clinical exploration study of yolt-203 in the treatment of type 1 primary hyperoxaluria (ph1)

Conditions: Type 1 Primary Hyperoxaluria

Summary: this study is a single-arm, open-label, single-dose, dose-escalation trial, aiming to evaluate the safety and tolerability of yolt-203 in the chinese population with type 1 primary hyperoxaluria (ph1); and to preliminarily assess the effect of a single dose of yolt-203 on the plasma oxalate level.in this study, the maximum screening period of the main study is 60 days, the treatment day is day 1 (d1), and the safety follow-up period is up to week 52 after administration. in addition, subjects within the first dose group can voluntarily receive a second treatment with the test drug at the effective dose level. after the end of the main study, the subjects will undergo long-term followup. according to the requirements of the "technical guidelines for long-term follow-up clinical studies of gene therapy products (trial)" issued by the cde, the long-term follow-up is up to 15 years after administration. the most updated protocol is v1.2 , 22 jan 2025


Eligibility criteria:
inclusion criteria: * the age is 2≤ years \<18 years old at the time of signing the informed consent. * have agxt gene mutations and be diagnosed with primary hyperoxaluria (ph1); egfr ≥ 30 ml/min/1.73m2. * at least 2 times of 24-hour urinary oxalate excretion ≥ 0.7 mmol/1.73m2/ day or the ratio of urinary oxalate to creatinine in a single urine collection must be higher than the upper limit of normal (uln) for the corresponding age. * if treated with vitamin b6, the treatment has been stable for 90 days before enrollment in the study and is willing to maintain the stable treatment plan unchanged during the study. * the patient himself/herself or the guardian voluntarily signs the informed consent. exclusion criteria: * the investigator judges that there is clinical evidence of systemic extrarenal oxalate deposition. * have any of the following laboratory parameter assessment results at screening: 1. alanine aminotransferase (alt) or aspartate aminotransferase (ast) \> 2 x the upper limit of normal (uln). 2. total bilirubin \> 1.5 x uln. if the increase in total bilirubin is caused by diagnosed gilbert's syndrome and the total bilirubin \< 2 x uln, it is eligible. 3. international normalized ratio (inr) \> 1.5 (patients on oral anticoagulants \[such as warfarin\] and with inr \< 3.5 will be allowed to participate). * known to have active human immunodeficiency virus (hiv) infection; or have evidence of current or chronic hepatitis c virus (hcv) or hepatitis b virus (hbv) infection. * the estimated glomerular filtration rate (gfr) at screening is less than 30 ml/min/1.73m² (for patients ≥ 18 years old, it will be calculated according to the modification of diet in renal disease \[mdrd\] formula; for patients \< 18 years old, it will be calculated according to the schwartz bedside formula). see the attachment. * have received an investigational drug within the last 30 days or 5 halflives (whichever is longer) before the first administration of the study drug, or have participated in the follow-up of another clinical study before randomization. * have a history of kidney or liver transplantation. * according to the investigator's opinion, have other medical conditions or comorbidities that may interfere with study compliance or data interpretation. * page 4 of 5 \[draft\] - * have a history of multiple drug allergies or allergic reaction history to oligonucleotides or lnp. * have a history of subcutaneous injection intolerance. * unwilling to comply with contraceptive requirements throughout the study participation period until 6 months after the end of the main study trial. * female patients are pregnant, planning to become pregnant or breastfeeding. * unwilling or unable to limit alcohol consumption throughout the study. alcohol consumption during the study exceeds 2 units per day (1 unit: approximately 125 ml of wine = approximately 29 ml of spirits = approximately 284 ml of beer, will be excluded. * the investigator believes that there is a history of alcohol abuse within 12 months before screening.