Current Environment:

Summary

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.

Conditions

Asthma

Recruitment Status

Recruiting

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.

Eligibility Criteria

Inclusion Criteria:

Ages 12 years and older
Ability to provide informed consent
Ability to perform pulmonary function tests
Female participants of childbearing potential must have a negative urine pregnancy test upon study entry
Female participants with reproductive potential must agree to use FDA-approved methods of birth control for the duration of the study2
Participant-reported physician or licensed medical practitioner diagnosis of asthma
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
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:

Chronic lung disease other than asthma, which may impair lung function
Current smoker or cessation of smoking ≤6 months prior to Visit 0 screening
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
Pregnant or breast feeding
Any other condition or abnormality that, in the opinion of the Principal Investigator, would compromise the safety of the patient or quality of data
Evidence that the participant or family may be unreliable or poorly adherent to their asthma treatment or study procedures
Planning to relocate away from the clinical center area before study completion
Currently participating in an investigational drug trial or participated in one within 30 days before screening
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
History of respiratory illness requiring antibiotics or systemic corticosteroids, including asthma exacerbations, within the past 4 weeks (evaluated at time of screening visit)
History of alcohol or illicit substance abuse within 6 months of screening
Neutropenia (<1,000/mm3) or thrombocytopenia (<100,000/mm3) or hemoglobin < 100 g/L (10 g/dL) or blood eosinophils > 1500/mm3 at screening
Administration of a live vaccine within 4 weeks of screening
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.

Intervention

Intervention Type

Intervention Name

Drug

Dupilumab

Other

Placebo

Phase

Phase 4

Gender

All

Minimum Age

12 Years

Maximum Age

N/A

Download Date

May 5, 2022

Principal Investigator

Wanda Phipatanakul

Primary Contact Information

Wanda Phipatanakul, MD, MS

857-218-5336

Wanda.Phipatanakul@childrens.harvard.edu

Amparito Cunningham

asthma@childrens.harvard.edu

For more information on this trial, visit clinicaltrials.gov.

Contact

For more information and to contact the study team: