The Tolerability and Effects of AZD8848 in Allergic Asthma Subjects Challenged With Inhaled Allergen

Study Overview
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Brief Summary
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AZD8848 is a new drug that is being tested for the treatment of asthma and allergic rhinitis (hayfever). This study will be in two parts and will include 59 asthmatic patients in total. The first part will investigate the tolerability and safety of AZD8848 while the second part will investigate both the therapeutic effect of AZD8848 and how well patients tolerate the drug.

Official Title
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A Double-blind, Placebo-controlled, Randomised, Parallel Group, Phase IIa Study to Investigate the Efficacy, Tolerability and Safety of 8 Doses of AZD8848 Administered Intranasally Once Weekly in Mild to Moderate Allergic Asthma Subjects Challenged With an Inhaled Allergen.

Conditions
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Allergic Asthma

Intervention / Treatment
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* Drug: AZD8848
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: FEV1 > 70 % of predicted normal pre-bronchodilator Documented history of asthma Presence of allergic sensitivity Exclusion Criteria: Clinically relevant disease and/or abnormality (past or present), which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results of the study, or the patient's ability to participate in the study. Symptomatic allergic rhinitis Any clinical relevant abnormal findings in physical examination or assessment which may put the patient at risk because of participation in the study

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD8848 (30 μg PILOT part and 60 μg MAIN part) | Drug: AZD8848<br>* Nasal spray, solution 0.6mg/ mL. Once weekly for 7 weeks, 8 doses in total.<br>|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Nasal spray, solution. Once weekly for 7 weeks, 8 doses in total.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1, Late Asthmatic Response (LAR) - Pre-treatment | Forced Expiratory Volume in 1 second (FEV1), Late Asthmatic Response (LAR), is derived as the ratio of FEV1 Area Under Curve 4-10 hour post allergen challenge (AUC 4-10h) (computed using the trapezoidal formula divided by time) and the pre-challenge FEV1 measurement. | Pre-treatment (Baseline measurement) | 
| FEV1, Late Asthmatic Response (LAR) - 1 Week After Last Dose | FEV1, Late Asthmatic Response (LAR), is derived as the ratio of FEV1 AUC 4-10h (computed using the trapezoidal formula divided by time) and the pre-challenge FEV1 measurement. | 1 week after last dose | 
| FEV1, Late Asthmatic Response (LAR) - 4 Weeks After Last Dose | FEV1, Late Asthmatic Response (LAR), is derived as the ratio of FEV1 AUC 4-10h (computed using the trapezoidal formula divided by time) and the pre-challenge FEV1 measurement. | 4 weeks after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1, Early Asthmatic Response (EAR) - Pre-treatment | FEV1, Early Asthmatic Response (EAR), is derived as the ratio of FEV1 Area Under Curve 0-2 hour post allergen challenge (AUC 0-2h) (computed using the trapezoidal formula divided by time) and the pre-challenge FEV1 measurement. | Pre-treatment (Baseline measurement) | 
| FEV1, Early Asthmatic Response (EAR) - 1 Week After Last Dose | FEV1, Early Asthmatic Response (EAR), is derived as the ratio of FEV1 AUC 0-2h (computed using the trapezoidal formula divided by time) and the pre-challenge FEV1 measurement. | 1 week after last dose | 
| FEV1, Early Asthmatic Response (EAR) - 4 Weeks After Last Dose | FEV1, Early Asthmatic Response (EAR), is derived as the ratio of FEV1 AUC 0-2h (computed using the trapezoidal formula divided by time) and the pre-challenge FEV1 measurement. | 4 weeks after last dose | 
| PC20 Methacholine Challenge - Pre-treatment, Pre Allergen Challenge | PC20 is the provocation concentration of Methacholine causing a 20% fall in FEV1 | Pre-treatment, pre allergen challenge | 
| PC20 Methacholine Challenge - Pre-treatment, Post Allergen Challenge | PC20 is the provocation concentration of Methacholine causing a 20% fall in FEV1 | Pre-treatment, post allergen challenge | 
| PC20 Methacholine Challenge - 1 Week After Last Dose, Pre Allergen Challenge | PC20 is the provocation concentration of Methacholine causing a 20% fall in FEV1 | 1 week after last dose, pre allergen challenge | 
| PC20 Methacholine Challenge - 1 Week After Last Dose, Post Allergen Challenge | PC20 is the provocation concentration of Methacholine causing a 20% fall in FEV1 | 1 week after last dose, post allergen challenge | 
| PC20 Methacholine Challenge - 4 Weeks After Last Dose, Pre Allergen Challenge | PC20 is the provocation concentration of Methacholine causing a 20% fall in FEV1 | 4 weeks after last dose, pre allergen challenge | 
| PC20 Methacholine Challenge - 4 Weeks After Last Dose, Post Allergen Challenge | PC20 is the provocation concentration of Methacholine causing a 20% fall in FEV1 | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Tumour Necrosis Factor Alpha (TNFα) - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, TNFα - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, TNFα - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, TNFα - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, TNFα - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, TNFα - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Interleukin-1β (IL-1β) - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-1β - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, IL-1β - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-1β - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, IL-1β - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-1β - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Interleukin-5 (IL-5) - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-5 - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, IL-5 - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-5 - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, IL-5 - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-5 - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Interleukin-6 (IL-6) - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-6 - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, IL-6 - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-6 - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, IL-6 - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-6 - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Interleukin-8 (IL-8) - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-8 - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, IL-8 - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-8 - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, IL-8 - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-8 - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Interleukin-10 (IL-10) - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-10 - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, IL-10 - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-10 - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, IL-10 - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-10 - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Interleukin-13 (IL-13) - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-13 - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, IL-13 - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-13 - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, IL-13 - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, IL-13 - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Total Cells/g - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Total Cells/g - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, Total Cells/g - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Total Cells/g - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Total Cells/g - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Total Cells/g - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Eosinophils - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Eosinophils - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, Eosinophils - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Eosinophils - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Eosinophils - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Eosinophils - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Neutrophils - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Neutrophils - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, Neutrophils - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Neutrophils - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Neutrophils - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Neutrophils - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Macrophages - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Macrophages - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, Macrophages - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Macrophages - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Macrophages - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Macrophages - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Lymphocytes - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Lymphocytes - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, Lymphocytes - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Lymphocytes - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Lymphocytes - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Lymphocytes - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Epithelial Cells - Pre-treatment, Pre Allergen Challenge |  | Pre-treatment, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Epithelial Cells - Pre-treatment, Post Allergen Challenge |  | Pre-treatment, post allergen challenge | 
| Sputum Cellularity and Cytokines, Epithelial Cells - 1 Week After Last Dose, Pre Allergen Challenge |  | 1 week after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Epithelial Cells - 1 Week After Last Dose, Post Allergen Challenge |  | 1 week after last dose, post allergen challenge | 
| Sputum Cellularity and Cytokines, Epithelial Cells - 4 Weeks After Last Dose, Pre Allergen Challenge |  | 4 weeks after last dose, pre allergen challenge | 
| Sputum Cellularity and Cytokines, Epithelial Cells - 4 Weeks After Last Dose, Post Allergen Challenge |  | 4 weeks after last dose, post allergen challenge |