Study of Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of REGN3500 in Adults With Moderate Asthma

Study Overview
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Brief Summary
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Purpose of this study is to assess the safety and tolerability of multiple ascending subcutaneous doses of REGN3500 to moderate asthmatics.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Effects of Subcutaneously Administered REGN3500 in Adult Patients With Moderate Asthma

Conditions
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Asthma, Moderate Asthma

Intervention / Treatment
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* Drug: REGN3500
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Body mass index (BMI) of 18 to 32 kg/m2 A diagnosis of moderate asthma (according to GINA 2015) for a period of at least 2 years prior to screening. Patient must use a stable medium daily dose level of inhaled corticosteroids (ICS) as defined by GINA guidelines, ie, total daily dose of ICS >400 μg and ≤800 μg/day of budesonide or equivalent for at least 1 month prior to screening and during the study A pre-bronchodilator forced expiratory volume in the first sec (FEV1) ≥60% and ≤90% of the predicted normal values at screening and pre-dose at screening A documented positive response to the reversibility test at the screening, defined as improvement in FEV1 ≥12% and ≥200 mL over baseline after 400 μg salbutamol Pmdi Willing and able to comply with clinic visits and study-related procedures Provide signed informed consent. Key Exclusion Criteria: Clinically significant abnormal CBC, clinical chemistry, and urine analysis at screening. Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, prior to screening. History of life-threatening asthma Occurrence of asthma exacerbations or respiratory tract infections within 4 weeks prior to screening. Diagnosis of any other airway/pulmonary disease such as Chronic Obstructive Pulmonary Disease (COPD) as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (GOLD 2016); or other lung diseases (eg, emphysema, idiopathic pulmonary fibrosis, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency or restrictive lung disease). Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 1 month prior to screening. Use of oral antibiotics/anti-infectives within 2 weeks prior to screening. Known sensitivity to doxycycline or tetracyclines, or to any of the components of the investigational product formulation. Recent (within the previous 2 months) bacterial, protozoal, viral, or parasite infection. History of tuberculosis or systemic fungal diseases Patients treated with a monoclonal antibody based therapy (such as an anti-IgE, anti-IL-5), a biologic therapy or immunotherapy (subcutaneous immunotherapy [SCIT], sublingual immunotherapy [SLIT], or oral immunotherapy [OIT]) in the previous 12 weeks prior to screening and during the study Note: Other protocol defined Inclusion/Exclusion criteria may 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>REGN3500 low dose or placebo | Drug: REGN3500<br>* REGN3500 dose<br>Drug: Placebo<br>* Matching placebo<br>|
| Experimental: Cohort 2<br>REGN3500 medium dose or placebo | Drug: REGN3500<br>* REGN3500 dose<br>Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events (TEAEs) after repeat subcutaneous administration |  | Up to 36 weeks | 
| Severity of TEAEs after repeat subcutaneous administration |  | Up to 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The concentration-time profile of REGN3500 after repeat subcutaneous administration |  | Up to 36 weeks | 
| Immunogenicity of REGN3500 assessed by measurement of anti-drug antibodies |  | Up to 36 weeks | 
| Percent change in total from baseline forced expiratory volume (FEV) at day 29 |  | Baseline to week 4 | 
| Percent change of the average of the prior 7 days of FEV1 at day 29 compared to average daily FEV1 during the last 14 days of screening |  | From -14 days screening to week 4 | 
| Absolute change from baseline fractional exhaled nitric oxide (FeNO) at day 29 |  | Baseline to week 4 | 
| Percent change from baseline FeNO at day 29 |  | Baseline to week 4 | 
| Change from baseline in biomarkers at day 29 |  | Baseline to week 4 | 
| Percent change from baseline in biomarkers at day 29 |  | Baseline to week 4 |