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

NCT06461702 | Recruiting Early Phase 1

• 1 other identifier: FH-YOLT-101-1
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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 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).

Conditions

Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• safety evaluation of YOLT-101

  The safety of YOLT-101 evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs)

  through week 52

Secondary Outcomes (6)

• pharmacokinetics of YOLT-101

  through Day 28

• pharmacodynamics

  through week 52

• pharmacodynamics

  through week 52

• pharmacokinetics of YOLT-101

  through Day 28

• pharmacokinetics of YOLT-101

  through Day 28

Study Arms (1)

YOLT-101

EXPERIMENTAL

Drug: YOLT-101

Interventions

YOLT-101 DRUG

The IP is administered intravenously at the predetermined dose.

YOLT-101

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women aged ≥ 18 years and ≤ 65 years (including boundary values) who signed informed consent.
• Meets the diagnostic criteria for familial hypercholesterolemia. When screening, there are mutations in the PCSK9 and/or ApoB and/or LDLR genes.
• \. When screening, the weight should be ≥ 40kg, and the body mass index (BMI) should be between 18-30 kg/m2 (including boundary values).
• \. During screening, subjects must meet the following laboratory standards: 5.1 Blood routine: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 100 × 109/L, hemoglobin count (HGB) ≥ 90 g/dL; 5.2 Liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) \< 2.0 × ULN, total bilirubin (TBIL) ≤ 1.5 × ULN; 5.3 Renal function: Serum creatinine (Cr) ≤ 1.5 × ULN, and glomerular filtration rate (GFR)\>60mL/min \* 1.73m2; 5.4 Coagulation function: prothrombin time (PT), activated partial thromboplastin time (APTT), international standardized ratio (INR)\<1.5 x ULN; 5.5 Low density lipoprotein cholesterol (LDL-C) ≥ 4.21mmol/L, and fasting triglycerides\<5.6mmol/L.
• \. The subjects and their partners must take effective contraceptive measures during the participation in this study until 6 months after the end of the main study.
• \. The subject must agree not to accept other lipid-lowering drugs for at least 28 days after receiving the investigational drug.
• \. Voluntarily sign informed consent.

You may not qualify if:

• Those who have used any prescription drugs that affect blood lipid metabolism within at least 14 days before receiving the study drug (or within 7 half lives of the drug, whichever is longer, applicable to small molecule/small nuclear acid drugs) or within 3 months (applicable to biological agents such as PCSK9 inhibitors), or who have used any over-the-counter drugs that affect blood lipid metabolism within at least 14 days before receiving the study drug (such as Chinese medicine/traditional Chinese patent medicines and simple preparations, vitamins, fish oil (\>1000mg/day), drugs containing red koji rice or health products, etc.), (Exception of those who have received stable non-cyclical hormone replacement therapy for more than 8 weeks and agree not to change the hormone treatment more than 28 days after the study drug administration); individuals who have participated in clinical studies of other lipid-lowering drugs and have accepted the investigational drugs within 6 months before the screening period.
• Poorly controlled hypertensive patients who have receive conventional treatments (systolic blood pressure (SBP) ≥ 160mmHg and/or diastolic blood pressure (DBP) ≥ 100mmHg).
• Poorly controlled diabetes patients (glycosylated hemoglobin\>8.5%).
• Individuals who are allergic to drugs or mRNA vaccine components contained in lipid nanoparticles (LNPs), or have experienced adverse reactions to LNP drug therapy, such as:
• After receiving LNP drug treatment, ALT or AST\>3.0 × ULN; 4.2 After receiving LNP drug treatment, INR\>1.5 or APTT/d-dimer\>1.5 × ULN; 4.3 Any infusion response that requires clinical intervention, slows down infusion rate, or stops LNP drugs treatment; 4.4 Any other adverse reactions that researchers believe are related to the treatment of LNP drugs.
• Within three months before the screening, individuals who smoke more than 5 cigarettes per day or consume an equal amount of nicotine or nicotine substitutes.
• Individuals with a history of alcohol abuse \[consuming more than 14 units of alcohol per week (1 unit ≈ 360mL of beer or 45mL of 40% liquor or 150mL of wine)\] within 3 months before the screening; Individuals positive for alcohol breath test during the screening or admission.
• Grade III-IV heart failure defined by the New York Heart Association (NYHA), or left ventricular ejection fraction\<50%, or prolonged QTc interval (\>470ms in females and\>450ms in males) found during the screening.
• Suffering poorly controlled severe arrhythmia , such as recurrent and highly symptomatic ventricular tachycardia with poorly drug controlled, atrial fibrillation with rapid ventricular reaction, or supraventricular tachycardia within three months before the screening.
• Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass grafting, severe deep vein thrombosis or pulmonary embolism within three months before the screening; Cerebrovascular accidents occurring within 6 months before the screening or planning for cardiac surgery or revascularization during the main study period.
• Suffering from diseases that have a significant impact on blood lipid levels and cannot be controlled, such as nephrotic syndrome, severe liver disease, Cushing's syndrome, thyroid dysfunction, etc. (Individuals with hypothyroidism who have undergone stable thyroid replacement therapy for ≥ 28 days before screening, have normal TSH testing, and agree to maintain the dose of thyroid replacement drugs unchanged during the study can be considered to be enrolled).
• Individuals who have donated more than 500 mL of blood within three months before screening.
• Those who are unable or unwilling to accept the medication treatment required before the investigational treatment.
• Patients who underwent antithrombotic treatment (such as warfarin, dabigatran, and apixaban) within 14 days prior to enrollment.
• Those who are prone to bleeding or have a history of coagulation disorders (such as cirrhosis, malignant hematological diseases, antiphospholipid antibody syndrome);

Sponsors & Collaborators

• The First Affiliated Hospital of Bengbu Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, 233004, China

RECRUITING

MeSH Terms

Conditions

Hyperlipoproteinemia Type II

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Wang Hongju

CONTACT

13955231336; 1649134019@qq.com

Zhou Huan

CONTACT

13665527160; zhouhuanbest@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2024
• First Posted: June 17, 2024
• Study Start: April 1, 2024
• Primary Completion: August 1, 2025
• Study Completion: December 1, 2025
• Last Updated: June 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)