Transthyretin amyloid cardiomyopathy
Conditions
Interventions
Experimental:YOLT-201
Sponsors
The FIrst Affiliated Hospital, College of Medicine, Zhejiang University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Male or female subjects aged >= 18 and = 150 meters at screening; 2.3 Echocardiogram evidence of cardiac involvement: left ventricular wall thickness (interventricular septum and/or posterior wall thickness >= 12 mm); 2.4 Brain natriuretic peptide N-terminal prohormone (NT-proBNP) 45 mL/min/1.73m^2 at screening; 4.4 Platelet count >= 100 × 10^9/L; 4.5 Coagulation function at screening: fibrinogen, activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) are all within the normal range; 4.6 Low-density lipoprotein (LDL) cholesterol = lower limit of normal (LLN); 4.8 Vitamin B12 level >= lower limit of normal (LLN). 5. Acceptance of ATTR-CM medication treatment: 5.1 Unable to receive existing ATTR-CM-related medication due to regional medical resources, health policies, personal financial capacity, or drug intolerance; 5.2 Despite receiving at least 6 months of ATTR-CM medication treatment, the subject's ATTR-CM condition still progresses (meeting at least one of the following): Increased hospitalizations related to heart failure; Worsening of NYHA classification; 6-MWT decrease of at least 30 meters; NT-proBNP increase by 30%; Troponin increase by 30%; Echocardiogram indicates: increase in left ventricular wall thickness by 2 mm, or decrease in left ventricular ejection fraction by >= 5%, or decrease in global longitudinal strain by >= 1%, or decrease in stroke volume by >= 5%, or worsening diastolic function; New conduction block on electrocardiogram. 6. No intake of alcohol from the start of the screening period to 28 days after receiving the trial treatment medication. 7. Female subjects must be postmenopausal for at least one year, or have undergone hysterectomy. 8. Male subjects and their partners must use highly effective contraceptive measures recognized by the doctor throughout the trial process and for at least 5 months after the trial ends. 9. Male subjects must not donate sperm within 84 days after receiving study medication. 10.Voluntary signing of informed consent.
Exclusion criteria
Exclusion criteria: 1. Amyloidosis that is not related to TTR protein degeneration, such as immunoglobulin light chain (AL) amyloidosis. 2. History of multiple myeloma. 3. Indeterminate monoclonal gammopathy (MGUS) and/or immunoglobulin free light chain (FLC) ratio alterations, unless fat, bone marrow, or cardiac biopsy confirms the absence of light chains but presence of TTR protein through mass spectrometry or immunoelectron microscopy. For chronic kidney disease (CKD) subjects with no monoclonal protein in blood and urine, the acceptable FLC ratio is 0.26 to 2.25. If the risks of biopsy outweigh the benefits, different results may be discussed with local hematologists, investigators, and medical monitors. 4. Allergy to any lipid nanoparticle (LNP) components, or history of exposure to LNP components or laboratory abnormalities or adverse reaction events related to their treatment: 4.1 Normal baseline, ALT or AST > 3 × ULN or appearance of baseline triple value after receiving LNP product. 4.2 Normal baseline, INR, APTT, or D-dimer > 1.5 × ULN; if baseline is higher than normal after receiving LNP product, it is 1.5 times the baseline value. 4.3 Any adverse reactions related to LNP product treatment are defined as grade 3 or higher (CTCAE). Injection site reactions (IRR) requiring treatment or discontinuation of infusion; slowing down the infusion rate to alleviate infusion-related reactions. The investigator believes that any adverse reaction events related to LNP treatment should be excluded. 5. Use of any of the following ATTR treatments within a certain period: 5.1 Patisiran (LNP small interfering RNA siRNA) treatment product (within 90 days after administration). 5.2 Previous treatment with Inotersen (antisense oligonucleotide ASO) (within 160 days after administration). 5.3 Previous use of Vutrisiran (investigational siRNA therapeutic GalNAc conjugate). 5.4 Tafamidis (TTR stabilizer): less than 10 days since last drug administration before study drug administration. 5.5 Diflunisal (TTR stabilizer): less than 3 days since last drug administration before study drug administration. 5.6 Doxycycline and/or tauroursodeoxycholic acid (TTR chaperone): less than 14 days since last drug administration before study drug administration. 5.7 Any other drugs used for the treatment of ATTR-CM: less than 30 days or 5 half-lives (whichever is longer) since last drug administration before study drug administration. 6. Other organic heart diseases, such as ischemic heart disease, uncontrolled hypertension, valvular heart disease, etc., leading to cardiomyopathy. 7. Current or previous NYHA class IV symptoms or worsening heart failure symptoms within 90 days before or during screening. 8. Hospitalization or invasive surgery due to cardiovascular and cerebrovascular diseases within 90 days before or during screening. For example, acute coronary syndrome, unstable angina, stroke, TIA, coronary artery reconstruction, cardiac device implantation, valvular repair, or major surgery, etc. 9. Expected to undergo invasive cardiovascular surgery (such as coronary artery stent, pacemaker implantation, etc.) within 28 days after medication. 10. Subjects who cannot or are unwilling to supplement vitamin A. 11. Subjects who cannot or are unwilling to accept the required medication treatment plan before treatment. 12. Antiplatelet (such as aspirin, clopidogrel) or antithrombotic treatment (such as warfarin, dabigatran, apixaban) within 14 days before study drug adm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse event rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Concentration of TTR protein in serum;Concentration of Serum prealbumin;Cardiac magnetic resonance imaging;The six-minute walk test;NYHA classification;KCCQ;Norfolk QOL-DN;EQ-5D-5L; | — |
Countries
China
Contacts
Public ContactTingbo Liang
The FIrst Affiliated Hospital, College of Medicine, Zhejiang University
Outcome results
None listed