Efficacy of TPI ASM8 During a 14-Day Allergen Challenge

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, 3-way crossover trial to evaluate the efficacy and safety of two different doses of inhaled TPI ASM8 administered daily for 14 days for the treatment of allergic asthma and allergen-induced asthma.

Detailed Description
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Two doses of TPI ASM8 will be compared to placebo and look at the effect on asthmatic responses after an allergen challenge during a 3-way cross over design. Sputum inflammation , mRNA gene expression on target receptors, ECP , biomarkers of mast cells activation et PK profile will be studied.

Official Title
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A Double-Blind,Randomized, Placebo-controlled, 3-Way Cross Over Study to Evaluate the Efficacy and Safety of 14 Days TPI ASM8 in Subjects With Asthma

Conditions
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Asthma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mild asthma, male and female aged 18-55 y.old Steroid-naive, non-smoker Dual responders Exclusion Criteria: Any chronic disease(unstable) Immunosuppressed, recent or ongoing steroid intake Methacholine PC 20 > 16 mg/mL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: TPI ASM8 low dose<br> | Drug: TPI ASM8<br>* ASM8 4mg/mL (low dose) daily for 14 days by inhalation<br>|
| Active Comparator: TPI ASM8 high dose<br> | Drug: TPI ASM8<br>* ASM8 4mg/mL (high dose) daily for 14 days by inhalation<br>|
| Placebo Comparator: Placebo<br> | Drug: TPI ASM8<br>* Placebo PBS solution daily for 14 days by inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the AUC of the late asthmatic response (LAR) between treatments and placebo | The area under the curve fo the late asthmatic response(% fall in FEV1)(between 3-7 hrs post allergen challenge) will be compared between the 2 doses of TPI ASM8 and the placebo | Day 14 (Between 3-7 hr post-AIC) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the early and late asthmatic responses between active treatments and placebo after 14 days treatment | Compare the % fall in FEV1 during the EAR and the LAR post-allergen challenge on Day 14. | Day 14 | 
| Compare the Methacholine Hyperresponsiveness (PC20) between treatment pre and post allergen challenge | We will compare the PC20( provocative concentration of methacholine) that cause a 20% fall in FEV1 | Day 13 and Day 15 (Pre & post AIC) | 
| Effect of ASM8 on mast cells (as measured by specific biomarkers) | The leukotriene E4 and 9-11B PGF2 wil be measured in urine and plasma to determine the level of mast cells activation following the allergen challenge | Day 14 (pre, post and and peri-AIC) | 
| Sputum inflammation indicators (Eos, neutrophils, etc.) | We will measure the levels of total cell counts and the differential to evaluate the degree of inflammation between treatments and placebo. | Day 14 and Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild to moderate asthma, Allergen inhalation challenge