A Phase IIb Study of AZD5462 in Patients With Chronic Heart Failure

Inclusion Criteria:

• Participants must have a pre-existing diagnosis of HF NYHA FC II to IV.

• Participants must be on stable HF standard of care medication for at least 4 weeksprior to consent and during the Screening period.

• Minimum body mass index (BMI) of 18 kilograms per meter square (kg/m^2) atScreening.

• For female participants, the participant must not be pregnant or lactating and mustbe of non-childbearing potential.

• All male participants should refrain from fathering a child or donating sperm until 3 months after the final study Follow-up Visit. Non-sterilised male participantsshould avoid fathering a child either by true abstinence or use of a condom for allsexual intercourse with a female partner of childbearing potential from the firstdose until 3 months after the final Follow-up Visit.

Exclusion Criteria:

• Historical or current evidence of a clinically significant disease or disorderincluding, but not limited to:

1. Myocardial infarction, stroke, transient ischaemic attack, coronary arterybypass grafting, or percutaneous coronary intervention within 12 weeks prior toconsent or transcatheter structural heart interventions or cardiac valvesurgery within 6 months prior to consent.

2. Sarcoidosis, restrictive cardiomyopathy, active myocarditis, constrictivepericarditis, or hypertrophic (obstructive) cardiomyopathy.

3. History of untreated clinically significant valve disease or a Screeningconfirmation of severe aortic stenosis, severe mitral stenosis, moderate orsevere aortic insufficiency or severe mitral insufficiency.

4. Amyloidosis, Fabry disease, or haemochromatosis.

5. Pericardial disease (i.e., visually significant white pericardium onechocardiogram).

6. Known coagulation disorders.

7. Current diagnosis of active hepatitis.

8. Severe pulmonary disease that is not expected to improve over time, as assessedby the investigator.

9. Decompensated HF or any cardiopulmonary hospitalisation, except plannedhospitalisation without worsening of cardiac or pulmonary functions, within 4weeks prior to consent or during the Screening period.

10. History of active malignancy within 2 years, except for fully excised ortreated basal cell carcinoma, or ≤ 2 squamous cell carcinomas of the skin andparticipants who are under investigation for breast or cervical cancer,including participants with a pap smear of grade ≥ 3.

• History of hypersensitivity to AZD5462 or any component of AZD5462 drug product.

• Known history of drug or alcohol abuse within 24 months of Screening.

• Congenital long QT syndrome or history of QT prolongation associated with othermedications that required discontinuation of that medication.

• Cardiac ventricular arrhythmia that requires treatment.

• History of or anticipated heart transplant.

• Current or planned cardiac resynchronization therapy/bi-ventricular pacemaker ormechanical assist device implantation.

• Any planned highly invasive cardiovascular procedure (eg, coronaryrevascularisation, ablation of atrial fibrillation/flutter etc).

• Positive hepatitis C antibody, or hepatitis B virus surface antigen at Screening.Participants with positive hepatitis B virus core antibody can be included in thestudy as long as hepatitis B virus surface antigen is negative, and there are noother signs of an active hepatitis B.

• Known to have historically tested positive for Human Immunodeficiency Virus.