A Phase 1/2 study of ALXN2350 in adult participants with BAG3-associated dilated cardiomyopathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alexion Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

5 Feb 2026 → ongoing

Decision date (initial)

2025-10-20

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Alexion Pharmaceuticals, Inc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response, Pharmacodynamic, Pharmacokinetic

Part A: To determine the safety and tolerability after a single IV infusion of ALXN2350 in participants with BAG3-associated DCM.
Part B : To evaluate clinical impact (efficacy) after a single IV infusion of ALXN2350 vs external control in participants with BAG3-associated DCM

Secondary objectives 12

1. Part A and B : To demonstrate cardiac stabilization after a single IV infusion of ALXN2350 vs external control in participants with BAG3-associated DCM.
2. Part A and B : To evaluate changes in cardiac structure and function after a single IV infusion of ALXN2350 vs external control in participants with BAG3-associated DCM over the duration of study
3. Part A and B : To characterize changes in cardiac serum biomarker NT-proBNP after a single IV infusion of ALXN2350 vs external control in participants with BAG3-associated DCM over the duration of study
4. Part A and B : To evaluate changes in cardiac structure and function after a single IV infusion of ALXN2350 vs external control in participants with BAG3 associated DCM over the duration of study
5. Part A and B : To evaluate the effects on functional measures after a single IV infusion of ALXN2350 vs external control in participants with BAG3--associated DCM
6. Part A and B : To evaluate cardiac events after a single IV infusion of ALXN2350 vs external control in participants with BAG3-associated DCM
7. Part A and B : To assess time to first severe cardiac event
8. Part A and B : To characterize health-related quality of life after a single IV infusion of ALXN2350 vs external control in participants with BAG3--associated DCM
9. Part A and B : To characterize changes in the cardiac biomarker troponin after a single IV infusion of ALXN2350 vs external control in participants with BAG3 associated DCM over the duration of study
10. Part A and B : To assess amount of vector shedding after a single IV infusion of ALXN2350 in participants with BAG3-associated DCM
11. Part A and B : Immune Function Assessments: To assess the immunogenicity after a single IV infusion of ALXN2350 in participants with BAG3-associated DCM for the duration of the study
12. Part B : To determine the safety and tolerability after a single IV infusion of ALXN2350 in participants with BAG3-associated DCM

Conditions and MedDRA coding

BAG3 Mutation Associated Dilated Cardiomyopathy

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

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. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Participant must be at least 18 years of age and no older than 70 years of age at the time of signing the informed consent.
2. Documented heterozygous pathogenic or likely pathogenic mutation in BAG3, interpreted according to the ACMG Guidelines, as confirmed by central laboratory. Pathogenic and likely pathogenic mutations may include deletions, frameshifting indels, premature truncations, disruption to an essential splice site, and/or sequence-altering missense variation with evidence supporting loss of function of the affected allele.
3. Have had medical history of diagnosis of DCM (as per national guidelines)
4. Participants must be on a stable combination of HF SoC medications (including angiotensin receptor-neprilysin inhibitor [ARNi], angiotensin-converting enzyme [ACE] inhibitor, angiotensin receptor blocker [ARB], beta-blocker, mineral corticoid receptor antagonists, and sodium-glucose cotransporter 2 [SGLT2] inhibitor) for at least 12 weeks prior to Stage 2 consent and during the Screening Period. If the participant is currently taking diuretics, then diuretics must also be stable for at least 2 weeks prior to Stage 2 consent (minor dose adjustments [<50%] in diuretics are allowed based on the Investigator’s judgment).
5. Participants must have adequate acoustic windows for echocardiography.

Exclusion criteria 10

1. Decompensated HF or any cardiopulmonary hospitalization within 4 weeks prior to Stage 2 consent, or during the screening period.
2. Pathogenic or likely-pathogenic missense genotype specifically affecting BAG3 amino acid 209 (eg, NP_004272.2:p.Pro209Leu), or presence of a pathogenic or likely pathogenic variant in another gene where that other gene is authoritatively recognized as causal for DCM
3. Presence of antibodies to AAV9 based on TAb assay at an MRD of 1:20.
4. Recipient of any major organ transplant (eg, heart, lung, liver, bone marrow, renal) or likelihood, in the Investigator’s opinion, of undergoing cardiac transplantation, LVAD, or cardiac surgery within 3 months of Stage 2 of Screening.
5. Any of the following within 3 months prior to Stage 2 consent: Acute coronary syndrome, stroke, transient ischemic attack, and cardiac procedures (pacemaker/ICD/ CRT-D implantation/coronary artery bypass grafting or percutaneous coronary intervention, coronary revascularization, ablation of atrial fibrillation/flutter, valve repair/replacement, aortic aneurysm surgery, etc).
6. Positive coronary artery ischemic evaluation or presence of obstructive coronary artery disease (defined by ≥70% obstruction in a major epicardial coronary artery or ≥50% left main disease). If a prior ischemic workup cannot be documented, a participant may undergo a coronary CCTA in Screening. A positive result would lead to exclusion. CCTA results that would exclude a participant are CAD RADS classifications 4, 5 or N.
7. Congenital long QT syndrome or prolonged QTcF >500msec.
8. Cardiac ventricular arrhythmia that requires treatment. However, participants with atrial fibrillation or flutter and controlled ventricular rate (eg resting HR < 110 bpm) are permitted. Participants with cardiac ventricular arrhythmia that are treated with antiarrhythmic agents (eg, amiodarone) and are stable are permitted.
9. History of untreated clinically significant valve disease or a Screening confirmation of severe aortic stenosis, severe mitral stenosis, moderate or severe aortic insufficiency or severe mitral insufficiency.
10. Clinically significant pericardial disease in the opinion of the Investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Part A : Incidence and severity of TEAEs and SAEs, and clinically significant safety findings (physical examinations, vital sign measurements, clinical laboratory assessments, and ECG results).

Secondary endpoints 7

1. Part B : Incidence and severity of TEAEs and SAEs, and clinically significant safety findings (physical examinations, vital sign measurements, clinical laboratory assessments, and ECG results).
2. Part A and B : CFB in cardiac serum biomarker NT‑proBNP through Week 52 and 78.
3. Part A and B : Incidence of cardiac events including heart failure hospitalization, sustained ventricular arrhythmias, appropriate implantable cardioverter defibrillator shock through Week 52 and 78.
4. Part A and B : Time to the first event of death, heart transplant, mechanical circulating support, or aborted sudden cardiac death through Week 52 and 78.
5. Part A and B : CFB of cardiac serum biomarker hs-TnT Week 52 and 78.
6. Part A and B : Amount of virus secreted in blood, feces, saliva, semen, and urine through Week 52 and 78.
7. Part A and B : Incidence of anti-AAV9 and anti BAG3 antibodies, response categories, and titer, in participants with BAG3-associated DCM treated with ALXN2350 through Week 52 and 78.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 11

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alexion Pharmaceuticals Inc.

Sponsor organisation

Alexion Pharmaceuticals Inc.

Address

121 Seaport Boulevard

City

Boston

Postcode

02210-2050

Country

United States

Scientific contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Public contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 54 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications