Clinical trial NCT00999466: The Tolerability and Effects of AZD8848 in Allergic Asthma Subjects Challenged With Inhaled Allergen
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Allergic Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2009-10-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: FEV1, Late Asthmatic Response (LAR) - Pre-treatment
timeFrame: Pre-treatment (Baseline measurement)
measure: FEV1, Late Asthmatic Response (LAR) - 1 Week After Last Dose
timeFrame: 1 week after last dose
measure: FEV1, Late Asthmatic Response (LAR) - 4 Weeks After Last Dose
timeFrame: 4 weeks after last dose
Secondary outcomes:
measure: FEV1, Early Asthmatic Response (EAR) - Pre-treatment
timeFrame: Pre-treatment (Baseline measurement)
measure: FEV1, Early Asthmatic Response (EAR) - 1 Week After Last Dose
timeFrame: 1 week after last dose
measure: FEV1, Early Asthmatic Response (EAR) - 4 Weeks After Last Dose
timeFrame: 4 weeks after last dose
measure: PC20 Methacholine Challenge - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: PC20 Methacholine Challenge - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: PC20 Methacholine Challenge - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: PC20 Methacholine Challenge - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: PC20 Methacholine Challenge - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: PC20 Methacholine Challenge - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Tumour Necrosis Factor Alpha (TNFα) - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, TNFα - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, TNFα - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, TNFα - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, TNFα - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, TNFα - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Interleukin-1β (IL-1β) - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-1β - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, IL-1β - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-1β - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, IL-1β - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-1β - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Interleukin-5 (IL-5) - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-5 - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, IL-5 - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-5 - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, IL-5 - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-5 - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Interleukin-6 (IL-6) - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-6 - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, IL-6 - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-6 - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, IL-6 - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-6 - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Interleukin-8 (IL-8) - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-8 - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, IL-8 - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-8 - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, IL-8 - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-8 - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Interleukin-10 (IL-10) - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-10 - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, IL-10 - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-10 - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, IL-10 - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-10 - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Interleukin-13 (IL-13) - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-13 - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, IL-13 - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-13 - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, IL-13 - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, IL-13 - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Total Cells/g - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Total Cells/g - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, Total Cells/g - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Total Cells/g - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Total Cells/g - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Total Cells/g - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Eosinophils - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Eosinophils - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, Eosinophils - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Eosinophils - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Eosinophils - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Eosinophils - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Neutrophils - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Neutrophils - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, Neutrophils - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Neutrophils - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Neutrophils - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Neutrophils - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Macrophages - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Macrophages - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, Macrophages - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Macrophages - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Macrophages - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Macrophages - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Lymphocytes - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Lymphocytes - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, Lymphocytes - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Lymphocytes - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Lymphocytes - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Lymphocytes - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Epithelial Cells - Pre-treatment, Pre Allergen Challenge
timeFrame: Pre-treatment, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Epithelial Cells - Pre-treatment, Post Allergen Challenge
timeFrame: Pre-treatment, post allergen challenge
measure: Sputum Cellularity and Cytokines, Epithelial Cells - 1 Week After Last Dose, Pre Allergen Challenge
timeFrame: 1 week after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Epithelial Cells - 1 Week After Last Dose, Post Allergen Challenge
timeFrame: 1 week after last dose, post allergen challenge
measure: Sputum Cellularity and Cytokines, Epithelial Cells - 4 Weeks After Last Dose, Pre Allergen Challenge
timeFrame: 4 weeks after last dose, pre allergen challenge
measure: Sputum Cellularity and Cytokines, Epithelial Cells - 4 Weeks After Last Dose, Post Allergen Challenge
timeFrame: 4 weeks after last dose, post allergen challenge
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca R&D Lund
name: Leif Eriksson, MD
role: STUDY_DIRECTOR
affiliation: Respiratory Clinical Trials
name: Brian Leaker, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leaker BR, Singh D, Lindgren S, Almqvist G, Eriksson L, Young B, O'Connor B. Effects of the Toll-like receptor 7 (TLR7) agonist, AZD8848, on allergen-induced responses in patients with mild asthma: a double-blind, randomised, parallel-group study. Respir Res. 2019 Dec 19;20(1):288. doi: 10.1186/s12931-019-1252-2.