severe oesinophilic asthma MedDRA version: 20.0 Level: LLT Classification code 10068462 Term: Eosinophilic asthma System Organ Class: 100000004855
Conditions
Interventions
Trade Name: Nucala
Pharmaceutical Form: Powder for solution for injection
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age = 18 years - Severe asthmatics for which the indication of a treatment by mepolizumab is posed by the clinician, according to the criteria of prescription defined in France: • a blood eosinophil level = 300 / µL in the last 12 months; • and at least one of the following two criteria: - at least two episodes of asthmatic exacerbations requiring treatment with oral corticosteroid (=3 days each) in the last 12 months despite a combination of high dose inhaled corticosteroids and a long-acting bronchodilator (LABA) ( stage 4/5 GINA); - or treatment with oral corticosteroids for at least six months in the last twelve months. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: - Refusal to sign a written consent to participation. - Contraindication to bronchial endoscopy (asthma exacerbation, contraindication to the use of Xylocaine 5% for oral solution) or contraindication to performing bronchial biopsies (taking anticoagulant or the combination of two antiplatelet treatments - Contraindication to mepolizumab according to the Summary of Product Characteristics - Pregnant or lactating woman - Not affiliated to a social security scheme
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: caractériser les modifications du remodelage et de l'inflammation bronchiques chez des patients avec asthme sévère à éosinophiles au cours des 12 premiers mois de traitement par mépolizumab; Secondary Objective: - Describe the clinical and functional response after 6 and 12 months of treatment. - Study the association of histopathological changes with the clinical and functional response to treatment. - Study the association of changes in markers of inflammation with the clinical and functional response to treatment. - To compare the evolution of bronchial remodeling and inflammation in patients treated for 12 months with mepolizumab in untreated patients (historical control group). - Subsequently test new pathophysiological hypotheses, by the constitution of a biological collection of serum, BAL and bronchial tissue slides, for the identification of biomarkers of interest. ;Timepoint(s) of evaluation of this end point: 12 months; Primary end point(s): Histological evaluation The histological elements that will be evaluated before initiation of treatment and after 6 and 12 months of treatment are as follows: • Thickness of the basement membrane measured on morphometric bronchial biopsies, expressed in microns (19). • Smooth muscle area, measured in morphometry in µm2 and expressed as a percentage of smooth muscle area reported on the surface of the biopsy (7). • Number of proliferating muscle cells evaluated by anti-proliferating cell nuclear antigen (PCNA) labeling in immunohistochemistry, expressed as a number of positive cells per muscle area. • Number of nerve endings evaluated by PGP9 labeling in immunohistochemistry and expressed in number of positive cells per biopsy area in mm2 (7). • Number of vascular sections, as measured by anti-CD31 anti | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Histological evaluation The histological elements that will be evaluated before initiation of treatment and after 6 and 12 months of treatment are as follows: • Thickness of the basement membrane measured on morphometric bronchial biopsies, expressed in microns (19). • Smooth muscle area, measured in morphometry in µm2 and expressed as a percentage of smooth muscle area reported on the surface of the biopsy (7). • Number of proliferating muscle cells evaluated by anti-proliferating cell nuclear antigen (PCNA) labeling in immunohistochemistry, expressed as a number of positive cells per muscle area. • Number of nerve endings evaluated by PGP9 labeling in immunohistochemistry and expressed in number of positive cells per biopsy area in mm2 (7). • Number of vascular sections, as measured by anti-CD31 antibody labeling, expressed as the number of sections per mm2. • Number of different inflammatory cells (eosinophils / neutrophils / mast cells / lymphocytes), in immunohistochemistry, expressed in number of positive cells per area of ??biopsies in mm2 (7,19). • Proportion of eosinophils expressing MBP / IL3R in immunohistochemistry (13) on biopsies, expressed as number of cells per biopsy area in mm2. Evaluation of bronchial and serum markers of inflammation Regarding the markers of inflammation in BAL and serum, the elements that will be evaluated before initiation of treatment and after 6 and 12 months of treatment, are as follows: • Concentrations of the different markers (interferon gamma, IL-13, periostin, IL17a and IL22, IL33, TSLP, fibulin-1, tenascin, fibronectin, MCP1, EGF, bFGF and PDGF-BB) measured by Luminex or ELISA in BAL and the serum. • Proportion of eosinophils expressing IL-3R on BAL in immunohistochemistry, expressed as a perce | — |
Countries
France
Contacts
Public ContactSophie Courtial-Destembert
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
Outcome results
None listed