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Efficacy and Safety Study of Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure
Bu çalışma, ileri evre kalp yetmezliği olan hastalarda MYDICAR adlı gen terapisini değerlendirmiştir. Tedavi, kalp kası hücrelerinde kalsiyum dengesini düzenleyen SERCA2a geninin bir kopyasını kalbe ulaştırmayı hedefler. Çalışmaya iskemik ya da iskemik olmayan kardiyomiyopatisi bulunan hastalar alınmış; önce açık etiketli doz artırma, ardından plasebo kontrollü randomize aşama yürütülmüştür. Faz 1/2 aşamasında tamamlanmıştır.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion Criteria: * Chronic ischemic or non-ischemic cardiomyopathy. Subjects with ischemic cardiomyopathy must have at least one major coronary vessel with Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow. * Left ventricular ejection fraction (LVEF) ≤35% * Diagnosis of New York Heart Association (NYHA) Class III/IV heart failure for a minimum of 3 months prior to screening * Maximal oxygen consumption (VO2 max) ≤20 mL/kg/min within 90 days prior to enrollment * An implantable cardioverter defibrillator (ICD) implanted a minimum of 30 days prior to enrollment * Treatment with appropriate heart failure therapy as tolerated * All women of childbearing potential must have a negative urine pregnancy test prior to administration of investigational product and agree to use adequate contraception. Men capable of fathering a child must agree to use barrier contraception or limit activity to post-menopausal, surgically sterilized, or a contraception-practicing partner, for 3 months after administration of investigational product. * Ability to sign Informed Consent Form (ICF) and Release of Medical Information Form Exclusion Criteria: * Any intravenous therapy with positive inotropes, vasodilators, or diuretics within 30 days prior to enrollment * Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic LV aneurysm * Cardiac surgery, percutaneous coronary intervention, or valvuloplasty within 30 days prior to enrollment * Clinically significant myocardial infarction (e.g., ST elevation MI \[STEMI\] or large non-STEMI) within 6 months prior to enrollment * Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted LVAD or cardiac shunt * Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LVRS, heart transplant, conventional revascularization procedure, or valvular repair within 6 months following enrollment * Patients with prior coronary artery bypass graft(s) (CABG) will reviewed on a case-by-case basis * No evidence of functional or viable myocardium * Exercise capacity primarily limited by obesity, peripheral vascular disease, intrinsic pulmonary disease or orthopedic problems and not by underlying heart failure * Known hypersensitivity to octafluoropropane (component of the intravenous echocardiography contrast agent, DEFINITY®) or other contrast dyes used for angiography; history of, or likely need for, high dose steroid pretreatment prior to contrast angiography * A left ventricle that is difficult to image or high quality echocardiography is not obtainable at screening * Significant left main or ostial right coronary lumenal stenosis in the opinion of the investigator * Expected survival \<1 year in the investigator's medical opinion * Suspected or active viral, bacterial, fungal, or parasitic infection within 48 hours prior to enrollment * Liver function tests (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], alkaline phosphatase) \>2x Upper Limit of Normal (ULN) within 30 days prior to enrollment or known intrinsic liver disease (e.g., cirrhosis, chronic hepatitis B or hepatitis C virus infection) * Current or likely need for hemodialysis within 12 months following enrollment * Bleeding diathesis or thrombocytopenia defined as platelet count \<50,000 platelets/μL * Anemia defined as hemoglobin \<10 g/dL * Known AIDS or HIV-positive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count \<1000 cells/mm3 * Previous participation in a study of gene transfer * Presence of neutralizing anti-AAV1 antibodies at titer ≥1:2 within 3 months of screening * Receiving investigational intervention or participating in another clinical study within 30 days or within 5 half-lives of the investigational drug administration prior to enrollment * Pregnancy or lactation * Recent history of psychiatric disease (including drug or alcohol abuse) that is likely to impair subject's ability to comply with protocol-mandated procedures, in the opinion of the investigator * Other concurrent medical condition(s) that, while not explicitly excluded by the protocol, could jeopardize the safety of the patient or objectives of the study