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

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.

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  • 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.