Moderate to Severe Asthma Clinical Trial
— EPIPHANYOfficial title:
Leveraging Pharmacogenomics in Asthma for Predication, Mechanism and Endotyping
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.
Status | Recruiting |
Enrollment | 120 |
Est. completion date | January 31, 2028 |
Est. primary completion date | June 30, 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 75 Years |
Eligibility | Inclusion Criteria: - Stated willingness to comply with all study procedures and availability for the duration of the study. - Stable asthma medications: No change in asthma medications for the past 2 months: 1. Use of medium or high dose inhaled corticosteroids (ICS) AND 2. Use of an additional asthma controller medication. - Baseline poor or uncontrolled asthma. - Evidence of asthma demonstrated by either bronchodilator reversibility (either at screening or by historical evidence) or methacholine responsiveness (by historical evidence). - Agreement to adhere to Lifestyle Considerations throughout study duration. Exclusion Criteria: - 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. - Receiving one or more immune-modulating therapies for diseases other than asthma. This includes biologics that are also approved for asthma. - Receiving methotrexate, mycophenolate (CellCept®), or azathioprine (Imuran®). - Receiving aero allergen immunotherapy and not on at least 3 months of maintenance allergen immunotherapy. - Underwent a bronchial thermoplasty within the last two years. - Born before 30 weeks of gestation. - Uncontrolled hypertension, defined as systolic blood pressure > 160 mm/Hg or diastolic blood pressure > 100 mm/Hg. - History of malignancy except non-melanoma skin cancer within the last five years. - History of smoking: 1. If <45 years old: Smoked for =5 pack-years* 2. If =45 years old: Smoked = 10 pack years. - Active use of any inhalant >1 time per month in the past year. - Substance abuse within the last year. - Unwillingness to practice medically acceptable birth control or complete abstinence during the study, current pregnancy, or lactation. - Requirement for daily systemic corticosteroids at the time of screening. - Respiratory infection within 1 month of screening. - Intubation for asthma in the last 12 months. - Any clinically significant abnormal findings in the history, physical examination, vital signs, electrocardiogram, hematology or clinical chemistry during run-in period, which in the opinion of the site investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant's ability to complete the entire duration of the study. - BMI > 38. - Allergic to any of the drugs, biologics or chemicals used in this study. |
Country | Name | City | State |
---|---|---|---|
United States | University of California, San Diego | La Jolla | California |
United States | Yale University | New Haven | Connecticut |
United States | Mayo Clinic | Scottsdale | Arizona |
Lead Sponsor | Collaborator |
---|---|
University of California, San Diego | Brigham and Women's Hospital, Harvard University, Mayo Clinic, National Heart, Lung, and Blood Institute (NHLBI), University of Arizona, Yale University |
United States,
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* Note: There are 16 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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). | After 16 weeks (for each biologic) | |
Primary | 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. | After 16 weeks (for each biologic) | |
Primary | 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. | After 16 weeks (for each biologic) | |
Secondary | 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 | Assessed through study completion, an average of 60 weeks | |
Secondary | 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. | Assessed through study completion, an average of 60 weeks | |
Secondary | 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) | Assessed through study completion, an average of 60 weeks | |
Secondary | Forced expiratory volume in 1 second (FEV1) | Lung function (FEV1) will be measured prior to bronchodilator administration by spirometry test. | Assessed through study completion, an average of 60 weeks |
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