NCT03694158

Investigating Dupilumab's Effect in Asthma by Genotype

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

• Status: Active Not Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: Boston Children's Hospital · Academic / Other
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Asthma

Interventions

Type	Name	Description
DRUG	Dupilumab	anti-IL4 receptor antagonist
OTHER	Placebo	Placebo for Dupilumab (packaged/administered the same as the active drug)

Timeline

• Start date: 2021-09-08
• Primary completion: 2027-01-01
• Completion: 2027-03-01
• First posted: 2018-10-03
• Last updated: 2026-02-23

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study