Dilated CardiomyopathyPhase 1PULSENCT07241104
A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy
A Phase 1 study testing AZD4063 in people with Dilated Cardiomyopathy, run by AstraZeneca at 4 sites in Netherlands.
Trial summary
The purpose of the study is to assess the safety, tolerability and the pharmacokinetics (PK) of AZD4063 after single dose administration in participants with phospholamban (PLN) R14del dilated cardiomyopathy. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Dilated Cardiomyopathy
- What is being tested?
- AZD4063
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 4 sitesNetherlands
- Study dates
- 1 Dec 2025to 22 Nov 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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 women of childbearing potential must have a negative pregnancy test at the Screening Visit.
Who cannot join
- 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
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- 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 have previously received AZD4063 as part of this study
- Participants who are part of a gene therapy trial
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
Netherlands4 sites, 4 recruiting
- Recruiting
Research Site
Amsterdam, 1081 HV
- Recruiting
Research Site
Groningen, 9713 GZ
- Recruiting
Research Site
Rotterdam, 3015 GD
- Recruiting
Research Site
Utrecht, 3584 CX
About this study
Official title: A Phase I First-in-human Study to Investigate Safety, Tolerability, and Pharmacokinetics of AZD4063 in Adults With Phospholamban R14del Dilated Cardiomyopathy
The purpose of the study is to assess the safety, tolerability and the pharmacokinetics (PK) of AZD4063 after single dose administration in participants with phospholamban (PLN) R14del dilated cardiomyopathy.
Read the detailed description
This is a Phase 1, first in human, unblinded, ascending dose study which will consist of a SAD (single ascending dose) part and an Optional part.
The SAD part of the study will assess the single doses of AZD4063 across 4 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
Optional cohorts may be added based on emerging safety, PK and PD data of the preceding cohorts.
- Conditions
- Dilated Cardiomyopathy
- Being tested
- AZD4063
- Keywords
- Single Ascending Dose, Phospholamban
- Medical subject headings
- Cardiomyopathy, Dilated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4063Drug
AZD4063 will be administered as solution for injection via subcutaneous route of administration.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (SAD): Dose 1 of AZD4063 | Experimental | Participants will receive Dose 1 of AZD4063 via SC injection in Cohort 1 of SAD. Receives: Drug: AZD4063 |
| Cohort 2 (SAD): Dose 2 of AZD4063 | Experimental | Participants will receive Dose 2 of AZD4063 via SC injection in Cohort 2 of SAD. Receives: Drug: AZD4063 |
| Cohort 3 (SAD): Dose 3 of AZD4063 | Experimental | Participants will receive Dose 3 of AZD4063 via SC injection in Cohort 3 of SAD. Receives: Drug: AZD4063 |
| Cohort 4 (SAD): Dose 4 of AZD4063 | Experimental | Participants will receive Dose 4 of AZD4063 via SC injection in Cohort 4 of SAD. Receives: Drug: AZD4063 |
| Optional Cohort 1 (SAD): Dose 5 of AZD4063 | Experimental | Participants will receive Dose 5 of AZD4063 via SC injection in the optional cohort of the study. This additional cohort will be added depending on the findings. Receives: Drug: AZD4063 |
| Optional Cohort 2 (SAD): Dose 6 of AZD4063 | Experimental | Participants will receive Dose 6 of AZD4063 via SC injection in the optional cohort of the study. This additional cohort will be added depending on the findings. Receives: Drug: AZD4063 |
| Optional Cohort 3 (SAD): Dose 7 of AZD4063 | Experimental | 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. Receives: Drug: AZD4063 |
| Optional Cohort 4 (SAD): Dose 8 of AZD4063 | Experimental | 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. Receives: Drug: AZD4063 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events (AEs)
The safety and tolerability of AZD4063 following the SC administration of single doses in participants with PLN R14del dilated cardiomyopathy will be evaluated.
Measured: Cohorts 1 and 2: Day 1 to 80; Cohorts 3 and 4: Day 1 to 210
Secondary outcomes (7)
Area under plasma concentration-time curve from 0 to infinity (AUCinf)
The AUCinf of single ascending doses of AZD4063 following SC administration will be evaluated.
Measured: Cohorts 1 and 2: Day 1 to 80; Cohorts 3 and 4: Day 1 to 210
Area under the plasma concentration-curve from 0 to the last quantifiable concentration (AUClast)
The AUClast of single doses of AZD4063 following SC administration will be evaluated.
Measured: Cohorts 1 and 2: Day 1 to 80; Cohorts 3 and 4: Day 1 to 210
Maximum plasma drug concentration (Cmax)
The Cmax of single doses of AZD4063 following SC administration will be evaluated.
Measured: Cohorts 1 and 2: Day 1 to 80; Cohorts 3 and 4: Day 1 to 210
Renal clearance (CLR)
The CLR of the single doses of AZD4063 following SC administration will be evaluated.
Measured: Cohorts 1 and 2: Day 1 to 94; Cohorts 3 and 4: Day 1 to Follow up (Day 224)
Cumulative amount of analyte excreted (Ae)
The Ae of single doses of AZD4063 following SC administration will be evaluated.
Measured: Cohorts 1 and 2: Day 1 to 94; Cohorts 3 and 4: Day 1 to Follow up (Day 224)
Fraction of dose excreted unchanged in urine (Fe)
The Fe of single doses of AZD4063 following SC administration will be evaluated.
Measured: Cohorts 1 and 2: Day 1 to 94; Cohorts 3 and 4: Day 1 to Follow up (Day 224)
Change in endomyocardial biopsy PLN messenger ribonucleic acid (mRNA levels) from baseline to estimated peak knockdown and estimated return-to-baseline
The effects of single ascending doses of AZD4063 on knockdown of PLN mRNA will be evaluated.
Measured: Cohorts 1 and 2: Day 1 to 94; Cohorts 3 and 4: Day 1 to Follow up (Day 224)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2025
- Study start1 Dec 2025
- Primary completion22 Nov 2027 (estimated)
- Study completion22 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dilated CardiomyopathyStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 23 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07241104
- Sponsor's protocol ID
- D8340C00001
- Acronym
- PULSE
- Status last verified
- Aug 2026
- First submitted
- 17 Nov 2025
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.