Severe asthma is a chronic inflammatory condition of the airways, characterized with wheezing, breathlessness, chest tightness and coughing. T2-high asthma is promoted by differentiated T helper cells driving eosinophil recruitment and the secretion of type 2 cytokines including IL-4, IL-5 and IL-13. Recent reports suggest that persistent T2 inflammation and eosinophilia in the lung are associated with mucus plugging, but its correlation with airway obstruction is poorly understood.
Conditions
Interventions
Trade Name: Dupixent
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Dupilumab
Current Sponsor code: DETACT
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Medical University of Vienna
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All patients who: • are =18 years of age • have a recorded clinical diagnosis of asthma (ICD-10 Code: J45) • meet the requirements for treatment of severe T2-high asthma for Dupilumab defined as: o FeNO > 25 ppB o two measurements of ?250 eosinophils /µl in the blood OR one measurement of blood eosinophils ?250 cells/µl during reduction of OCS dosing if treated with oral corticosteroids and/or one measurement of sputum = 2% or BAL eosinophils = 1% • have a history of treatment with monoclonal antibodies for asthma if a wash out period of 2 half-lives or 1 month (whatever is longer) has passed 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 5 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: Patients who: • are pregnant as determined by a ß-HCG test • have severe anatomic variations or deviations that do not allow bronchoscopy • suffer from additional others confounding underlying lung disorder including but not limited to: o Bronchiectasis, chronic obstructive pulmonary disorder (COPD), pulmonary fibrosis, emphysema, o Cystic fibrosis, any known parasitic infections and lung cancer. • show pulmonary conditions with symptoms of asthma and blood eosinophilia, including but not limited to: o Churg-Strauss syndrome, o allergic bronchopulmonary aspergillosis o hypereosinophilic syndrome • suffer from a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study • have clinically meaningful comorbidity as determined by the evaluating committee • experience of an asthma exacerbation within 4 weeks prior to the first main visit • immune disorder and/or immunosuppressive treatment (e.g. cyclosporine), ongoing biological treatment of asthma (e.g., mepolizumab, omalizumab, benralizumab) or last biological treatment 2 half-lives or 1 month before the first main visit • have a history of drug and alcohol abuses • are currently smoking or are former smokers for less than 6 months with >10 pack years should be excluded from this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to investigate the effect of dupilumab treatment on mucus plugging in severe asthma patients with blood eosinophilia. Therefore, we plan to apply computer tomography to investigate mucus plugging and thoroughly examine different airway samples from T2-high severe asthmatic patients at a cellular, molecular, microbiological and metabolomic level. This study will help to unravel underlying treatment mechanisms of dupilumab therapy in severe asthmatics. ;Secondary Objective: Secondary objectives of this study are to evaluate the effect of dupilumab: •on cellular composition and activation pattern of bronchoalveolar lavage (BAL) immune cells •on cellular activation profile in lung tissue •on inflammatory mediator expression in the BAL and lung tissue •on composition of the lung microbiome (BAL) •blood eosinophils •daily measured Fractional exhaled Nitric Oxide levels (FeNO) •daily measured lung function ;Primary end point(s): Characteristics of Mucus plugging evaluated with CT-scan after a Treatment with Dupilumab for 20 weeks. ;Timepoint(s) of evaluation of this end point: CT scans will be performed two times as no-contrast CTs. The score of the extent of air-trapping, bronchial wall thickening and mucus plugging per pulmonary segment based will be evaluated. The bronchoscopy may either be clinically indicated (not study-related) to evaluate the status of severe asthma and define treatment options, or study-specific if not clinically indicated. In the most cases is the CT Scan on baseline clinically indicated and the CT after 20 weeks of therapy with Dupilumab will be study-specific. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): baseline demographics, clinical characteristics, biomarker level, inflammatory pattern (e.g. cellular distribution/cytokine levels), lung microbiome with the severity of mucus plugs • baseline demographics, clinical characteristics, biomarker level, inflammatory pattern (e.g. cellular distribution/cytokine levels), lung microbiome with treatment response determined by lung function, patients related outcomes, UHCR, number of asthma exacerbations and uOCS mucus plugging with treatment response determined by lung function, patients related outcomes, UHCR, number of asthma exacerbations and uOCS to evaluate mucus plugs as a viable parameter for treatment response And we want to evluate: • if changes in daily measured FeNO interferes with daily measured lung function parameters;Timepoint(s) of evaluation of this end point: In this prospective exploratory pilot study, we plan to include 10 patients with severe asthma indicated for Dupixent treatment. The individual study duration will be no longer than 26 weeks (4-week run in + 20 weeks of routine visits + 2-week follow-up) including 14 scheduled site visits. - | — |
Countries
Austria
Contacts
Public ContactUniv. Prof. Dr. Marco Idzko
Medical University of Vienna, Clinic for Internal Medicine II, Department of Pulmonology
Outcome results
None listed