Skip to main content
TrialFinder
TrialFinder is for informational purposes only and does not provide medical advice. Always talk to your doctor about whether a trial is right for you.
RECRUITINGPhase 1INTERVENTIONAL

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

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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. Who Should NOT Join This Trial: - Participants with positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody - Known to have tested positive for Human weakened immune system 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) ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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: 1. Alanine Transaminase \>2 upper normal limit (ULN) 2. Aspartate Transaminase \>2 ULN 3. Total bilirubin \> 2 x ULN 4. Estimated GFR \< 30 mL/min/1.73 m2 5. Hemoglobin \<10g/dL * Any vital sign values with the following deviations at Screening 1. Systolic blood pressure \> 160 mmHg 2. Diastolic blood pressure \> 100 mmHg 3. 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

Treatments Being Tested

DRUG

AZD4063

AZD4063 will be administered in the SAD and MAD part of the study as solution for injection via subcutaneous route of administration.

Locations (4)

Research Site
Amsterdam, Netherlands
Research Site
Groningen, Netherlands
Research Site
Rotterdam, Netherlands
Research Site
Utrecht, Netherlands