.	Baseline, Week 52
Secondary	Change From Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) in High Eosinophils Subpopulation	Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug. The high eosinophils subpopulation consists of all patients with blood eosinophil count = 250 cells/µL at baseline.	Baseline, Week 52
Secondary	Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score in Overall Population	AQLQ is a 32-item instrument administered as a self-assessment. AQLQ+12 is a modified version of AQLQ developed to measure functional impairments of participants aged 12-70 years. It is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Participants were asked to recall their experiences during the last 2 weeks and respond to each question on a 7-point scale (1=severe impairment, 7=no impairment), where higher scores indicated "better quality of life." Overall AQLQ+12 score is the mean of all 32 responses.	Baseline, Week 52
Secondary	Change From Baseline to Week 52 in Asthma Control Questionnaire-5 (ACQ-5) Score in Overall Population	The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/ limitation) scale. The ACQ-5 score is the average of the individual item scores and ranges from 0 to 6. Higher scores indicates worsening of condition.	Baseline, Week 52
Secondary	Change From Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) in Overall Population	Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug.	Baseline, Week 52