A study of AZD4063 in PLN R14del dilated cardiomyopathy - PULSE

Inclusion Criteria

• Inclusion Criteria:
• - Participants must be 18 to 80 years of age inclusive, at the time of Screening
• - Participants with pre-existing positive screening for R14 del PLN mutation
• - Participants with screening Left ventricular eject fraction ≤ 45% as assessed by echocardiography
• - Participants with New York Heart Association (NYHA) function class I-III
• - Participants on stable medical therapy for at least 6 weeks prior to Screening and during the Screening period, with no significant improvement in heart failure
• - Participants with implantable cardioverter-defibrillator (ICD) or Cardiac resynchronization therapy device (CRT-D)
• - Participants with Body mass index (BMI) within the range 18-35 kg/m2
• - Females of childbearing potential must not be lactating, and if heterosexually active must agree to use an approved method of highly effective contraception
• - All females must have a negative pregnancy test at the Screening Visit.
• Exclusion Criteria:
• - Participants with positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody
• - Known to have tested positive for Human immunodeficiency virus (HIV)
• - Any known genetic mutation associated with hereditary electrical or structural disease
• - Congenital long QT syndrome
• - QTcF < 350 ms
• - Known Short QT syndrome (SQTS) or family history of SQTS
• - Catecholaminergic polymorphic ventricular tachycardia (CPVT as calcium ion channelopathy) and recent hospitalization for heart failure or significant ventricular arrhythmia within 3 months
• - Participants with sustained ventricular arrhythmia requiring treatment and considered clinically not stable by the Investigator
• - History of subendocardial Late Gadolinium Enhancement (LGE) suggestive of previous myocardial infarction and/or significant coronary artery disease (50% > stenosis in one major epicardial coronary artery or need for previous percutaneous coronary intervention or coronary artery bypass grafting)
• - Routinely scheduled outpatient intravenous infusions for heart failure
• - Uncontrolled hypertension
• - Significant primary valvular disease
• - Congenital heart disease
• - Left ventricular wall thickness of > 13 mm or with any relative with hypertrophic cardiomyopathy (HCM)
• - Recent acute presentation of myocarditis
• - Restrictive or peripartum cardiomyopathy; infiltrative disorders (sarcoidosis)
• - Alcohol consumption in excess
• - Any laboratory values with the following deviations:
• a) Alanine Transaminase >2 upper normal limit (ULN)
• b) Aspartate Transaminase >2 ULN
• c) Total bilirubin > 2 x ULN
• d) Estimated GFR < 30 mL/min/1.73 m2
• e) Hemoglobin <10g/dL
• - Any vital sign values with the following deviations at Screening
• (a) Systolic blood pressure > 160 mmHg
• (b) Diastolic blood pressure > 100 mmHg
• (c) Pulse rate > 100 beats per minute
• - Toxin exposure, systemic disease known to cause Dilated Cardiomyopathy (DCM)
• - History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity
• - Any history of cardiotoxic drug exposure with documented cardiomyopathy
• - Noncardiac condition that limits expected lifespan to less than 1 year
• - Participation in another clinical study with a study intervention administered in the last 3 months
• - Participants with a known hypersensitivity to AZD4063
• - Participants who are part of a gene therapy trial