This is a multi-center, double-blind, placebo-controlled, randomized trial of dupilumab adjunctive therapy for prevention of asthma exacerbations in urban children and adolescents with T2-high exacerbation-prone asthma.
Protocol CAUSE-01 PANDA is a multicenter, double-blind, placebo-controlled, randomized trial of dupilumab adjunctive therapy for the reduction of asthma exacerbations in urban children and adolescents 6 to 17 years with T2-high exacerbation-prone asthma. Approximately 240 participants will be randomized 2:1 to one of two study arms: 1) guidelines-based asthma treatment + dupilumab, or 2) guidelines-based asthma treatment + placebo. Study treatment will continue for 1 year with an additional 3 months of follow-up following completion of study treatment. An initial Screening Visit will be followed by a 4-week run-in period. After the run-in, participants who continue to meet eligibility criteria will be randomized to one of the 2 treatment arms and receive their first injection. Over the next 2 weeks, participants will return to the clinic for 3 early treatment response visits. Participants will receive injections of dupilumab, or placebo administered subcutaneously every two weeks (Q2W), or every four weeks (Q4W), over 12 months. Each participant will have Evaluation and Management (E\&M) visits every 3 months where their asthma and rhinitis will be assessed and adjustments made to their medications based on asthma guidelines. Participants will be asked to monitor and self-report cold symptoms throughout the treatment period. Participants will be asked to complete up to three paired cold visits. At the time of a cold, participants will be asked to come into the clinic for collection of blood and nasal secretions for associated mechanistic studies. Approximately three days after the clinic visit, participants will complete symptom assessments and will be asked to collect nasal samples at home
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
240
Children's Hospital Colorado: Allergy Program
Aurora, Colorado, United States
Children's National Medical Center: Children's Research Institute
Washington D.C., District of Columbia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago: Division of Allergy and Immunology
Chicago, Illinois, United States
Number of asthma exacerbations during the 12-month treatment period
Asthma exacerbation defined as a prescription of a course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following dosage: the course for prednisone, prednisolone, or methylprednisolone will be at least 20 mg daily dose for 3 of 5 consecutive days. The course for dexamethasone will be at least a 10 mg single daily dose. If a corticosteroid burst for the treatment of an asthma exacerbation is prescribed by a non-CAUSE clinician, it will be counted regardless of dose.
Time frame: Week 4 (Treatment initiation) - Week 54 (Completion of treatment)
Pulmonary Function Measured by Spirometry: Forced Expiratory Volume in 1 Second (FEV1) % Predicted
FEV1 is air volume exhaled in 1 second during spirometry. FEV1 percent of predicted value is FEV1 converted to a percentage of normal, based on height, weight, and race. This measurement will be performed by trained and certified clinical research staff according to American Thoracic Society standards as performed routinely in usual care as part of subspecialist management of asthma.
Time frame: Week 4 to Week 68
Days with symptoms, nights with symptoms, and day and night albuterol use.
Number of days with asthma symptoms as defined by the participant report of daytime asthma symptoms over the preceding 14-day period. Number of nights with asthma symptoms as defined by participant report of nighttime asthma symptoms over the preceding 14-day period. Number of days with albuterol use as defined by participant report of days of albuterol (bronchodilator) use over the preceding 14-day period. Number of nights albuterol use as defined by participant report of nights of albuterol (bronchodilator) use over the preceding 14-day period.
Time frame: Week 4 to Week 68
Asthma control measured by the Asthma Control Questionnaire-5
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Boston Children's Hospital: Department of Immunology
Boston, Massachusetts, United States
Washington University at St. Louis
St Louis, Missouri, United States
Icahn School of Medicine at Mount Sinai: Division of Clinical Immunology, Immunology Institute
New York, New York, United States
Columbia University Medical Center: Division of Pediatric Pulmonology
New York, New York, United States
Cincinnati Children's Hospital Medical Center: Asthma Center
Cincinnati, Ohio, United States
The Asthma Control Questionnaire-5 is a validated tool that will be used to assess overall asthma control over the last 4 weeks. The Range is 0-6, with higher scores indicating worse asthma control.
Time frame: Week 4 to Week 60
Time to first asthma exacerbation
Time between initiation of treatment and first asthma exacerbation or the end of participant follow-up visits.
Time frame: Week 4 to Week 68
Quality of life as measured by the PROMIS Asthma Impact Short Forms (Pediatric or Parent Proxy).
As measured by the pediatric patient-reported (ages 8-17) or proxy-reported (ages 6-7) PROMIS Asthma Impact Short Forms.
Time frame: Week 4 to Week 68
Asthma burden as measured by Combined Asthma Severity Index (CASI)
The Composite Asthma Severity Index (CASI) is a comprehensive severity scale combining multiple facets of asthma severity: impairment, risk, and treatment. The CASI score ranges from 0 to 20 points, with higher scores indicating higher levels of severity, and includes 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations.
Time frame: Week 4 to Week 68
Rhinitis symptoms as measured by Modified Rhinitis Symptoms Utility Index (MRSUI)
The Modified Rhinitis Symptom Utility Index (MRSUI) assesses the frequency and severity (degree of bothering: not bothered, somewhat bothered, bothered a lot) of the participant's (1) stuffy or blocked nose, (2) runny nose, (3) sneezing, (4) itchy, watery eyes, and (5) itchy nose or throat over the preceding 14-day period.
Time frame: Week 4 - Week 68
Related adverse events and serious adverse events in the course of treatment
The number of adverse events (AEs) by severity and relationship to study drug will be used to assess safety. The number of serious adverse events (SAEs) by severity and relationship to study drug will be used to assess safety.
Time frame: Week 4 to Week 68