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.
The study design mirrors standard of care for this study population (moderate to severe asthmatics) in that the procedures are drugs and not outside of standard of care and not experimental. The drugs were chosen based on safety, availability, and their use in patient care. The use of the drugs/biologics and other asthma related processes and procedures are not experimental. Eligible participants will have the option of receiving Symbicort as their controller medication, during their involvement in the study. The study focuses on a series of pre- and post-therapy characterizations or 'evoked phenotypes' that are not studied in traditional randomized clinical trials. Specifically, in a broad spectrum of 120 moderate-severe nonsmoking asthmatics, after evaluating pharmacologic response to systemic corticosteroids, each subject will undergo 'evoked phenotypes' with anti-IL-5R (benralizumab) and anti-IL-4Rα (dupilumab) in a random order along with comprehensive transcriptomic data interrogation prior to and during each therapeutic intervention. A specific strength of our approach is the longitudinal assessment of within individual response related to therapeutic immunomodulation combined with state-of-the-art computational methods that will further define disease biology. Current biomarkers are inadequate to distinguish responders and non-responders because they are not sensitive or specific enough for true predictive precision medicine. This study will use novel genomics approaches to assess and predict responses using therapy-induced phenotypes across a spectrum of asthma severity and endotypes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
Dupilumab, 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, an interleukin-5 receptor treatment, will be administered through a subcutaneous injection every 4 weeks (Q4W). Participants may self-administer injection after proper training.
Mayo Clinic
Scottsdale, Arizona, United States
RECRUITINGUniversity of California, San Diego
La Jolla, California, United States
RECRUITINGYale University
New Haven, Connecticut, United States
RECRUITINGPredicting 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).
Time frame: After 16 weeks (for each biologic)
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.
Time frame: After 16 weeks (for each biologic)
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.
Time frame: After 16 weeks (for each biologic)
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
Time frame: Assessed through study completion, an average of 60 weeks
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.
Time frame: Assessed through study completion, an average of 60 weeks
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)
Time frame: Assessed through study completion, an average of 60 weeks
Forced expiratory volume in 1 second (FEV1)
Lung function (FEV1) will be measured prior to bronchodilator administration by spirometry test.
Time frame: Assessed through study completion, an average of 60 weeks
Clinical Trial Operations and Data Management Specialist UA-DCC
CONTACT
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