A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy

NCT ID: NCT07241104

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-01

Study Completion Date

2027-11-22

Brief Summary

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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.

Detailed Description

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This is a Phase 1, first in human, unblinded, ascending dose study which will be comprised of: 3 single ascending dose (SAD) cohorts, 3 multiple ascending dose (MAD) cohorts and optional cohorts.

The SAD part of the study will assess the single doses of AZD4063 across 3 cohorts. It will consist of:

* A screening period
* A treatment period: The participants will receive a single dose of AZD4063 by subcutaneous (SC) injection
* A follow-up period

The MAD part of the study will initiate on receiving the data from SAD cohort with available safety, PK and pharmacodynamics (PD) data from all cohorts. This part of the study will consist of:

* A screening period
* A treatment period: The participants will receive multiple doses of AZD4063 by SC injection
* A follow-up period

Optional cohorts may be added based on emerging safety, PK and PD data of the SAD and MAD cohorts.

Conditions

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Dilated Cardiomyopathy

Keywords

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Single Ascending Dose Multiple Ascending Dose Phospholamban

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1 (SAD): Dose 1 of AZD4063

Participants will receive Dose 1 of AZD4063 via SC injection in Cohort 1 of SAD.

Group Type EXPERIMENTAL

AZD4063

Intervention Type DRUG

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

Cohort 2 (SAD): Dose 2 of AZD4063

Participants will receive Dose 2 of AZD4063 via SC injection in Cohort 2 of SAD.

Group Type EXPERIMENTAL

AZD4063

Intervention Type DRUG

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

Cohort 3 (SAD): Dose 3 of AZD4063

Participants will receive Dose 3 of AZD4063 via SC injection in Cohort 3 of SAD.

Group Type EXPERIMENTAL

AZD4063

Intervention Type DRUG

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

Cohort 1 (MAD): Dose 4 of AZD4063

Participants will receive Dose 4 of AZD4063 via SC injection in Cohort 1 of MAD.

Group Type EXPERIMENTAL

AZD4063

Intervention Type DRUG

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

Cohort 2 (MAD): Dose 5 of AZD4063

Participants will receive Dose 5 of AZD4063 via SC injection in Cohort 2 of MAD.

Group Type EXPERIMENTAL

AZD4063

Intervention Type DRUG

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

Cohort 3 (MAD): Dose 6 of AZD4063

Participants will receive Dose 6 of AZD4063 via SC injection in Cohort 3 of MAD.

Group Type EXPERIMENTAL

AZD4063

Intervention Type DRUG

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

Optional Cohort 1 (SAD): Dose 7 of AZD4063

Participants will receive Dose 7 of AZD4063 via SC injection in the optional cohort of the study. This additional cohort will be added depending on the findings.

Group Type EXPERIMENTAL

AZD4063

Intervention Type DRUG

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

Optional Cohort 2 (SAD): Dose 8 of AZD4063

Participants will receive Dose 8 of AZD4063 via SC injection in the optional cohort of the study. This additional cohort will be added depending on the findings.

Group Type EXPERIMENTAL

AZD4063

Intervention Type DRUG

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

Optional Cohort 1 (MAD): Dose 9 of AZD4063

Participants will receive Dose 9 of AZD4063 via SC injection in the optional cohort of the study. This additional cohort will be added depending on the findings.

Group Type EXPERIMENTAL

AZD4063

Intervention Type DRUG

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

Optional Cohort 2 (MAD): Dose 10 of AZD4063

Participants will receive Dose 10 of AZD4063 via SC injection in the optional cohort of the study. This additional cohort will be added depending on the findings.

Group Type EXPERIMENTAL

AZD4063

Intervention Type DRUG

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

Interventions

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AZD4063

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Amsterdam, , Netherlands

Site Status NOT_YET_RECRUITING

Research Site

Groningen, , Netherlands

Site Status RECRUITING

Research Site

Rotterdam, , Netherlands

Site Status RECRUITING

Research Site

Utrecht, , Netherlands

Site Status NOT_YET_RECRUITING

Countries

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Netherlands

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

Phone: 1-877-240-9479

Email: [email protected]

Other Identifiers

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D8340C00001

Identifier Type: -

Identifier Source: org_study_id