Dose Finding Study for QAW039 in Asthma

Phase 2

Completed

Conditions: Asthma

Interventions: Drug: QAW039
Drug: Montelukast
Drug: Placebo

Registration Number: NCT01437735

Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1043

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
QAW039 po dose 4	QAW039	-
QAW039 po dose 7	QAW039	-
QAW039 po dose 9	QAW039	-
QAW039 po dose 11	QAW039	-
Montelukast po 10 mg	Montelukast	Comparator leukotriene receptor antagonist (LRTA)
QAW039 po dose 3	QAW039	-
QAW039 po dose 6	QAW039	-
QAW039 po dose 1	QAW039	-
QAW039 po dose 10	QAW039	-
QAW039 po dose 12	QAW039	-
Placebo	Placebo	-
QAW039 po dose 2	QAW039	-
QAW039 po dose 5	QAW039	-
QAW039 po dose 8	QAW039	-
QAW039 po dose 13	QAW039	-

Primary Outcome Measures

Name	Time	Method
Change in trough Forced Expiratory Volume in 1 second (FEV1) from baseline to week 12	Baseline and week 12	Forced Expiratory Volume in 1 second (FEV1) (measured in litters), and the trough measurement is taken 24 hours after morning dose on the previous day.

Secondary Outcome Measures

Name	Time	Method
Comparison of efficacy of QAW039 with that of active comparator as an add-on therapy to Inhaled Corticosteroids (ICS)	Baseline and week 12	Forced Expiratory Volume in 1 second (FEV1) measurement taken 24 hours after the morning dose on the previous day. The Asthma Control Questionnaire (ACQ)consisting of 7 items: 5 on system assessment, 1 on rescue bronchodilator use and 1 assessing the patients for FEV1 result against the predicted result for a person of similar age and stature. Each item is graded on a scale of 0-6, and a mean score of 1.5 or greater is considered to demonstrate inadequate asthma control in this trial. The minimal important difference that is considered clinically important is a change of 0.5 in the mean score.
Change in Asthma Control Questionnaire (ACQ) score from baseline to week 12	Baseline and week 12	The Asthma Control Questionnaire (ACQ) is a validated questionnaire consisting of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 assessing the patients Forced Expiratory Volume in 1 second (FEV1) result against the predicted result for a person of similar age and stature. Each item is graded on a scale of 0-6, and a mean score of 1.5 or greater is considered to demonstrate inadequate asthma control in this trial. The minimal important difference that is considered clinically important is a change of 0.5 in the mean score.
Comparison of vital signs, ECG, laboratory tests and adverse events across QAW039 doses and placebo.	Baseline and week 12	Comparisons of vital signs (i.e. systolic and diastolic blood pressure, pulse rate), ECG (e.g. quantitative assessments - heart rate, QTcF, PRS, PR intervals), laboratory tests (haematology, clinical chemistry and urinalysis) and adverse events across QAW039 doses and placebo.
Assess the effect of QAW039 on asthma symptoms as measured by asthma control diary.	Baseline and week 12	The asthma control diary mimics the Asthma Control Questionnaire (ACQ), but is recorded daily by the patient, rather than at each visit. As for the ACQ, the ACD consists of 7 questions.
Change in Forced Expiratory Volume in 1 second (FEV1) from baseline to weeks 2, 4 and 8.	Baseline, week 2, week 4 and week 8	Forced Expiratory Volume in 1 second (FEV1) (measured in litters), and the measurement is taken 24 hours after the morning dose on the previous day.
Change in the Asthma Control Questionnaire (ACQ) score from baseline to weeks 2, 4 and 8.	Baseline, week 2, week 4 and week 8	The Asthma Control Questionnaire (ACQ) is a validated questionnaire consisting of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 assessing the patients Forced Expiratory Volume in 1 second (FEV1) result against the predicted result for a person of similar age and stature. Each item is graded on a scale of 0-6, and a mean score of 1.5 or greater is considered to demonstrate inadequate asthma control in this trial. The minimal important difference that is considered clinically important is a change of 0.5 in the mean score.
Change in the dose response relationship among QAW039 doses with respect to Forced Expiratory Volume in 1 second (FEV1) after 12 weeks treatment.	Baseline and week 12	Forced Expiratory Volume in 1 second (FEV1) (measured in litters), and the measurement is taken 24 hours after the morning dose on the previous day.