Dose escalation
toxicity, Blindness
ADVERSE EVENTS, ADVERSE EVENT, ADVERSE EVENT, BLINDNESS
Based on preclinical studies, this study applied 4 dose levels, from 5, 15, 30 to 50 mg/kg. The study started from the lowest dose group and proceeded, to the next dose level only after safety assessment was confirmed not reaching the below-listed criteria for dose escalation termination. For the safety assessment, dose limit toxicity (DLT) was observed for at least 7 days. Blindness was kept when assessing the data of all subjects of the current dose group. No subject participated in two or more dose groups.The dose escalation termination criteria were: (1) more than 1/2 participants had drug-related adverse events (AEs) ≥ grade 2 (CTCAE 5.0), or (2) more than 1/4 participants had drug-related AEs ≥ grade 3, or (3) 1 drug-related serious adverse event (SAE). Termination criteria for sentinels was that at least 1 participant had drug-related AEs ≥ grade 3 or 1 drug-related SAE. All AEs were graded using CTCAEv5.0 (Common Terminology Criteria for Adverse Event) and coded with MedDRA23.1 (Medical Dictionary for Regulatory Activities).