Type 1 Primary HyperoxaluriaEarly Phase 1NCT06511349
Clinical Exploration Study of YOLT-203 in the Treatment of Type 1 Primary Hyperoxaluria (PH1)
A Early Phase 1 study testing YOLT-203 in people with Type 1 Primary Hyperoxaluria, run by RenJi Hospital at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Type 1 Primary Hyperoxaluria
- What is being tested?
- YOLT-203
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteChina
- Study dates
- 15 Jul 2024to 31 Dec 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Deparment of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
Shanghai, Shanghai Municipality, 200127
Qiang Xia, MD, PhD, 021-58752345, xiaqiang@medmail.com.cn
About this study
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.
Read the detailed description
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.
- Conditions
- Type 1 Primary Hyperoxaluria
- Being tested
- YOLT-203
- Medical subject headings
- Primary hyperoxaluria type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YOLT-203Drug
The IP is administered intravenously at the predetermined dose.
| Study group | Role | What they receive |
|---|---|---|
| TOLT-203 | Experimental | Not described Receives: Drug: YOLT-203 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Measured: through week 52
Secondary outcomes (8)
pharmacokinetics of YOLT-203
The Peak Plasma Concentration (Cmax) of YOLT-203. 0.5 predose,2,6,24,48,72,144,312 hours
Measured: through Day 14
pharmacokinetics of YOLT-203
Area under the plasma concentration versus time curve (AUC). 0.5 predose,2,6,24,48,72,144,312 hours
Measured: through Day 14
pharmacokinetics of YOLT-203
Tmax
Measured: through Day 28
pharmacokinetics of YOLT-203
T1/2
Measured: through Day 28
pharmacodynamics
After medication, at 1, 2, 4, 8, 16, 24, 36, and 52 weeks, the changes in blood glycolic acid levels
Measured: through week 52
pharmacodynamics
After medication, at 2, 8, 16, 24, and 52 weeks, the changes in 24-hour urinary oxalic acid excretion compared to the baseline value.
Measured: through week 52
pharmacodynamics
After medication, at 1, 2, 4, 8, 16, 24, 36, and 52 weeks, the changes in 24-hour urinary glycolic acid excretion
Measured: through week 52
pharmacodynamics
After medication, at 1, 2, 4, 8, 16, 24, 36, and 52 weeks, the changes in eGFR.
Measured: through week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2024
- Study start15 Jul 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 Primary HyperoxaluriaStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 0.3mg/kg,0.45mg/kg,0.6mg/kg,35mg
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06511349
- Sponsor's protocol ID
- PH1-YOLT-203-001
- Status last verified
- May 2025
- First submitted
- 4 Jul 2024
- Last updated
- 16 May 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Exploration Study of YOLT-203 in the Treatment of Type 1 Primary Hyperoxaluria (PH1)
- ClinicalTrials.gov ID
- NCT06511349
- Acronym / sponsor ID
- PH1-YOLT-203-001
- Conditions
- Type 1 Primary Hyperoxaluria
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Study start
- 15 Jul 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 19 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 0.3mg/kg,0.45mg/kg,0.6mg/kg,35mg
| Arm | Type | Receives |
|---|---|---|
| TOLT-203 | Experimental | Drug: YOLT-203 |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (16 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| YOLT-203The IP is administered intravenously at the predetermined dose. | Drug | TOLT-203 |
Primary outcome
Safety and Tolerability
Time frame: through week 52
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
8 secondary outcomes
pharmacokinetics of YOLT-203
Time frame: through Day 14
pharmacokinetics of YOLT-203
Time frame: through Day 14
pharmacokinetics of YOLT-203
Time frame: through Day 28
pharmacokinetics of YOLT-203
Time frame: through Day 28
pharmacodynamics
Time frame: through week 52
pharmacodynamics
Time frame: through week 52
pharmacodynamics
Time frame: through week 52
pharmacodynamics
Time frame: through week 52
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
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Study of YOLT-203 in Children and Adults With Primary Hyperoxaluria Type 1 (PH1)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Deparment of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
Shanghai, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing YOLT-203 in people with Type 1 Primary Hyperoxaluria, run by RenJi Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability (time frame: through week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2025.