Hypercholesterolemia or mixed hyperlipidemia
Conditions
Interventions
Phase Ib YKYY015 injection group:Dosage Form: Injection
Strength: 0.5ml : 100mg (calculated as YKYY015)
Dosage and Administration: For phase Ib, participants shall be assigned to corresponding dosage
Phase Ib YKYY015 placebo group:Dosage Form: Injection
Strength: 0.5 mL : 0 mg (calculated as YKYY015)
Dosage and Administration: The ingredients include sodium chloride and water for injection. For ph
Phase IIa YKYY015 injection group:Based on the results of the phase Ib study, 1 - 2 target dosages will be selected for further exploration and evaluation of efficacy. Eligible participants will recei
Phase IIa YKYY015 placebo group:Based on the results of the phase Ib study, 1 - 2 target dosages will be selected for further exploration and evaluation of efficacy. Eligible participants will receive
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Individuals who voluntarily comply with the visitation schedule and requirements specified in the program and sign a written informed consent form. 2. At the time of signing the informed consent form, adults aged 18 to 65 years (inclusive of both endpoints) of any gender. 3. Participants with primary hypercholesterolemia or mixed dyslipidemia (applicable to phase Ib cohort 2 and phase IIa) who have undergone at least 4 weeks of low-fat dietary control prior to screening and have not received lipid-lowering drug therapy for at least 4 weeks before screening (applicable to phase Ib cohort 1) or have received stable-dose lipid-lowering drug therapy for at least 4 weeks with no change in the lipid-lowering drug regimen during the trial (applicable to phase Ib cohort 2 and phase IIa). 4. Body Mass Index (BMI) within the range of 19 to 35 kg/m² (inclusive of both endpoints). 5. Screening blood lipid requirements must simultaneously meet the following conditions: Fasting serum LDL-C >= 2.6 mmol/L (>= 100 mg/dL) and = 1 year).
Exclusion criteria
Exclusion criteria: 1. Any poorly controlled or severe disease that may cause secondary elevation of LDL-C or abnormal lipid levels, interfere with the interpretation of clinical study results, or place participants at significant risk. 2. Positive test results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), human immunodeficiency virus (HIV) antibody, or Treponema pallidum antibody. 3. Participants with alanine aminotransferase (ALT), total bilirubin (TBIL), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or gamma-glutamyl transpeptidase (GGT) levels exceeding 2 times the upper limit of normal (ULN). 4. Individuals with serum creatinine levels exceeding the upper limit of normal during screening. 5. Individuals with an International Normalized Ratio (INR) exceeding the normal range. 6. Participants with thyroid dysfunction, defined as thyroid-stimulating hormone (TSH) >8.5 mIU/L (hypothyroid participants may be considered for inclusion if they have undergone stable thyroid hormone replacement therapy for =28 days prior to the first administration of the investigational drug, achieved normal TSH levels, and agree to continue treatment with the original thyroid hormone replacement dosage during the study) (applicable to phase Ib cohort 2 and phase IIa). 7. Allergic to two or more drugs, or known to be allergic to the investigational drug or similar investigational drugs. 8. Individuals with intolerance to subcutaneous injections or those with relevant abdominal scarring (from surgery, burns, etc.) that impedes subcutaneous administration. 9. Use of PCSK9 inhibitors (including evolocumab injection, alescumab injection, etc.) within 28 days or 5 half-lives prior to the first dose of study drug (whichever is longer), or participation in another clinical study. 10. Use of siRNA-based drugs within 6 months prior to the first administration of the investigational drug, or use of Inclisiran Injection within the past year. 11. Use of any systemic steroids known to affect lipid metabolism or with clear weight-loss effects, fish oil >1000 mg/day, medications/health supplements containing red yeast rice (e.g., Lipid Control, Lipid Control Plus, etc.), or orlistat within 28 days prior to receiving the investigational drug. 12. Substance Abuse: History of substance abuse prior to signing the informed consent form, or positive drug screening results. 13. Alcohol abusers: Those with a weekly alcohol consumption exceeding 14 units (1 unit = 10 grams of alcohol) within one month prior to signing the informed consent form, or who are unable to abstain from alcohol during the trial period, or who test positive in the alcohol breath test. 14. Heavy smokers: Daily smoking volume >= 10 cigarettes within the 3 months preceding signing the informed consent form. 15. Donated blood or experienced blood loss exceeding 400 mL within 3 months prior to the first administration of the investigational drug. 16. Presence of New York Heart Association (NYHA) Class III–IV heart failure, unstable angina, symptomatic peripheral vascular disease, or severe arrhythmia within the past 12 months; or a history of myocardial infarction, ischemic stroke, intracerebral hemorrhage, or major cardiovascular/cerebrovascular procedures (including percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]). 17. SBP > 140 mmHg or DBP > 90 mmHg (applicable to Phase Ib Cohort 1) or uncontrolled hypertension despite dual antihypertensive therap
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage change in low - density lipoprotein cholesterol from baseline;Incidence and severity of adverse events;Incidence rate of laboratory test abnormalities;Electrocardiograms;Vital Signs (Blood Pressure, Pulse, Respiration, and Body Temperature);Physical examination; | — |
Secondary
| Measure | Time frame |
|---|---|
| Total cholesterol ;High-density lipoprotein cholesterol ;Non high-density lipoprotein cholesterol ;Very low-density lipoprotein ;Apolipoprotein B;Apolipoprotein A1;Triglycerides;Lipoprotein(a);Pharmacokinetic parameters;Proprotein convertase subtilisin / kexin 9 (PCSK9);Drug-resistant antibodies; | — |
Countries
China
Contacts
Public ContactZhang Shuyang / Han Xiaohong
Peking Union Medical College Hospital
Outcome results
None listed