Clinical trial NCT02555683: Study of Efficacy and Safety of QAW039 in Patients With Severe Asthma Inadequately Controlled With Standard of Care Asthma Treatment.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
QAW039
allergic asthma
allergy triggered asthma
reactive asthma
asthma attack
difficulty breathing
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-09-21
Enrollment: 894
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in High Eosinophils Subpopulation
timeFrame: Baseline, Week 52
measure: Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in Overall Population
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: 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
timeFrame: 52 weeks
measure: Change From Baseline to Week 52 in Asthma Control Questionnaire-5(ACQ-5) Score in High Eosinophils Subpopulation
timeFrame: Baseline, Week 52
measure: Change From Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) in High Eosinophils Subpopulation
timeFrame: Baseline, Week 52
measure: Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score in Overall Population
timeFrame: Baseline, Week 52
measure: Change From Baseline to Week 52 in Asthma Control Questionnaire-5(ACQ-5) Score in Overall Population
timeFrame: Baseline, Week 52
measure: Change From Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) in Overall Population
timeFrame: Baseline, Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Gilbert
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state: Arizona
city: Litchfield Park
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city: Little Rock
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city: Redondo Beach
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city: Riverside
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city: Torrance
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city: Westminster
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city: New Haven
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state: Connecticut
city: Brandon
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state: Florida
city: New Smyrna Beach
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state: Florida
city: Orlando
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state: Florida
city: Orlando
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city: Ormond Beach
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city: Sebring
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city: Winter Park
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city: Gainesville
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state: Georgia
city: Marietta
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city: Crowley
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city: Bangor
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state: Maine
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city: White Marsh
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city: Ypsilanti
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city: Picayune
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city: Lincoln
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city: Omaha
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city: New York
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state: North Carolina
city: Gastonia
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state: North Carolina
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city: New Bern
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city: Whiteville
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city: Wilmington
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city: Winston-Salem
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city: Canton
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state: Ohio
city: Cincinnati
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city: Maumee
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state: Ohio
city: Oklahoma City
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state: Oklahoma
city: Jefferson Hills
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state: Pennsylvania
city: Pittsburgh
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state: Pennsylvania
city: East Providence
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state: Rhode Island
city: Boerne
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state: Texas
city: McKinney
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state: Texas
city: Plano
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state: Texas
city: San Antonio
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state: Virginia
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: Buenos Aires
country: Argentina
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city: Ciudad Autonoma de Bs As
country: Argentina
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city: Bedford Park
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Clayton
country: Australia
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state: Victoria
city: Footscray
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Heidelberg
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Innsbruck
country: Austria
facility: Novartis Investigative Site
state: Tyrol
city: Amstetten
country: Austria
facility: Novartis Investigative Site
city: Feldkirch
country: Austria
facility: Novartis Investigative Site
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Thalheim bei Wels
country: Austria
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city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Genk
country: Belgium
facility: Novartis Investigative Site
state: Limburg
city: Aalst
country: Belgium
facility: Novartis Investigative Site
city: Brussel
country: Belgium
facility: Novartis Investigative Site
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facility: Novartis Investigative Site
city: Bruxelles
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city: Herentals
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city: Ottignies
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city: Porto Alegre
country: Brazil
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state: Porto Alegre RS
city: Rio de Janeiro
country: Brazil
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state: RS
city: Blumenau
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state: Santa Catarina
city: Florianopolis
country: Brazil
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state: SC
city: Sao Bernardo do Campo
country: Brazil
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state: SP
city: Sao Paulo
country: Brazil
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state: SP
city: Sao Paulo
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state: SP
city: Sao Paulo
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city: Guang Zhou
country: China
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state: Guang Dong Province
city: Haikou
country: China
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state: Hainan
city: Shijiazhuang
country: China
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state: Hebei
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country: China
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state: Hubei
city: Nanjing
country: China
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state: Jiangsu
city: Nanjing
country: China
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state: Jiangsu
city: Nanchang
country: China
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state: Jiangxi
city: Chang Chun
country: China
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state: Jilin
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state: Liaoning
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country: China
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state: Shanxi
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country: China
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state: Zhejiang
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country: China
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country: China
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city: Tianjin
country: China
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country: Denmark
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city: Tallinn
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city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Helsinki
country: Finland
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city: HUS
country: Finland
facility: Novartis Investigative Site
city: OYS
country: Finland
facility: Novartis Investigative Site
city: Tampere
country: Finland
facility: Novartis Investigative Site
city: Montpellier cedex 5
country: France
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state: Herault
city: Dijon
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facility: Novartis Investigative Site
city: Le Kremlin Bicetre
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city: Lyon Cedex 04
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city: Marseille
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facility: Novartis Investigative Site
city: Nantes
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city: Paris
country: France
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city: Reims Cedex
country: France
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city: Strasbourg Cedex
country: France
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
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state: Baden-Württemberg
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Halle
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Landsberg
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
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city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
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city: Neu Isenburg
country: Germany
facility: Novartis Investigative Site
city: Rosenheim
country: Germany
facility: Novartis Investigative Site
city: Rostock
country: Germany
facility: Novartis Investigative Site
city: Rudersdorf
country: Germany
facility: Novartis Investigative Site
city: Witten
country: Germany
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Ciudad
country: Guatemala
facility: Novartis Investigative Site
state: Gautemala
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
state: GTM
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
state: GTM
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Eger
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: Gyor
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: Hajdunanas
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: Mako
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: Szazhalombatta
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: Torokbalint
country: Hungary
facility: Novartis Investigative Site
state: Pest
city: Komarom
country: Hungary
facility: Novartis Investigative Site
city: Pecs
country: Hungary
facility: Novartis Investigative Site
city: Reykjavik
country: Iceland
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Daugavpils
country: Latvia
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city: Daugavpils
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
state: LTU
city: Klaipeda
country: Lithuania
facility: Novartis Investigative Site
state: LTU
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
state: LTU
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
state: LTU
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
state: LTU
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
state: LT
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
city: Klaipeda
country: Lithuania
facility: Novartis Investigative Site
city: Bulacan
country: Philippines
facility: Novartis Investigative Site
city: Manila
country: Philippines
facility: Novartis Investigative Site
city: Quezon City
country: Philippines
facility: Novartis Investigative Site
city: Kielce
country: Poland
facility: Novartis Investigative Site
state: POL
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Biaystok
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Strzelce Opolskie
country: Poland
facility: Novartis Investigative Site
city: Ploiesti
country: Romania
facility: Novartis Investigative Site
state: Prahova
city: Constanta
country: Romania
facility: Novartis Investigative Site
state: ROM
city: Timisoara
country: Romania
facility: Novartis Investigative Site
state: Timis
city: Arad
country: Romania
facility: Novartis Investigative Site
city: Bragadiru
country: Romania
facility: Novartis Investigative Site
city: Brasov
country: Romania
facility: Novartis Investigative Site
city: Brasov
country: Romania
facility: Novartis Investigative Site
city: Brasov
country: Romania
facility: Novartis Investigative Site
city: Brasov
country: Romania
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
city: Deva
country: Romania
facility: Novartis Investigative Site
city: Oradea
country: Romania
facility: Novartis Investigative Site
city: Sangiorgiu De Mures
country: Romania
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
state: SGP
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: Liestal
country: Switzerland
facility: Novartis Investigative Site
city: Lugano
country: Switzerland
facility: Novartis Investigative Site
city: St Gallen
country: Switzerland
facility: Novartis Investigative Site
city: Zurich
country: Switzerland
facility: Novartis Investigative Site
city: Cambridge
country: United Kingdom
facility: Novartis Investigative Site
state: Cambrigdeshire
city: Darlington
country: United Kingdom
facility: Novartis Investigative Site
state: Durham
city: London
country: United Kingdom
facility: Novartis Investigative Site
state: GBR
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
state: South Yorkshire
city: Bradford
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Cardiff
country: United Kingdom
facility: Novartis Investigative Site
city: Chertsey
country: United Kingdom
facility: Novartis Investigative Site
city: East Yorkshire
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: Nottingham
country: United Kingdom
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
city: Tyne And Wear
country: United Kingdom
facility: Novartis Investigative Site
city: Wakefield
country: United Kingdom
facility: Novartis Investigative Site
city: Wishaw
country: United Kingdom
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
state: VNM
city: Hanoi
country: Vietnam
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Brightling CE, Gaga M, Inoue H, Li J, Maspero J, Wenzel S, Maitra S, Lawrence D, Brockhaus F, Lehmann T, Brindicci C, Knorr B, Bleecker ER. Effectiveness of fevipiprant in reducing exacerbations in patients with severe asthma (LUSTER-1 and LUSTER-2): two phase 3 randomised controlled trials. Lancet Respir Med. 2021 Jan;9(1):43-56. doi: 10.1016/S2213-2600(20)30412-4. Epub 2020 Sep 24.