What is the mechanism of action of this treatment?

Heart Failure (HF) treatments often target the underlying mechanisms that impair cardiac function. Common treatments include ACE inhibitors and angiotensin II receptor blockers (ARBs), which reduce blood pressure and decrease the heart's workload by inhibiting the renin-angiotensin-aldosterone system. Beta-blockers slow the heart rate and reduce myocardial oxygen demand. Diuretics help eliminate excess fluid, reducing the strain on the heart. SERCA2a enzyme replacement therapy, which is being studied, aims to correct defective intracellular calcium hemostasis, thereby improving cardiac contractile function and energetics. Additionally, it enhances nitric oxide-mediated vasodilatation, improving coronary blood flow. These mechanisms are crucial for HF patients as they help restore efficient heart function, reduce symptoms, and improve overall quality of life.

What side effects are associated with this type of intervention?

Common treatments for heart failure, such as ACE inhibitors, aldosterone receptor blockers, and calcium antagonists, have various side effects. ACE inhibitors can cause cough, elevated blood potassium levels, low blood pressure, and kidney dysfunction. Aldosterone receptor blockers may lead to hyperkalemia (high potassium levels), kidney impairment, and gynecomastia (breast tissue enlargement in men). Calcium antagonists can cause dizziness, headache, swelling in the lower extremities, and constipation. These treatments aim to improve heart function and blood flow, similar to the goals of SERCA2a enzyme replacement therapy.

What prior FDA approvals exist?

FDA-approved treatments for heart failure that target intracellular calcium handling and nitric oxide pathways include beta-blockers, ACE inhibitors, and ARBs, which help reduce myocardial oxygen consumption and improve cardiac function. Additionally, drugs like digoxin improve intracellular calcium levels, enhancing cardiac contractility. While specific enzyme replacement therapies like SERCA2a are still under investigation, these approved treatments share the goal of improving cardiac function and hemodynamics in heart failure patients.

What other types of research exist?

Promising alternatives to SERCA2a enzyme replacement for heart failure patients include: 1) Angiotensin receptor-neprilysin inhibitors (ARNIs) like sacubitril/valsartan, which improve cardiac function and outcomes by enhancing natriuretic peptides and inhibiting the renin-angiotensin system. 2) Sodium-glucose co-transporter 2 (SGLT2) inhibitors, which have shown benefits in heart failure by reducing hospitalization and improving cardiovascular outcomes. 3) Gene therapy targeting calcium handling proteins other than SERCA2a, such as phospholamban (PLN) inhibitors, which can enhance calcium reuptake and improve cardiac contractility. 4) Advanced pharmacologic agents like omecamtiv mecarbil, a cardiac myosin activator that directly increases cardiac contractility without increasing intracellular calcium levels.

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Enzyme Replacement

SRD-001 for Heart Failure (MUSIC-HFrEF1 Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Sardocor Corp.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Maximal, optimized heart failure therapy; ICD

Chronic ischemic or non-ischemic cardiomyopathy

Must not have

Restrictive cardiomyopathy, hypertrophic cardiomyopathy, acute myocarditis, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease or discrete left ventricular (LV) aneurysm

Inadequate hepatic and renal function

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 and 12 months

Summary

This trial uses a harmless virus to deliver a gene that helps heart cells produce a beneficial protein. It targets patients with severe heart failure who don't respond well to other treatments. The treatment works by improving calcium handling in heart cells, which enhances heart function and blood flow. Gene therapy has recently emerged as a powerful tool offering the promise of a new paradigm for alleviating heart failure.

Who is the study for?

This trial is for adults with heart failure and reduced ejection fraction (LVEF ≤35%). Participants must be in NYHA class III/IV, have an ICD implanted, and be on the best possible heart failure medications. People with poor liver or kidney function, recent cancer treatments (except certain skin cancers), likely need for a heart transplant or mechanical support soon, or specific other heart conditions are not eligible.

What is being tested?

The study tests whether SRD-001 can improve heart muscle function by correcting calcium handling inside cells. It's compared to a placebo. The idea is that fixing SERCA2a enzyme levels could help hearts pump better and improve blood flow through arteries by aiding vessel relaxation.

What are the potential side effects?

Potential side effects aren't specified here but may include reactions at the injection site, changes in blood pressure or heartbeat due to improved cardiac function, and possibly immune responses if the body reacts to SRD-001 as foreign.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am on the best possible treatment for heart failure and have an ICD.

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I have a long-term heart muscle condition.

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I have severe heart condition symptoms.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have specific heart or thyroid conditions.

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My liver and kidney functions are not normal.

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I have had heart surgery or use a heart support device.

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I haven't had cancer in the last 5 years, except for skin cancer or early stage cancer that was surgically removed.

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I may need a heart transplant or a mechanical support device soon due to unstable heart function.

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I am likely to undergo a heart-related surgery within 6 months after treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 and 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 and 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 and 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change from baseline in LV function/remodeling

Change from baseline in physical parameter

Change from baseline in symptomatic parameters

+2 more

Secondary study objectives

Concomitant medication use

Incidence of abnormal ECG results

Incidence of abnormal findings from interrogation of implantable cardioverter defibrillator

+3 more

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: SRD-001Experimental Treatment1 Intervention

3E13 or 4.5E13 vg; one-time intracoronary infusion

Group II: PlaceboPlacebo Group1 Intervention

One-time intracoronary infusion

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Heart Failure (HF) treatments often target the underlying mechanisms that impair cardiac function. Common treatments include ACE inhibitors and angiotensin II receptor blockers (ARBs), which reduce blood pressure and decrease the heart's workload by inhibiting the renin-angiotensin-aldosterone system. Beta-blockers slow the heart rate and reduce myocardial oxygen demand. Diuretics help eliminate excess fluid, reducing the strain on the heart. SERCA2a enzyme replacement therapy, which is being studied, aims to correct defective intracellular calcium hemostasis, thereby improving cardiac contractile function and energetics. Additionally, it enhances nitric oxide-mediated vasodilatation, improving coronary blood flow. These mechanisms are crucial for HF patients as they help restore efficient heart function, reduce symptoms, and improve overall quality of life.

Effect of a calcium-sensitizing positive inotropic agent MCI-154 and its combined use with enalapril on postischemic contractile dysfunction of dog hearts.Effects of angiotensin II receptor blocker (candesartan) in daunorubicin-induced cardiomyopathic rats.