Measuring the Effect of Dupilumab Treatment on Mucociliary Clearance (MCC) in Subjects With Moderate to Severe Asthma

Study Overview
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Brief Summary
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Single center, randomized, placebo- controlled study to assess change in mucociliary clearance of moderate to severe asthma patients after treatment with dupilumab or placebo.

Official Title
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A Randomized, Placebo-controlled, Parallel Group Study Designed to Assess the Change in Mucociliary Clearance After 12 Weeks of Treatment With Dupilumab in Patients With Moderate to Severe Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Dupilumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate - Severe Th2 (Type 2) High asthma, as defined by Forced Expiratory Volume in one second (FEV1) <90% predicted, on medium to high dose inhaled corticosteroids (ICS) with or without a second controller Age > 18 Inhaled steroid doses of 500micrograms (mcg) per day or more (Fluticasone equivalent) Reversibility >/= 12% at screening or within the past 2 years, or a positive methacholine challenge test within the past 2 years, or a positive methacholine challenge during screening FEV1/Forced Vital Capacity (FVC)<75% Blood Eosinophils (EOS) >300 cells per mm3 Exhaled Nitric Oxide (FeNO) >25 parts per billion (ppb) Asthma Control Test (ACT) score <20 Exclusion Criteria: Pregnant, nursing, or unwilling to test for pregnancy Current smoker or >10 pack year smoking history Body Mass Index (BMI)>37 Respiratory infection in the last 30 days Use of antibiotics or oral prednisone in the last 30 days Current or previous use of dupilumab Current or recent use of anti-IL-5 therapies Any other criteria that place the subject at unnecessary risk Diagnosis of other lung diseases including Chronic Obstructive Pulmonary Disease (COPD) History of non-skin cell cancer in the last 5 years Drug or alcohol addiction in the last 5 years Any other uncontrolled disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dupilumab<br>Two injections of Dupilumab will be administered at Week 0/Visit 3 as a loading dose. Subsequently one injection of Dupilumab will be given every 2 weeks ± 3 days at home by the patient. The doses of investigational product must be separated by ≥11 days to avoid an overdose. | Drug: Dupilumab<br>* Dupilumab is supplied as a sterile aqueous solution for SC injection at the concentration of 175 mg/mL in glass pre-filled syringe to deliver 200 mg in 1.14mL.<br>|
| Placebo Comparator: Placebo<br>Two injections of placebo will be administered at Week 0/Visit 3 as a loading dose. Subsequently one injection of placebo will be given every 2 weeks ± 3 days at home by the patient. The doses must be separated by ≥11 day. | Other: Placebo<br>* Sterile placebo for dupilumab will be provided in identically matched glass pre-filled syringe to deliver 200 mg in 1.14mL, which will match dupilumab 200 mg (1.14mL).<br>* Other names: Sucrose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mucociliary clearance (MCC) rate | MCC is measured using an aerosol-based nuclear imaging technique | Measured at 12 weeks after the start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FEV1% predicted | Assessed using spirometry after bronchodilator administration. | Measured from baseline to 12 weeks after start of treatment | 
| Change in ACT score | Measured via the Asthma Control Test questionnaire. Scores range from 5 (poor control of asthma) to 25 (complete control of asthma). | Measured from baseline to 12 weeks after start of treatment | 
| Change in sputum eosinophils and T2 gene mean | Measured via sputum induction to obtain airway cells and fluid from patients. | Measured from baseline to 12 weeks after start of treatment | 
| Change in mucus plugging score by CT | Radiologists will visually assess the presence or absence of mucus plugging in segmental airways and will provide a mucus plugging score | Measured from baseline to 12 weeks after start of treatment | 
| Whole lung MCC90, AAC90 | Measured via mucociliary clearance imaging | Measured from baseline to 12 weeks after start of treatment | 
| Peripheral and central lung MCC90, MCC240, AAC90 | Measured via mucociliary clearance imaging | Measured from baseline to 12 weeks after start of treatment |