Clinical trial NCT01437735: Dose Finding Study for QAW039 in Asthma
Official title: A Randomized, Placebo-controlled, Dose-ranging, Multi-centre Trial of QAW039 (1-450 mg p.o.), to Investigate the Effect on FEV1 and ACQ in Patients With Moderate-to-severe, Persistent, Allergic Asthma, Inadequately Controlled With ICS Therapy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
QAW039
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-09-21
Enrollment: 1043
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to demonstrate a clinically significant improvement in Forced Expiratory Volume in one second (FEV1) in moderate to severe allergic asthmatics inadequately controlled by Inhaled Corticosteroid (ICS) therapy. Patients will be treated with QAW039, an active comparator, or placebo. This will be a randomized, placebo-controlled, dose-ranging, multi-centre trial.


Eligibility criteria: Inclusion Criteria:

* Physician diagnosis of asthma, as per the Global Initiative for Asthma (GINA) (2009) guidelines, and currently prescribed Inhaled Corticosteroids (ICS) therapy.
* Patients with a pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) value of 40% to 80% of individual predicted value.
* Patients should be allergic or atopic, as diagnosed historically or prior to entry into the study.
* Patients who are demonstrated to have reversible airway obstruction or airways hyper-reactivity or have shown either of such responses in previous test(s) within the last year.
* An Asthma Control Questionnaire (ACQ) score ≥ 1.5 at randomization.

Exclusion Criteria:

* Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (\> 5 mIU/mL).
* Patients with serious co-morbidities including uncontrolled diabetes (HbA1c≥8%), heart failure, cancer, neurodegenerative diseases, rheumatoid arthritis and other autoimmune diseases, other lung diseases including chronic bronchitis, chronic obstructive pulmonary diseases or emphysema or other conditions characterized by eosinophilia and pulmonary symptoms (i.e. Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, eosinophilic pneumonia, etc.).
* Acute illness other than asthma at the start of the study
* History of life-threatening asthma, including a history of significant hypercarbia (pCO2\>45mmHg), prior intubation, respiratory arrest, or seizures as a result of asthma.
* Patients who have had a respiratory tract infection within 4 weeks of the screening visit. Patients who develop a respiratory tract infection between screening and the randomization visit must be screen failed, and may be permitted to re-enroll at a later date.
* Current smokers or ex-smokers who stopped smoking within 6 months prior to screening or have a smoking history of ≥ 10 pack years.

Primary outcomes:
measure: Change in trough Forced Expiratory Volume in 1 second (FEV1) from baseline to week 12
timeFrame: Baseline and week 12
Secondary outcomes:
measure: Change in Asthma Control Questionnaire (ACQ) score from baseline to week 12
timeFrame: Baseline and week 12
measure: Change in Forced Expiratory Volume in 1 second (FEV1) from baseline to weeks 2, 4 and 8.
timeFrame: Baseline, week 2, week 4 and week 8
measure: Change in the Asthma Control Questionnaire (ACQ) score from baseline to weeks 2, 4 and 8.
timeFrame: Baseline, week 2, week 4 and week 8
measure: Change in the dose response relationship among QAW039 doses with respect to Forced Expiratory Volume in 1 second (FEV1) after 12 weeks treatment.
timeFrame: Baseline and week 12
measure: Comparison of vital signs, ECG, laboratory tests and adverse events across QAW039 doses and placebo.
timeFrame: Baseline and week 12
measure: Comparison of efficacy of QAW039 with that of active comparator as an add-on therapy to Inhaled Corticosteroids (ICS)
timeFrame: Baseline and week 12
measure: Assess the effect of QAW039 on asthma symptoms as measured by asthma control diary.
timeFrame: Baseline and week 12
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Encinitas
country: United States
facility: Novartis Investigative Site
state: California
city: Huntington Beach
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Orange
country: United States
facility: Novartis Investigative Site
state: California
city: Riverside
country: United States
facility: Novartis Investigative Site
state: California
city: San Diego
country: United States
facility: Novartis Investigative Site
state: California
city: San Diego
country: United States
facility: Novartis Investigative Site
state: California
city: San Jose
country: United States
facility: Novartis Investigative Site
state: California
city: San Mateo
country: United States
facility: Novartis Investigative Site
state: California
city: Stockton
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facility: Novartis Investigative Site
state: California
city: Centennial
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facility: Novartis Investigative Site
state: Colorado
city: Denver
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Sarasota
country: United States
facility: Novartis Investigative Site
state: Florida
city: Savannah
country: United States
facility: Novartis Investigative Site
state: Georgia
city: River Forest
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Bangor
country: United States
facility: Novartis Investigative Site
state: Maine
city: Wheaton
country: United States
facility: Novartis Investigative Site
state: Maryland
city: North Dartmouth
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Minneapolis
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Warrensburg
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Omaha
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Omaha
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Papillion
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Skillman
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Canton
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Lake Oswego
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Medford
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Erie
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Lincoln
country: United States
facility: Novartis Investigative Site
state: Rhode Island
city: Charleston
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Fort Worth
country: United States
facility: Novartis Investigative Site
state: Texas
city: Waco
country: United States
facility: Novartis Investigative Site
state: Texas
city: South Burlington
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facility: Novartis Investigative Site
state: Vermont
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Florencio Varela
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
state: Rosario
city: San Miguel de Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Mendoza
country: Argentina
facility: Novartis Investigative Site
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
city: Feldbach
country: Austria
facility: Novartis Investigative Site
city: Grieskirchen
country: Austria
facility: Novartis Investigative Site
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Thalheim bei Wels
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Ruse
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Varna
country: Bulgaria
facility: Novartis Investigative Site
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Bogota
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Armenia
country: Colombia
facility: Novartis Investigative Site
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
city: Bogotá
country: Colombia
facility: Novartis Investigative Site
city: Medellín
country: Colombia
facility: Novartis Investigative Site
city: Ferolles-Attily
country: France
facility: Novartis Investigative Site
city: Lyon cedex 04
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Pessac
country: France
facility: Novartis Investigative Site
city: Reims
country: France
facility: Novartis Investigative Site
city: Strasbourg Cedex
country: France
facility: Novartis Investigative Site
city: Tarbes Cedex
country: France
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Heraklion - Crete
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Antigua Guatemala
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Balassagyarmat
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Deszk
country: Hungary
facility: Novartis Investigative Site
city: Gyor
country: Hungary
facility: Novartis Investigative Site
city: Mosonmagyarovar
country: Hungary
facility: Novartis Investigative Site
city: Nyiregyhaza
country: Hungary
facility: Novartis Investigative Site
city: Százhalombatta
country: Hungary
facility: Novartis Investigative Site
city: Torokbalint
country: Hungary
facility: Novartis Investigative Site
city: Panjim
country: India
facility: Novartis Investigative Site
state: Goa
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Mysore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Indore
country: India
facility: Novartis Investigative Site
state: Madhya Pradesh
city: Nagpur
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Pune
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Ludhiana
country: India
facility: Novartis Investigative Site
state: Punjab
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facility: Novartis Investigative Site
state: Rajasthan
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country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Coimbatore
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facility: Novartis Investigative Site
state: Tamil Nadu
city: Nagpur - Maharashtra
country: India
facility: Novartis Investigative Site
city: Firenze
country: Italy
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state: FI
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Parma
country: Italy
facility: Novartis Investigative Site
state: PR
city: Nishio-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Kasuga-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Kitakyushu
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Kitakyushu
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Yanagawa
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Mizunami-city
country: Japan
facility: Novartis Investigative Site
state: Gifu
city: Hatsukaichi-city
country: Japan
facility: Novartis Investigative Site
state: Hiroshima
city: Asahikawa-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
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city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Himeji-city
country: Japan
facility: Novartis Investigative Site
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city: Higashiibaraki-gun
country: Japan
facility: Novartis Investigative Site
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facility: Novartis Investigative Site
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facility: Novartis Investigative Site
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facility: Novartis Investigative Site
state: Kagawa
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country: Japan
facility: Novartis Investigative Site
state: Kanagawa
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facility: Novartis Investigative Site
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facility: Novartis Investigative Site
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facility: Novartis Investigative Site
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facility: Novartis Investigative Site
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country: Japan
facility: Novartis Investigative Site
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country: Japan
facility: Novartis Investigative Site
state: Osaka
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country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Osakasayama
country: Japan
facility: Novartis Investigative Site
state: Osaka
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country: Japan
facility: Novartis Investigative Site
state: Saitama
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country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Hamamatsu
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Hamamatsu
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Chiyoda-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Edogawa-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Kiyose-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Minato-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Setagaya-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Tachikawa
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Taito
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Toshima-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Fukuoka
country: Japan
facility: Novartis Investigative Site
city: Hiroshima
country: Japan
facility: Novartis Investigative Site
city: Kochi
country: Japan
facility: Novartis Investigative Site
city: Kyoto
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Mexicali
country: Mexico
facility: Novartis Investigative Site
state: Baja California
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: México
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Zapopan
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: Nuevo León
city: Almelo
country: Netherlands
facility: Novartis Investigative Site
city: Harderwijk
country: Netherlands
facility: Novartis Investigative Site
city: Cercado De Lima
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Jesus Maria
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Miraflores
country: Peru
facility: Novartis Investigative Site
state: Lima
city: San Borja
country: Peru
facility: Novartis Investigative Site
state: Lima
city: San Isidro
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Santiago de Surco
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Katowice
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
state: District 1
city: Bucharest
country: Romania
facility: Novartis Investigative Site
state: District 1
city: Bucharest
country: Romania
facility: Novartis Investigative Site
state: District 3
city: Craiova
country: Romania
facility: Novartis Investigative Site
state: Dolj
city: Iasi
country: Romania
facility: Novartis Investigative Site
state: Jud. Iasi
city: Arad
country: Romania
facility: Novartis Investigative Site
city: Arad
country: Romania
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Deva
country: Romania
facility: Novartis Investigative Site
city: Barnaul
country: Russian Federation
facility: Novartis Investigative Site
city: Barnaul
country: Russian Federation
facility: Novartis Investigative Site
city: Chelyabinsk
country: Russian Federation
facility: Novartis Investigative Site
city: Chelyabinsk
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Ryazan
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St.-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Yaroslavl
country: Russian Federation
facility: Novartis Investigative Site
city: Amanzimtoti
country: South Africa
facility: Novartis Investigative Site
city: Benoni
country: South Africa
facility: Novartis Investigative Site
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
city: Durban
country: South Africa
facility: Novartis Investigative Site
city: Gatesville
country: South Africa
facility: Novartis Investigative Site
city: Port Elizabeth
country: South Africa
facility: Novartis Investigative Site
city: Pretoria
country: South Africa
facility: Novartis Investigative Site
city: Pretoria
country: South Africa
facility: Novartis Investigative Site
city: Fatih / Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Mersin
country: Turkey
facility: Novartis Investigative Site
city: Yenisehir/Izmir
country: Turkey
facility: Novartis Investigative Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
state: Newcastle
city: Bradford
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow - Scotland
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Bateman ED, Guerreros AG, Brockhaus F, Holzhauer B, Pethe A, Kay RA, Townley RG. Fevipiprant, an oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids. Eur Respir J. 2017 Aug 24;50(2):1700670. doi: 10.1183/13993003.00670-2017. Print 2017 Aug.