Alpha-1 Antitrypsin Deficiency
Conditions
Interventions
55 mg dose group:YOLT-202 Injection Therapy(55mg)
45mg dose group:YOLT-202 Injection Therapy(45mg)
35mg dose group:YOLT-202 Injection Therapy(35mg)
Sponsors
Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Male or female (including boundary value) aged >=18 years old and <=70 years old at the time of signing informed consent; 2. Homozygous for a PiZZ mutation diagnosed with AATD and confirmed by genetic testing; 3. The total AAT level in the blood is less than 11 µM or equivalent mg/dL protein; 4. Patients receiving augmentative therapy must be willing to discontinue augmentative therapy at least 6 weeks prior to signing the Informed Consent Form (ICF) and for the duration of the study (unless clinically indicated).
Exclusion criteria
Exclusion criteria: 1. Body mass index (BMI) >35 kg/m^2; 2. Lung or liver transplant patients or on the waiting list for lung or liver transplantation, or have undergone lung volume reduction surgery; 3. Clinical evidence of severe bronchiectasis, as judged by the investigator (e.g., excessive sputum production or recurrent infections requiring antibiotics [>4 times per year]); 4. FEV1 after bronchodilator use at screening = =10 kilopascals (kPa); (2) Known history of cirrhosis or complications of cirrhosis (e.g., varicose veins, ascites, hepatic encephalopathy); (3) If the patient has previously undergone liver biopsy, there is >=F2 grade liver fibrosis; (4) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceeds 1.5 times the upper limit of normal (ULN); (5) The total bilirubin level exceeds the upper limit of normal; If there is documented Gilbert syndrome, total bilirubin exceeds 2 times the upper limit of normal; (6) The international normalized ratio (INR) at screening was >=1.2. If deemed appropriate by the investigator and/or prescribing physician, patients may discontinue the use of anticoagulants for an appropriate washout period, or reverse with vitamin K, and repeat INR less than 1.2 will be acceptable if needed; (7) Positive for hepatitis B surface antigen (HBsAg); (8) Positive for hepatitis C virus (HCV) antibody. If HCV antibodies are positive, HCV RNA polymerase chain reaction (PCR) must be negative; 6. Those who are allergic to the drugs contained in lipid nanoparticles (LNPs) or the components of LNP-mRNA vaccines, or have had adverse reactions due to LNP drug treatment; 7. Smoking more than 5 cigarettes per day or ingesting the same amount of nicotine or nicotine substitute within 6 months before screening; 8. History of alcohol abuse within 6 months prior to screening [those who drink more than 14 units of alcohol per week (1 unit ˜ 360mL of beer or 45mL of spirits with 40% alcohol or 150mL of wine)]; or those who test positive on the alcohol breath study at screening, or at the time of admission. 9. Patients with hypertension (systolic blood pressure (SBP) >=180mmHg and/or diastolic blood pressure (DBP) >=110mmHg) who are poorly controlled by conventional treatment; 10. Patients with poorly controlled diabetes mellitus (glycosylated hemoglobin >=9%); 11. Presence of class III.-IV heart failure as defined by the New York Heart Association (NYHA) at screening, or left ventricular cardiac ejection fraction 470ms, male>450ms); 12. Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass grafting, severe deep vein thrombosis or pulmonary embolism within 3 months prior to screening; Poorly controlled severe cardiac arrhythmias, such as recurrent and highly symptomatic ventricular tachycardia, tachyventricular reactive atrial fibrillation, or supraventricular tachycardia that are poorly controlled by medications, within 3 months prior to screening; or plan to undergo cardiac surgery or cardiac revascularization during the main study period, etc.; 13. Cerebrovascular accident occurred within 6 months before screening; 14. Patients with known or suspected systemic viral, parasitic or fungal infections, or patients with active infections who are expected to require antibiotic treatment within 14 days of screening; 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events;Vital signs;Physical examination findings;12-lead ECG findings;Imaging findings;Laboratory findings; | — |
Secondary
| Measure | Time frame |
|---|---|
| AAT protein; | — |
Countries
China
Contacts
Public ContactXia Qiang
Renji Hospital, Shanghai Jiao Tong University School of Medicine
Outcome results
None listed