E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate-to-severe, persistent, allergic asthma, inadequately controlled with ICS therapy |
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E.1.1.1 | Medical condition in easily understood language |
|
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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001705 |
E.1.2 | Term | Allergic asthma |
E.1.2 | System Organ Class | 100000004855 |
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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 |
To demonstrate a clinically significant improvement in morning FEV1 in moderate to severe allergic asthmatics inadequately controlled by ICS therapy treated with QAW039 for 12 weeks compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
- To demonstrate that QAW039 provides significantly superior control of asthmatic symptoms in these patients as measured by the ACQ, compared to placebo.
- To estimate the onset of efficacy as measured by spirometry assessments and the ACQ after 2, 4, 8 and 12 weeks of treatment.
- To characterize the dose response relationship among QAW039 doses with respect to trough FEV1 after 12 weeks of treatment.
- To assess safety and tolerability of QAW039 in a moderate to severe asthmatic population, particularly with regard to vital signs, ECG, heart rate, laboratory tests and adverse events, as compared to placebo.
- To compare the efficacy of QAW039 to that of montelukast as an add-on therapy to ICS in
inadequately controlled moderate-to-severe asthmatics.
- To assess the effect of QAW039 on asthma symptoms as measured by the Juniper asthma
diary. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- Sputum substudy (including Holter monitoring)
- Pharmacogenetic (separated ICF) |
|
E.3 | Principal inclusion criteria |
1. Written informed consent must be obtained before any assessment is performed
2. Males and females of any race who are between 18 and 65 years old at the time informed
consent is obtained.
3. Physician diagnosis of asthma, as per GINA (2009) guidelines, and currently prescribed ICS therapy.
4. Patients with a pre-bronchodilator FEV1 value of 40% to 80% of individual predicted value at screening and at randomization, and the value at the randomization should be within 15% of the screening FEV1. The results of spirometry should meet the ATS/ERS criteria for acceptability and repeatability.
5. Patients must be allergic or atopic, as diagnosed historically or at screening visit by either a skin prick test (≥ 3mm diameter above background) or a positive specific IgE (e.g. RAST/CAP) test (≥0.35 IU eq./ml).
6. Patients who are demonstrated to have reversible airway obstruction or airways hyperreactivity or have shown either of such responses in previous test(s) within 5 years.
• Reversible airway obstruction demonstrated at screening is defined as either: a. an increase of ≥12% and ≥200 ml in FEV1 over the patient’s pre-bronchodilator
value in litres or
b. an increase of ≥10% in % of predicted FEV1 over the patient’s prebronchodilator % of predicted FEV1
within 10-15 minutes after inhaling a total of 360 μg of albuterol or 400 μg salbutamol via MDI (reversibility test). The administration of albuterol or salbutamol for the reversibility test is to be within 30 minutes after pre-bronchodilator spirometry.
• A positive airways hyper-reactivity (AHR) test result is defined as a provoked fall in FEV1 of 20% (PC20) by methacholine at ≤8 mg/ml when not on ICS or ≤16 mg/ml on ICS therapy.
7. An ACQ score ≥ 1.5 at randomisation. |
|
E.4 | Principal exclusion criteria |
1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives
of enrollment, whichever is longer.
2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical
classes (CRTh2 antagonists).
3. History of long QT syndrome or whose current QTc interval (Fridericia’s) is prolonged > 450 msec for males and females at screening as assessed by central ECG interpretation.
4. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
5. 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 hCG laboratory test (> 5 mIU/mL).
6. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use effective contraception during the study and for 4 days (5
half-lives) after treatment. Effective contraception methods are defined in the protocol.
7. Patients with serious co-morbidities including, but not limuted to, uncontrolled diabetes (HbA1c ≥8%), heart failure, cancer, neurodegenerative diseases, rheumatoid arthritis and other autoimmune
diseases, other lung diseases including chronic bronchitis, chronic obstructive pulmonary disease or emphysema or other conditions characterised by eosinophilia and pulmonary symptoms (i.e. Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis,
eosinophilic pneumonia, etc.).
8. Acute illness other than asthma at the start of the study
9. History of life-threatening asthma, including a history of significant hypercarbia (pCO2>45mmHg), prior intubation, respiratory arrest, or seizures as a result of asthma.
10. History of alcohol or other substance abuse.
11. 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.
12. Patients who have been hospitalized due to their asthma, or that have required treatment
with systemic steroids, within 6 weeks of the screening visit.
13. Patients with clinically significant laboratory abnormalities (not associated with the study
indication) at screening including (but not limited to):
• Total white blood cell count <2500 cells/μL at screening.
• AST or ALT>2.0 X ULN or total bilirubin >1.3 X ULN at screening.
• Estimated Glomerular Filtration Rate (eGFR) by the MDRD equation <55 mL/minute/1.73 m2 at screening.
14. Patients who have a clinically significant abnormality on a 12-lead ECG recorded within
one month prior to or at screening.
15. Current smokers or ex-smokers who stopped smoking within 6 months prior to screening or have a smoking history of ≥ 10 pack years.
16. Patients with a body mass index (BMI) < 17 or > 40 kg/m2. |
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E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- ACQ
- Trough FEV1
- Jumper asthma diary
- Vital signs |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- ACQ (visit 2 to 10 included)
- Trough FEV1 (visit 2 to 10 included)
- Jumper asthma diary (visit 3 to 10 included)
- Vital signs (visit 2 to 10 included) |
|
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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 15 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 63 |
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 |
Argentina |
Colombia |
Guatemala |
India |
Japan |
Mexico |
Peru |
South Africa |
United States |
Venezuela, Bolivarian Republic of |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 15 |