Back to resultsEffects of Interleukin (IL)- 4R-alpha Inhibition on Respiratory Microbiome and Immunologic Correlates in Severe Asthma
Primary Purpose
Asthma
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Dupilumab
Sponsored by
About this trial
This is an interventional basic science trial for Asthma focused on measuring Inhaled corticosteroids, Dupilumab
Eligibility Criteria
Inclusion Criteria:
- Physician-diagnosed/managed severe asthma patients that are clinically eligible for dupilumab
- Current treatment with a medium-to-high-dose inhaled glucocorticoid (fluticasone propionate at a total daily dose of greater or equal (≥) 440 μg or equipotent equivalent) plus up to at least one additional controller (e.g., a long-acting β2-agonist or leukotriene receptor antagonist)
- Eosinophilic asthma phenotype (blood eosinophil level >300) or asthma requiring daily oral corticosteroids
- Asthma that is uncontrolled, as defined by a score on the Asthma Control Test of 19 or lower, or a worsening of asthma in the past year that led to an asthma hospitalization, Emergency Department visit, or 3 days of oral corticosteroids
- Severity of asthma that, in the opinion of the subject's asthma care specialist, requires dupilumab for control
- For women of childbearing age: agree to use birth control or remain abstinent during the duration of the study.
Exclusion Criteria:
- Patients with diagnosis of other chronic lung diseases (e.g. Chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, Churg-Strauss syndrome, Allergic bronchopulmonary aspergillosis, etc.)
- Current smoker or reported smoking within 1 month of the screening visit (tobacco or any inhaled recreational product)
- Greater than 10 total pack-year of cigarette smoking history
- Treatment with oral corticosteroids for an asthma exacerbation 1 month prior to screening or during the screening period
- Use of any biologic therapy for asthma within the past 3 months
- Respiratory or Gastrointestinal illness within 1 month prior to screening or during the screening period
- Treatment with antibiotics for acute infections within six weeks prior to screening or during the screening period.
- Pregnancy at enrollment or during the study
- Known hypersensitivity to dupilumab or its excipients
Sites / Locations
- University of Michigan
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dupilumab
Arm Description
Outcomes
Primary Outcome Measures
Changes in alpha-diversity of respiratory microbiota
This will be profiled from induced sputum.
Changes in alpha-diversity of respiratory microbiota
This will be profiled from induced sputum.
Changes in alpha-diversity of respiratory microbiota
This will be profiled from induced sputum.
Change in beta-diversity of respiratory microbiota
This will be profiled from induced sputum.
Change in beta-diversity of respiratory microbiota
This will be profiled from induced sputum.
Change in beta-diversity of respiratory microbiota
This will be profiled from induced sputum.
Change in relative abundances of microbiota members
This will be profiled from induced sputum.
Change in relative abundances of microbiota members
This will be profiled from induced sputum.
Change in relative abundances of microbiota members
This will be profiled from induced sputum.
Change in respiratory bacterial burden
This will be profiled from induced sputum.
Change in respiratory bacterial burden
This will be profiled from induced sputum.
Change in respiratory bacterial burden
This will be profiled from induced sputum.
Changes in alpha-diversity of stool microbiota
This will be based on stool samples.
Changes in alpha-diversity of stool microbiota
This will be based on stool samples.
Changes in alpha-diversity of stool microbiota
This will be based on stool samples.
Change in beta-diversity of stool microbiota
This will be based on stool samples.
Change in beta-diversity of stool microbiota
This will be based on stool samples.
Change in beta-diversity of stool microbiota
This will be based on stool samples.
Secondary Outcome Measures
Forced expiratory volume ( FEV1) / forced vital capacity (FVC) ratio
This will be based on Spirometry
Forced expiratory volume (FEV1)
This will be based on Spirometry
Change in Fractional exhaled nitric oxide (FeNO)
Asthma Control Test (ACT)
This is a self-administered 5 item questionnaire. The ACT score is the sum of the values for all 5 items. The scores range from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control. An ACT score >19 indicates well-controlled asthma; the minimal clinically important difference in score is 3.
Mini Asthma Quality of Life Questionnaire Score (mAQLQ)
This is a patient self-administered questionnaire with 15 questions covering 4 domains: Symptoms (5 questions), Activity Limitations (4 questions), Emotional Function (3 questions), and Environmental Stimuli (3 questions). Scores range from 0-6 (lower is worse). The mini AQLQ score is calculated as the average of domain items. The minimum clinically important difference is 0.5.
Overall score (average of 15 questions): add up responses to all questions, and divide by 15.
Sino-nasal outcome test (SNOT-22)
This is a 22 item questionnaire. Each item is rated as follows: 0=no problem, 1=very mild problem, 2=mild or slight problem, 3=moderate problem, 4=severe problem, 5=problem as bad as it can be. The score ranges between 0 and 110. A higher score means worse outcome.
Change in prescribed maintenance corticosteroid use (inhaled or oral), between baseline and 4 months.
Number of asthma exacerbations requiring at least 3 days of oral corticosteroids
Full Information
NCT ID
NCT05036733
First Posted
August 30, 2021
Last Updated
August 14, 2023
Sponsor
University of Michigan
Collaborators
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05036733
Brief Title
Effects of Interleukin (IL)- 4R-alpha Inhibition on Respiratory Microbiome and Immunologic Correlates in Severe Asthma
Official Title
Effects of IL-4R-alpha Inhibition (Dupixent) Inhibition On The Respiratory Microbiome And Immunologic Correlates In Patients With Severe Asthma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
February 22, 2022 (Actual)
Primary Completion Date
June 29, 2023 (Actual)
Study Completion Date
June 29, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
Regeneron Pharmaceuticals
4. Oversight
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
5. Study Description
Brief Summary
The overall goal of this study is to understand biological responses related to dupilumab treatment among severe asthma patients.
Not all asthma is the same, and characteristics of asthma vary from person to person. The study will investigate whether the study drug can help to improve the health of participants lungs, boost immune response, as well as improve quality of life.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Inhaled corticosteroids, Dupilumab
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dupilumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Dupilumab
Other Intervention Name(s)
Dupixent
Intervention Description
Participants will receive 8 doses of Dupilumab. The initial loading dose (visit 1) of 600 milligrams (two 300 milligram injections) will be given subcutaneously (SQ). Then the participants will receive 300 milligrams SQ every other week (q 2 weeks) either at a study visit or self-administered at home between visits.
Additionally, participants will complete questionnaires, have specimens collected, as well as perform breathing procedures at various timepoints.
Primary Outcome Measure Information:
Title
Changes in alpha-diversity of respiratory microbiota
Description
This will be profiled from induced sputum.
Time Frame
Baseline (before dupilumab), 1 month
Title
Changes in alpha-diversity of respiratory microbiota
Description
This will be profiled from induced sputum.
Time Frame
Baseline (before dupilumab), 4 month
Title
Changes in alpha-diversity of respiratory microbiota
Description
This will be profiled from induced sputum.
Time Frame
1 month, 4 months
Title
Change in beta-diversity of respiratory microbiota
Description
This will be profiled from induced sputum.
Time Frame
Baseline (before dupilumab), 1 month
Title
Change in beta-diversity of respiratory microbiota
Description
This will be profiled from induced sputum.
Time Frame
Baseline (before dupilumab), 4 month
Title
Change in beta-diversity of respiratory microbiota
Description
This will be profiled from induced sputum.
Time Frame
1 month, 4 months
Title
Change in relative abundances of microbiota members
Description
This will be profiled from induced sputum.
Time Frame
Baseline (before dupilumab), 1 month
Title
Change in relative abundances of microbiota members
Description
This will be profiled from induced sputum.
Time Frame
Baseline (before dupilumab), 4 month
Title
Change in relative abundances of microbiota members
Description
This will be profiled from induced sputum.
Time Frame
1 month, 4 months
Title
Change in respiratory bacterial burden
Description
This will be profiled from induced sputum.
Time Frame
Baseline (before dupilumab), 1 month
Title
Change in respiratory bacterial burden
Description
This will be profiled from induced sputum.
Time Frame
Baseline (before dupilumab), 4 month
Title
Change in respiratory bacterial burden
Description
This will be profiled from induced sputum.
Time Frame
1 month, 4 months
Title
Changes in alpha-diversity of stool microbiota
Description
This will be based on stool samples.
Time Frame
Baseline (before dupilumab), 1 month
Title
Changes in alpha-diversity of stool microbiota
Description
This will be based on stool samples.
Time Frame
Baseline (before dupilumab), 4 month
Title
Changes in alpha-diversity of stool microbiota
Description
This will be based on stool samples.
Time Frame
1 month, 4 months
Title
Change in beta-diversity of stool microbiota
Description
This will be based on stool samples.
Time Frame
Baseline (before dupilumab), 1 month
Title
Change in beta-diversity of stool microbiota
Description
This will be based on stool samples.
Time Frame
Baseline (before dupilumab), 4 month
Title
Change in beta-diversity of stool microbiota
Description
This will be based on stool samples.
Time Frame
1 month, 4 months
Secondary Outcome Measure Information:
Title
Forced expiratory volume ( FEV1) / forced vital capacity (FVC) ratio
Description
This will be based on Spirometry
Time Frame
up to 4 months
Title
Forced expiratory volume (FEV1)
Description
This will be based on Spirometry
Time Frame
up to 4 months
Title
Change in Fractional exhaled nitric oxide (FeNO)
Time Frame
Baseline, 4 months
Title
Asthma Control Test (ACT)
Description
This is a self-administered 5 item questionnaire. The ACT score is the sum of the values for all 5 items. The scores range from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control. An ACT score >19 indicates well-controlled asthma; the minimal clinically important difference in score is 3.
Time Frame
up to 4 months
Title
Mini Asthma Quality of Life Questionnaire Score (mAQLQ)
Description
This is a patient self-administered questionnaire with 15 questions covering 4 domains: Symptoms (5 questions), Activity Limitations (4 questions), Emotional Function (3 questions), and Environmental Stimuli (3 questions). Scores range from 0-6 (lower is worse). The mini AQLQ score is calculated as the average of domain items. The minimum clinically important difference is 0.5.
Overall score (average of 15 questions): add up responses to all questions, and divide by 15.
Time Frame
up to 4 months
Title
Sino-nasal outcome test (SNOT-22)
Description
This is a 22 item questionnaire. Each item is rated as follows: 0=no problem, 1=very mild problem, 2=mild or slight problem, 3=moderate problem, 4=severe problem, 5=problem as bad as it can be. The score ranges between 0 and 110. A higher score means worse outcome.
Time Frame
up to 4 months
Title
Change in prescribed maintenance corticosteroid use (inhaled or oral), between baseline and 4 months.
Time Frame
Baseline, 4 months
Title
Number of asthma exacerbations requiring at least 3 days of oral corticosteroids
Time Frame
up to 4 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Physician-diagnosed/managed severe asthma patients that are clinically eligible for dupilumab
Current treatment with a medium-to-high-dose inhaled glucocorticoid (fluticasone propionate at a total daily dose of greater or equal (≥) 440 μg or equipotent equivalent) plus up to at least one additional controller (e.g., a long-acting β2-agonist or leukotriene receptor antagonist)
Eosinophilic asthma phenotype (blood eosinophil level >300) or asthma requiring daily oral corticosteroids
Asthma that is uncontrolled, as defined by a score on the Asthma Control Test of 19 or lower, or a worsening of asthma in the past year that led to an asthma hospitalization, Emergency Department visit, or 3 days of oral corticosteroids
Severity of asthma that, in the opinion of the subject's asthma care specialist, requires dupilumab for control
For women of childbearing age: agree to use birth control or remain abstinent during the duration of the study.
Exclusion Criteria:
Patients with diagnosis of other chronic lung diseases (e.g. Chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, Churg-Strauss syndrome, Allergic bronchopulmonary aspergillosis, etc.)
Current smoker or reported smoking within 1 month of the screening visit (tobacco or any inhaled recreational product)
Greater than 10 total pack-year of cigarette smoking history
Treatment with oral corticosteroids for an asthma exacerbation 1 month prior to screening or during the screening period
Use of any biologic therapy for asthma within the past 3 months
Respiratory or Gastrointestinal illness within 1 month prior to screening or during the screening period
Treatment with antibiotics for acute infections within six weeks prior to screening or during the screening period.
Pregnancy at enrollment or during the study
Known hypersensitivity to dupilumab or its excipients
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yvonne Huang, MD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Effects of Interleukin (IL)- 4R-alpha Inhibition on Respiratory Microbiome and Immunologic Correlates in Severe Asthma
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