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

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ClinicalTrials.gov Identifier: NCT03694158
Recruitment Status : Recruiting
First Posted : October 3, 2018
Last Update Posted : December 6, 2022
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Regeneron Pharmaceuticals
HealthBeacon Plc
Merck Sharp & Dohme LLC
Sanofi
Information provided by (Responsible Party):
Wanda Phipatanakul, Boston Children's Hospital

Tracking Information
First Submitted Date  ICMJE October 1, 2018
First Posted Date  ICMJE October 3, 2018
Last Update Posted Date December 6, 2022
Actual Study Start Date  ICMJE September 8, 2021
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2021)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
The rate of asthma exacerbation [ 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:
  1. Systemic steroid (oral, intravenous, or intramuscular) use prescribed by a licensed medical provider for wheezing episode with or without a clinical visit
  2. Unscheduled visit for acute asthma/wheezing care (physician office, urgent care intervention, emergency department, or hospitalization)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 5, 2021)
  • 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
  • Change in CASI score [ Time Frame: average of 4,12, 24, 36, and 48 week ]
    The change in CASI score from baseline
Original Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigating Dupilumab's Effect in Asthma by Genotype
Official Title  ICMJE Effect of IL-4RαR576 Polymorphism on Response to Dupilumab in Asthma, a Genotype-stratified, Randomized, Placebo- Controlled Trial
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE 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
Condition  ICMJE Asthma
Intervention  ICMJE
  • Drug: Dupilumab
    anti-IL4 receptor antagonist
    Other Name: Dupixent®
  • Other: Placebo
    Placebo for Dupilumab (packaged/administered the same as the active drug)
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Dupilumab
  • Placebo Comparator: Placebo group
    Placebo (preparation, administration, packaging, and labeling all equivalent to the treatment) administered subcutaneously every two weeks.
    Intervention: Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2021)
150
Original Estimated Enrollment  ICMJE
 (submitted: October 1, 2018)
126
Estimated Study Completion Date  ICMJE March 2024
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Wanda Phipatanakul, MD, MS 857-218-5336 Wanda.Phipatanakul@childrens.harvard.edu
Contact: Claudina Luna asthma@childrens.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03694158
Other Study ID Numbers  ICMJE P00029072
U01AI143514 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Wanda Phipatanakul, Boston Children's Hospital
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Boston Children's Hospital
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • Regeneron Pharmaceuticals
  • HealthBeacon Plc
  • Merck Sharp & Dohme LLC
  • Sanofi
Investigators  ICMJE
Principal Investigator: Wanda Phipatanakul Boston Children's Hospital
PRS Account Boston Children's Hospital
Verification Date December 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP