Transthyretin amyloid polyneuropathy
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 cut-off value) when signing the ICF; 3. ATTR-PN is clearly diagnosed (the following 4 items must be met at the same time): a. According to the results of electromyography and clinical symptoms, it is clearly diagnosed as chronic sensory neuropathy and (or) chronic autonomic neuropathy, with or without motor neuropathy, with or without family history; b. The Neuropathy Impairment Score (NIS) during the screening period is 5-130 (including the cut-off value); c. At least one of the following is met: i. Genetic testing confirms the presence of TTR gene mutation; ii. Biopsy or imaging confirms the presence of tissue deposition of TTR amyloid protein; d. Screening polyneuropathy disability (PND) score <=3b; 4. 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; 5. 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; 6. Be able to understand this study and voluntarily sign the ICF.
Exclusion criteria
Exclusion criteria: 1. Amyloidosis attributed to non-TTR, such as light-chain amyloidosis (AL); 2. Known leptomeningeal transthyretin amyloidosis; 3. 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); 4. 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 >= III), severe arrhythmias requiring drug treatment, liver, kidney or metabolic diseases, and active gastrointestinal bleeding, or other unstable systemic diseases determined by the investigator; 5. Active infection or uncontrollable infection requiring intravenous treatment within 14 days before enrollment; 6. 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 12.8) 400 pg/mL; d. Hemoglobin 4.2 mmol/L; g. Vitamin A 90 kg at the screening visit; 8. Women of childbearing potential or breastfeeding; 9. Subjects with known allergies to any LNP component; 10. Use of the following medications within the specified time frame: a. Previous use of NTLA-2001 or 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, the last dose is later than 14 days before the study treatment; d. Diflunisal, the last dose is later than 3 days before the study treatment; e. Doxycycline and/or taurodeoxycholic acid, the last dose is later than 14 days before the study treatment; f. Other experimental drugs for the treatment of ATTR-PN: before the study treatment, the last dose does not exceed 30 days or 5 half-lives (whichever is longer); 11. Other central nervous system involvement determined by the investigator that is not suitable for participation in this study; 12. Other types of hereditary neuropathy, sensory motor or autonomic neuropathy of other known causes (such as diabetic neuropathy, autoimmune disease-related neuropathy, etc.); 13. Type 1 diabetes or diagnosed with type 2 diabetes for =5 years; 14. Plan to undergo invasive cardiovascular surgery within 28 days after medication (such as coronary artery stent, pacemaker placement, etc.); 15. Anticoagulant therapy within 14 days before medication (such as warfarin, dabigatran, apixaban, etc.); 16. The researcher believes that the expected survival period does not exceed 2 years; 17. Vitamin A deficiency that requires clinical treatment; 18. History of cirrhosis; 19. Liver, heart or other solid organ transplantation, bone marrow transplantation or planned transplantation within 1 year. Patients with a history of corneal transplantati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hematology;Chemistry;Urinalysis;Thyroid Function Tests;Vitamin A;Retinol Binding Protein (RBP);C-reactive protein;Complement;Cytokines; | — |
Countries
China
Contacts
Public ContactYicheng Zhu, Ruin Chen
Peking Union Medical College Hospital
Outcome results
None listed