Efficacy and Safety of Four Escalating Dose Regimens of TPI ASM8 in Patients With Allergic Asthma

Study Overview
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Brief Summary
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During this proposed clinical trial, the investigators intend to evaluate the pharmacodynamic anti-inflammatory properties and safety of TPI ASM8, by investigating the effect on sputum eosinophils and the airway responses during an allergen challenge at different dose levels.

Detailed Description
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The early and late asthmatic response were both significantly attenuated by the highest dose of ASM8. The methacholine challenge and other parameters (ECP, mRNA knockdown on CCR3 and B-Chain of IL-3-Il-5 and GMCSF were attenuated by ASM8.

Official Title
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A Single Center, Open Label, Stepwise, Dose Profiling Study to Evaluate the Efficacy and Safety of Four Dose Regimens of Inhaled TPI ASM8 in Patients With Allergic Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: TPI ASM8
* Drug: TPI ASM8
* Drug: TPI ASM8
* Drug: TPI ASM8


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women 18 to 65 years of age Generally good health; steroid naïve (or who have not taken inhaled/oral corticosteroid within last month) mild to moderate, stable, allergic asthma as defined by ATS criteria History of episodic wheeze and shortness of breath Forced expiratory volume in one 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. Exclusion Criteria: 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 30 days, or need for antihistamines within 72 hours of each allergen or methacholine challenge, immunosuppressives, nonsteroidal anti-inflammatory drugs, or anticoagulants (intermittent doses of short-acting β2-agonist are allowed).

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose level No.1<br>TPI ASM8 1 mg BID | Drug: TPI ASM8<br>* 4 mg/mL, 1 mg BID for 4 days<br>* Other names: ASM8;|
| Experimental: Dose level No.2<br>TPI ASM8 2 mg BID | Drug: TPI ASM8<br>* 4 mg/mL, 2 mg BID for 4 days<br>* Other names: ASM8;|
| Experimental: Dose level No.3<br>TPI ASM8 4mg BID | Drug: TPI ASM8<br>* 4 mg/mL, 4 mg BID for 4 days<br>* Other names: ASM8;|
| Experimental: Dose level No.4<br>TPI ASM8 8 mg Die | Drug: TPI ASM8<br>* 4 mg/mL, 8 mg OD for 4 days<br>* Other names: ASM8;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum eosinophils (%) on Day 4 versus Screening for each dose level. |  | 7 and 24 hrs post-allergen challenge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability. |  | Throughout the study | 
| Plasma and sputum pharmacokinetic profile at the two highest dose levels. |  | Dose level 3 and 4 |