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 | 17.0 |
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 |
To evaluate the effect of tralokinumab compared with placebo on the
annualised asthma exacerbation rate in adult and adolescent subjects with
asthma that is inadequately controlled with inhaled corticosteroid plus longacting
β2-agonist. |
Valutare l’effetto della somministrazione di tralokinumab verso placebo sul tasso annuale di riacutizzazione dell’asma in soggetti adulti e adolescenti con asma inadeguatamente controllato in trattamento con corticosteroidi inalatori in aggiunta a β2-agonisti a lunga durata d’azione. |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of tralokinumab with regards to lung function.
To assess the effect of tralokinumab with regards to asthma symptoms.
To assess the effect of tralokinumab with regards to asthma specific health-related quality of life.
To assess the effect of tralokinumab with regards to ACQ-6 defined asthma control.
To assess the effect of tralokinumab with regards to ER and urgent care visits and hospitalizations due to asthma.
To assess the effect of tralokinumab with regards to health care resource utilization and productivity loss due to asthma.
To assess the effect of tralokinumab with regards to health related quality of life.
To assess the effect of tralokinumab with regards to asthma symptoms and asthma control.
To evaluate the PK and immunogenicity of tralokinumab.
To evaluate the safety and tolerability of tralokinumab. |
Valutare l’effetto di tralokinumab sulla funzionalità polmonare.
Valutare l’effetto di tralokinumab sui sintomi dell’asma.
Valutare l’effetto di tralokinumab sulla qualità della vita correlata specificatamente all’asma.
Valutare l’effetto di tralokinumab sul controllo dell’asma classificato secondo l’Asthma Control Questionnaire-6.
Valutare l’effetto del tralokinumab sugli accessi in pronto soccorso, visite mediche urgenti e sulle ospedalizzazioni dovute all’asma.
Valutare l’effetto del tralokinumab sull’utilizzo delle risorse sanitarie e sulla perdita di produttività causata dall’asma.
Valutare l’effetto del tralokinumab sullo stato di salute correlato alla qualità della vita.
Valutare l’effetto del tralokinumab sui sintomi dell'asma e il controllo dell'asma.
Valutare la farmacocinetica e immunogenicità di tralokinumab.
Valutare la sicurezza e la tollerabilità di tralokinumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 12 -75 years
2. Documented physician-diagnosed asthma at least 12 months prior to enrollment.
3. Documented treatment with ICS at a total daily dose corresponding to ≥500μg fluticasone
propionate dry powder formulation equivalents and a LABA for at least 3 months.
4. Morning pre-BD FEV1 value of ≥40 and <80% value (<90% for patients 12 to 17 years of
age) of their PNV
5. Post-BD reversibility of ≥12% and ≥200 mL in FEV1
6. ACQ-6 score ≥1.5
7. At least 2 documented asthma exacerbations in the 12 months prior to the date of informed consent. |
1. Età compresa tra i 18 e i 75 anni (in Italia), 12 e 75 anni (internazionale).
2. Asma documentato e diagnosticato da un medico almeno 12 mesi prima dell’arruolamento.
3. Trattamento documentato con ICS corrispondente alla dose totale giornaliera ≥ 500μg di fluticasone propinato in formulazione di polvere secca in aggiunta a un β2-agonista a lunga durata d’azione (LABA) da almeno 3 mesi.
4. Valore mattutino pre-BD di FEV1 ≥40 e <80% (<90% per i pazienti dai 12 ai 17 anni di età se applicabile) dal valore normale predetto PNV.
5. Reversibilità in FEV1 nel post-broncodilatatore ≥12% e ≥200 mL.
6. Punteggio dell’ACQ-6 ≥1.5
7. Almeno 2 riacutizzazioni di asma documentate nei 12 mesi precedenti la data della firma del consenso informato. |
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E.4 | Principal exclusion criteria |
1. Clinically important pulmonary disease other than asthma
2. History of anaphylaxis following any biologic therapy
3. Hepatitis B, C or HIV
4. Pregnant or breastfeeding
5. History of cancer
6. Current tobacco smoking or a history of tobacco smoking for ≥ 10 pack-years
7. Previous receipt of tralokinumab |
1. Patologie polmonari clinicamente importanti oltre l’asma
2. Storia di anafilassi a qualunque terapia biologica
3. Epatite B, C o HIV
4. gravidanza o allattamento
5. storia di tumore
6. Paziente fumatore o ex fumatore con un consumo ≥ 10 pack-years
7. Precedente trattamento con tralokinumab |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Annual asthma exacerbation rate |
tasso annuale di riacutizzazione dell’asma |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 0 to Week 52 |
da settimana 0 a settimana 52 |
|
E.5.2 | Secondary end point(s) |
1. Percent change from baseline to Week 52 in pre-dose/pre-bronchodilator forced expiratory volume in 1 second.
2. Change from baseline to Week 52 in daily asthma symptom score.
3. Change from baseline to Week 52 in Asthma Quality of Life Questionnaire for 12 Years and Older total score.
4. Change from baseline to Week 52 in Asthma Control Questionnaire-6 defined asthma control.
5. Time to first asthma exacerbation and proportion of subjects with ≥1 asthma exacerbation.
6. Annualised asthma exacerbation rate that is associated with an ER or urgent care visit, or a hospitalization.
7. Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questionnaire and European Quality of Life -5 Dimensions - 5 Levels Daily Living Quesitonnaire.
8. Rescue medication use, Home peak expiratory flow (morning and evening).
9. Night-time awakening due to asthma.
10. Pharmacokinetic parameters and Anti-Drug Antibodies.
11. Safety and Tolerability of tralokinumab assessed by the reporting of adverse events/serious adverse events and assessments for physical examination, electocardiogram, laboratory values and vital signs.
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1. Percentuale di cambiamento rispetto al basale alla settimana 52 del volume espiratorio massimo nel primo secondo pre-dose/pre-broncodilatatore.
2. Cambiamento dal baseline alla settimana 52 nel punteggio giornaliero dei sintomi dell'asma.
3. Cambiamento dal baseline alla settimana 52 nel punteggio totale del Standardised Asthma Quality of Life Questionnaire for 12 Years and Older
4. Cambiamento dal baseline alla settimana 52 nel controllo dell'asma definito dall'Asthma Control Questionnaire-6.
5. Tempo alla prima riacutizzazione d’asma e proporzione di pazienti ≥1 riacutizzazioni di asma.
6. Tasso annuale di riacutizzazioni d’asma che sono associati ad accessi al pronto soccorso, a visite mediche urgenti o a ospedalizzazione.
7. Questionari: Work Productivity, Activity Impairment, Classroom Impairment e European Quality of Life -5 Dimensions - 5 Levels Daily Living.
8. Uso di farmaci d’emergenza, picco di flusso espiratorio monitorato da casa (mattino e sera).
9. Risveglio notturno dovuto all’asma.
10. Parametri farmacocinetici e anticorpi anti-farmaco.
11. Sicurezza e tollerabilità di tralokinumab valutata sulla reportistica di eventi avversi/eventi avversi seri e la valutazione di esami fisici, elettrocardiogramma, valori di laboratorio e segni vitali. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 0 to Week 52 (except PK and ADA, 0 to Week 72 weeks) |
dalla settimana 0 alla settimana 52 (eccetto PK e ADA, da settimana 0 a settimana 72) |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | 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 | 18 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 53 |
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 |
Canada |
Chile |
Hong Kong |
Italy |
Japan |
Mexico |
Philippines |
Russian Federation |
South Africa |
Ukraine |
United Kingdom |
United States |
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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 | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 15 |