exacerbating asthma MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Tezepelumab
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Tezepelumab
CAS Number: 1572943-04-4
Current Sponsor code: MEDI9929
Other descriptive n
Sponsors
University Hospital of Montpellier
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Admitted to screening visit: • Minimum age: 18 • Maximum age: 85 • Able to perform an inspiratory and expiratory thoracic computed tomography (CT) scan, plus a nasal CT • Physician-diagnosed asthma according to GINA criteria • Disease with clinical impact: at least 1 severe or 2 moderate exacerbations† in the previous 12 months despite treatment according to the best standards of care • Maximal inhaled therapy comprising high dose ICS and at least a second controller according to GINA Based on results of screening visit and run-in: • Post-bronchodilator forced expiratory volume in 1 second (FEV1) predicted values must be at 25-90% • Asthma Control Questionnaire 6 (ACQ6) > 1.5 • Oral corticosteroid maintenance therapy (if used) is ?7.5 mg/day • In stable condition for the 4-week run-in period • On CT scan, the average percentage wall area index at the B1 and B8 bronchi (generation 3) is >65% 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 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: • CT abnormalities evocative of any respiratory condition other than asthma‡ • Treatment regimen discordant with best practices • Pulmonary disease other than asthma‡ requiring treatment during the previous 12 months • A smoking history of >20 pack years • Biological therapy§ during the past 3 months • Absence of signed consent • Non-beneficiary of the French social security, single-payer health insurance system • Presence of any condition (physical, psychological or other) that might, in the investigator’s opinion, hinder study performance†† • The patient is unavailable or unwilling to participate in future visits • Potential interference from other studies‡‡ • Protected populations according to the French public health code§§ • Male or female patients seeking to conceive a child
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare the change-from-baseline in the average percentage bronchial wall area (%WA = (wall area (mm2)/ (wall area (mm2) + lumen area (mm2)))×100) for patients with asthma and undergoing 6 months of tezepelumab treatment with a similar population treated via placebo;Secondary Objective: Continued treatment effects associated with longer treatment (12 months) or remanence after treatment stopping at 6 months will also be quantified. Study arms will additionally be compared in terms of: •Changes in radiomics (CT-scan data); •Changes in exacerbation rates and lung function; •Changes in serum club cell secretory protein (CCSP); •Changes in nasal single-cell transcriptomic signatures. This study also has an exploratory component designed to characterize the physiological repair environment. In depth radiomic and transcriptomic (including single-cell analyses) profiling will be performed. Finally, the capacity of baseline data to predict the response to tezepelumab will also be explored. ;Primary end point(s): the %WA at the B1 and B8 bronchi, generations 3, 4 and 5;Timepoint(s) of evaluation of this end point: between baseline and 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical outcomes • Presence/absence of nasal polyposis • Annualized exacerbation rates • Days alive and not exacerbating • Days alive and not hospitalized • Pre- and post-bronchodilator spirometry [forced expiratory volume in 1 second (FEV1; litres and percent predicted), forced vital capacity (FVC; litres and percent predicted) and the FEV1/FVC ratio (litres/litres)) • Pre- and post-bronchodilator plethysmography [total lung capacity (TLC; litres and percent predicted), residual volume (RV; litres and percent predicted) and the TLC/RV ratio (litres/litres)] (only at baseline, 6 months and 12 months) • Inspiratory and expiratory oscillometry parameters: (i) the machine used; (ii) resistance at 5 Hz (R5), (iii) resistance at 20 Hz (R20), (iv) R20-R5, (v) reactance at 5 Hz (X5). Validated questionnaires • Asthma Control Questionnaire 6 (ACQ6) • Breathlessness, Cough and Sputum Scale (BCSS) • Sino Nasal Outcome Test 22 (SNOT-22) • St George Respiratory Questionnaire (SGRQ) • The European Community Respiratory Health Survey (ECRHS) III Main questionnaire, items 21-23 Bloodwork Club cell secretory protein (CCSP), an emerging blood marker associated with pulmonary function and cellular cross-talk (Berg et al. 2002; Gamez et al. 2015; Knabe et al. 2019; Knabe et al. 2016; Londhe et al. 2011), will be assayed. In addition, a serum collection will be created for the study to enable ancillary studies. Nasal brushing analyses Nasal brushings will be used for transcriptomic analyses at baseline and single-cell analyses longitudinally. Single cell analyses Single cell analyses will be performed on a subset of patients from volunteer centres (properly equipped and willing to prepare cell fixation from nasal brushings) Safety In addition to standard adverse event reporting performed throughout the study, injection site reactions will also be specifically recorded. ;Timepoint(s) of evaluation of this end point: Baseline, 6 and 12 months | — |
Countries
France
Contacts
Public ContactFanny CARDON
University Hospital of Montpellier
Outcome results
None listed