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Investigating Dupilumab's Effect in Asthma by Genotype (IDEA)

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ClinicalTrials.gov Identifier: NCT03694158
Recruitment Status : Not yet recruiting
First Posted : October 3, 2018
Last Update Posted : August 20, 2021
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Wanda Phipatanakul, Boston Children's Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Asthma Drug: Dupilumab Other: Placebo Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a genotype stratified, double-blind, randomized, placebo-controlled, parallel-group, phase IV clinical trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blind, placebo controlled.
Primary Purpose: Treatment
Official Title: Effect of IL-4RαR576 Polymorphism on Response to Dupilumab in Asthma, a Genotype-stratified, Randomized, Placebo- Controlled Trial
Estimated Study Start Date : September 2021
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Dupilumab

Arm Intervention/treatment
Experimental: 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.
Drug: Dupilumab
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.
Other: Placebo
Placebo for Dupilumab (packaged/administered the same as the active drug)




Primary Outcome Measures :
  1. The rate of asthma exacerbations [ Time Frame: 48 week treatment period ]
    An exacerbation is an asthma attack for which a clinician prescribed a course of systemic steroids, whether or not the patient took the steroids.


Secondary Outcome Measures :
  1. Change in pre-bronchodilator lung function [ Time Frame: average of week 4,12, 24,36 and 48 week ]
    the change in pre-bronchodilator FEV1% predicted from baseline

  2. Change in CASI score [ Time Frame: average of 4,12, 24, 36, and 48 week ]
    The change in CASI score from baseline



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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


Contacts
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Contact: Wanda Phipatanakul, MD, MS 857-218-5336 Wanda.Phipatanakul@childrens.harvard.edu
Contact: Amparito Cunningham asthma@childrens.harvard.edu

Locations
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United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Contact: Amparito Cunningham, MD. MPH.    857-218-5531    Amparito.Cunningham@childrens.harvard.edu   
Contact: Conor Brockway    857-218-3819    conor.brockway@childrens.harvard.edu   
Principal Investigator: Wanda Phipatanakul, MD.MS.         
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Contact: Angeles Cinelli       mcinelli@bwh.harvard.edu   
Principal Investigator: Eliot Israel, MD         
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
Contact: Sherae Hereford, RN    313-207-2453    sherefo3@hfhs.org   
Principal Investigator: Haejin Kim, MD.         
United States, New Jersey
Atlantic Health System
Cedar Knolls, New Jersey, United States, 07927
Contact: Beverly Obipso    908-934-0555 ext 78625    Beverly.Obispo@atlantichealth.org   
Principal Investigator: John Oppenheimer, MD         
Sponsors and Collaborators
Boston Children's Hospital
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Wanda Phipatanakul Boston Children's Hospital
Publications:
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Responsible Party: Wanda Phipatanakul, Professor of Pediatrics, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT03694158    
Other Study ID Numbers: P00029072
U01AI143514 ( U.S. NIH Grant/Contract )
First Posted: October 3, 2018    Key Record Dates
Last Update Posted: August 20, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases