Dose Finding Study for QAW039 in Asthma

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Asthma

Intervention / Treatment
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* Drug: QAW039
* Drug: Montelukast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QAW039 po dose 1<br> | Drug: QAW039<br>* QAW039 po<br>|
| Experimental: QAW039 po dose 2<br> | Drug: QAW039<br>* QAW039 po<br>|
| Experimental: QAW039 po dose 3<br> | Drug: QAW039<br>* QAW039 po<br>|
| Experimental: QAW039 po dose 4<br> | Drug: QAW039<br>* QAW039 po<br>|
| Experimental: QAW039 po dose 5<br> | Drug: QAW039<br>* QAW039 po<br>|
| Experimental: QAW039 po dose 6<br> | Drug: QAW039<br>* QAW039 po<br>|
| Experimental: QAW039 po dose 7<br> | Drug: QAW039<br>* QAW039 po<br>|
| Experimental: QAW039 po dose 8<br> | Drug: QAW039<br>* QAW039 po<br>|
| Experimental: QAW039 po dose 9<br> | Drug: QAW039<br>* QAW039 po<br>|
| Experimental: QAW039 po dose 10<br> | Drug: QAW039<br>* QAW039 po<br>|
| Experimental: QAW039 po dose 11<br> | Drug: QAW039<br>* QAW039 po<br>|
| Experimental: QAW039 po dose 12<br> | Drug: QAW039<br>* QAW039 po<br>|
| Experimental: QAW039 po dose 13<br> | Drug: QAW039<br>* QAW039 po<br>|
| Active Comparator: Montelukast po 10 mg<br>Comparator leukotriene receptor antagonist (LRTA) | Drug: Montelukast<br>* Montelukast 10 mg po<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in trough Forced Expiratory Volume in 1 second (FEV1) from baseline to 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. | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Asthma Control Questionnaire (ACQ) score from baseline to 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. | Baseline and week 12 | 
| Change in Forced Expiratory Volume in 1 second (FEV1) from baseline to weeks 2, 4 and 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. | Baseline, week 2, week 4 and week 8 | 
| Change in the Asthma Control Questionnaire (ACQ) score from baseline to weeks 2, 4 and 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. | Baseline, week 2, week 4 and week 8 | 
| Change in the dose response relationship among QAW039 doses with respect to Forced Expiratory Volume in 1 second (FEV1) after 12 weeks treatment. | 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. | Baseline and week 12 | 
| Comparison of vital signs, ECG, laboratory tests and adverse events across QAW039 doses and placebo. | 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. | Baseline and week 12 | 
| Comparison of efficacy of QAW039 with that of active comparator as an add-on therapy to Inhaled Corticosteroids (ICS) | 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. | Baseline and week 12 | 
| Assess the effect of QAW039 on asthma symptoms as measured by asthma control diary. | 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. | Baseline and week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, QAW039