Transthyretin amyloid cardiomyopathy
Conditions
Interventions
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Gender is not limited; 2. Age is 18-80 years old (including the cutoff value) when signing the ICF; 3. ATTR-CM is clearly diagnosed (the following two requirements must be met at the same time): a. Left ventricular posterior wall thickness >=12mm; b. At least one of the following is met: i. Genetic testing confirms TTR gene mutation; ii. Biopsy or imaging confirms tissue deposition of TTR amyloid protein; 4. NT-proBNP >=600 pg/mL and =150 m at screening; 6. New York Heart Association (NYHA) heart function class II~III at screening; 7. Female subjects should meet one of the following conditions: a. Postmenopausal female subjects (defined as no menstruation for 12 consecutive months without other medical reasons before screening); b. Complete sterilization surgery (including hysterectomy, bilateral salpingectomy and bilateral oophorectomy) at least 1 month before screening; 8. Male subjects with childbearing potential must agree to take active contraceptive measures during the screening period and within 180 days after administration (see Section 10.4 for contraceptive requirements) and agree not to participate in sperm donation; 9. Be able to understand this study and voluntarily sign the ICF.
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will be excluded from the study: 1. Amyloidosis attributed to non-TTR, such as light-chain amyloidosis (AL); 2. Hepatitis B (positive hepatitis B virus surface antigen and HBV-DNA copy number greater than the lower limit of detection), hepatitis C (positive hepatitis C virus antibody and HCV RNA quantitative higher than the lower limit of detection), syphilis (positive helical antibody) or human immunodeficiency virus infection (HIV positive); 3. Any unstable systemic disease: including but not limited to unstable angina, cerebrovascular accident or transient ischemic attack (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Association [NYHA] heart function class = IV), severe arrhythmias requiring drug treatment, liver, kidney or metabolic diseases, and active gastrointestinal bleeding, or other unstable systemic diseases determined by the investigator; 4. Active infection or uncontrolled infection requiring intravenous treatment within 14 days before enrollment; 5. Subjects meet the following laboratory criteria at screening: a. AST, ALT, TBIL, and international normalized ratio (INR)>1.5 times the upper limit of normal (ULN); b. Glomerular filtration rate (eGFR, calculation formula see Appendix 12.5) =45 mL/min/1.73 m2; c. Hemoglobin 4.2 mmol/L; f. Vitamin A 90 kg at the screening visit; 7. Women of childbearing potential or breastfeeding; 8. Subjects known to be allergic to any LNP component; 9. Use of the following drugs within the specified time frame: a. Previous use of other gene editing drugs targeting TTR; b. The washout period of Patisiran is less than 90 days, the washout period of Vutrisiran is less than 90 days, the washout period of Inotersen is less than 160 days, and the washout period of Eplontersen is less than 160 days before administration; c. Tafamidis: less than 14 days from the last use to the washout before study treatment; d. Diflunisal: less than 3 days from the last use to the washout before study treatment; e. Doxycycline and/or taurodeoxycholic acid: less than 14 days from the last use to the washout before study treatment; f. Other experimental drugs for the treatment of ATTR-CM: less than 30 days or 5 half-lives (whichever is longer) from the last use to the washout before study treatment; 10. Type 1 diabetes or diagnosed with type 2 diabetes for =5 years; 11. Plan to undergo invasive cardiovascular surgery (such as coronary artery stent, pacemaker placement, etc.) within 28 days after medication; 12. Antiplatelet (such as aspirin, clopidogrel, etc.) or anticoagulant therapy (such as warfarin, dabigatran, apixaban, etc.) treatment within 14 days before administration; 13. The researcher believes that the expected survival period does not exceed 2 years; 14. Vitamin A deficiency that requires clinical treatment; 15. History of cirrhosis; 16. Liver, heart or other solid organ transplantation, bone marrow transplantation or planned transplantation within 1 year. Patients with a history of corneal transplantation or planned corneal transplantation are not excluded. 17. Suffering from malignant tumors within 5 years before screening, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hematology;Chemistry;Coagulation;Urinalysis;Thyroid function tests;Vitamin A;Vitamin B12;Retinol Binding Protein;C reactive protein;Complement;Cytokines; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics;Pharmacodynamics;Immunogenicity;Efficacy evaluation; | — |
Countries
China
Contacts
Public ContactShuyang Zhang; Tianzhuang
Peking Union Medical College Hospital
Outcome results
None listed