In this study, a new method will be used to evaluate response to 2 approved biologic therapies, and assess how well each patient responds to each asthma treatment. This study will measure the response to these treatments using genomic and biologic measurements obtained from participants biosamples.
By evaluating response to 2 different biologic therapies, this study has the potential to provide an in-depth understanding of the mechanisms underlying severe asthma that will inform and change treatment decisions, and may ultimately lead to a change in the way that asthma patients are evaluated for potential personalized therapies and maximize the probability that the subject will respond to treatment.
Stated willingness to comply with all study procedures and availability for the duration of the study.
Use of medium or high dose inhaled corticosteroids (ICS) AND
Use of an additional asthma controller medication.
Baseline poor or uncontrolled asthma.
Current participation in an interventional trial (e.g. drugs, diets, etc.).
Currently on an asthma biologic or having been on biologic within 3 months of screening.
Enrollment in a clinical trial where the study medication was administered within the past 60 days or within 5 half-lives (whichever is greater).
Physician diagnosis of other chronic pulmonary disorders associated with asthma-like symptoms, including, but not limited to, cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways.
Crossover
Dupilumab
Biological/VaccineDupilumab, an interleukin-4 receptor treatment, will be administered through a subcutaneous injection, the initial dose of 600 mg will be administered at two different injection sites (300 mg per injection), followed by a single dose of 300 mg administered every other week (Q2W). Participants may self-administer injection after proper training.
Benralizumab
Biological/VaccineBenralizumab, an interleukin-5 receptor treatment, will be administered through a subcutaneous injection every 4 weeks (Q4W). Participants may self-administer injection after proper training.
Predicting asthma outcomes and therapeutic responses
The primary outcomes of our therapeutic assessments are the genomic signatures that will identify novel predictive biomarkers and provide mechanistic insights to the heterogeneous response to a specific therapy. Our genomic signatures will focus on global gene expression using RNA sequencing (RNA-Seq).
Responses to the biologic therapies at the single cell level
Single cell (sc) RNA-Seq on sputum and blood samples will be assayed at baseline and after each evoked (drug) phenotype.
Unique asthma subgroups clinical and molecular endotype approaches
Clinical and molecular endotype will be independently assessed for their prognostic association with treatment response through scRNA-seq and RNA-sequencing data at baseline and following therapy.
Asthma Control Questionnaire (ACQ)
A simple questionnaire (6-item questionnaire) to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or as a result of treatment
CompEx events
CompEx is a composite outcome specific to asthma that combines clinically relevant deteriorations captured by diary events with exacerbations, thereby providing an increase in power compared to using exacerbations alone. CompEx events include exacerbations and deterioration events.
Asthma Quality of Life Questionnaire (AQLQ)
A disease-specific health-related quality of life instrument that taps both physical and emotional impact of disease. (32 items with 2-week recall)
Forced expiratory volume in 1 second (FEV1)
Lung function (FEV1) will be measured prior to bronchodilator administration by spirometry test.
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University of California, San Diego
Lead sponsor
Mayo Clinic
Collaborator
Yale University
Collaborator
University of Arizona
Collaborator
Harvard University
Collaborator
Brigham and Women's Hospital
Collaborator
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
