In vivo base editing gene therapy for heterozygous familial hypercholesterolemia: a phase 1 trial.
Ping Wan, Siyuan Tang, Dongni Lin...
https://pubmed.ncbi.nlm.nih.gov/41776075Actively Recruiting
Early Phase 1
Age: 18Years - 75Years
All Genders
ID06458010
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
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating YOLT-101, a drug given by injection, in patients with familial hypercholesterolemia to assess its safety and tolerability. This early phase trial aims to find the optimal biological dose (OBD) of YOLT-101, defined as the dose that reduces plasma PCSK9 protein levels by 60% to 95% from baseline by day 28 after administration. Additionally, the study will preliminarily examine how a single dose of YOLT-101 affects plasma lipid and lipoprotein levels. Participants receive a single intravenous injection of YOLT-101 at one of several doses: 0.2 mg/kg, 0.4 mg/kg, 0.6 mg/kg, 40 mg, or 50 mg. The study includes a screening period up to 42 days before treatment day (Day 1) and a safety follow-up lasting up to 52 weeks after the dose. When the OBD is identified, more participants may be added at that dose level for confirmation. Participants in the first dose group may choose to receive a second dose at the OBD level. After the main study, long-term follow-up will continue for up to 15 years as per gene therapy product guidelines. Throughout the study, participants will be monitored for safety through various assessments including laboratory tests and observation for adverse effects. Researchers will evaluate the safety of YOLT-101 through week 52 and study its pharmacokinetics and pharmacodynamics up to day 28 and week 52, respectively. This extensive follow-up aims to capture both short-term and long-term effects of the drug. The total participation may span over 15 years to ensure comprehensive evaluation.
CONDITIONS
Brief Title
Clinical Exploration Trial of YOLT-101 in the Treatment of Familial Hypercholesterolemia (FH)
Who Can Participate
Age: 18Years - 75Years
All Genders
Eligibility Criteria
You may qualify if you...
- Male or female aged 18 to 75 years at the time of signing informed consent
- Diagnosed with familial hypercholesterolemia
- Mutation present in PCSK9 and/or ApoB and/or LDLR gene at screening
- Weight of at least 40 kg and Body Mass Index (BMI) greater than 18 kg/m² at screening
- Meet laboratory criteria including: ANC ≥1.5×10⁹/L, Platelets ≥100×10⁹/L, Hemoglobin ≥90 g/dL; liver function tests AST, ALT, ALP <2.0×ULN, Total Bilirubin ≤1.5×ULN; renal function serum creatinine ≤1.5×ULN, GFR >60 mL/min/1.73m²; coagulation tests PT, APTT, INR <1.5×ULN; fasting triglycerides <5.6 mmol/L
- On stable moderate or higher intensity statin therapy for at least 4 weeks with LDL-C ≥2.6 mmol/L or ≥1.8 mmol/L if evidence of atherosclerosis
- Use effective contraception during the study and for at least 6 months after
- Voluntarily sign informed consent
You will not qualify if you...
- Use of prescription or non-prescription drugs affecting lipid metabolism other than statins within specified timeframes before study medication
- Poorly controlled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg)
- Poorly controlled diabetes (HbA1c >8.5%)
- Allergy or adverse reactions to lipid nanoparticle-based drug treatments
- Smoking more than 5 cigarettes per day or nicotine use in past 3 months
- History of alcohol abuse or positive alcohol breath test at screening
- NYHA class III-IV heart failure, low ejection fraction, or prolonged QTc interval
- Severe arrhythmias not well controlled by medication
- Recent serious cardiovascular events or surgeries within specified timeframes
- Uncontrollable diseases affecting lipid levels such as severe liver disease or thyroid dysfunction
- Blood donation over 500 mL within past 3 months
- Unable or unwilling to follow required medication plan
- Recent antithrombotic treatment within 14 days before enrollment
- History of bleeding or coagulation disorders
- Expected survival less than 2 years
- Known or suspected systemic infections or positive viral tests at screening
- Recent or planned organ or bone marrow transplantation
- History of malignant tumors within 5 years except certain cured skin or cervical cancers
- History of drug abuse within past 3 years
- Pregnant or breastfeeding women
- Other significant diseases or mental illnesses affecting participation
- Unwillingness to comply with study procedures
- Other investigator-determined unsuitable conditions for trial participation
AI-Screening
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Single administration with follow-up through Week 52
Participants receive a single intravenous dose of YOLT-101 as part of the treatment.
Approximately weekly visits through Week 52 for safety and pharmacodynamic assessments
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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