Effect of Inhaled TD-8236 on Allergen-induced Asthmatic Response

Study Overview
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Brief Summary
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This will be a randomized, double-blind, placebo-controlled study. The study will use a three-period, six-sequence, complete-block, cross-over study design to characterize two doses of inhaled TD-8236 compared to placebo in subjects with mild asthma and a known response to an allergen. Each of the three periods will be 14 days, followed by a washout period before the next period.

Official Title
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A Randomized, Double-blind, Placebo-controlled, 3-period Crossover Study to Evaluate the Effects of Repeated Doses of Inhaled TD-8236 and Impact on Airway Responses Following Allergen Challenge in Patients With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: TD-8236
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 to 65 years of age Willing and able to give informed consent and comply with study requirements Documented physician-diagnosed asthma for ≥ 4 months prior to Screening Body mass index (BMI) ≥ 18.0 and ≤ 35.0 kg/m2 at Screening and weighs ≥ 50 kg at Screening. Women of child bearing potential must have a negative pregnancy test Males and females must use a highly efficient birth control method Pre-bronchodilator FEV1 ≥ 70% predicted Documented allergy to at least one common allergen Dual responder to inhaled bronchial challenges Additional inclusion criteria apply Exclusion Criteria: Positive for hepatitis A, B or C, HIV or tuberculosis Clinically significant abnormalities of laboratory evaluations Have abnormal ECG measurements Any sign of respiratory tract infection within 6 weeks of screening Have a current bacterial, parasitic, fungal or viral infection History of life-threatening asthma Uses or have used tobacco or nicotine-containing products within 6 months prior to screening Additional exclusion criteria apply

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TD-8236 Dose A (low dose)<br>TD-8236 Dose A (QD x 14 days) | Drug: TD-8236<br>* The study drug will be administered by inhalation in the morning for 14 days during each period. A washout period of at least 21 days will exist between subsequent periods.<br>|
| Experimental: TD-8236 Dose B (high dose)<br>TD-8236 Dose B (QD x 14 days) | Drug: TD-8236<br>* The study drug will be administered by inhalation in the morning for 14 days during each period. A washout period of at least 21 days will exist between subsequent periods.<br>|
| Placebo Comparator: Placebo<br>Placebo (QD x 14 days) | Drug: Placebo<br>* The placebo will be administered by inhalation in the morning for 14 days during each period. A washout period of at least 21 days will exist between subsequent periods.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve of Change From Baseline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14 | Values are reported as a weighted mean derived by calculating the AUC change from baseline over the relative time interval, divided by the time interval. | Day 14 of treatment period: 3 to 8 hours after allergen challenge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve of Percentage Change From Baseline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14 | Values are reported as a weighted mean derived by calculating the AUC percentage change from baseline over the relative time interval, divided by the time interval. | Day 14 of treatment period: 3 to 8 hours after allergen challenge | 
| Maximum Decline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14 |  | Day 14 of treatment period: 3 to 8 hours after allergen challenge | 
| Maximum Percentage Decline in Forced Expiratory Volume (in 1 Second) (FEV1) From 3 to 8 Hours After Inhaled Allergen Challenge at Day 14 |  | Day 14 of treatment period: 3 to 8 hours after allergen challenge | 
| Area Under the Concentration-time Curve Over One 24-hour Dosing Interval (AUC0-24) of TD-8236 in Plasma |  | Day 14 of treatment period: Pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose | 
| Maximum Observed Plasma Concentration (Cmax) of TD-8236 in Plasma During Dosing Interval |  | Day 14 of treatment period: Pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose | 
| Time to Maximum Observed Concentration (Tmax) of TD-8236 in Plasma Over a Dosing Interval |  | Day 14 of treatment period: Pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose | 
| Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | A TEAE was defined as any adverse event (AE) that begins on or after the date of first dose of study drug up to the date of last dose of study drug plus the number of days in the follow-up period. The severity of TEAEs were also assessed and were classified as mild, moderate or severe per the definitions below: Mild - The AE is noticeable to the participant and/or the investigator, but does not interfere with routine activity. Moderate - The AE interferes with routine activity, but responds to symptomatic therapy or rest. Severe - The AE significantly limits the participant's ability to perform routine activities despite symptomatic therapy. | Day 1 to end of follow-up (up to approximately 98 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TD-8236, Asthma, Proof of concept