Hyperlipoproteinemia(a)
Conditions
Interventions
YKYY032 injection group:Dosage Form: Injection
Strength: 0.5ml : 100mg (calculated as YKYY032)
Dosage and Administration: Participants shall be assigned to corresponding dosage groups (A1-A6 )and rece
YKYY032 placebo group:Dosage Form: Injection
Strength: 0.5ml : 0mg (calculated as YKYY032)
Dosage and Administration: Participant shall be assigned to corresponding dosage groups (A1-A6) and receive a
Sponsors
Peking University First Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Inclusion criteria
Inclusion criteria: 1. The participant voluntarily signs an Informed Consent Form (ICF) prior to any study-related procedures. 2. Between 18-60 years of age, inclusive, including male and female. 3. Lp(a) >=75 nmol/L or >= 30 mg/dL at screening and baseline. 4. Body mass index (BMI) of 19 to 28 kg/m2 inclusive and body weight not less than 50 kg for male, no lesse than 45kg for female. 5. Fertile men and women are willing to use effective contraception from the time of signing the ICF until 12 months after receiving YKYY032, including abstinence, condoms, intrauterine devices, etc. Reproductive-age female participants have a negative serum pregnancy test result at screening and baseline. 6. Participants are able to communicate effectively with the investigators and understand and comply with the requirements of this trial.
Exclusion criteria
Exclusion criteria: 1. A history of past or existing metabolic diseases, central nervous system, cardiovascular system, respiratory system, digestive system (liver, kidneys, gastrointestinal tract), urinary system, endocrine system, musculoskeletal system, hematologic system, immune system, psychiatric disorders, peripheral nerves, muscular system diseases, or other chronic diseases (excluding mild fatty liver) or serious diseases that may confound study results or affect participant safety; 2. A history of malignant tumors within the past 5 years (excluding cured basal cell carcinoma of the skin and carcinoma in situ of the cervix), or currently being evaluated for potential malignant tumors; 3. Any history or evidence of active bleeding or coagulation disorders; 4. A history of intolerance to subcutaneous injections or significant abdominal scarring that may significantly affect the administration of the investigational drug or the evaluation of local safety; 5. Individuals with known severe allergies, non-allergic drug reactions, or multiple drug/non-drug allergies (atopic constitution), or with a known history of clinically significant hypersensitivity, intolerance, or allergy to N-acetylgalactosamine (GalNAc) or oligonucleotide drugs; 6. Those who test positive for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), syphilis treponemal antibody (TP-Ab), or human immunodeficiency virus antibody (HIV-Ab); 7. Individuals who have had severe infections within the three months prior to screening, including but not limited to severe pneumonia, lung abscess, meningitis, cellulitis, etc., and who are deemed by the investigator as unsuitable to participate in this trial. Abnormalities in laboratory and auxiliary examinations: 8. Participants who show abnormalities in physical examination, vital signs, laboratory tests (excluding Lp(a)), or other auxiliary examinations during screening or baseline, and are deemed clinically significant by the investigator, or whose participation in the study may pose unacceptable risks, should be excluded if they meet the following laboratory criteria: (1) Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >1.5 times the upper limit of normal (ULN); (2) Total bilirubin >1.5 × ULN; (3) Serum creatinine > ULN; (4) Fasting triglycerides (TG) >=500 mg/dL (5.6 mmol/L); (5) Low-Density Lipoprotein Cholesterol (LDL-C) >=4.1 mmol/L; (6) QTcF interval >=450 msec (male) or >=470 msec (female); (7) In-office blood pressure: seated systolic BP >=140 mmHg, seated diastolic BP >=90 mmHg; (8) Fasting blood glucose >=7.0 mmol/L (126 mg/dl) or glycated hemoglobin (HbA1c) >=6.5%; Medication Treatment Status: 9. Received small interfering RNA (siRNA) treatment or participated in a clinical trial and used the investigational drug within 12 months prior to screening, or participated in antisense oligonucleotides (ASOs) treatment or clinical trial and used the investigational drug within 6 months prior to screening; 10. Participated in any other clinical trial and used the investigational drug within 3 months prior to screening; 11. Received any treatment targeting Lp(a) or any medication or therapy that significantly affects Lp(a) levels within 6 months prior to screening (including but not limited to statins, PCSK9 inhibitors, prescription-dose niacin, fibrates, or estrogen/estrogen receptor modulators); 12. Used any prescription drugs, over-the-counter drugs, vitamins, supplements, and/or herbal products w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Adverse Events;Incidence of Serious Adverse Events;Adverse Events of Special Interest (injection site reactions; hypersensitivity reactions; liver-related Treatment Emergent Adverse Events: liver function abnormalities consistent with Hy's law);Vital signs (pulse rate, blood pressure, body temperature, respiratory rate);Physical examination;12-lead Electrocardiogram;Clinical laboratory tests (complete blood count, blood biochemistry, urinalysis, and coagulation function); | — |
Secondary
| Measure | Time frame |
|---|---|
| Plasma PK parameters;Urine PK parameters;Lipoprotein(a), Low-Density Lipoprotein Cholesterol, High-Density Lipoprotein Cholesterol, non-High-Density Lipoprotein Cholesterol, Total Cholesterol, Triglycerides, Apolipoprotein B,Oxidized Phospholipids-Apolipoprotein B (OxPL-ApoB), and Oxidized Phospholipids-Apolipoprotein A (OxPL-ApoA);Incidence of Anti-Drug Antibody(ADA)and Neutralizing Antibody(NAb);Corrected QT Interval(c-QTc)assessment;High-Sensitivity C-Reactive Protein,Plasminogen; | — |
Countries
China
Contacts
Public ContactLi Jianping/Zhou Ying
Peking University First Hospital
Outcome results
None listed