Actively Recruiting

Early Phase 1
Age: 18Years - 75Years
All Genders
NCT06458010

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

Led by RenJi Hospital · Updated on 2025-04-30

20

Participants Needed

1

Research Sites

87 weeks

Total Duration

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AI-Summary

What this Trial Is About

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 lipoprotein levels. 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 .

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years - 75Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Male or female aged 18 to 75 years at consent
  • Diagnosed with familial hypercholesterolemia
  • Mutation in PCSK9 and/or ApoB and/or LDLR gene at screening
  • Weight at least 40 kg and BMI over 18 kg/m2 at screening
  • Meet specified laboratory criteria for blood counts, liver, kidney, coagulation, and triglycerides
  • On stable moderate or higher intensity statin therapy for at least 4 weeks with LDL-C levels meeting criteria
  • Use effective contraception during the study and for at least 6 months after main study
  • Voluntarily sign informed consent
Not Eligible

You will not qualify if you...

  • Use of prescription or non-prescription drugs affecting lipid metabolism other than statins within specified timeframes before study
  • Poorly controlled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg)
  • Poorly controlled diabetes (HbA1c >8.5%)
  • Allergy or adverse reactions to lipid nanoparticle-based drugs
  • Smoking more than 5 cigarettes per day or equivalent nicotine use within 3 months
  • Alcohol abuse or positive alcohol test within 3 months
  • NYHA class III-IV heart failure, low ejection fraction, or prolonged QTc interval
  • Poorly controlled severe arrhythmias within 3 months
  • Recent serious cardiovascular events or planned cardiac surgery during study
  • Uncontrollable diseases affecting lipid levels, except stable thyroid replacement therapy
  • Blood donation over 500 mL within 3 months
  • Unable or unwilling to follow treatment plan
  • Recent antithrombotic treatment within 14 days
  • History of bleeding or coagulation disorders
  • Expected survival less than 2 years
  • Known or suspected infections or planned antibiotics within 14 days
  • Positive for hepatitis B, hepatitis C, or HIV antibodies at screening
  • Recent organ or bone marrow transplantation or planned transplant during trial
  • History of malignant tumors within 5 years except certain cured cancers
  • History of drug abuse within 3 years
  • Pregnant or breastfeeding women
  • Other diseases interfering with trial participation
  • Severe mental illness not controlled by medication
  • Unwillingness to comply with study procedures
  • Other investigator-determined unsuitability for participation

AI-Screening

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Trial Site Locations

Total: 1 location

1

Deparment of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, China, 200127

Actively Recruiting

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How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

1

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