Assessment of Safety, Tolerability, Immunogenicity, and Pharmacokinetics of AZD3427

Exclusion Criteria

• Both Part A and Part B will exclude participants with any of the following:
• • Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study drug or planned surgical procedure before study completion
• • History of vascular and left ventricular aneurysms or prior dissections
• • Any history of joint hypermobility, Marfan’s syndrome, or any connective tissue disorder
• • Clinical signs and symptoms consistent with Coronavirus disease-19 or confirmed infection within the last 4 weeks
• • History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity injection devices or to drugs with a similar chemical structure or class to AZD3427 or any component of AZD3427
• In addition, Part A will exclude participants with any of the following:
• • Alanine Aminotransferase (ALT) > Upper limit of normal (ULN)
• • Aspartate Aminotransferase (AST) > ULN
• • Total bilirubin > ULN (unless due to Gilbert’s syndrome)
• • Creatinine > ULN
• • White blood cell (WBC) count < Lower limit of normal (LLN)
• • Hemoglobin < LLN
• • Prolonged QTcF > 450 m
• • Shortened QTcF < 340 ms
• • Family history of long QT syndrome
• • PR (PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation)
• • PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third-degree atrioventricular (AV) block, or AV dissociation
• • Persistent or intermittent complete bundle branch block, incomplete bundle branch block, or intraventricular conduction delay with QRS > 110 ms. Participants with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of eg, ventricular hypertrophy or pre-excitation
• In addition, Part B will exclude participants with any of the following:
• • Atrial fibrillation or flutter occurring in the past year
• • Clinically significant ventricular arrhythmias under treatment
• • High-degree AV block II-III or sinus node dysfunction
• • Implanted permanent pacemaker or implantable cardioverter defibrillator for which the participant is pacing-dependent
• • Severe right-sided valvular heart disease; severe mitral regurgitation; moderate or severe mitral stenosis, severe aortic regurgitation and mild, moderate or severe aortic stenosis
• • Other conditions where vasodilatory therapy may be contraindicated (hypertrophic obstructive cardiomyopathy, and restrictive cardiomyopathy)
• • Congenital heart disease
• • NYHA HF Class IV
• • Occurrence in the last 6 months of acute coronary syndrome, percutaneous coronary intervention, cerebrovascular accident or transient ischemic attack, HF hospitalization; history or suspicion of cardiac amyloidosis
• • ALT > 1.5 × ULN
• • AST > 1.5 × ULN
• • Total bilirubin > ULN (unless due to Gilbert’s syndrome)
• • Impaired renal function, defined as eGFR < 30 mL/min/1.73m^2 assessed by the Chronic Kidney Disease Epidemiology Collaboration equation
• • WBC < LLN
• • Hemoglobin < 10g/L
• • PR (PQ) interval prolongation (> 220 ms)
• • Participants with persistent BBB and QRS (ECG interval measured from the onset of the QRS complex to the J point) duration > 130 ms. Participants with intraventricular conduction delay and QRS duration < 130 ms