Study of REGN3500 and Dupilumab in Patients With Asthma

Study Overview
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Brief Summary
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To assess the effects of REGN3500, dupilumab, and REGN3500 plus dupilumab, compared with placebo, on changes in inflammatory gene expression signatures in sputum induced after a bronchial allergen challenge (BAC) in adults with mild allergic asthma, at week 4 after treatment initiation compared with those at screening.

Official Title
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A Randomized, Placebo-controlled, Parallel Panel Study to Assess the Effects of REGN3500, Dupilumab, and Combination of REGN3500 Plus Dupilumab on Markers of Inflammation After Bronchial Allergen Challenge in Patients With Allergic Asthma

Conditions
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Asthma, Allergic

Intervention / Treatment
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* Drug: REGN3500
* Drug: Dupilumab
* Drug: Placebo
* Drug: Fluticasone propionate


Participation Criteria
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Eligibility Criteria
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KEY Inclusion Criteria: Male or female aged between 18 and 60 years Has a Body Mass Index {BMI) of 17 to 33 kg/m2 at pre-study screening Has a history of mild allergic asthma for at least 6 months Is a non-smoker or ex-smoker for at least 12 months KEY Exclusion Criteria: Has a history of life-threatening asthma Has been hospitalized or has attended the emergency room for asthma in the 12 months prior to screening Has a history of severe allergies or history of an anaphylactic reaction Has a history of drug or alcohol abuse within a year prior to the screening visit Note: other protocol defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: REGN3500<br>REGN3500: masked and randomized dosing regimen per protocol (part 1 only) | Drug: REGN3500<br>* Intravenous (IV) use<br>|
| Experimental: Dupilumab<br>Dupilumab: masked and randomized dosing regimen per protocol (part 1 only) | Drug: Dupilumab<br>* Subcutaneous (SC) use<br>* Other names: Dupixent;|
| Experimental: REGN3500 plus dupilumab<br>REGN3500 plus dupilumab: masked and randomized dosing regimen per protocol (part 1 only) | Drug: REGN3500<br>* Intravenous (IV) use<br>Drug: Dupilumab<br>* Subcutaneous (SC) use<br>* Other names: Dupixent;|
| Experimental: Placebo<br>Placebo: masked and randomized dosing regimen per protocol (part 1 only) | Drug: Placebo<br>* Matching placebo<br>|
| Active Comparator: Fluticasone propionate<br>Fluticasone propionate: open label dosing regimen per protocol (part 2 only) | Drug: Fluticasone propionate<br>* Inhalation use<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in bronchial allergen challenge (BAC)-induced changes in sputum inflammatory markers in individuals treated with REGN3500, dupilumab and the combination of REGN3500 plus dupilumab or placebo |  | Screening (pre-treatment) to week 4 after treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (TEAEs) |  | Baseline to week 42 | 
| Severity of TEAEs |  | Baseline to week 42 | 
| Serum concentration-time profile of REGN3500 | Assessed by maximum plasma concentration [Cmax] | Baseline to week 42 | 
| Serum concentration-time profile of REGN3500: Tmax (time at Cmax) |  | Baseline to week 42 | 
| Serum concentration-time profile of REGN3500: AUClast (area under the curve to the last measurable concentration) |  | Baseline to week 42 | 
| Immunogenicity of REGN3500 and dupilumab | Assessed by measurement of anti-drug antibodies (ADAs) | Baseline to week 42 | 
| Serum concentration of total IL-33 after single IV dose |  | Up to Week 42 | 
| Difference in the BAC-induced changes in sputum inflammatory mRNA signature in individual patients treated with fluticasone |  | Screening (pre-treatment) to day 4 after treatment initiation |