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

Inclusion Criteria:

Part A will include healthy men and non-pregnant, non-lactating females of non-childbearing potential with a body mass index (BMI) of 18-30 kg/m^2 and a weight of 55-100 kg. One cohort will require participants be of Japanese descent
Part B will include men and non-pregnant, non-lactating females of non-childbearing potential
Participants have a BMI of 18-40 kg/m^2 and a weight of 55-136 kg
Participants with a diagnosis of stage C HF New York Heart Association (NYHA) Class I-III on stable medical therapy for at least 12 weeks
Participants with diagnosis of HFrEF will be defined as those with EF ≤ 40% and HF with EF ≥ 41%
Participants either with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) > 125 pg/mL or BNP > 35 pg/mL (46)

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