Status:
ACTIVE_NOT_RECRUITING
Study of YOLT-202 in the Treatment of Alpha-1 Antitrypsin Deficiency (AATD)
Lead Sponsor:
RenJi Hospital
Conditions:
Alpha-1 Antitrypsin Deficiency (AATD)
Eligibility:
All Genders
18-70 years
Phase:
EARLY_PHASE1
Brief Summary
This is a single-arm, open-label, single-dose, dose-escalation exploratory study to evaluate the safety and tolerability of a single dose of YOLT-202 in patients with AATD and determine the optimal bi...
Detailed Description
This is a single-arm, open-label, single-dose, dose-escalation exploratory study to evaluate the safety and tolerability of a single dose of YOLT-202 in patients with AATD, determine the OBD of YOLT-2...
Eligibility Criteria
Inclusion
- Inclusion Criteria:
- Male or female (inclusive) aged ≥ 18 and ≤ 70 years old at the time of signing informed consent.
- Diagnosed with AATD and genetically confirmed as homozygous PiZZ mutation.
- Blood total AAT level \< 11 μM or equivalent protein in mg/dL.
- Patients receiving augmentation therapy must be willing to discontinue it at least 6 weeks prior to signing the informed consent form (ICF) and throughout the study period, unless clinically indicated.
- Exclusion criteria
- Body mass index (BMI) \> 35 kg/m2.
- Patients who have undergone lung or liver transplantation, are on the waiting list for lung or liver transplantation, or have had lung volume reduction surgery (LVRS).
- Clinical evidence of severe bronchiectasis, as judged by the investigator (e.g., excessive sputum production or recurrent infections requiring antibiotics \[\> 4 times per year\]).
- FEV1 ≤ 30% of predicted value after bronchodilator use at screening
- Liver disease with any of the following:
- Measured liver stiffness (FibroScan) ≥ 10 kilopascals (kPa).
- Known history of hepatic cirrhosis or associated complications (e.g., varices, ascites, hepatic encephalopathy).
- ≥ F2 hepatic fibrosis in patients with prior liver biopsy.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 times the upper limit of normal (ULN).
- Total bilirubin \> ULN; or \> 2 times the ULN if Gilbert's syndrome is documented.
- International normalized ratio (INR) ≥ 1.2 at screening. If deemed appropriate by the investigator and/or the prescribing physician, anticoagulants may be discontinued for a washout period or reversed with vitamin K. If necessary, a repeat INR \< 1.2 is acceptable.
- Hepatitis B surface antigen (HBsAg) positive.
- Hepatitis C virus (HCV) antibody positive. If HCV antibody is positive, HCV RNA PCR must be negative.
- Allergy to the drugs contained in lipid nanoparticles (LNP) or LNP-mRNA vaccines, or previous history of adverse reactions to LNP-based drugs;
- Smoking more than 5 cigarettes per day or consuming the equivalent amount of nicotine or nicotine replacement products within the past 6 months before screening.
- History of alcohol abuse within the past 6 months before screening (drinking more than 14 units of alcohol per week \[1 unit ≈ 360 mL of beer or 45 mL of 40% alcohol or 150 mL of wine\]); or positive alcohol breath test at the time of screening or admission.
- Patients with poorly controlled hypertension by conventional treatments (systolic blood pressure \[SBP\] ≥ 180 mmHg and/or diastolic blood pressure \[DBP\] ≥ 110 mmHg).
- Patients with poorly controlled diabetes (hemoglobin A1c ≥ 9%).
- Presence of New York Heart Association (NYHA) class III-IV heart failure, left ventricular ejection fraction \< 50%, or prolonged QTc interval (female \> 470 ms, male \> 450 ms) at the time of screening.
- Myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, coronary artery bypass grafting, severe deep vein thrombosis or pulmonary embolism within 3 months before screening; poorly controlled severe arrhythmias within the past 3 months before screening, such as poorly controlled recurrent and highly symptomatic ventricular tachycardia, rapid ventricular response atrial fibrillation, or supraventricular tachycardia; or planned cardiac surgery or cardiac revascularization during the main study period.
- Cerebrovascular accidents within 6 months before screening;
- Known or suspected systemic viral, parasitic, or fungal infections, or active infections requiring expected antibiotic therapy within 14 days after screening.
- Human immunodeficiency virus (HIV) antibody positive at screening.
- Anticoagulant therapy within 14 days before enrollment (such as warfarin, dabigatran, apixaban).
- Patients with bleeding tendency or history of coagulation disorders (such as liver cirrhosis, malignant hematological diseases, antiphospholipid antibody syndrome);
- Expected survival time less than 2 years.
- History of malignant tumors within the past 5 years (excluding cured skin basal cell carcinoma, skin squamous cell carcinoma, cervical carcinoma in situ, low-grade prostate carcinoma in situ, and cured thyroid basal cell carcinoma).
- History of drug abuse within the past 3 years.
- Pregnant or lactating women.
- Patients with other diseases in the blood system, digestive system, central nervous system, or endocrine system that the investigator believes will interfere with evaluation or limit participation in the trial.
- Inability or unwillingness to cooperate or comply with pretreatment medication requirements or study procedures.
- Any other condition deemed unsuitable for the clinical trial participation by the investigator.
Exclusion
Key Trial Info
Start Date :
June 18 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
March 1 2027
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT07193615
Start Date
June 18 2025
End Date
March 1 2027
Last Update
September 26 2025
Active Locations (1)
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1
Ren Ji Hospital Affiliated to Shanghai Jiao Tong University
Shanghai, China