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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003561 |
E.1.2 | Term | Asthma, unspecified |
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 evaluate the efficacy of brodalumab compared with placebo as measured by the change in asthma control (based on the Asthma Control Questionnaire [ACQ]) from baseline at week 24 in subjects with inadequately controlled asthma and high reversibility despite standard of care. |
Valutare l'efficacia di brodalumab rispetto al placebo, come misurato dalla variazione del controllo dell'asma (sulla base del questionario di controllo dell'asma [ACQ]) dal basale alla settimana 24 nei soggetti con asma non adeguatamente controllata ed elevata reversibilità nonostante il trattamento standard |
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E.2.2 | Secondary objectives of the trial |
Key Secondary Objectives:
To evaluate the effect of brodalumab compared to placebo at week 24 on:
• asthma exacerbations (event rate defined as the number of events per subject year)
• ACQ in inhaled corticosteroid (ICS)+long acting β-agonist (LABA) strata
• asthma exacerbations (event rate) in ICS + LABA strata |
Valutare l'effetto di brodalumab rispetto al placebo alla settimana 24 su:
• esacerbazioni asmatiche (tasso di eventi definita come il numero di eventi per anno/soggetto)
• ACQ per corticosteroidi per via inalatoria (ICS) + β-agonisti a lunga durata d'azione (LABA)
• esacerbazioni asmatiche (tasso di eventi) con ICS + LABA |
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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 |
Brodalumab Pharmacokinetic Substudy Objective: To characterize the pharmacokinetics of brodalumab
Biomarker development and pharmacogentic substudy (optional):
Objective: to collect samples for biomarker analysis; to investigate the effects of genetic variation in disease genes and drug target genes on asthma and/or subject response to brodalumab |
Sottostudio farmacocinetico su Brodalumab: Caratterizzare la farmacocinetica di brodalumab
sviluppo di biomarker e sottostudio farmacogenetico (opzionale):
Obiettivo: raccogliere campioni per l'analisi dei biomarker; studiare gli effetti della variazione genetica nelle malattie dei geni e i geni bersaglio del farmaco per l'asma e /o la risposta dei soggetti a brodalumab
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E.3 | Principal inclusion criteria |
- Men or women ≥ 18 to ≤ 75 years of age at the time of screening
- Diagnosis of asthma, and presently has reversibility over pre-bronchodilator FEV1 of ≥ 20% at screening and ≥ 15% at baseline, demonstrated in the office with SABA inhalation (up to 8 puffs) or nebulized equivalent (up to 2 treatments with 2.5 mg albuterol/salbutamol)
- Percent of predicted FEV1 ≥ 40% and ≤ 80% at screening and baseline visits
- ICS ≥ 200 and ≤ 1000/μg/day fluticasone powder or equivalent. Stable ICS dose for ≥ 30 days before screening. Must have used ICS for at least the last 3 consecutive months prior to screening
- Ongoing asthma symptoms with ACQ composite score at screening and baseline ≥ 1.5 points
- At least 1 asthma exacerbation in the year before screening
- Nonsmoker or ex-smoker with < 10/pack-years (eg, 1 pack per day for 10 years) who stopped ≥ 1 year before screening |
- Uomini o donne ≥ 18 a ≤ 75 anni di età al momento dello screening
- Diagnosi di asma, ed attuale reversibilità pre-broncodilatatrice FEV1 ≥ 20% allo screening e ≥ 15% al basale, ha dimostrato in sede con l'inalazione di SABA (fino a 8 puff) o equivalenti nebulizzati (fino a 2 trattamenti con 2,5 mg albuterol / salbutamol)
- Percentuale di FEV1 ≥ 40% e ≤ 80% alle visite di screening e basale
- ICS ≥ 200 e ≤ 1000/μg/die con fluticasone polvere o equivalente. Dosaggio ICS stabile per ≥ 30 giorni prima dello screening. Deve essere utilizzato un ICS per almeno gli ultimi 3 mesi consecutivi prima dello screening
- Sintomi di asma in corso con punteggio ACQ composito allo screening e al basale ≥ 1,5 punti
- Almeno 1 riacutizzazione asmatica nel corso dell'anno prima dello screening
- Non-fumatori o ex-fumatori con <10/pacchetti-anno(ad esempio, 1 pacchetto al giorno per 10 anni) che hanno smesso ≥ 1 anno prima dello screening
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E.4 | Principal exclusion criteria |
- History of chronic obstructive pulmonary disease or other chronic pulmonary condition other than asthma
- Any, systemic disease considered by the investigator to be clinically significant and uncontrolled or unstable (eg, diabetes, liver disease, renal failure, congestive heart failure, coronary artery disease, myocardial infarction or unstable angina within 12 months prior to screening, angina pectoris within 12 months before screening).
For full detail, please refer to section 4.2 of the protocol.
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- Storia di broncopneumopatia cronica ostruttiva o altra patologia cronica polmonare diverse da asma
- Qualsiasi malattia sistemica considerate dallo sperimentatore essere clinicamente significativa e non controllata o instabile (ad esempio, diabete, malattie del fegato, insufficienza renale, insufficienza cardiaca congestizia, malattia coronarica, infarto miocardico o angina instabile nei 12 mesi precedenti lo screening, angina pectoris nei 12 mesi precedenti lo screening).
Per il dettaglio completo, fare riferimento al paragrafo 4.2 del protocollo.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in ACQ composite score from baseline at week 24
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Modifica del punteggio ACQ composito dal basale alla settimana 24 |
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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) |
Key Secondary:
• number of asthma exacerbations (defined by use of oral corticosteroids) from baseline to week 24
• change in ACQ from baseline at week 24 in ICS+LABA strata
• number of asthma exacerbations from baseline to week 24 in ICS+LABA strata |
• numero di esacerbazioni d'asma (definito mediante l'uso di corticosteroidi per via orale) dal basale alla settimana 24
• cambiamento del punteggio ACQ dal basale alla settimana 24 in ICS + LABA
• numero di esacerbazioni asmatiche dal basale alla settimana 24 in ICS + LABA
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• number of asthma exacerbations (defined by use of oral corticosteroids) from baseline to week 24
• change in ACQ from baseline at week 24 in ICS+LABA strata
• number of asthma exacerbations from baseline to week 24 in ICS+LABA strata
Full details can be found in table 1 "schedule of Assessments in the protocol" |
• numero di esacerbazioni d'asma (definito mediante l'uso di corticosteroidi per via orale): dal basale alla settimana 24
• cambiamento del punteggio ACQ: dal basale alla settimana 24 in ICS + LABA
• numero di esacerbazioni asmatiche: dal basale alla settimana 24 in ICS + LABA
I dettagli sono presenti nella tabella 1 "schedule of Assessments" presente nel protocollo |
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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 | Yes |
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 | 2 |
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 | 8 |
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 |
Australia |
Canada |
France |
Germany |
Italy |
New Zealand |
Poland |
Russian Federation |
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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"LVLS" |
Last Visit Last Subject |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |