Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Shanghai Juvensis Therapeutics Biotechnology Company Limited | UNKNOWN |
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active Comparator: JV001 | Experimental | Subjects will receive a single intracoronary infusion of JV001 at a dose of 2×10^11vg/kg, and 6×10^11vg/kg. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JV001 | Biological | JV001 (AAV9/modTERT) will be delivered by a percutaneous method in the catheter laboratory. Dose: 2×10^11vg/kg,or 6×10^11vg/kg. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 28 days |
| Incidence of adverse events and serious adverse events within 1 year of administration | To evaluate the safety of JV001 treatment | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Left ventricular ejection fraction | Changes in left ventricular ejection fraction (LVEF as percentage) as assessed by echocardiography | Baseline, Week 12, Week 26, Week 52 |
| Myocardial remodeling assessed by Cardiac Magnetic Resonance (CMR) Imaging |
| Measure | Description | Time Frame |
|---|---|---|
| Change in standard uptake value (SUV) of 18F-fluorodeoxyglucose-positron emission tomography (PET) imaging from baseline to Week 26. | To evaluate the changes myocardial viability of subjects at 26 weeks after medication from baseline | Baseline, Week 26 |
| Late gadolinium enhancement (LGE) by Cardiac Magnetic Resonance (CMR) Imaging |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai East Hospital | Shanghai | Shanghai Municipality | 200120 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31073128 | Background | Schultheiss HP, Fairweather D, Caforio ALP, Escher F, Hershberger RE, Lipshultz SE, Liu PP, Matsumori A, Mazzanti A, McMurray J, Priori SG. Dilated cardiomyopathy. Nat Rev Dis Primers. 2019 May 9;5(1):32. doi: 10.1038/s41572-019-0084-1. | |
| 30150400 | Background | Chang ACY, Chang ACH, Kirillova A, Sasagawa K, Su W, Weber G, Lin J, Termglinchan V, Karakikes I, Seeger T, Dainis AM, Hinson JT, Seidman J, Seidman CE, Day JW, Ashley E, Wu JC, Blau HM. Telomere shortening is a hallmark of genetic cardiomyopathies. Proc Natl Acad Sci U S A. 2018 Sep 11;115(37):9276-9281. doi: 10.1073/pnas.1714538115. Epub 2018 Aug 27. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D002311 | Cardiomyopathy, Dilated |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D006332 | Cardiomegaly |
| D009202 | Cardiomyopathies |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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
| 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. | 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. | 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. | 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 | 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. | 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. | Baseline, Week 12, Week 26, Week 52 |
To evaluate the changes myocardial fibrosis of subjects at 26 weeks after medication from baseline |
| Baseline, Week 26 |
| Biomarkers for Heart Failure and Prognosis | Change in growth stimulation expressed gene 2 (ST2, ng/ml) Change in Heart-type fatty acid binding protein (H-FABP, ng/ml) Change in High-sensitivity cardiac troponin (hs-cTn, ng/ml) | Baseline, Week 2, Week 4, Week 12, Week 26, Week 52 |
| Change in Human procollagen Ⅲ propeptide (PⅢP) for cardiac fibrosis in blood samples | Human procollagen Ⅲ propeptide (PⅢP) is an indication of myocardial fibrosis. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in interleukin 1-beta (IL-1β) measured using blood samples (pg/ml) | IL-1β (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in interleukin 2 (IL-2) measured using blood samples (pg/ml) | IL-2 (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in interleukin 4 (IL-4) measured using blood samples (pg/ml) | IL-4 (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in interleukin 5 (IL-5) measured using blood samples (pg/ml) | IL-5 (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in interleukin 6 (IL-6) measured using blood samples (pg/ml) | IL-6 (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in interleukin 8 (IL-8) measured using blood samples (pg/ml) | IL-8 (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in interleukin 10 (IL-10) measured using blood samples (pg/ml) | IL-10 (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in interleukin 12p70 (IL-12p70) measured using blood samples (pg/ml) | IL-12p70 (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in interleukin 17 (IL-17) measured using blood samples (pg/ml) | IL-17 (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in interferon-alpha (IFN-α) measured using blood samples (pg/ml) | IFN-α (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in interferon-gamma (IFN-γ) measured using blood samples (pg/ml) | IFN-γ (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in tumor necrosis factor-alpha (TNF-α) measured using blood samples (pg/ml) | TNF-α (in pg/mL), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in immunoglobulin A (IgA) measured using blood samples (g/L) | IgA (in g/L), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in immunoglobulin M (IgM) measured using blood samples (g/L) | IgM (in g/L), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| Change in immunoglobulin G (IgG) measured using blood samples (g/L) | IgG (in g/L), an inflammatory marker, will be measured in blood samples to assess changes from baseline. | Baseline, Week 4, Week 12, Week 26, Week 52 |
| 21307849 | Background | Sahin E, Colla S, Liesa M, Moslehi J, Muller FL, Guo M, Cooper M, Kotton D, Fabian AJ, Walkey C, Maser RS, Tonon G, Foerster F, Xiong R, Wang YA, Shukla SA, Jaskelioff M, Martin ES, Heffernan TP, Protopopov A, Ivanova E, Mahoney JE, Kost-Alimova M, Perry SR, Bronson R, Liao R, Mulligan R, Shirihai OS, Chin L, DePinho RA. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature. 2011 Feb 17;470(7334):359-65. doi: 10.1038/nature09787. Epub 2011 Feb 9. |
| 30710128 | Background | Wang D, Tai PWL, Gao G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov. 2019 May;18(5):358-378. doi: 10.1038/s41573-019-0012-9. |
| D000083083 |
| Laminopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |