E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
In patients with severe asthma and high eosinophil counts (≥250 cells/μl) receiving SoC asthma therapy, to demonstrate the efficacy (as measured by rate of moderate-to-severe asthma exacerbations) of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, at the end of the 52-week active-treatment epoch.
In patients with severe asthma receiving SoC asthma therapy, to demonstrate the efficacy (as measured by rate of moderate-to-severe
asthma exacerbations) of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, at the end of the 52-week active-treatment epoch. |
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E.2.2 | Secondary objectives of the trial |
In patients with severe asthma and high eosinophil counts (≥250 cells/μl) receiving SoC asthma therapy to demonstrate the efficacy of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, with respect to change from baseline, at the end of the 52-week active-treatment epoch, in AQLQ+12 scores, ACQ-5 score and pre-dose FEV1.
In all patients with severe asthma receiving SoC asthma therapy to demonstrate the efficacy of at least one dose level of QAW039 (150 mg or 450 mg once daily), compared with placebo, with respect to change from baseline, at the end of the 52-week active-treatment epoch, in : AQLQ+12 scores , ACQ-5 score and pre-dose FEV1.
To assess the safety of QAW039 (150 mg and 450 mg once daily), compared with placebo, with respect to adverse events, ECGs, vitals sign, laboratory tests and hypersensitivity reactions. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
-For patients aged ≥18 years, FEV1 of ≤80% of the predicted normal value for the patient, after withholding bronchodilators at Visit 1 and Visit 101. For patients aged 12 to <18 years, FEV1 of ≤ 90% of the predicted normal value for the for the patient, after withholding bronchodilators at Visit 1 and Visit 101.
-An ACQ score ≥1.5.
-A history of 2 or more asthma exacerbations within the 12 months prior to entering the study.
Other inclusion criteria apply. See protocol for full details |
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E.4 | Principal 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, and >2 mg of pitavastatin
Other exclusion criteria apply. See protocol for full details |
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduction in the rate of moderate-to-severe asthma exacerbations. A severe asthma exacerbation is defined as treatment with ‘rescue’ systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with ‘rescue’ systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours); or death due to asthma. A moderate asthma exacerbation is defined as treatment with ‘rescue’ systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change from baseline in AQLQ+12 score. AQLQ+12 consists of 32 questions each scaled from 1 to 7, where 1 indicates maximal impairment and 7 indicates no impairment.
- Change from baseline in ACQ-5 score. The ACQ- 5 consists of 5 questions on a 7-point scale (0=no impairment, 6=maximum impairment).
- Change from baseline in pre-dose FEV1 (liters).
- Adverse event monitoring. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 120 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Brazil |
China |
Denmark |
Estonia |
Finland |
France |
Germany |
Guatemala |
Hungary |
Iceland |
Ireland |
Latvia |
Lithuania |
Luxembourg |
Philippines |
Poland |
Romania |
Singapore |
Sweden |
Switzerland |
United Kingdom |
United States |
Vietnam |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |