This is a single-arm, open-label, dose-escalation study designed to enroll approximately 5-30 patients with TDT or SCD. The objectives are to evaluate the safety and tolerability in patients following intravenous administration of YOLT-204 and to preliminarily assess its effect on fetal hemoglobin levels in plasma.
In this study, the maximum screening period of the main study is 60 days, the treatment day is Day 0 (D0), and the safety follow-up period is up to Week 52 after administration.
Male or female subjects aged 14 to 35 years (inclusive).
The subject and/or their legal guardian has been fully informed about the study and has voluntarily signed a written ICF.
KPS score ≥ 70 for subjects aged 16 years or older; LPS score ≥ 70 for subjects under 16 years of age.
Detailed medical records regarding red blood cell transfusions within the 2-year period prior to signing the ICF are available, including the volume or number of units transfused, as well as pre- and post-transfusion red blood cell and hemoglobin levels.
History of multiple drug allergies or allergic reaction history to oligonucleotides or LNP;
Presence of clinically significant active bacterial, viral, fungal, or parasitic infection as judged by the investigator at screening;
White blood cell (WBC) count < 3 × 109/L and/or platelet count < 100 × 109/L at screening (using pre-lymphodepletion results if lymphodepletion is considered);
Uncorrected hemorrhagic disorders;