Transthyretin amyloid cardiomyopathy
Conditions
Interventions
TBD:YOLT-206 Injection Therapy
45mg:YOLT-206 35mg Injection Therapy
35mg:YOLT-206 35mg Injection Therapy
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. Aged 18–80 years (inclusive), male or femalf. 2. 45–90 kg (inclusive) at screening. 3. Confirmed ATTR-CM according to the Expert Consensus on Diagnosis and Treatment of Transthyretin Amyloid Cardiomyopathy. 4. TTR gene mutation verified by genetic testing. 5. Laboratory Standards at Screening: (1)Total bilirubin (TBIL) = 45 mL/min/1.73 m^2 (CKD-EPI formula). (4) Platelet count >= 100 × 10^9/L. (5) INR = 0.70 µmol/L (200 ng/mL) and vitamin B12 >= LLN. (7) LDL-C = 3 months with documented disease progression (per investigator) meeting >= 1 criterion: (1)Increased heart failure hospitalizations;(2)Worsening NYHA class; (3) >= 5-point decline in KCCQ score; (4) >= 30 m decline in 6-minute walk test (6-MWT); (5) >= 30% increase in NT-proBNP; (6) >= 30% increase in troponin I; (7) >= 2 mm increase in LV wall thickness on echocardiogram; (8) >= 5% decline in LVEF, >= 1% decline in global longitudinal strain, or >= 5% decline in stroke volume;(9) New conduction block. 7. Agreement to abstain from alcohol from screening through Day 28 post-dosf. 8. Non-pregnant/non-breastfeeding females and males with female partners must use highly effective contraception from screening through 1 year after study completion. 9. Signed written informed consent. 10. Agreement to avoid other ATTR therapies for >= 8 weeks post-YOLT-206 dosing. 11. Clinical Status at Screening: (1)NYHA class II–III.(2)6-MWT >= 120 m. (3) NT-proBNP = 12 mm.
Exclusion criteria
Exclusion criteria: 1. Amyloidosis not caused by TTR protein (e.g., light-chain amyloidosis). 2. Evidence of ATTR meningovascular involvement. 3. Known hypersensitivity to any lipid nanoparticle (LNP) component or prior LNP exposure associated with treatment-related laboratory abnormalities or adverse events. 4. Concomitant ATTR Therapies (within specified washout periods): Vutrisiran: Use within 2 years. Patisiran/Inotersen/Eplontersen: Use within 1 year. Tafamidis: Use within 10 days before investigational drug dosing. Diflunisal: Use within 3 days. Doxycycline and/or TUDCA: Use within 14 days. Prior gene-editing therapies: Any history. Other ATTR investigational agents: Last dose =4 drinks/day or 8/week for women; >=5/day or 15/week for men; 1 drink = 14 g ethanol) within 3 years. 16. Anticipated survival <1 year. 17. NYHA Class IV heart failure within 90 days of screening. 18. Polyneuropathy Disability (PND) score IV or lower limb neuropathy severely impairing ambulation. 19. Cardiomyopathy due to non-TTR causes (e.g., hypertensive, valvular, ischemic). 20. Positive serum pregnancy test, lactating, or planning pregnancy/lactation during the study. 21. Any condition deemed unsuitable for study participation by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse event rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Troponin I;NYHA classification;6min walking distance ;Concentration of Transthyretin in serum;EQ-5D-5L;Norfolk QOL-DN;NT-proBNP;KCCQ Score;Ultrasonic cardiogram indicators; | — |
Countries
China
Contacts
Public ContactTingbo Liang
The FIrst Affiliated Hospital, College of Medicine, Zhejiang University
Outcome results
None listed