Study of YOLT-202 in the Treatment of Alpha-1 Antitrypsin Deficiency (AATD)

NCT07193615 | Active Not Recruiting Early Phase 1

• 1 other identifier: AATD-YOLT-202-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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 biologically active dose (OBD) of YOLT-202.

Conditions

Alpha-1 Antitrypsin Deficiency (AATD)

Outcome Measures

Primary Outcomes (1)

• Safety of YOLT-202 in subjects after administration

  Numbers and percentages of patients with adverse events (AE)

  Baseline to 52 weeks post-dose

Secondary Outcomes (5)

• Pharmacokinetics parameter of YOLT-202

  30 minutes pre-dose, 2 hours, 6 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours and 504 hours post-dose

• Pharmacokinetic (PK) parameter of YOLT-202

  30 minutes pre-dose, 2 hours, 6 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours and 504 hours post-dose

• Pharmacokinetic (PK) parameter of YOLT-202

  30 minutes pre-dose, 2 hours, 6 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours and 504 hours post-dose

• Pharmacokinetic (PK) parameters of YOLT-202

  30 minutes pre-dose, 2 hours, 6 hours, 24 hours, 48 hours, 72 hours,168 hours,336 hours and 504 hours post-dose

• Changes in blood AAT protein level

  Weeks 1, 2, 3 and 52 post-dose

Study Arms (1)

Single arm

EXPERIMENTAL

Dose groups: 35mg, 45mg, 55mg, TBD (During the dose-escalation process, the investigator and the sponsor may decide, based on actual circumstances, whether to add new dose groups or repeat completed dose groups for the exploratory study).

Drug: YOLT-202

Interventions

YOLT-202 DRUG

The IP is administered intravenously at the predetermined dose; Administration frequency: Once

Also known as: AATD-YOLT-202-001

Single arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Ren Ji Hospital Affiliated to Shanghai Jiao Tong University

Shanghai, China

Location

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2025
• First Posted: September 26, 2025
• Study Start: June 18, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)