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