Multiple Dose ASM8 in Mild Asthmatics

Study Overview
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Brief Summary
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To determine the safety and efficacy of multiple doses of ASM8 antisense oligonucleotides in asthmatics.

Detailed Description
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This is a double-blind, placebo-controlled, crossover trial to evaluate the safety, tolerability and efficacy of inhaled ASM8 for the treatment of allergen-induced asthma. Individuals with stable, mild to moderate allergic asthma by American Thoracic Society (ATS) criteria (1), with a history of episodic wheeze and shortness of breath, will be eligible for enrolment. The study is divided into 2 parts.

Official Title
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A Double-blind, Placebo-controled, Crossover Study To Evaluate the Efficacy, Safety and Tolerability of Inhaled ASM8-003 in Subjects With Mild Allergic Asthma.

Conditions
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Asthma

Intervention / Treatment
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* Drug: ASM8


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1: Men and women 18 to 65 years of age; generally good health; mild to moderate, stable, allergic asthma as defined by ATS criteria (1); history of episodic wheeze and shortness of breath; forced expiratory volume in 1 second (FEV1) at baseline ≥70% of the predicted value; able to comprehend and follow all required study procedures; willing and able to sign an informed consent form. Part 2: Methacholine challenge at baseline (PC20 ≤16 mg/mL); positive skin-prick test to common aeroallergens (cat, dust mite, grass, pollen) and positive allergen-induced early and late airway bronchoconstriction. Exclusion Criteria: Part 1 and Part 2: Significant acute or chronic medical or psychiatric illness; known coagulopathy, worsening of asthma or respiratory infection in the preceding 6 weeks; use of inhaled or oral corticosteroids within the last 28 days, antihistamines, immunosuppressives, nonsteroidal anti-inflammatory drugs, or anticoagulants (intermittent doses of short-acting β2-agonist are allowed); use of medications that may interact with ASM8; investigational drug use within 30 days; any clinically significant abnormality on screening laboratory determinations; current tobacco use in previous 3 months or 10 pack-years; pregnant or lactating women; women actively seeking pregnancy or who are not using adequate contraception; history of serious adverse effect (SAE) or hypersensitivity to any drug; 20% decrease in FEV1 or FVC with baseline saline in methacholine challenge during screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ASM8|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the allergen-induced late asthmatic response (LAR) between ASM8 and placebo |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the safety and tolerability of ASM8. |  |  | 
| Comparison of the allergen-induced early asthmatic response (EAR) between ASM8 and placebo. |  |  | 
| Comparison of the allergen-induced airway hyperresponsiveness between ASM8 and placebo. |  |  | 
| Comparison of the allergen-induced changes in sputum eosinophils at 7 and 24 hours post allergen, between the ASM8 and placebo. |  |  | 
| Determination of the plasma and sputum pharmacokinetic profile of single- and repeated-doses of ASM8 in patients with mild asthma. |  |  | 
| Determination of the pharmacodynamic activity of ASM8 on specific gene expression, protein levels, differential cell counts, and eosinophilic cationic protein (ECP), as measured in sputum samples. |  |  | 
| Relief medication use in the ASM8 versus placebo |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild asthma