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: NCT02555683
• Other study ID #: CQAW039A2307
• Secondary ID: 2015-002553-35
• Status: Completed
• Phase: Phase 3
• Start date: December 11, 2015
• Est. completion date: November 4, 2019

Study information

• Verified date: April 2020
• 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 150 mg and QAW039 450 mg, compared with 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 at baseline (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 or QA039 450 mg or placebo was added to standard of care, 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 safety study (CQAW039A2315) directly after the Week 52 study visit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 894
• Est. completion date: November 4, 2019
• Est. primary completion date: October 21, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent and assent (if applicable).

• Male and female patients aged =12 years (or =lower age limit allowed by health authority and/or ethics committee/institutional review board approvals).

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

• Evidence of airway reversibility or airway hyper- reactivity.

• FEV1 of =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 greater than 20 mg of simvastatin, greater than 40 mg of atorvastatin, greater than 40 mg of pravastatin, or greater than 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	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Australia	Novartis Investigative Site	Bedford Park	South Australia
Australia	Novartis Investigative Site	Clayton	Victoria
Australia	Novartis Investigative Site	Footscray	Victoria
Australia	Novartis Investigative Site	Heidelberg	Victoria
Australia	Novartis Investigative Site	Melbourne	Victoria
Austria	Novartis Investigative Site	Amstetten
Austria	Novartis Investigative Site	Feldkirch
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Innsbruck	Tyrol
Austria	Novartis Investigative Site	Thalheim bei Wels
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Wien
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Aalst
Belgium	Novartis Investigative Site	Brussel
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Eghezee
Belgium	Novartis Investigative Site	Erpent
Belgium	Novartis Investigative Site	Genk	Limburg
Belgium	Novartis Investigative Site	Herentals
Belgium	Novartis Investigative Site	Kortrijk
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Ottignies
Brazil	Novartis Investigative Site	Blumenau	Santa Catarina
Brazil	Novartis Investigative Site	Florianopolis	SC
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Porto Alegre	Porto Alegre RS
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Sao Bernardo do Campo	SP
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	Sao Paulo	SP
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chang Chun	Jilin
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Chengdu
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Guang Zhou	Guang Dong Province
China	Novartis Investigative Site	Haikou	Hainan
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Nanchang	Jiangxi
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shenyang	Liaoning
China	Novartis Investigative Site	Shenyang	Liaoning
China	Novartis Investigative Site	Shijiazhuang	Hebei
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Xian	Shanxi
Denmark	Novartis Investigative Site	Copenhagen NV
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	HUS
Finland	Novartis Investigative Site	OYS
Finland	Novartis Investigative Site	Tampere
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Le Kremlin Bicetre
France	Novartis Investigative Site	Lyon Cedex 04
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Montpellier cedex 5	Herault
France	Novartis Investigative Site	Nantes
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Reims Cedex
France	Novartis Investigative Site	Strasbourg Cedex
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Heidelberg	Baden-Württemberg
Germany	Novartis Investigative Site	Landsberg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Neu Isenburg
Germany	Novartis Investigative Site	Rosenheim
Germany	Novartis Investigative Site	Rostock
Germany	Novartis Investigative Site	Rudersdorf
Germany	Novartis Investigative Site	Witten
Greece	Novartis Investigative Site	Thessaloniki	GR
Guatemala	Novartis Investigative Site	Ciudad	Gautemala
Guatemala	Novartis Investigative Site	Guatemala City	GTM
Guatemala	Novartis Investigative Site	Guatemala City	GTM
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Hungary	Novartis Investigative Site	Eger	HUN
Hungary	Novartis Investigative Site	Gyor	HUN
Hungary	Novartis Investigative Site	Hajdunanas	HUN
Hungary	Novartis Investigative Site	Komarom
Hungary	Novartis Investigative Site	Mako	HUN
Hungary	Novartis Investigative Site	Pecs
Hungary	Novartis Investigative Site	Szazhalombatta	HUN
Hungary	Novartis Investigative Site	Torokbalint	Pest
Iceland	Novartis Investigative Site	Reykjavik
Ireland	Novartis Investigative Site	Dublin
Ireland	Novartis Investigative Site	Dublin
Latvia	Novartis Investigative Site	Daugavpils
Latvia	Novartis Investigative Site	Daugavpils
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Kaunas	LTU
Lithuania	Novartis Investigative Site	Kaunas	LT
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Klaipeda	LTU
Lithuania	Novartis Investigative Site	Vilnius	LTU
Lithuania	Novartis Investigative Site	Vilnius	LTU
Lithuania	Novartis Investigative Site	Vilnius	LTU
Philippines	Novartis Investigative Site	Bulacan
Philippines	Novartis Investigative Site	Manila
Philippines	Novartis Investigative Site	Quezon City
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Biaystok
Poland	Novartis Investigative Site	Kielce	POL
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Strzelce Opolskie
Romania	Novartis Investigative Site	Arad
Romania	Novartis Investigative Site	Bragadiru
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Cluj Napoca
Romania	Novartis Investigative Site	Cluj Napoca
Romania	Novartis Investigative Site	Constanta	ROM
Romania	Novartis Investigative Site	Deva
Romania	Novartis Investigative Site	Oradea
Romania	Novartis Investigative Site	Ploiesti	Prahova
Romania	Novartis Investigative Site	Sangiorgiu De Mures
Romania	Novartis Investigative Site	Timisoara	Timis
Singapore	Novartis Investigative Site	Singapore	SGP
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	Liestal
Switzerland	Novartis Investigative Site	Lugano
Switzerland	Novartis Investigative Site	St Gallen
Switzerland	Novartis Investigative Site	Zurich
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Bradford	West Yorkshire
United Kingdom	Novartis Investigative Site	Cambridge	Cambrigdeshire
United Kingdom	Novartis Investigative Site	Cardiff
United Kingdom	Novartis Investigative Site	Chertsey
United Kingdom	Novartis Investigative Site	Darlington	Durham
United Kingdom	Novartis Investigative Site	East Yorkshire
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	London	GBR
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Plymouth
United Kingdom	Novartis Investigative Site	Sheffield	South Yorkshire
United Kingdom	Novartis Investigative Site	Tyne And Wear
United Kingdom	Novartis Investigative Site	Wakefield
United Kingdom	Novartis Investigative Site	Wishaw
United States	Novartis Investigative Site	Bangor	Maine
United States	Novartis Investigative Site	Bellevue	Nebraska
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Boerne	Texas
United States	Novartis Investigative Site	Brandon	Florida
United States	Novartis Investigative Site	Canton	Ohio
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Corning	New York
United States	Novartis Investigative Site	Crowley	Louisiana
United States	Novartis Investigative Site	East Providence	Rhode Island
United States	Novartis Investigative Site	Fairfax	Virginia
United States	Novartis Investigative Site	Gainesville	Georgia
United States	Novartis Investigative Site	Gaithersburg	Maryland
United States	Novartis Investigative Site	Gastonia	North Carolina
United States	Novartis Investigative Site	Gilbert	Arizona
United States	Novartis Investigative Site	Hawaiian Gardens	California
United States	Novartis Investigative Site	Jefferson Hills	Pennsylvania
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Litchfield Park	Arizona
United States	Novartis Investigative Site	Little Rock	Arkansas
United States	Novartis Investigative Site	Livonia	Michigan
United States	Novartis Investigative Site	Marietta	Georgia
United States	Novartis Investigative Site	Maumee	Ohio
United States	Novartis Investigative Site	McKinney	Texas
United States	Novartis Investigative Site	Monroe	North Carolina
United States	Novartis Investigative Site	New Bern	North Carolina
United States	Novartis Investigative Site	New Haven	Connecticut
United States	Novartis Investigative Site	New Smyrna Beach	Florida
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Newport Beach	California
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Ormond Beach	Florida
United States	Novartis Investigative Site	Peoria	Arizona
United States	Novartis Investigative Site	Picayune	Mississippi
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Plano	Texas
United States	Novartis Investigative Site	Redondo Beach	California
United States	Novartis Investigative Site	Riverside	California
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Sebring	Florida
United States	Novartis Investigative Site	Torrance	California
United States	Novartis Investigative Site	Westminster	California
United States	Novartis Investigative Site	White Marsh	Maryland
United States	Novartis Investigative Site	Whiteville	North Carolina
United States	Novartis Investigative Site	Wilmington	North Carolina
United States	Novartis Investigative Site	Winston-Salem	North Carolina
United States	Novartis Investigative Site	Winter Park	Florida
United States	Novartis Investigative Site	Ypsilanti	Michigan
United States	Novartis Investigative Site	Zachary	Louisiana
Vietnam	Novartis Investigative Site	Hanoi
Vietnam	Novartis Investigative Site	Ho Chi Minh
Vietnam	Novartis Investigative Site	Ho Chi Minh	VNM

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  China,  Denmark,  Estonia,  Finland,  France,  Germany,  Greece,  Guatemala,  Hungary,  Iceland,  Ireland,  Latvia,  Lithuania,  Philippines,  Poland,  Romania,  Singapore,  Spain,  Switzerland,  United Kingdom, 

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.	Baseline, Week 52
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).	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 High Eosinophils Subpopulation	The AQLQ+12 is comprised of a total of 32 individual questions that span a total of four domains: symptoms, activity limitation, emotional function, and environmental stimuli.; Patients were asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The AQLQ+12 yields individual domain scores, which is the mean of all items in each domain, and an overall score, which is the mean of all 32 individual responses. Higher scores indicate less impairment in health-related quality of life. The high eosinophils subpopulation consists of all patients with blood eosinophil count = 250 cells/µL at baseline.	52 weeks
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. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the ACQ-5 score is the mean of the 5 questions: therefore, between 0 (totally controlled) and 6 (severely uncontrolled). 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	The AQLQ+12 is comprised of a total of 32 individual questions that span a total of four domains: symptoms, activity limitation, emotional function, and environmental stimuli.; Patients were asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The AQLQ+12 yields individual domain scores, which is the mean of all items in each domain, and an overall score, which is the mean of all 32 individual responses. Higher scores indicate less impairment in health-related quality of life.	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. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the ACQ-5 score is the mean of the 5 questions: therefore, between 0 (totally controlled) and 6 (severely uncontrolled).	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