A Study to Evaluate the Effect of AZD8154 Administered Via Nebulizer Once Daily in Subjects With Mild Allergic Asthma Challenged With an Inhaled Allergen

Medical conditions

A worsening of asthma or a respiratory tract infection from 6 weeks prior to Visit 1 or during the screening period, requiring a change of treatment.

Any history of life-threatening asthma attack or asthma attack requiring admission to an intensive care unit and/or ventilation.

A medical history or evidence of medical conditions which in the Investigator's opinion makes it undesirable for the subject to participate in the study, including but not limited to:

1. lung disease (excluding sleep apnea) other than mild allergic asthma

2. history of diabetes, metabolic syndrome, Gilbert syndrome, hepatic impairment, hypertriglyceridemia, or familial lipid disorders

3. clinically significant hypotensive episodes or symptoms of fainting, dizziness, or light headedness

4. cardiovascular disease, particularly coronary artery disease, hypertension, congestive heart failure or any clinically important abnormalities in rhythm, conduction or morphology of the ECG at rest that may interfere with the interpretation of QT interval corrected (QTc) interval changes.

5. significant neurologic disease, including transient ischemic attack, stroke, or seizure disorder

6. alcoholism, drug dependency or abuse

7. latent or chronic infection (eg, recurrent sinusitis, genital or ocular herpes, urinary tract infection) or at risk of infection (eg, surgery) within 90 days of screening

8. malignancy in the previous 5 years other than superficial basal cell carcinoma.

Prolonged QT interval corrected using Fridericia's formula (QTcF) \>450 milliseconds (ms) based on ECG (at Visit 1 or Visit 6 pre-dose) or family history of long QT syndrome

Persistent or intermittent bundle branch block, intermittent second or third degree atrial ventricular (AV) block or AV dissociation (at Visit 1 or Visit 6).

Current smokers. Ex-smokers must not have smoked or used nicotine or cannabis products (including e-cigarettes) for a minimum of 6 months prior to enrolment and should not have a smoking history ≥10 pack years.

Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate) as judged by the Investigator.

Prior/concomitant therapy

Intention to use any concomitant medication that is not permitted or failure to undergo the required washout period for a prohibited medication.

Chronic use of any other medication for treatment of allergic lung disease other than short acting β2-agonist.

Subject who has a scheduled in-patient surgery or hospitalization during the study.

Previous use of a mechanistic target of rapamycin (mTOR) antagonist (eg, rapamycin, everolimus) or PI3K inhibitor (selective or non-selective PI3K inhibitor).

Prior/concurrent clinical study experience

Participation in another clinical study with an investigational product administered from 30 days (or 5 half lives) before Visit 1.

Note: refer to prohibited/restricted medications list for required washouts from previous investigational treatments.

Subjects with a known hypersensitivity (as judged by the Investigator) to drugs with a similar class to AZD8154.

Previously received AZD8154 or randomized to treatment in the present study.

Diagnostic assessments

Clinically significant abnormalities in laboratory test results at Visit 1 or during the screening period as judged by the Investigator.

Any values outside the normal range for the following parameters at Visit 1:

1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥1.5 times the upper limit of normal (ULN).

2. Absolute neutrophil count ≤1.5 x 109/L.

Positive serology at Visit 1 (HIV-1; HIV-2; Hepatitis B \& C).

Subjects with latent or active tuberculosis (TB), as confirmed by a positive QuantiFERON® - TB Gold test or as judged by the Investigator at Visit 1.

Note: subjects will be allowed to continue with screening and baseline assessments whilst the results are pending but must not be randomized into the study until the test results confirm the subject does not have TB.

Other exclusions

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, staff at the study site, and other third party staff involved in the study).

Judgement by the Investigator that the subject should not participate in the study if the subject is unlikely or unwilling to comply with study procedures, restrictions and requirements.

Female subjects who are currently pregnant (confirmed with positive pregnancy test) or breast feeding or planning a pregnancy (also applies to male subjects), within the study period or 1 month following the last dose of study treatment.

1. Previous allogeneic bone marrow transplant.

2. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genomic sample collection.

What this study is about