Myocardial Telomere Recapping Study for Dilated Cardiomyopathy

Last updated: July 12, 2024
Sponsor: Shanghai East Hospital
Overall Status: Active - Not Recruiting

Phase

1

Condition

Chest Pain

Circulation Disorders

Congestive Heart Failure

Treatment

JV001

Clinical Study ID

NCT05837143
JV001-02
  • Ages 18-75
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • DCM≥1year;

  • NYHA II-IV;

  • LVEF ≤35%;

  • Received maximally tolerated guideline-directed medical therapy (GDMT) for at least 3 months before enrollment with persistent heart failure; or unable to toleratestandardized pharmacotherapy recommended by guidelines (according to clinical data),but in which investigators assessed participants who could benefit from the studydrug; or hospitalized for heart failure more than 2 times within 1 year andrequiring intravenous diuretic therapy, while the condition is stable for more than 2 weeks;

  • Have the ability to understand and voluntarily sign informed consent before thetrial, and be able to complete the study in accordance with the requirements of thetrial protocol;

  • Male or female: (1) male subjects must agree to use contraception for at least 6months after treatment visit; (2) the female subjects were not pregnant orbreastfeeding; (3) Females of childbearing potential agree to comply withcontraceptive guidance for at least 6 months after administration (see Appendix 1)

Exclusion

Exclusion Criteria:

  • Patients with heart failure caused by heart diseases other than dilatedcardiomyopathy (including but not limited to severe valvular heart disease,hyperthyroidism, congenital heart disease, acute viral myocarditis, acute coronarysyndrome, hypertrophic obstructive cardiomyopathy, pericardial disease, myocardialamyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or leftventricular aneurysm).

  • Coronary angiography has a degree of narrowing of the left main coronary artery (LM), left anterior descending branch (LAD), left circumflex branch (LCX) or rightcoronary artery (RCA) > 50%.

  • Uncontrolled arrhythmias that the investigator believes would affect this trial.

  • Acute myocardial infarction within 6 months before screening

  • Previous presence of subjects with immunological abnormalities that theinvestigators believe could affect this trial (including but not limited tocongenital immunodeficiency, lupus erythematosus, primary vasculitis, systemicsclerosis, antiphospholipid syndrome, autoimmune liver disease, autoimmunethyroiditis).

  • Those who have a history of tumor for less than 5 years or currently have a tumor,or those who have precancerous lesions confirmed by pathological examination (including but not limited to breast ductal carcinoma in situ, cervical dysplasia,etc.)

  • Known progress liver disease (active hepatitis A, chronic hepatitis B or C virusinfection, non-cardiogenic cirrhosis, etc.)

  • Acute infection developed within 2 weeks prior to screening requiring intravenousantibiotic therapy, or current infection requiring anti-infective therapy.

  • Those who have a history of disseminated herpes simplex infection or recurrent (> 1times) or disseminated herpes zoster.

  • Percutaneous coronary intervention (PCI), coronary bypass grafting (CABG),Implantable Cardioverter Defibrillator (ICD)/permanent pacemaker/Cardiacresynchronisation therapy (CRT) implantation, radiofrequency ablation, ventricularvolume reduction, valve repair or plasty, intra-aortic balloon counterpulsation,passive restraint devices (e.g., CorCap™ cardiac support devices), cardiac assistdevice implantation, heart transplantation, or other cardiac surgery may be receivedwithin 3 months prior to screening or within 3 months after administration.

  • Those who donated ≥ 400 mL of blood within 4 weeks prior to screening, or who hadsignificant blood loss equivalent to at least 400 mL, or who received bloodtransfusions within 8 weeks.

  • Subjects with contraindications for coronary angiography

  • Contraindications for Magnetic Resonance Imaging (MRI) detection, including but notlimited to: pacemaker, defibrillator, artificial heart valve, metal clip afteraneurysm surgery, drug perfusion device implanted in the body, any electronic deviceimplanted in the body (neurostimulator, bone growth stimulator), intravascularembolization steel ring, filter, ECG recording monitor, shrapnel or iron sand in thebody, fixed steel plate and nails after fracture surgery, cochlear implant,intraocular metal foreign body, etc.; Claustrophobia, etc.

  • Those who have a history of substance abuse within the past five years or have useddrugs in the 3 months prior to the test.

  • Are participating in other clinical trials, or have been completed less than 3months after the end of other clinical trials.

  • Abnormal liver function: ALT or AST > 3 times the upper limit of normal value (ULN).

  • Abnormal renal function: glomerular filtration rate < 30 mL/min ordialysis-dependent.

  • Hematologic disorders: thrombocytopenia is defined as <50,000 platelets/μL within 30days prior to screening; Anaemia is defined as haemoglobin <10 g/dL within 30 daysprior to screening or dependence on blood transfusion; Neutropenia is defined as anabsolute neutrophil value < 1500 mm^3 within 30 days prior to screening.

  • Acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)positive, or previously diagnosed immunodeficiency with an absolute neutrophil count < 1000 cells/mm^3.

  • Those who are positive for treponema pallidum antibodies and positive for rapidplasma reagin test (RPR).

  • AAV9 neutralizing antibody titer > 1:50

  • Subjects with a history of active tuberculosis or active or inactive TB infection atscreening.

  • 4 weeks prior to screening, or those who plan to receive a live (attenuated) vaccineduring the trial.

  • Those who smoked more than 20 cigarettes per day or habitually usednicotine-containing products in the 3 months prior to screening, drank more than 14units of alcohol per week (1 unit of alcohol = 360mL of beer or 45mL of spirits or 150mL of wine with 40% alcohol content) or took alcohol-containing products 2 daysbefore administration.

  • The investigators believe that there are other conditions that would have an impacton intolerance to this treatment or endpoint evaluation.

Study Design

Total Participants: 12
Treatment Group(s): 1
Primary Treatment: JV001
Phase: 1
Study Start date:
March 30, 2023
Estimated Completion Date:
December 30, 2025

Study Description

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.

Connect with a study center

  • Shanghai East Hospital

    Shanghai, Shanghai 200120
    China

    Site Not Available

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