Familial HypercholesterolemiaEarly Phase 1NCT06458010

Clinical Exploration Trial of YOLT-101 in the Treatment of Familial Hypercholesterolemia (FH)

A Early Phase 1 study testing YOLT-101 in people with Familial Hypercholesterolemia, run by RenJi Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

This study is a single arm, open, single dose escalation trial aimed at evaluating the safety and tolerability of YOLT-101 administration in patients with familial hypercholesterolemia; Determination of YOLT-101 OBD; Preliminary evaluation of the effects of single administration of YOLT-101 on plasma lipid and… Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Familial Hypercholesterolemia
What is being tested?: YOLT-101
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteChina
Study dates: 24 May 2024to 25 Jan 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 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female, aged 18 to 75 years inclusive, at the time of signing informed consent.
Meets the diagnostic criteria for familial hypercholesterolemia.
At screening, there is a mutation in the PCSK9 and/or ApoB and/or LDLR gene.
At screening, weight is ≥40kg, and Body Mass Index (BMI) is >18kg/m^2.
At screening, subjects must meet the following laboratory criteria:
5.1 Hematology: Absolute Neutrophil Count (ANC) ≥1.5×10^9/L, Platelet (PLT) ≥100×10^9/L, Hemoglobin (HGB) ≥90 g/dL; 5.2 Liver Function: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) <2.0×Upper Limit of Normal (ULN), Total Bilirubin (TBIL) ≤1.5×ULN; 5.3 Renal Function: Serum Creatinine (Cr) ≤1.5×ULN, and Glomerular Filtration Rate (GFR) >60mL/min1.73m^2; 5.4 Coagulation Function: Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), International Normalized Ratio (INR) <1.5×ULN; 5.5 Fasting Triglycerides <5.6mmol/L.

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On moderate intensity or higher statin therapy (statin treatment stable for 4 weeks) with LDL-C ≥2.6mmol/L; for those with evidence of atherosclerosis, LDL-C ≥1.8mmol/L. (Evidence of atherosclerosis includes: 1. History of myocardial infarction, angina, coronary artery revascularization, non-embolic ischemic stroke or transient ischemic attack, intermittent claudication; 2. Presence of advanced subclinical atherosclerosis: Coronary artery calcium score > 100 Agatston units, or above the 75th percentile for age and sex; or coronary artery CT angiography showing stenosis > 50%, or multiple vessels with non-obstructive plaques.)
Subjects and their partners must use effective contraceptive measures during the study period and for at least 6 months after the end of the main study.
Voluntarily sign informed consent.

Who cannot join

Within at least 14 days (or 5 half-lives of the drug, whichever is longer, for small molecule/small nucleic acid drugs) or 2 months (for biological agents such as PCSK9 inhibitors) or 1 year (for PCSK9 small nucleic acid drugs) before accepting the study medication, those who have used prescription drugs that affect lipid metabolism other than statins, or those who have used any non-prescription drugs affecting lipid metabolism within at least 14 days before accepting the study medication (such as traditional Chinese medicine/patent Chinese medicine, vitamins, fish oil (>1000mg/day), drugs or health products containing red yeast rice, etc.; except for those who have been on stable non-cyclic hormone replacement therapy for more than 8 weeks and agree not to change the treatment plan for at least 28 days after receiving the trial medication); those who are currently participating in other clinical studies of lipid-lowering drugs and have used study medication.
Patients with poorly controlled hypertension (systolic blood pressure (SBP) ≥160mmHg and/or diastolic blood pressure (DBP) ≥100mmHg).
Patients with poorly controlled diabetes (glycated hemoglobin >8.5%).
Those allergic to drugs or components of LNP-mRNA vaccines contained in lipid nanoparticles (LNP), or those who have experienced adverse reactions due to LNP-based drug treatment, such as: 4.1 After receiving LNP-based drug treatment, ALT or AST > 3.0×ULN; 4.2 After receiving LNP-based drug treatment, INR > 1.5 or APTT/d-dimer > 1.5×ULN; 4.3 Any infusion reaction that requires clinical intervention or slows down or stops the infusion of LNP-based drug treatment; 4.4 Any other adverse reactions deemed related to LNP-based drug treatment by the investigator.
Within 3 months before screening, those who smoke more than 5 cigarettes per day or consume an equivalent amount of nicotine or nicotine replacement products.
Within 3 months before screening, those with a history of alcohol abuse [consuming more than 14 units of alcohol per week (1 unit ≈ 360mL beer or 45mL of liquor with 40% alcohol or 150mL of wine)]; or those who test positive for alcohol breath research at screening or admission.

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At screening, those with New York Heart Association (NYHA) defined class III-IV heart failure, or left ventricular ejection fraction <50%, or prolonged QTc interval (females >470ms, males >450ms).
Within 3 months before screening, those with poorly controlled severe arrhythmias, such as recurrent and highly symptomatic ventricular tachycardia, rapid ventricular response atrial fibrillation, or supraventricular tachycardia that is not well controlled with medication.
Within 3 months before screening, those with myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass grafting, severe deep vein thrombosis, or pulmonary embolism; those who have had a cerebrovascular accident within 6 months before screening or plan to undergo cardiac surgery or revascularization during the main study period.
Those with diseases that significantly affect lipid levels and are uncontrollable, such as nephrotic syndrome, severe liver disease, Cushing's syndrome, thyroid dysfunction, etc. (those with hypothyroidism before screening who have been on stable thyroid replacement therapy for ≥28 days, with normal TSH testing, and agree to maintain the thyroid replacement drug dose unchanged during the study may be considered for inclusion).
Those who have donated more than 500 mL of blood within 3 months before screening.
Those who cannot or are unwilling to accept the required medication treatment plan before treatment.
Those who have undergone antithrombotic treatment (such as warfarin, dabigatran, apixaban) within 14 days before enrollment.
Those with a history of easy bleeding or coagulation disorders (such as liver cirrhosis, malignant hematological diseases, antiphospholipid antibody syndrome).
Those with an expected survival of less than 2 years.
Those known or suspected to have systemic viral, parasitic, or fungal infections, or those expected to receive antibiotic treatment within 14 days after screening.
Those who test positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody at screening.
Those who have undergone liver, heart, or other solid organ transplantation or bone marrow transplantation within 1 year before screening or plan to undergo transplantation during the trial period.
Those with a history of malignant tumors within 5 years before screening (except for cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, cervical carcinoma in situ, low-grade prostatic intraepithelial neoplasia, and cured basal cell carcinoma of the thyroid).
Those with a history of drug abuse within 3 years before screening.
Women who are pregnant or breastfeeding.
Those with other hematopoietic system, digestive system, or central nervous system (including cerebrovascular diseases, degenerative diseases) diseases that the investigator believes will interfere with evaluation or limit participation in the trial.
Those with severe mental illnesses that the investigator believes cannot be adequately controlled by drug treatment.
Those unwilling to comply with the research procedures or unwilling to fully cooperate.
Other situations deemed by the investigator as not suitable for participation in clinical trials.

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

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
Recruiting

Other trials in China

About this study

Note: OBD is defined as the dosage at which plasma PCSK9 protein levels decrease between 60% and 95% from baseline on the 28th day after YOLT-101 administration. OBD ≤ Maximum Tolerable Dose (MTD).

In this study, the longest screening period for the main study was 42 days, the treatment day was Day 1 (D1), and the safe follow-up period was up to 52 weeks after medication. In the main study, when OBD occurs, additional subjects will be added to the dose group (specific number of cases will be negotiated between the cooperating organization and investigators) for further validation. In addition, subjects in the first dose group can voluntarily receive a second drug administration of OBD level.

After the completion of the main study, participants will undergo long-term follow-up. According to the Technical Guidelines for Long term Follow up Clinical Research of Gene Therapy Products (Trial) released by CDE, a long-term follow-up until 15 years after the medicine administration is required .

Read the detailed description

Protocol (V1.2, 6 May 2024) has been approved on 14 May 2024 Protocol (V1.3 ,23 May 2024) has been approved on 12 Jun 2024 Protocol (V1.4 ,24 Jun 2024) has been approved on 15 Jul 2024 Protocol (V1.5 ,18 Oct 2024) has been approved on 28 Oct 2024 Protocol (V1.6 ,27 Nov 2024) has been approved on 27 Dec 2024 Protocol (V1.7 ,6 Jan 2025) has been approved on 27 Jan 2025 Protocol (V1.8 ,19 Feb 2025) has been approved on 24 Mar 2025

Conditions: Familial Hypercholesterolemia
Being tested: YOLT-101
Medical subject headings: Hyperlipoproteinemia Type II

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

YOLT-101Drug
The IP is administered intravenously at the predetermined dose.

Study groups in NCT06458010
Study group	Role	What they receive
Single Arm	Experimental	dosage group: 0.2mg/kg, 0.4mg/kg, 0.6mg/kg,40mg,50mg; dosage form: injection; frequency of administration: once. Receives: Drug: YOLT-101

What is being measured

The primary outcome is the main question the study is designed to answer.

safety evaluation of YOLT-101
The safety of YOLT-101 evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs).
Measured: through week 52

Secondary outcomes (6)

pharmacokinetics of YOLT-101
The Peak Plasma Concentration (Cmax) of YOLT-101. 0.5 predose,2,12,24,48,72,144,312,648hours.
Measured: through Day 28
pharmacodynamics
The effect of YOLT-101 on serum levels of LDL-C
Measured: through week 52
pharmacodynamics
The effect of YOLT-101 on plasma levels of PCSK9
Measured: through week 52
pharmacokinetics of YOLT-101
Area under the plasma concentration versus time curve (AUC); 0.5 predose,2,12,24,48,72,144,312,648hours.
Measured: through Day 28
pharmacokinetics of YOLT-101
Tmax;
Measured: through Day 28
pharmacokinetics of YOLT-101
T1/2
Measured: through Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 May 202425 Jan 2026

First posted13 Jun 2024
Study start24 May 2024
Primary completion25 Jan 2026 (estimated)
Study completion25 Jan 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Familial HypercholesterolemiaStudies 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: 0.2mg/kg, 0.4mg/kg, 0.6mg/kg, 40mg, 50mg
Masking: None (open label)
Enrolment: 20 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06458010
Sponsor's protocol ID: FH-YOLT-101-001
Status last verified: Apr 2025
First submitted: 17 May 2024
Last updated: 30 Apr 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Wan P, Tang S, Lin D, Lu Y, Long M, Xiao L, Jiang Y, Liao J, Ma X, Liu Y, Yu W, Ott M, Wang ZJ, Wu Y, Yang T, Xia Q. In vivo base editing gene therapy for heterozygous familial hypercholesterolemia: a phase 1 trial. Nat Med. 2026 Mar;32(3):1045-1051. doi: 10.1038/s41591-026-04254-4. Epub 2026 Mar 3.
PubMed 41776075

Interested in taking part?

Each site lists its own contact. Pick the site nearest to you.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia
Not yet recruitingObservational study
An Observational Study to Evaluate Treatment Patterns in High, Very High and Extreme Cardiovascular Risk Patients With Hypercholesterolemia, Including Familial Hypercholesterolemia
Hypercholesterolaemia, Familial Hypercholesterolaemia
Active, not recruitingObservational study
Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients With Homozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia (HoFH), Major Adverse Cardiovascular Events (MACE)
Active, not recruitingObservational study
Assessment of the Prevalence of Steatotic Liver Disease Associated With Metabolic Dysfunction in Patients With Heterozygous Familial Hypercholesterolemia
Heterozygous Familial Hypercholesterolemia

All Familial Hypercholesterolemia trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Clinical Exploration Trial of YOLT-101 in the Treatment of Familial Hypercholesterolemia (FH)
ClinicalTrials.gov ID: NCT06458010
Acronym / sponsor ID: FH-YOLT-101-001
Conditions: Familial Hypercholesterolemia
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 20 participants (estimated)
Lead sponsor: RenJi HospitalUniversity, hospital or other
Study start: 24 May 2024 (actual)
Primary completion: 25 Jan 2026 (estimated)
Study completion: 25 Jan 2026 (estimated)
First posted: 13 Jun 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.

Note: OBD is defined as the dosage at which plasma PCSK9 protein levels decrease between 60% and 95% from baseline on the 28th day after YOLT-101 administration. OBD ≤ Maximum Tolerable Dose (MTD).

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Masking: None (open label)
Number of arms: 1
Model description: 0.2mg/kg, 0.4mg/kg, 0.6mg/kg, 40mg, 50mg

Arm	Type	Receives
Single Arm	Experimental	Drug: YOLT-101dosage group: 0.2mg/kg, 0.4mg/kg, 0.6mg/kg,40mg,50mg; dosage form: injection; frequency of administration: once.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Male or female, aged 18 to 75 years inclusive, at the time of signing informed consent.
Meets the diagnostic criteria for familial hypercholesterolemia.
At screening, there is a mutation in the PCSK9 and/or ApoB and/or LDLR gene.
At screening, weight is ≥40kg, and Body Mass Index (BMI) is >18kg/m^2.
At screening, subjects must meet the following laboratory criteria:

Key exclusion criteria (25 listed)

Within at least 14 days (or 5 half-lives of the drug, whichever is longer, for small molecule/small nucleic acid drugs) or 2 months (for biological agents such as PCSK9 inhibitors) or 1 year (for PCSK9 small nucleic acid drugs) before accepting the study medication, those who have used prescription drugs that affect lipid metabolism other than statins, or those who have used any non-prescription drugs affecting lipid metabolism within at least 14 days before accepting the study medication (such as traditional Chinese medicine/patent Chinese medicine, vitamins, fish oil (>1000mg/day), drugs or health products containing red yeast rice, etc.; except for those who have been on stable non-cyclic hormone replacement therapy for more than 8 weeks and agree not to change the treatment plan for at least 28 days after receiving the trial medication); those who are currently participating in other clinical studies of lipid-lowering drugs and have used study medication.
Patients with poorly controlled hypertension (systolic blood pressure (SBP) ≥160mmHg and/or diastolic blood pressure (DBP) ≥100mmHg).
Patients with poorly controlled diabetes (glycated hemoglobin >8.5%).
Those allergic to drugs or components of LNP-mRNA vaccines contained in lipid nanoparticles (LNP), or those who have experienced adverse reactions due to LNP-based drug treatment, such as: 4.1 After receiving LNP-based drug treatment, ALT or AST > 3.0×ULN; 4.2 After receiving LNP-based drug treatment, INR > 1.5 or APTT/d-dimer > 1.5×ULN; 4.3 Any infusion reaction that requires clinical intervention or slows down or stops the infusion of LNP-based drug treatment; 4.4 Any other adverse reactions deemed related to LNP-based drug treatment by the investigator.
Within 3 months before screening, those who smoke more than 5 cigarettes per day or consume an equivalent amount of nicotine or nicotine replacement products.

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-101The IP is administered intravenously at the predetermined dose.	Drug	Single Arm

Primary outcome

safety evaluation of YOLT-101
Time frame: through week 52
The safety of YOLT-101 evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs).

6 secondary outcomes

pharmacokinetics of YOLT-101
Time frame: through Day 28
pharmacodynamics
Time frame: through week 52
pharmacodynamics
Time frame: through week 52
pharmacokinetics of YOLT-101
Time frame: through Day 28
pharmacokinetics of YOLT-101
Time frame: through Day 28
pharmacokinetics of YOLT-101
Time frame: through Day 28

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 30 Apr 2025.
Derived from this study: PubMed 41776075Wan P, Tang S, Lin D, Lu Y, Long M, Xiao L, Jiang Y, Liao J, Ma X, Liu Y, Yu W, Ott M, Wang ZJ, Wu Y, Yang T, Xia Q. In vivo base editing gene therapy for heterozygous familial hypercholesterolemia: a phase 1 trial. Nat Med. 2026 Mar;32(3):1045-1051. doi: 10.1038/s41591-026-04254-4. Epub 2026 Mar 3.
Individual participant dataSharing planned: No

Related trials for Familial Hypercholesterolemia

Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia
Not yet recruitingObservational study
An Observational Study to Evaluate Treatment Patterns in High, Very High and Extreme Cardiovascular Risk Patients With Hypercholesterolemia, Including Familial Hypercholesterolemia
Hypercholesterolaemia, Familial Hypercholesterolaemia
Active, not recruitingObservational study
Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients With Homozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia (HoFH), Major Adverse Cardiovascular Events (MACE)
Active, not recruitingObservational study
Assessment of the Prevalence of Steatotic Liver Disease Associated With Metabolic Dysfunction in Patients With Heterozygous Familial Hypercholesterolemia
Heterozygous Familial Hypercholesterolemia

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

021-58752345

xiaqiang@medmail.com.cn

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-101 in people with Familial Hypercholesterolemia, 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 9 inclusion and 25 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 30 Apr 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 evaluation of YOLT-101 (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?

On the ClinicalTrials.gov record for NCT06458010, which also lists 1 linked publication.

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 30 Apr 2025.