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 |
Asma allergico, da moderato a grave, persistente, non adeguatamente controllato dalla terapia con ICS |
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E.1.1.1 | Medical condition in easily understood language |
Allergic asthma |
Asma allergica |
|
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 | 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 |
L’obiettivo primario è di dimostrare, rispetto a placebo, un miglioramento clinicamente significativo nel FEV1 misurato al mattino in pazienti con asma da moderato a grave non adeguatamente controllato dalla terapia con ICS a basso dosaggio, trattati con QAW039 per 12 settimane confrontati con placebo. |
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. |
|
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 addon 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. |
dimostrare, rispetto a placebo, che QAW039 garantisce un controllo significativamente maggiore dei sintomi asmatici in questi pazienti, valutati con ACQ. stimare l’inizio dell’efficacia valutata con valori spirometrici ed con l’ACQ dopo 2, 4, 8 e 12 settimane di trattamento. caratterizzare la relazione dose-risposta delle dosi di QAW039 considerando il valore minimo di FEV1 dopo 12 settimane di trattamento. valutare, rispetto a placebo, la sicurezza e la tollerabilità di QAW039 nei pazienti con asma da moderato a grave, con particolare riguardo ai segni vitali, all’ECG, alla frequenza cardiaca, agli esami di laboratorio e agli eventi avversi. |
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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 |
PHARMACOGENETIC:
Vers:v02
Date:2012/03/26
Title:N.A.
Objectives:please see Protocol page 68
PHARMACOKINETIC/PHARMACODYNAMIC:
Vers:v02
Date:2012/03/26
Title:N.A.
Objectives:please see Protocol 9.5.5 ''Pharmacokinetics'' page 67
OTHER SUBSTUDIES:
- Sputum substudy (including Holter monitoring)
|
FARMACOGENETICA:
Vers:v02
Data:2012/03/26
Titolo:N.A. (Studio complementare di farmacogenetica all'interno del protocollo)
Obiettivi:per favore vedere ''Protocol page 68''
FARMACOCINETICA/FARMACODINAMICA:
Vers:v02
Data:2012/03/26
Titolo:N.A. (studio incluso nel protocollo)
Obiettivi:per favore vedere Protocol punto 9.5.5 ''Pharmacokinetics'' pagina 67
ALTRI SOTTOSTUDI:
- Sputum sottostudio (incluso Holter monitoring)- Studio complementare sull’espettorato
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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 XML File Identifier: fT+qvPFsDJR/SoeZLPdlFymdiyU= Page 22/35 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. |
Soggetti di sesso maschile e femminile di qualsiasi etnia, di età compresa tra 18 e 65 anni al momento della sottoscrizione del consenso informato. Pregressa Diagnosi di asma, in accordo con le linee guida [GINA] e attualmente in terapia con ICS. Pazienti con valore di FEV1 pre-broncodilatatore compreso tra il 40% e l’80% del valore predetto allo screening e alla randomizzazione, e con valore alla randomizzazione entro il 15% del FEV1 allo screening. Pazienti allergici o atopici, come da diagnosi pregressa o prima dell’ingresso in studio. Pazienti con dimostrata ostruzione reversibile delle vie aeree o iperreattività delle vie aeree o pazienti che hanno presentato una di queste due condizioni a precedenti test negli ultimi 5 anni. Punteggio ACQ ≥ 1.5 alla randomizzazione |
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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 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. ChurgStrauss 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. |
Utilizzo di altri farmaci sperimentali al momento dell’arruolamento o entro 30 giorni o 5 emivite dall’arruolamento, a seconda di quale di questi periodi sia più lungo. Anamnesi positiva per ipersensibilità ad uno qualsiasi dei farmaci in studio o a farmaci di classi chimiche simili (antagonisti CRTh2). Anamnesi positiva per sindrome del QT lungo o pazienti il cui intervallo QTc (formula di Fridericia) allo screening, con valutazione centralizzata dell’ECG, è > 450 msec per gli uomini e per le donne. Anamnesi positiva per neoplasia maligna a carico di qualsiasi organo o sistema (ad eccezione del carcinoma cutaneo basocellulare localizzato), trattata o non trattata, nei 5 anni precedenti, indipendentemente dall’evidenza di recidiva locale o metastasi. Donne in gravidanza o allattamento, con la gravidanza definita come lo stato di una donna dopo il concepimento e fino al termine della gestazione, confermata dalla positività di un test di laboratorio hCG (> 5 mlU/mL). Le donne potenzialmente fertili, definite come tutte le donne fisiologicamente in grado di iniziare una gravidanza, devono utilizzare un metodo contraccettivo efficace durante lo studio e per 5 giorni (5 emivite) dopo il trattamento. Pazienti con co-morbilità serie compresi, a titolo esemplificativo, diabete non controllato (HbA1c ≥8%), insuficienza cardiaca, tumore, malattie neurodegenerative, artrite reumatoide e altre malattie autoimmuni, altre patologie polmonari comprese bronchite cronica, malattia polmonare ostruttiva cronica o enfisema. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Morning FEV1 |
FEV1 al mattino |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 2 to 10 included |
Visita 2 a visita 10 inclusa |
|
E.5.2 | Secondary end point(s) |
- ACQ - Trough FEV1 - Jumper asthma diary - Vital signs |
- ACQ - Valore minimo di FEV1 - Diario di controllo dell'asma - Segni vitali |
|
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) |
- ACQ (visita 2 alla visita 10 inclusa) - FEV1 (visita 2 alla visita 10 inclusa) - Diario di controllo dell'asma (visita 3 alla visita 10 inclusa) - Segni Vitali(visita 2 alla visita 10 inclusa) |
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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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
- Stesso farmaco ad altro dosaggio |
- same IMP used at different dosage |
|
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 59 |
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 |
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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
|
LVLS (16 JUNE 2013) |
LVLS (16-06-2013) |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 17 |
E.8.9.2 | In all countries concerned by the trial days | 0 |