E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate-to-severe, persistent asthma, inadequately controlled
with ICS therapy. |
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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 | 18.1 |
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 |
The primary objective is to assess the efficacy of QAW039 (450 mg qd) compared to placebo with respect to the change in trough FEV1 from baseline to 12 weeks of post-baseline treatment in non-atopic asthmatic patients who, at randomization, were inadequately controlled on low dose ICS (100 μg fluticasone BID) background therapy. |
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E.2.2 | Secondary objectives of the trial |
The key secondary objective is to demonstrate that QAW039 provides superior control of asthmatic symptoms to placebo in non-atopic asthmatic patients, as measured by the asthma control questionnaire (ACQ-6)
Secondary Objectives:
• To compare the efficacy of QAW039 as an add-on therapy to
background ICS (100 μg fluticasone BID) with an increased dose of ICS (250 μg fluticasone BID) in inadequately controlled atopic asthmatics
• To compare the efficacy of QAW039 as an add-on therapy to background ICS (100 μg fluticasone BID) between non-atopic and atopic asthmatic patients
• To assess safety and tolerability of QAW039 in the non-atopic asthmatic population as compared to placebo
For further secondary and exploratory objectives please see protocol section 2. |
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E.2.3 | Trial contains a sub-study | No |
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 aged ≥18 years
3. Patients with a diagnosis of persistent asthma (according to GINA2011) for a period of at least 6 months prior to screening
4. Patients with a pre-bronchodilator FEV1 value of 40% to 80% of individual predicted value at screening and prior to treatment. The FEV1 results should meet the ATS/ERS criteria for acceptability and repeatability (in case of screening failure due to ATS/ERS criteria,
rescreening is allowed once)
5. Patients must be either non-atopic as defined by:
a. A history of perennial symptoms with no clear inhaled allergic trigger AND
b. A negative skin prick test (< 3mm diameter above background) either historically or at Screening AND
c. A negative specific IgE (e.g. RAST/CAP) test (<0.35 IU eq./ml)either historically or against a defined panel of common aeroallergens
OR
atopic/allergic as diagnosed historically or at Screening 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 hyper-reactivity or have shown either of such responses in previous test(s) within the last year
• 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 liters or
b. an increase of ≥10% in % of predicted FEV1 over the patient’s pre-bronchodilator % 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. The use of either histamine < 10mg/ml or acetylcholine < 20mg/ml in place of methacholine is also acceptable.
7. An ACQ7 score ≥ 1.5 prior to treatment. |
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E.4 | Principal exclusion criteria |
1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives 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 measured at runin (Fridericia’s) is prolonged > 450 msec for males and females and confirmed by a central assessor
4. Pregnant or nursing (lactating) women
5. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment
6. Acute illness other than asthma at the start of the study
7. History of life-threatening asthma, including a history of significant hypercarbia (pCO2>45mmHg), prior intubation, respiratory arrest, or seizures as a result of asthma
8. Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening
9. Patients who have a clinically significant abnormality on a 12 lead ECG recorded within one month prior to screening. Patients who have a clinically significant abnormality on a 12-lead ECG recorded at run-in
10. Patients with serious co-morbidities including, but not limited to, uncontrolled diabetes (HbA1c ≥8%), heart failure, cancer, neurodegenerative diseases, rheumatoid arthritis and other autoimmune diseases |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to evaluate superiority of QAW039 over placebo (with low-dose ICS as the background therapy) for the non-atopic group. The primary efficacy variable is the change from baseline in trough FEV1 (24-hour post morning dose) measured. Trough is defined as the FEV1 measurement at 23 hr. 10 min post dose on the preceding day. The baseline FEV1 is defined as the FEV1 assessments taken in the clinic at Visit 202. |
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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) |
The secondary variables include the change from baseline in ACQ-6. The baseline is defined as the assessment measured at Visit 202 (Day 14), i.e. the first day of treatment period.
For more details / other assessments please see protocol section 6. |
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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 | Yes |
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) | 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 | No |
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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Belgium |
Colombia |
Czech Republic |
Germany |
India |
Korea, Republic of |
Poland |
Romania |
South Africa |
United States |
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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
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 19 |