Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Reduced Ejection Fraction

Официальное название

A Phase 1/2 Trial of the Safety and Efficacy of SRD-001 (AAV1/SERCA2a) in Subjects With Heart Failure With Reduced Ejection Fraction

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат SRD-001
  AAV1/SERCA2a
• Препарат Placebo
  SRD-001 matching placebo

Первичные конечные точки

• Change from baseline in symptomatic parameters [Срок оценки: Baseline to Month 6 and Month 12]
• Change from baseline in symptomatic parameters [Срок оценки: Baseline to Month 6 and Month 12]
• Change from baseline in physical parameter [Срок оценки: Baseline to Month 6 and Month 12]
• Change from baseline in LV function/remodeling [Срок оценки: Baseline to Month 6 and Month 12]
• Rate of recurrent events [Срок оценки: Baseline to Month 6 and Month 12]
• Rate of adverse events [Срок оценки: 6 and 12 months]

Вторичные конечные точки (6)

• Proportion of subjects who complete the trial [Срок оценки: 12 months]
• Concomitant medication use [Срок оценки: 6 and 12 months]
• Incidence of abnormal laboratory test results [Срок оценки: Baseline to Month 6 and Month 12]
• Incidence of abnormal ECG results [Срок оценки: Baseline to Month 6 and Month 12]
• Incidence of abnormal physical examination findings [Срок оценки: Baseline to Month 6 and Month 12]
• Incidence of abnormal findings from interrogation of implantable cardioverter defibrillator [Срок оценки: Baseline to Month 6 and Month 12]

Критерии участия

Main Inclusion Criteria:

• Chronic ischemic or non-ischemic cardiomyopathy
• NYHA class III/IV
• LVEF ≤35%
• Guideline-directed medical therapy for heart failure; ICD

Main Exclusion Criteria:

• Restrictive cardiomyopathy, hypertrophic cardiomyopathy, acute myocarditis, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease or discrete left ventricular (LV) aneurysm
• Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), mechanical circulatory support device (MCSD) or cardiac shunt
• Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LVRS, conventional revascularization procedure or valvular repair in the 6 months following treatment
• Likely need for an immediate heart transplant or MCSD implant due to hemodynamic instability
• Inadequate hepatic and renal function
• Diagnosis of, or treatment for, any cancer within the last 5 years except for basal cell carcinoma or carcinomas in situ where surgical excision was considered curative

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 5 центров

• San Diego Cardiac Center — San Diego
• University of California, San Francisco — San Francisco
• Washington University in Saint Louis — St Louis
• University of Texas Southwestern Medical Center — Dallas
• University of Washington Medicine — Seattle

Идентификаторы

NCT: NCT04703842 · SRD-001-1001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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