It is believed that targeted SERCA2a enzyme replacement in HFrEF patients will correct defective intracellular Ca2+ hemostasis, resulting in improved cardiac contractile function and energetics which will, in turn, translate to improved clinical outcomes. Additionally, it is hypothesized that correcting SERCA2a dysfunction will also improve coronary blood flow through correction of the impaired endothelium-dependent nitric oxide-mediated vasodilatation observed in heart failure.
MUSIC-HFrEF1 is an interventional study of SRD-001, an adeno-associated virus serotype 1 (AAV1) vector expressing the transgene for sarco(endo)plasmic reticulum Ca2+ ATPase 2a isoform (SERCA2a), in anti-AAV1 neutralizing antibody (NAb) negative subjects with ischemic or non-ischemic cardiomyopathy and New York Heart Association (NYHA) class III/IV symptoms of heart failure with reduced ejection fraction (HFrEF). The Phase 1 trial is an open-label, uncontrolled study investigating two doses of SRD-001 at 3E13 and 4.5E13 viral genomes (vg) in 3-4 participants at each dose level. The Phase 2 trial is a randomized, double-blind, placebo-controlled trial with prospective assignment to a single dose of either SRD-001 or placebo in a 1:1 ratio and a total sample size of N=50.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
57
San Diego Cardiac Center
San Diego, California, United States
RECRUITINGUniversity of California, San Francisco
San Francisco, California, United States
RECRUITINGWashington University in Saint Louis
St Louis, Missouri, United States
RECRUITINGUniversity of Texas Southwestern Medical Center
Dallas, Texas, United States
RECRUITINGUniversity of Washington Medicine
Seattle, Washington, United States
RECRUITINGChange from baseline in symptomatic parameters
New York Heart Association classification (I, II, III or IV)
Time frame: Baseline to Month 6 and Month 12
Change from baseline in symptomatic parameters
Quality of life as assessed by Kansas City Cardiomyopathy Questionnaire: 0-24, very poor to poor; 25-49, poor to fair; 50-74, fair to good; and 75-100, good to excellent
Time frame: Baseline to Month 6 and Month 12
Change from baseline in physical parameter
Distance walked during the 6MWT
Time frame: Baseline to Month 6 and Month 12
Change from baseline in LV function/remodeling
Left ventricular end systolic volume (LVESV) as assessed by echocardiography
Time frame: Baseline to Month 6 and Month 12
Rate of recurrent events
HF-related hospitalization, ambulatory worsening heart failure, all-cause death, MCSD and transplant
Time frame: Baseline to Month 6 and Month 12
Rate of adverse events
Treatment-emergent adverse events
Time frame: 6 and 12 months
Proportion of subjects who complete the trial
Those who complete the trial vs withdraw consent, are lost to follow-up, or withdrawn due to an AE or other reason
Time frame: 12 months
Concomitant medication use
Changes in heart failure related medications
Time frame: 6 and 12 months
Incidence of abnormal laboratory test results
Hematologic, serum chemistries, NT-proBNP and troponin
Time frame: Baseline to Month 6 and Month 12
Incidence of abnormal ECG results
New arrhythmias
Time frame: Baseline to Month 6 and Month 12
Incidence of abnormal physical examination findings
Change from baseline in physical examination findings
Time frame: Baseline to Month 6 and Month 12
Incidence of abnormal findings from interrogation of implantable cardioverter defibrillator
New arrhythmias
Time frame: Baseline to Month 6 and Month 12
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