Effect of IL-4RαR576 Polymorphism on Response to Dupilumab in Adolescents and Adults With Asthma (I-DAG)
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|ClinicalTrials.gov Identifier: NCT03694158|
Recruitment Status : Not yet recruiting
First Posted : October 3, 2018
Last Update Posted : May 2, 2019
|Condition or disease||Intervention/treatment||Phase|
|Asthma||Drug: Dupilumab Other: Placebo||Phase 4|
This is a double-blind, randomized, placebo-controlled parallel-group phase 2 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 2-4 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||126 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This is a genotype stratified, double-blind, randomized, placebo-controlled, parallel-group, phase 2 clinical trial|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Double blind, placebo controlled.|
|Official Title:||Effect of IL-4RαR576 Polymorphism on Response to Dupilumab in Adolescents and Adults With Asthma|
|Estimated Study Start Date :||October 2019|
|Estimated Primary Completion Date :||October 2023|
|Estimated Study Completion Date :||October 2023|
Experimental: Treatment group
Dupilumab (Dupixent®) administered subcutaneously every two weeks. An initial dose of 400 mg (two 200 mg injections) followed by 200 mg given every other week or an initial dose of 600 mg (two 300 mg injections) followed by 300 mg given every other week for patients requiring concomitant oral corticosteroids or with comorbid moderate-to-severe atopic dermatitis for which DUPIXENT is indicated, start with an initial dose of 600 mg followed by 300 mg given every other week.
anti-IL4 receptor antagonist
Other Name: Dupixent®
Placebo Comparator: Placebo group
Placebo (preparation, administration, packaging, and labeling all equivalent to the treatment) administered subcutaneously every two weeks.
Placebo for Dupilumab (packaged/administered the same as the active drug)
- The rate of asthma exacerbations [ Time Frame: 48 week treatment period ]
asthma exacerbation as defined as wheezing episode lasting >24 hours and associated with Albuterol and/or Levalbuterol use any of the following:
- Systemic steroid (oral, intravenous, or intramuscular) use prescribed by a licensed medical provider for wheezing episode with or without a clinical visit
- Unscheduled visit for acute asthma/wheezing care (physician office, urgent care intervention, emergency department, or hospitalization)
- Change in pre-bronchodilator lung function [ Time Frame: the change in FEV1% predicted from baseline will be measured at week 48 (the end of treatment) and at week 72 (the end of the observation period) ]the change in pre-bronchodilator FEV1% predicted from baseline
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03694158
|Contact: Wanda Phipatanakul, MD, MS||857-218-5336||Wanda.Phipatanakul@childrens.harvard.edu|
|Contact: Jennifer Rooneyfirstname.lastname@example.org|
|United States, Massachusetts|
|Boston Children's Hospital||Not yet recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Amparito Cunningham Amparito.Cunningham@childrens.harvard.edu|
|Principal Investigator: Wanda Phipatanakul, MD,MS|
|Study Chair:||Wanda Phipatanakul||Boston Children’s Hospital|