Chinese Phase II Trail of AS1501 in Acute-on-chronic Liver Failure (ACLF) Patients

\*\*Document Name: This Trial is a Phase II Clinical Study.docx\*\* \*\*Document Content:\*\* * This trial is a Phase II clinical study, conducted in two stages: * \*\*Phase IIa:\*\* A sentinel, single-arm design will be employed. A total of 12 early ACLF subjects are expected to be enrolled in the 0.5 mg/kg dose group. The first 2 subjects will serve as sentinels and be enrolled sequentially to receive a single intravenous dose. If no drug-related SAEs (Serious Adverse Events) occur in these 2 sentinel subjects within 2 weeks after the first dose, the remaining 10 subjects will be enrolled. Otherwise, the dose will be reduced for further exploration. After receiving a single intravenous dose, subjects will undergo a 20-day washout period. If no drug-related ≥Grade 3 AEs (Adverse Events) occur during this 20-day washout period, and safety/tolerability is jointly confirmed by the investigator and sponsor, the subject will enter the multiple-dose phase (once weekly \[Day 21 as the first dose of multiple administration\], for 4 consecutive weeks). If any drug-related ≥Grade 3 AE occurs, the dose will be reduced for further exploration, with the specific dose determined by the sponsor and investigator. If a subject drops out during the washout period after a single dose, additional subjects may be enrolled to ensure at least 12 subjects enter the multiple-dose phase. * After all 12 early ACLF subjects in the 0.5 mg/kg dose group complete continuous dosing, the DMC (Data Monitoring Committee) will assess the safety of this dose group. If any of the following occur in the 0.5 mg/kg group, the DMC will discuss whether to proceed with dose escalation: \> 1) ≥1/3 of subjects experience drug-related Grade 3 SAEs; \> 2) Any drug-related Grade 4 or higher SAEs. * If the DMC determines that dose escalation criteria are met, an additional 12 early ACLF subjects will be enrolled to receive the 1 mg/kg dose group. The same enrollment rules as the 0.5 mg/kg group apply: the first