A Randomised, Double-blind, Parallel Group, Placebo Controlled, 4-Week, Phase II Study to Evaluate the Effect of AZD4604 on Airway Inflammation and Biomarkers in Adults with Asthma - ARTEMISIA

Exclusion Criteria

• - A severe asthma exacerbation within 8 weeks prior to Visit 1.
• - History of herpes zoster reactivation (shingles).
• - Clinically important pulmonary disease other than asthma, eg, active lung infection, chronic obstructive pulmonary disease (COPD), bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, history or planned lung lobectomy, alpha-1 anti-trypsin deficiency, primary ciliary dyskinesia, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, and hyper-eosinophilic syndrome.
• - Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator.
• - Any clinically significant cardiac or cerebrovascular disease.
• - History of venous thromboembolism.
• - Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). Positivity for hepatitis B virus (HBV) surface antigen is a reason for exclusion.
• - Current or prior history of alcohol or drug abuse (including marijuana), as judged by the investigator. Positive drug screening result that cannot be justified by participant’s medical history and its relevant treatment (over-the-counter product or a valid prescription), or history of or current alcohol or drug abuse (including marijuana and marijuana-containing valid prescriptions), as judged by the investigator.
• - History of malignancy other than superficial basal cell carcinoma.
• - Treatment with systemic corticosteroid (short-term or maintenance) use within 8 weeks (oral) or 12 weeks (intramuscular) before Visit 1.
• - Any immunosuppressive therapy (including hydroxychloroquine, methotrexate, cyclosporine, and tacrolimus) within 12 weeks prior to Visit 1.
• - Treatment with marketed biologics including benralizumab, mepolizumab, reslizumab, omalizumab, dupilumab, and tezepelumab within 6 months or 5 half-lives of Visit 1, whichever is longer.
• - Inhaled corticosteroid plus fast-acting β2 agonist as a rescue medication (eg, Symbicort, Fostair, or Airsupra Maintenance and Reliever Treatment) is not allowed 30 days prior to Visit 1, during screening, run-in and baseline periods, throughout the treatment period, and preferably until 1 week after the last administration of the IMP.
• - Live, attenuated, or mRNA vaccines within 4 weeks of Visit 1.
• - Immunoglobulin therapy or blood products within 4 weeks of Visit 1.
• - Any immunotherapy within 6 months of Visit 1, except for stable maintenance dose allergen-specific immunotherapy started at least 4 weeks prior to Visit 1 and expected to continue through to the end of the follow-up period.
• - Anticoagulants (including vitamin K antagonists and Factor Xa inhibitors). Antiplatelet agents are allowable if in the opinion of the investigator they can be safely withheld for 7 days prior to the procedure.
• - Participants with a known hypersensitivity to AZD4604 or any of the excipients of the product.
• -Abnormal findings identified on physical examination, ECG, or laboratory testing include, but not limited to: Alanine aminotransferase/transaminase (ALT) or aspartate aminotransferase/transaminase AST ≥ 1.5 × upper limit of normal (ULN), Total bilirubin (TBL) ≥ ULN (unless due to known Gilbert’s disease), Evidence of chronic liver disease, International Normalised Ratio (INR) > 1.5, Platelet count < 150,000 per microliter, Abnormal vital signs, after 5 minutes of supine or sitting rest (confirmed by 1 controlled measurement), defined as any of the following: Systolic blood pressure (BP) < 80 mmHg or ≥ 150 mmHg, Diastolic BP < 50 mmHg or ≥ 95 mmHg, Pulse < 50 bpm or > 100 bpm, Signs of pulmonary oedema or volume overload, Any clinically significant rhythm, conduction, or morphology abnormalities in the ECG including but not limited to QT interval corrected using Fridericia’s formula (QTcF) > 450 ms.
• For female participants only – currently pregnant (confirmed with positive pregnancy test) or breastfeeding.
• - Current smokers or participants with smoking history ≥ 10 pack-years.
• - Participants with a known long-term exposure to occupational asbestos, silica, radon, heavy metals, and polycyclic aromatic hydrocarbons.
• - Positive, first-degree family history of primary lung cancer.
• - Positive urine cotinine test at Visit 1 and at any timepoint throughout the study.
• - Major surgery within 8 weeks prior to Visit 1, or planned inpatient surgery, major dental procedure or hospitalisation during screening, treatment, or follow-up periods.