E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
severe eosinophilic asthma |
ernstig eosinofiel astma |
|
E.1.1.1 | Medical condition in easily understood language |
Treatment of patients with severe asthma that do not sufficiently respond to current treatment |
Behandeling van patiënten met ernstig asthma die niet goed op huidige therapie responderen |
|
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 | 20.0 |
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 |
|
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 |
Understanding the differences in mechanism of treatment between nucala and fasenra |
Het begrijpen van de verschillen in werkingsmechanisme tussen nucal en fasenra |
|
E.2.2 | Secondary objectives of the trial |
1. To determine the kinetics of eosinophils in rectal tissue in patients treated with either nucala or fasenra
2. To study the effects of nucala on tissue eosinphils of patients previously treated with fasenra and vice versa |
1. Het vaststellen van de kinetiek van rectaalweefsel eosinofiele granulocyten in patienten die worden behandeld met nucala of fasenra.
2. Het bestuderen van de effecten van nucala op eosinofiele granulocyten in rectaalweefsel in patienten die eerst worden behandeld met fasenra en vice versa |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 18 • Diagnosis of severe refractory eosinophilic asthma • Eligible for mepolizumab or benralizumab therapy according the national recommendations for severe asthma of the Dutch society for lung diseases and tuberculosis (NVALT guideline 2013): Patients with asthma, for whom alternative diagnoses are excluded, comorbidity optimally treated, provoking factors minimized and therapy compliance optimized, but despite this still have insufficient asthma control (≥ 1.5 ACQ-7 or other questionnaire) or frequent (≥2 annually) severe exacerbations (systemic CS needed) while routinely using high-dose asthma medication (≥ 1000 mcg/day fluticasone propionate equivalent and/or daily OCS in combination with LABA or other controller medication); or patients who can achieve asthma control only with systemic CS and are therefore are risk for adverse effects or the corticosteroids. • Treated with mepolizumab or benralizumab for at least 4 months. • Before treatment with biologics a blood eosinophilia (≥ 150 eosinophils/microl blood) irrespective of steroid use |
• Age ≥ 18 • Diagnosis of severe refractory eosinophilic asthma • Eligible for mepolizumab or benralizumab therapy according the national recommendations for severe asthma of the Dutch society for lung diseases and tuberculosis (NVALT guideline 2013): Patients with asthma, for whom alternative diagnoses are excluded, comorbidity optimally treated, provoking factors minimized and therapy compliance optimized, but despite this still have insufficient asthma control (≥ 1.5 ACQ-7 or other questionnaire) or frequent (≥2 annually) severe exacerbations (systemic CS needed) while routinely using high-dose asthma medication (≥ 1000 mcg/day fluticasone propionate equivalent and/or daily OCS in combination with LABA or other controller medication); or patients who can achieve asthma control only with systemic CS and are therefore are risk for adverse effects or the corticosteroids. • Treated with mepolizumab or benralizumab for at least 4 months. • Before treatment with biologics a blood eosinophilia (≥ 150 eosinophils/microl blood) irrespective of steroid use |
|
E.4 | Principal exclusion criteria |
• Any infection (eg. HIV, Hepatitis, STDs) • Insulin dependent diabetes • Smoking at present or in the last 12 months and/or a past history of more than 10 pack years • Proven allergic bronchopulmonary aspergillosis • Auto-immune diseases • Use of medication, excluding: o Anticonceptives o Pain killers, if used on average less than once a week • exuberant alcohol consumption (for males > 36 glasses per week, for females >24 glasses per week) • Drug use • History of cancer • Use of biologicals other than mepolizumab or benralizumab • daily oral steroid therapy during the three months preceding inclusion |
• enige infectie (bijv. HIV, Hepatitis, SOAs) • Insuline afhankelijke diabetes • Roken gedurende de laatste 12 maanden of meer dan 10 pakjesjaren • Aangetoonde allergische bronchopulmonale aspergillose • Auto-immuun ziekte(n) • Gebruik van geneesmiddelen anders dan o Astma medicatie o Anticonceptiva o Pijnstillers, wanneer gemiddeld gebruik minder dan één per week • Overmatig alkoholgebruik (voor mannen > 36 glazen per week), voor vrouwen >24 glazen/week • Gebruik van recreational drugs • Kanker/genezen van kanker • Gebruik van biologicals anders dan mepolizumab of benralizumab • Dagelijks gebruik van orale steroiden gedurende drie maanden voor start van de studie |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The number of eosinophils in rectal tissue |
Het aantal van eosinofielen in rectaal weelsel |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Biopsies will be taken only one time point in patients treated > 3 months with nucala or fasenra |
Biopsies worden genomen éénmalig in patiënten behandeld > 3 maanden met nucala of fasenra |
|
E.5.2 | Secondary end point(s) |
1. Deuterium enrichment in DNA of tissue eosinophils
2. Het aantal van eosinofielen in rectaal weelsel |
1. Deuterium verrijking in DNA van weefsel eosinofiele granulocyten
2. Het aantal van eosinofielen in rectaal weefsel |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Biopsies will be taken only one time point in patients treated > 3 months with nucala or fasenra
2. Biopsies will be taken t=0 (no treatment with biological), t=6 months after treatment with nucala or fasenra, cross-over, t=12 months after treatment with fasenra or nucala |
1. Biopsies worden genomen éénmalig in patiënten behandeld > 3 maanden met nucala of fasenra
2. Biopsies worden genomen t=0 (geen behandeling met biological), t=6 maanden na behandeling met nucala of fasenra, cross-over, t=12 maanden na behandeling met fasenra of nucala |
|
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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
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 | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |