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Gene Therapy Trial Report

Summary

Clinical Exploration Study of YOLT-203 in the Treatment of Type 1 Primary Hyperoxaluria (PH1)


NCTID NCT06511349 (View at clinicaltrials.gov)
Description
Development Status Active
Indication Type 1 Primary Hyperoxaluria
Disease Ontology Term DOID:0111670
Compound Name YOLT-203
Sponsor RenJi Hospital
Funder Type Other
Recruitment Status
Enrollment Count 21 (ESTIMATED)
Results Posted Not Available

Therapy Information


Target Gene/Variant HAO1
Therapy Type Gene editing
Therapy Route In-vivo
Mechanism of Action Gene inactivation
Route of Administration Intravenous
Drug Product Type MRNA, LNP
Delivery System Lipid encapsulation
Vector Type LNP
Editor Type YolCas12
Dose 1 0.3 mg/kg
Dose 2 0.6 mg/kg
Dose 3 1.0 mg/kg

Study Record Dates


Current Stage Early phase1
Submit Date 2024-07-04
Completion Date 2026-12-31
Last Update 2025-05-16

Participation Criteria


Eligible Age >=2 Years
Standard Ages Child, Adult, Older adult
Sexes Eligible for Study ALL
Eligibility Criteria
Inclusion Criteria: * The age is ≥ 2 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 extra-renal 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 half-lives (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. * 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.
View Inclusion and Exclusion Criteria at ClinicalTrials.gov

Locations


No.of Trial Sites 1
Locations China

Regulatory Information


Has US IND False
FDA Designations Orphan Drug Designation, Rare Pediatric Disease Designation
Recent Updates First patient dosed (8/5/24), US IND application cleared November 2025

Resources/Links