RecruitingPhase 1NCT07241104

A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy

A Phase I First-in-human Study to Investigate Safety, Tolerability, and Pharmacokinetics of AZD4063 in Adults With Phospholamban R14del Dilated Cardiomyopathy

Sponsor

AstraZeneca

Enrollment

31 participants

Start Date

Dec 1, 2025

Study Type

INTERVENTIONAL

Conditions

Dilated Cardiomyopathy

Summary

The purpose of the study is to assess the safety, tolerability and the pharmacokinetics (PK) of AZD4063 after single and multiple dose administration in participants with phospholamban (PLN) R14del dilated cardiomyopathy.

Eligibility

Min Age: 18 YearsMax Age: 80 Years

Inclusion Criteria9

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 Criteria34

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:
Alanine Transaminase \>2 upper normal limit (ULN)
Aspartate Transaminase \>2 ULN
Total bilirubin \> 2 x ULN
Estimated GFR \< 30 mL/min/1.73 m2
Hemoglobin \<10g/dL
Any vital sign values with the following deviations at Screening
Systolic blood pressure \> 160 mmHg
Diastolic blood pressure \> 100 mmHg
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