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

NCT06892301 | Active Not Recruiting Early Phase 1 DMC

• 1 other identifier: PH1-YOLT-203-01
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Type 1 Primary Hyperoxaluria

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse events

  An Adverse Event(AE) is any untoward medical occurrence in a participant or clinical investigational participant adminstered a medicinal product and which does not necessarily have a casual relationship with this treatment

  through week 52

Secondary Outcomes (8)

• The Peak Plasma Concentration (Cmax) of YOLT-203

  through Day 14

• Area under the plasma concentration versus time curve (AUC)of YOLT-203

  through Day 14

• Time to Maximum Plasma Concentration (Tmax)of YOLT-203

  through Day 14

• Drug half-life (T1/2)of YOLT-203

  through Day 14

• The changes in blood glycolic acid levels

  through week 52

Study Arms (1)

Open Label single dose

EXPERIMENTAL

YOLT-203

Drug: YOLT-203

Interventions

YOLT-203 DRUG

The IP is administered intravenously at the predetermined dose.

Open Label single dose

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• The investigator judges that there is clinical evidence of systemic extrarenal oxalate deposition.
• Have any of the following laboratory parameter assessment results at screening:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 x the upper limit of normal (ULN).
• 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.
• 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.

Sponsors & Collaborators

• Guangzhou Women and Children's Medical Center: lead

Study Sites (1)

Guangzhou Women and Children's Medical Center

Guangzhou, Guangdong, 510623, China

Location

MeSH Terms

Conditions

Primary hyperoxaluria type 1

Study Officials

• Wenhao Zhou, PhD, MD

  Guangzhou Women and Children's Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 0.45mg/kg

Study Record Dates

• First Submitted: February 26, 2025
• First Posted: March 24, 2025
• Study Start: February 27, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 24, 2025

Record last verified: 2025-02

Locations

CN (1)