Safety, Tolerability and Clinical Activity of ASM-024 in Subjects With Mild Allergic Asthma

Study Overview
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Brief Summary
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The study will assess the safety, tolerability and clinical activity of ASM-024 in subjects with mild allergic asthma.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Three-Way Crossover Study to Evaluate the Safety, Tolerability and Clinical Activity of ASM-024 Administered by Inhalation Once Daily to Subjects With Mild Allergic Asthma

Conditions
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Mild Allergic Asthma

Intervention / Treatment
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* Drug: ASM-024
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide written informed consent; Male or female subjects, ≥18 years and ≤ 50 years of age; Female subjects of childbearing potential must have a negative pregnancy test (serum b-HCG) at Pre-Screening, and a negative urine pregnancy test immediately before the first administration of the study drug for each of the three Treatment Periods. Sexually active females must be willing to use adequate contraception. Male subjects must be willing to use a condom with a spermicide for the duration of their participation in the study, plus an additional 30 days following study drug administration and ensure that their partner is using a highly effective method of birth control such as combined oral contraceptives, implants, injectables or a IUD. Male subjects must ensure that their female partner is willing to use adequate contraception; Diagnosis of mild allergic asthma that meets the following criteria: Stable on inhaled short-acting beta-2-agonists p.r.n. as the only medication for asthma. Presence of both early asthmatic response (EAR) (at least 20 % fall in FEV1 within 3 hours after allergen inhalation) and late asthmatic response (LAR) (at least 15 % fall in FEV1). Baseline methacholine (PC20) ≤ 16 mg/mL. FEV1 of at least 70 % of the predicted value at Pre-Screening and Screening / Baseline; BMI ≥ 19 and ≤ 35 kg/m²; Body weight ≥ 40 kg; Positive skin prick test to at least one common aeroallergen. Exclusion Criteria: Any lung disease other than mild allergic asthma; Pregnant or nursing women or women intending to conceive during the course of the study or have a positive serum pregnancy test at Pre-Screening or a positive urine pregnancy test during the study; Women of childbearing potential (unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years) not using a highly effective method of birth control. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e., less than 1 % per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, intra-uterine devices (IUDs), sexual abstinence or a partner who has undergone a vasectomy; Respiratory tract infections or worsening of asthma within 6 weeks before Screening/Baseline; Baseline methacholine PC20 > 16 mg/mL at Screening / Baseline; Current cigarette smokers or former smokers with a smoking history of greater than 10 pack years or who stopped smoking within the 12 months preceding enrolment in the study; Use of any nicotine containing products within 6 months before Pre-Screening; Any of the following concomitant medications: Any medication that are known to prolong QT / QTc interval. Oral or inhaled corticosteroids within 28 days preceding Pre-Screening or systemic corticosteroids within 90 days of Pre-Screening. Long acting beta-2-agonists within one week preceding Baseline. Use of inhaled short-acting β2- agonists or anticholinergics within 8 hours before all study visits to the clinic. Known or suspected allergy or sensitivity to nicotine or cholinergic drugs or any drug with similar chemical structure; Clinically significant ECG abnormalities at Pre-Screening including clinically significant or marked baseline prolongation of QT / QTc interval (e.g. repeated demonstration of a QTc interval of > 450 ms). Other non clinically significant findings such as sinus bradycardia, sinus arrhythmia, borderline first degree AV block (up to 205 ms), left ventricular hypertrophy (on voltage criteria for a subject less than 40 years old for instance) are permissible if judged to be acceptable by the Qualified investigator; Family history of additional risk factors for TdP (e.g., family history of Long QT Syndrome.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASM-024<br>ASM-024 once daily by inhalation | Drug: ASM-024<br>* ASM-024 50 mg of ASM-024 or 200 mg once daily by inhalation<br>|
| Placebo Comparator: Placebo<br>Placebo once daily by inhalation | Drug: Placebo<br>* Placebo once daily by inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late asthmatic response (LAR) | LAR as measured by the peak drop in FEV1 from 3 to 7 hours post-allergen challenge | Day 8 of each treatment period | 
| Early asthmatic response (EAR) | EAR as measured by the peak drop in FEV1 from 0 to 3 hours post-allergen challenge | Day 8 of every treatment period | 
| Airway hyperresponsiveness | Difference between methacholine PC20 measured 24 hours following allergen challenge and methacholine PC20 measured 24 hours before allergen challenge | Days -1, 7 and 9 of each treatment period | 
| Safety and tolerability |  | Physical examination: Day 9, vital signs: Days -1, 1, 7, 8 and 9; twelve-lead ECG: Days 1, 7, 8 and 9 , AEs throughout the study, safety laboratory assessments Day 1 and 9 and Chest X-Ray: Day 9 of the final treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LAR's FEV1 AUC | From 3 to 7 hours post-allergen challenge | Day 8 of every treatment period | 
| FEV1 | 24 hours post-allergen challenge | Day 9 | 
| EAR's FEV1 AUC | From 0 to 3 hours post-allergen challenge | Day 8 | 
| Change in FEV1 | Before inhalation of ASM-024 and as soon as possible following inhalation of ASM-024 | Days 1, 7, 8 and 9 | 
| Induced sputum eosinophil count and eosinophil and neutrophil percentages |  | Days -1, 7 and 9 of every Treatment Period | 
| Blood eosinophil count |  | Days -1 and 9 of every Treatment Period | 
| Total and differential WBC count |  | Days -1 and 9 of every Treatment Period |