Investigating Dupilumab's Effect in Asthma by Genotype

NCT ID: NCT03694158

Last Updated: 2025-08-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-08

Study Completion Date

2027-03-31

Brief Summary

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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

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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

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Asthma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a genotype stratified, double-blind, randomized, placebo-controlled, parallel-group, phase IV clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double blind, placebo controlled.

Study Groups

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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.

Group Type EXPERIMENTAL

Dupilumab

Intervention Type DRUG

anti-IL4 receptor antagonist

Placebo group

Placebo (preparation, administration, packaging, and labeling all equivalent to the treatment) administered subcutaneously every two weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo for Dupilumab (packaged/administered the same as the active drug)

Interventions

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Dupilumab

anti-IL4 receptor antagonist

Intervention Type DRUG

Placebo

Placebo for Dupilumab (packaged/administered the same as the active drug)

Intervention Type OTHER

Other Intervention Names

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Dupixent®

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

HealthBeacon Plc

INDUSTRY

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Sanofi

INDUSTRY

Sponsor Role collaborator

Boston Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Wanda Phipatanakul

Professor of Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Wanda Phipatanakul, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

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Boston Children's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Henry Ford Health System

Detroit, Michigan, United States

Site Status RECRUITING

Montefiore Einstein Clinical Research Center

The Bronx, New York, United States

Site Status RECRUITING

MetroHealth System

Cleveland, Ohio, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Wanda Phipatanakul, MD, MS

Role: CONTACT

857-218-5336

Research Manager

Role: CONTACT

857-218-5336

Facility Contacts

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IDEA Study Recruiter

Role: primary

857-218-5336

Angeles Cinelli

Role: primary

IDEA Study Recruiter

Role: primary

313-207-2453

Hemraj Komal, MPH

Role: primary

718-839-7562

Sunit Jariwala, MD

Role: backup

609-937-1023

David Kaelber, MD.PHD. MPH.

Role: primary

216-780-3722

Hailey Chesnick, BSN.RN

Role: backup

216-778-7478

Elizabeth Beothy

Role: primary

215-549-5023

Audreesh Banerjee, MD

Role: backup

215-549-5023

References

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Lai PS, Massoud AH, Xia M, Petty CR, Cunningham A, Chatila TA, Phipatanakul W. Gene-environment interaction between an IL4R variant and school endotoxin exposure contributes to asthma symptoms in inner-city children. J Allergy Clin Immunol. 2018 Feb;141(2):794-796.e3. doi: 10.1016/j.jaci.2017.08.023. Epub 2017 Sep 21. No abstract available.

Reference Type BACKGROUND
PMID: 28943468 (View on PubMed)

Massoud AH, Charbonnier LM, Lopez D, Pellegrini M, Phipatanakul W, Chatila TA. An asthma-associated IL4R variant exacerbates airway inflammation by promoting conversion of regulatory T cells to TH17-like cells. Nat Med. 2016 Sep;22(9):1013-22. doi: 10.1038/nm.4147. Epub 2016 Aug 1.

Reference Type BACKGROUND
PMID: 27479084 (View on PubMed)

Other Identifiers

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U01AI143514

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P00029072

Identifier Type: -

Identifier Source: org_study_id

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