The Goal of this study is to investigate if individuals ages 12 years and older, carrying the IL-4RαR576 gene variant, will have a greater response to therapy acting directly on the anti-IL-4R. This will be conducted by examining the effect of a 48 week therapy with dupilumab on the rate of asthma exacerbations.



Eligible Ages
Over 12 Years
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

  1. Ages 12 years and older 2. Ability to provide informed consent 3. Ability to perform pulmonary function tests 4. Female participants of childbearing potential must have a negative urine pregnancy test upon study entry 5. Female participants with reproductive potential must agree to use FDA-approved methods of birth control for the duration of the study2 6. Participant-reported physician or licensed medical practitioner diagnosis of asthma 7. Treatment with medium to high dose ICS (400 mcg to maximum of 2000 mcg per day of fluticasone propionate or equivalent) for at least 3 months with a stable dose ≥1 month prior to screening OR used a biologic medication for asthma within the past 8 weeks 8. History of asthma exacerbation in the past year An exacerbation is an asthma attack for which a clinician prescribed a course of systemic (oral, IV, IM) steroids whether or not the patient took the steroids OR An increase of >50% of baseline inhaled corticosteroid dose for ≥3 days OR An unscheduled visit for acute asthma attack (licensed medical practitioner/nurse office, urgent care intervention, emergency department, or hospitalization)

Exclusion Criteria

  1. Chronic lung disease other than asthma, which may impair lung function 2. Current smoker or cessation of smoking ≤6 months prior to Visit 0 screening 3. Current use of any electronic (e) "vaping" device (e.g., e-cigarette, e-cig, mod, vape pen, JUUL, e-cigar, e-hookah, e-pipe, vape pods) or cessation ≤ 6 months prior to screening 4. Pregnant or breast feeding 5. Any other condition or abnormality that, in the opinion of the Principal Investigator, would compromise the safety of the patient or quality of data 6. Evidence that the participant or family may be unreliable or poorly adherent to their asthma treatment or study procedures 7. Planning to relocate away from the clinical center area before study completion 8. Currently participating in an investigational drug trial or participated in one within 30 days before screening 9. Currently being treated with immunosuppressive/immunomodulatory or other investigational agents or biologics for conditions other than asthma, or used a biologic for a non-asthma indication within the past 6 months 10. History of respiratory illness requiring antibiotics or systemic corticosteroids, including asthma exacerbations, within the past 4 weeks (evaluated at time of screening visit) 11. History of alcohol or illicit substance abuse within 6 months of screening 12. Neutropenia (<1,000/mm3) or thrombocytopenia (<100,000/mm3) or hemoglobin < 100 g/L (10 g/dL) or blood eosinophils > 1500/mm3 at screening 13. Administration of a live vaccine within 4 weeks of screening 14. Currently receiving allergen immunotherapy (food or aeroallergen) other than an established maintenance regimen implemented continuously for a minimum of 2 months. Individuals receiving aeroallergen immunotherapy must be willing to stay on it for the duration of the study.

Study Design

Phase 4
Study Type
Intervention Model
Parallel Assignment
Intervention Model Description
This is a genotype stratified, double-blind, randomized, placebo-controlled, parallel-group, phase IV clinical trial
Primary Purpose
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Double blind, placebo controlled.

Arm Groups

ArmDescriptionAssigned Intervention
Treatment group
Dupilumab (Dupixent®) administered subcutaneously every two weeks. An initial dose of 600 mg (two 300 mg injections) followed by 300 mg given every other week.
  • Drug: Dupilumab
    anti-IL4 receptor antagonist
    Other names:
    • Dupixent®
Placebo Comparator
Placebo group
Placebo (preparation, administration, packaging, and labeling all equivalent to the treatment) administered subcutaneously every two weeks.
  • Other: Placebo
    Placebo for Dupilumab (packaged/administered the same as the active drug)

Recruiting Locations

MetroHealth System
Cleveland, Ohio 44109
David Kaelber, MD.PHD. MPH.

More Details

Boston Children's Hospital

Study Contact

Wanda Phipatanakul, MD, MS

Detailed Description

This is a double-blind, randomized, placebo-controlled parallel-group phase 4 clinical trial. Patients will be genotyped and categorized as those with: 1) the wild type allele (Q576/Q576), 2) heterozygous allele (Q576/R576), or 3) homozygous mutant allele (R576/R576); the genotype associated with more severe disease. After a run-in period of 2-12 weeks to determine asthma control, subjects who fulfill all inclusion/exclusion criteria will be randomized to receive either subcutaneous Dupilumab or placebo (1:1 randomization allocation ratio). This study addresses fundamental mechanisms by which the IL-4Rα-R576 variant drives the TH2/TH17 disease endotype and the influence of this variant on response to Dupilumab therapy. It brings together individuals with deep clinical and scientific expertise in allergic diseases, including epidemiology, genetics, inflammation, and tolerance mechanisms to investigate, in a coordinated strategy, the hypothesis that the IL-4Rα-R576 variant drives TH2/TH17 cell inflammation by subverting allergen-specific iTreg cells into TH17 cells. Asthmatics bearing this endotype will be particularly likely to favorably respond to Dupilumab therapy by virtue of its prevention of iTreg cell reprogramming into TH17-like cells, potentially leading to their long-term stability and potential for sustained immune tolerance.


Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.