Investigating Dupilumab's Effect in Asthma Based on Genetic Variants

Effect of IL-4RαR576 Polymorphism on Response to Dupilumab in Asthma, a Genotype-stratified, Randomized, Placebo- Controlled Trial

This study is testing if people aged 12 and older with a specific gene variant respond better to Dupilumab treatment for asthma compared to those who don't have the variant.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: Boston Children's Hospital (other)
• Drugs / interventions: immunotherapy, dupilumab
• Locations: 7 sites (Boston, Massachusetts and 6 other locations)
• Trial ID: NCT03694158 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to determine if individuals aged 12 and older with the IL-4RαR576 gene variant respond better to Dupilumab therapy for asthma. It is a double-blind, randomized, placebo-controlled study that will categorize participants based on their genotype and assess the impact of Dupilumab on asthma exacerbations over 48 weeks. The study will explore the mechanisms by which the IL-4Rα-R576 variant influences asthma severity and treatment response. Participants will undergo a run-in period to establish asthma control before being randomized to receive either Dupilumab or a placebo.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 12 years and older with a confirmed diagnosis of asthma and the IL-4RαR576 gene variant.

Not a fit: Patients without the IL-4RαR576 gene variant or those with well-controlled asthma may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more personalized and effective asthma treatments for patients with specific genetic profiles.

How similar studies have performed: Other studies have shown promising results in targeting specific genetic variants for asthma treatment, suggesting this approach may be effective.

Eligibility criteria

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.

Where this trial is running

Boston, Massachusetts and 6 other locations

• Boston Children's Hospital — Boston, Massachusetts, United States (RECRUITING)
• Brigham and Women's Hospital — Boston, Massachusetts, United States (RECRUITING)
• Henry Ford Health System — Detroit, Michigan, United States (RECRUITING)
• Atlantic Health System — Cedar Knolls, New Jersey, United States (RECRUITING)
• Montefiore Einstein Clinical Research Center — Bronx, New York, United States (RECRUITING)
• MetroHealth System — Cleveland, Ohio, United States (RECRUITING)
• University of Pennsylvania — Philadelphia, Pennsylvania, United States (RECRUITING)

Study contacts

• Principal investigator: Wanda Phipatanakul — Boston Children's Hospital
• Study coordinator: Wanda Phipatanakul, MD, MS

Conditions: Asthma