The CUPID-3 Trial 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 one dose of SRD-001 at 3E13 viral genomes (vg) in 4 to 8 subjects.~The Phase 2 is a randomized, double-blind, placebo-controlled trial with prospective assignment to a single dose of either SRD-001 at 3E13 vg or placebo in a 1:1 ratio and a total sample size of N=50.
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.