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

March 18, 2025 updated by: Guangzhou Women and Children's Medical Center
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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510623
        • Guangzhou Women And Children's Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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.

  • 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.
    • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Open Label single dose
YOLT-203
Drug: YOLT-203
The IP is administered intravenously at the predetermined dose.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse events
Time Frame: through week 52
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The Peak Plasma Concentration (Cmax) of YOLT-203
Time Frame: through Day 14
The Peak Plasma Concentration (Cmax) of YOLT-203 in the plasma after a dose is given
through Day 14
Area under the plasma concentration versus time curve (AUC)of YOLT-203
Time Frame: through Day 14
Area under the plasma concentration versus time curve (AUC). 0.5 predose,6,24,48,144,and312 hours after treatment
through Day 14
Time to Maximum Plasma Concentration (Tmax)of YOLT-203
Time Frame: through Day 14
Tmax is the time it takes for YOLT-203 to reach the maximun concentration (Tmax) after administration
through Day 14
Drug half-life (T1/2)of YOLT-203
Time Frame: through Day 14
The amount of time it takes for the plasma YOLT-203 drug concentration to drop to half
through Day 14
The changes in blood glycolic acid levels
Time Frame: through week 52
After medication, at 1, 2, 4, 8, 16, 24, 36, and 52 weeks, the changes in blood glycolic acid levels
through week 52
The changes in 24-hour urinary oxalic acid excretion
Time Frame: through week 52
After medication, at 1,2,4, 8, 16, 24, 36and 52 weeks, the changes in 24-hour urinary oxalic acid excretion compared to the baseline value.
through week 52
The changes in 24-hour urinary glycolic acid excretion
Time Frame: through week 52
After medication, at 1, 2, 4, 8, 16, 24, 36, and 52 weeks, the changes in 24-hour urinary glycolic acid excretion
through week 52
The changes in eGFR
Time Frame: through week 52
After medication, at 1, 2, 4, 8, 16, 24, 36, and 52 weeks, the changes in eGFR.
through week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Guangzhou Women and Children's Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Wenhao Zhou, PhD, MD, Guangzhou Women And Children's Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 27, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 26, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 25, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PH1-YOLT-203-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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