The aim of this study is to determine the safety and feasibility of giving an adeno-associated viral vector expressing a modified telomerase protein (TERT), driven by cardiac troponin T promoter (AAV9-cTnT-modTERT), to 12 dilated cardiomyopathic patients.
It is an open-label, 6+6 design study involving two dosages ( 2×10\^11vg/kg, and 6×10\^11vg/kg) aimed to explore the safety, pharmacokinetics, immunology, and preliminary efficacy of JV001.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
JV001 (AAV9/modTERT) will be delivered by a percutaneous method in the catheter laboratory. Dose: 2×10\^11vg/kg,or 6×10\^11vg/kg.
Shanghai East Hospital
Shanghai, Shanghai Municipality, China
Dose-limiting toxicity (DLT) within 28 days of a single intracoronary infusion of JV001
To evaluate the DLT occurred within 28 days after JV001 infusion
Time frame: 28 days
Incidence of adverse events and serious adverse events within 1 year of administration
To evaluate the safety of JV001 treatment
Time frame: 1 year
Left ventricular ejection fraction
Changes in left ventricular ejection fraction (LVEF as percentage) as assessed by echocardiography
Time frame: Baseline, Week 12, Week 26, Week 52
Myocardial remodeling assessed by Cardiac Magnetic Resonance (CMR) Imaging
Changes in left ventricular mass (absolute (ml) and index (ml/m2). Changes in left ventricular diastolic volume (ml). Changes in right ventricular diastolic volume (ml). Changes in left ventricular stroke volume
Time frame: Baseline, Week 26
Change in N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) from baseline to Week 2, 4, 12, 26, 52
To evaluate the changes in NT-proBNP of subjects at 2, 4, 12, 26, and 52 weeks after medication from baseline. NT-proBNP is a biomarker for heart failure with a higher level indicating increased mortality and cardiovascular hospitalization in patients with heart failure.
Time frame: Baseline, Week 2, Week 4, Week 12, Week 26, Week 52
Change in 6-minute Walk Test (6MWT) from baseline to Week 12,26,52
The 6MWT measures the distance walked in meters during a 6-minute test. Lower scores compared to baseline indicate worsening in function, and higher scores compared to baseline indicate improvement in function.
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Time frame: Baseline, Week 12, Week 26, Week 52
Change in total immunoglobulin and neutralizing antibodies from baseline to Week 2, Week 4, Week 12, Week 26, Week 52
Evaluate the changes in the formation of Anti-AAV9 antibodies.
Time frame: Baseline, Week 2, Week 4, Week 12, Week 26, Week 52
Change in vector DNA levels in subjects' biological samples from baseline to Day 1, Day2, Day7, Week 2, Week 4, Week 12, Week 26, Week 52
To evaluate the changes of AAV viral load in subjects' biological samples from baseline
Time frame: Baseline, Day 1, Day2, Day7, Week 2, Week 4, Week 12, Week 26, Week 52
Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) score from baseline to Week 12,26,52
The MLHFQ is a patient-report questionnaire used to assess the quality of life of heart failure patients. Higher scores indicate a lower quality of life.
Time frame: Baseline, Week 12, Week 26, Week 52
Change of New York Heart Association (NYHA) functional classification from baseline to Week 12,26,52
The NYHA functional classification is the most commonly used classification system for patients with heart failure. Changes from baseline to a higher class indicate a worsening in symptoms.
Time frame: Baseline, Week 12, Week 26, Week 52