Exploring YOLT-203 for treating Type 1 Primary Hyperoxaluria

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

This study is testing a new treatment called YOLT-203 to see if it can safely lower oxalate levels in people with Type 1 Primary Hyperoxaluria.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: 2 Years and up
• Sex: All
• Sponsor: RenJi Hospital (other)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06511349 on ClinicalTrials.gov

What this trial studies

This clinical exploration focuses on the safety and tolerability of YOLT-203 in patients with Type 1 Primary Hyperoxaluria (PH1). It is a single-arm, open-label trial that involves a dose-escalation and dose-expansion approach, assessing the effects of a single dose on plasma oxalate levels. Participants will undergo a screening period of up to 60 days, followed by treatment and a safety follow-up extending to 52 weeks. The study aims to determine the optimal biologically effective dose based on safety and efficacy data collected during the trial.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 2 years and older with AGXT gene mutations diagnosed with primary hyperoxaluria and specific urinary oxalate excretion levels.

Not a fit: Patients with clinical evidence of systemic extra-renal oxalate deposition or significant liver enzyme abnormalities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce plasma oxalate levels in patients with PH1, potentially improving their health outcomes.

How similar studies have performed: While this approach is novel, previous studies on similar treatments for hyperoxaluria have shown promising results, indicating potential for success.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Deparment of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University — Shanghai, Shanghai Municipality, China (RECRUITING)

Conditions: Type 1 Primary Hyperoxaluria