A Study to Evaluate the Effect of Dupilumab on Exercise Capacity in Adult Patients With Asthma

Study Overview
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Brief Summary
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The primary objective of the study is to demonstrate that dupilumab treatment improves exercise capacity in patients with moderate-to-severe asthma. The secondary objectives of the study are: To demonstrate that dupilumab treatment increases physical activity of daily living in patients with moderate-to-severe asthma To demonstrate that dupilumab treatment improves pre- and post-exercise lung function in patients with moderate-to-severe asthma

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Effect of Dupilumab on Exercise Capacity in Patients With Moderate-to-Severe Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: dupilumab
* Drug: Matching placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: A physician diagnosis of asthma Pre-bronchodilator FEV1 between 30% and 75% predicted at both the screening and baseline visits Bronchodilator reversibility defined as >200 mL and 12% increase in FEV1 post-administration of a short-acting beta agonist (SABA). A patient may also qualify if there is a documented history of bronchodilator reversibility or positive methacholine challenge test within 12 months prior to the screening visit Stable background therapy for at least 3 months with a stable dose ≥4 weeks prior to the baseline visit of a medium-to-high dose ICS (fluticasone propionate ≥250 to 1000 μg twice daily [BID] or equivalent) in combination with at least a second controller medication (eg, long-acting beta agonist [LABA], long-acting muscarinic antagonist [LAMA], leukotriene receptor antagonist [LTRA], theophylline, etc.); a third controller is allowed and with the same stabilization requirements Blood eosinophil count ≥300 cells/μL for patients not on maintenance OCS at the screening visit ACQ-5 score ≥1.5 at the screening and baseline visits Key Exclusion Criteria: Body mass index >35 kg/m2 at screening Current smoking, vaping or tobacco chewing or cessation of any of these within 6 months prior to randomization, or >10 pack years smoking history Patients who require supplemental oxygen at screening Clinically significant cardiac disease as described in the protocol Uncontrolled hypertension at screening or baseline Participation in exercise or physical rehabilitation program within last 6 months prior to screening or planned during the study Previous use of dupilumab Anti-IgE therapy (eg, omalizumab [Xolair®]) within 130 days prior to visit 1 or any other biologic therapy (including anti-IL5, anti-IL-5R, anti-IL4Rα, anti-IL-13 mAb) or systemic immunosuppressant (eg, methotrexate, any anti-tumor necrosis factor mAbs, Janus kinase inhibitors, B- and/or T-cell targeted immunosuppressive therapies) to treat inflammatory disease or autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis) and other diseases, within 3 months or 5 half-lives prior to screening, whichever is longer Exposure to another investigative drug (monoclonal antibodies as well as small molecules) within a period prior to screening, of <3 months or <5 half-lives (whichever is longer) Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study Women of childbearing potential (WOCBP)* who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 12 weeks after the last dose NOTE: Other protocol defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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 |
| --- | --- |
| Experimental: dupilumab<br>A loading dose at the start of the treatment followed by once every two weeks (Q2W). | Drug: dupilumab<br>* Pre-filled syringe administered by subcutaneous (SC) injections<br>* Other names: SAR231893;|
| Experimental: Matching placebo<br>Matching dupilumab | Drug: Matching placebo<br>* Pre-filled syringe administered by subcutaneous (SC)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in constant work rate exercise endurance time |  | Up to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in average number of steps walked per day | Based on accelerometry data | Up to week 12 | 
| Change in total energy expenditure | Metabolic equivalents of tasks [METs]. Based on accelerometry data | Up to week 12 | 
| Change in the mean duration of moderate-to-vigorous physical activity | Defined as ≥3 METs. Based on accelerometry data | Up to week 12 | 
| Change in pre- and post-exercise Forced Expiratory Volume in One Second (FEV1) | Based on spirometry data | Up to week 12 |