ClinicalTrials.gov record NCT06511349
Clinical Exploration Study of YOLT-203 in the Treatment of Type 1 Primary Hyperoxaluria (PH1)
Clinical Exploration Study of YOLT-203 in the Treatment of Type 1 Primary Hyperoxaluria (PH1)
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
An early-phase, open-label, single-arm study giving a single intravenous dose of YOLT-203 to people with Type 1 Primary Hyperoxaluria (PH1). The study uses dose-escalation and dose-expansion to assess safety, tolerability, and pharmacokinetics/pharmacodynamics. Participants have safety follow-up through week 52 and planned long-term follow-up for up to 15 years.
What it is studying. Whether a single intravenous dose of YOLT-203 is safe and tolerable in people with PH1, how the drug behaves in the body (pharmacokinetics and pharmacodynamics), and its effects on plasma and urinary oxalate, glycolic acid, and kidney function.
What the researchers hope to learn. To assess the safety and tolerability of YOLT-203, characterize its pharmacokinetics and pharmacodynamics, and measure changes in plasma oxalate, 24-hour urinary oxalate, glycolic acid levels, and estimated glomerular filtration rate (eGFR).
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
This study is a single-arm, open-label, single-dose, dose-escalation, and dose-expansion trial, aiming to assess the safety and tolerability of YOLT-203 in Chinese patients with Primary Hyperoxaluria Type 1 (PH1), and to preliminarily evaluate the effect of a single dose of YOLT-203 on plasma oxalate levels. In this study, the maximum duration of the screening period is 60 days, with the treatment day being Day 1 (D1), and the safety follow-up period extending to the 52nd week after dosing. Additionally, in the dose-escalation phase, after the first dose cohort, investigators will conduct a comprehensive evaluation based on safety, pharmacokinetic (PK), and pharmacodynamic (PD) data, and following discussion at the Safety Review Committee (SRC) meeting, subjects may voluntarily receive a second administration of the study drug at an effective dose level. After the completion of the main study, subjects will undergo long-term follow-up. In accordance with the requirements of the "Technical Guidance for Clinical Research on Long-term Follow-up of Gene Therapy Products (Trial)" issued by the Center for Drug Evaluation (CDE), long-term follow-up will be conducted for up to 15 years after dosing.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- YOLT-203
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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:
- 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 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.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Detailed description from the registry
As of December 2024, the clinical study of YOLT-203 for the treatment of type 1 primary hyperoxaluria (PH1) has completed enrollment and dosing for two cases at 0.3mg/kg and three cases at 0.45mg/kg, as well as a 28-day follow-up for all participants. On December 6, 2024, a meeting was held to discuss the safety and efficacy data of all participants in the two dosage groups and to make decisions on the next steps of the research plan. Based on the safety and efficacy data from all participants in this project, the sponsor and investigators reached a consensus after a meeting discussion: YOLT-203 has good safety, and 0.45mg/kg is the anticipated biologically effective dose (OBD). According to the protocol design, the meeting decision was made to stop dose escalation and repeat a group at the anticipated effective dose (0.45mg/kg), continuing to enroll 1-3 more participants for exploratory studies.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
After a screening period (up to 60 days), participants receive a single intravenous dose of the study drug on Day 1 and attend multiple clinic visits with blood tests for safety and pharmacokinetics and repeated 24-hour urine collections to measure oxalate and related markers. Follow-up safety visits continue through week 52; in the dose‑escalation phase some participants may be offered a second dose after review. The study also includes long-term follow-up for up to 15 years after dosing. Visits include frequent early blood draws and scheduled urine collections timed over the first year.
How the study is structured. Interventional treatment study. Single-arm, open-label, sequential dose-escalation followed by dose-expansion. Participants receive a predetermined single intravenous dose of YOLT-203; dose decisions use safety, PK, and PD data and Safety Review Committee input. Safety is followed through week 52, with additional long-term follow-up planned up to 15 years. No masking.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in China. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on primary hyperoxaluria
Important dates
- Study start
- Jul 15, 2024
- Primary completion
- Dec 31, 2026 (estimated)
- Study completion
- Dec 31, 2026 (estimated)
- Target enrollment
- 21 participants (estimated)
- Last updated on registry
- May 16, 2025
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- RenJi Hospital
Participating sites (1)
- Deparment of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityRecruiting
Shanghai, Shanghai Municipality, 200127 · China
- Qiang Xia, MD, PhD · 021-58752345 · xiaqiang@medmail.com.cn
Terms used on this page · explanations by MedicalUpdates.ai
- single-arm
- All participants receive the same treatment or follow the same plan. There is no comparison group within the study.
- open-label
- No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
- dose-escalation
- Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
- screening period
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- safety follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- cohort
- A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
- pharmacokinetic
- How the body absorbs, distributes, breaks down and removes a drug. It is studied by measuring drug levels or related substances at set times after a dose.
- pharmacodynamic
- What a drug does to the body, for example how it changes a blood marker or a symptom, and how that relates to the dose.
- study drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- long-term follow-up
- Observation that continues for years after the study treatment, often required for gene and cell therapies.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- eGFR
- A blood-test estimate of how well the kidneys are filtering. Lower numbers mean reduced kidney function; many studies set a minimum value.
- upper limit of normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- 5 half-lives
- The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
- randomization
- Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- sponsor
- The organisation or person that initiates the study and has authority over it. The sponsor may be a company, hospital, university, government agency or individual, and is not necessarily the organisation that funds the study.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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