Clinical trial NCT02563067: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-09-29
Enrollment: 877
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 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)

Detailed 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

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in High Eosinophils Subpopulation
timeFrame: 52 weeks
measure: Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in Overall Population
timeFrame: 52 weeks
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: Baseline, Week 52
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:
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city: Caba
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city: Mar del Plata
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city: Ranelagh, Partido De Berazate
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city: Athens
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city: Ahmedabad
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state: Gujarat
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city: Bangalore
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city: Nagpur
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city: Pune
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city: Jaipur
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city: Rehovot
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city: Ancona
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state: AN
city: Acquaviva delle Fonti
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state: BA
city: Bari
country: Italy
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state: BA
city: Brescia
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city: Catania
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state: CT
city: Catanzaro
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city: Cona
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state: FE
city: Foggia
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city: Messina
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state: ME
city: Padova
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city: Pisa
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facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: N.Novgorod
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city: Novosibirsk
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city: Saint Petersburg
country: Russian Federation
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city: Saint Petersburg
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city: Sestroretsk
country: Russian Federation
facility: Novartis Investigative Site
city: Stavropol
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city: Belgrade
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city: Belgrade
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city: Kragujevac
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city: Dubravka
country: Slovakia
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state: Bratislava
city: Bardejov
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state: Slovak Republic
city: Bojnice
country: Slovakia
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state: Slovak Republic
city: Liptovsky Hradok
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facility: Novartis Investigative Site
state: Slovak Republic
city: Bratislava
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facility: Novartis Investigative Site
city: Komarno
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country: South Africa
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country: South Africa
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Jerez
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facility: Novartis Investigative Site
state: Cadiz
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Lugo
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facility: Novartis Investigative Site
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city: Palma De Mallorca
country: Spain
facility: Novartis Investigative Site
state: Islas Baleares
city: Girona
country: Spain
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city: Guadalajara
country: Spain
facility: Novartis Investigative Site
city: Las Palmas de Gran Canaria
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
Study officials:
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.