This study is a single-arm, open-label, single-dose, dose-escalation, and dose-expansion trial, aiming to assess the safety and tolerability of YOLT-203 in Chinese patients with Primary Hyperoxaluria Type 1 (PH1), and to preliminarily evaluate the effect of a single dose of YOLT-203 on plasma oxalate levels. In this study, the maximum duration of the screening period is 60 days, with the treatment day being Day 1 (D1), and the safety follow-up period extending to the 52nd week after dosing. Additionally, in the dose-escalation phase, after the first dose cohort, investigators will conduct a comprehensive evaluation based on safety, pharmacokinetic (PK), and pharmacodynamic (PD) data, and following discussion at the Safety Review Committee (SRC) meeting, subjects may voluntarily receive a second administration of the study drug at an effective dose level. After the completion of the main study, subjects will undergo long-term follow-up. In accordance with the requirements of the "Technical Guidance for Clinical Research on Long-term Follow-up of Gene Therapy Products (Trial)" issued by the Center for Drug Evaluation (CDE), long-term follow-up will be conducted for up to 15 years after dosing.
As of December 2024, the clinical study of YOLT-203 for the treatment of type 1 primary hyperoxaluria (PH1) has completed enrollment and dosing for two cases at 0.3mg/kg and three cases at 0.45mg/kg, as well as a 28-day follow-up for all participants. On December 6, 2024, a meeting was held to discuss the safety and efficacy data of all participants in the two dosage groups and to make decisions on the next steps of the research plan. Based on the safety and efficacy data from all participants in this project, the sponsor and investigators reached a consensus after a meeting discussion: YOLT-203 has good safety, and 0.45mg/kg is the anticipated biologically effective dose (OBD). According to the protocol design, the meeting decision was made to stop dose escalation and repeat a group at the anticipated effective dose (0.45mg/kg), continuing to enroll 1-3 more participants for exploratory studies.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
The IP is administered intravenously at the predetermined dose.
Deparment of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
Shanghai, Shanghai Municipality, China
RECRUITINGSafety and Tolerability
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Time frame: through week 52
pharmacokinetics of YOLT-203
The Peak Plasma Concentration (Cmax) of YOLT-203. 0.5 predose,2,6,24,48,72,144,312 hours
Time frame: through Day 14
pharmacokinetics of YOLT-203
Area under the plasma concentration versus time curve (AUC). 0.5 predose,2,6,24,48,72,144,312 hours
Time frame: through Day 14
pharmacokinetics of YOLT-203
Tmax
Time frame: through Day 28
pharmacokinetics of YOLT-203
T1/2
Time frame: through Day 28
pharmacodynamics
After medication, at 1, 2, 4, 8, 16, 24, 36, and 52 weeks, the changes in blood glycolic acid levels
Time frame: through week 52
pharmacodynamics
After medication, at 2, 8, 16, 24, and 52 weeks, the changes in 24-hour urinary oxalic acid excretion compared to the baseline value.
Time frame: through week 52
pharmacodynamics
After medication, at 1, 2, 4, 8, 16, 24, 36, and 52 weeks, the changes in 24-hour urinary glycolic acid excretion
Time frame: through week 52
pharmacodynamics
After medication, at 1, 2, 4, 8, 16, 24, 36, and 52 weeks, the changes in eGFR.
Time frame: through week 52
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