A Single Dose Escalation Study of PCSK9 Inhibitor (JS002) in Health Subjects
A Single Dose Escalation Study of PCSK9 Inhibitor (JS002) in Health Subjects
JS002 is a recombinant humanized Anti- PCSK9 monoclonal antibody; This is a phase Ia,
 randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability,
 pharmacokinetics, and pharmacodynamics of a single subcutaneous injection of JS002 in healthy
 subjects.

 In this study, the dose ascending design includes five dose level cohorts (15 mg, 50 mg, 150
 mg, 300 mg, and 450 mg) administered by subcutaneous injection, and three intravenous
 administration cohorts (15 mg, 150 mg, and 450 mg). Each cohort will enroll 8 to 12 subjects
 (distribution of study drug and placebo in a 3:1 ratio).

 The duration of the study is 84-day per subjects.
Inclusion Criteria:

 1. Healthy men or women aged 18 to 45 years old at screening visit;

 2. Have the ability to read and understand, volunteer to participate in the study, and
 signed written informed consent.

 3. The body mass index (BMI) at screening visit was in the range of 18 to 30 kg/m2
 (inclusive) and the body weight ≥ 50 kg.

 4. The sitting blood pressure ≥90/60 mmHg and <140/90 mmHg at screening visit.

 5. Serum LDL-C level ≥ 70 mg/dL (1.8 mmol/L) and < 190 mg/dL (4.9 mmol/L) at screening
 visit.

 6. Serum Triglyceride (TG) level < 250 mg/dL (2.8 mmol/L) at screening visit.

 7. No fertility [female: documented hysterectomy, bilateral oophorectomy, tubal ligation
 or other female permanent sterilization, or menopause (menopause for more than one
 year)], or those with fertility are willing to take, during the entire study period,
 strict and effective contraceptive measures, in addition, female subjects with
 fertility should have a negative blood/urine pregnancy test at screening visit.

 Exclusion Criteria:

 1. Subjects who meet any of the following criteria will be excluded from the study:

 2. Evolocumab and/or Alirocumab, or other targeted drugs to PCSK9, has been used at any
 time.

 3. Any therapeutic or research biological agents has been used during the first 6 months
 of baseline/random (Day 0).

 4. Participated in any clinical study within 3 months prior to baseline/random (Day 0).

 5. Any drug or health supplement that affects blood lipids or lipid metabolism during the
 first 30 days of baseline/random (Day 0), including but not limited to: Probucol,
 statins (e.g. Atorvastatin, Rosuvastatin, etc.), cholesterol absorption inhibitors
 (such as Ezetimibe), bile acid sequestrants (such as Cholestyramine), red yeast and
 hawthorn preparations, fibrates, high-purity fish oil preparations (or omega-fatty
 acids ≥ 1000 mg / day) and niacin preparation (nicotinic acid ≥ 50 mg), etc.

 6. Start a new intense exercise or diet control within 30 days of random (Day 0) or major
 changes to previous diet and lifestyle (including exercise, smoking and drinking). The
 following conditions occur before the baseline/random (Day 0) 1 day (ie Day-1) need to
 be excluded:

 -  Creatine kinase (CK) ≥ 3 times the upper limit of normal (ULN) (Note: related to
 exercise), or

 -  Urinary cotinine is positive, or

 -  Positive alcohol saliva test.

 7. Previous or concomitant diseases (such as nephrotic syndrome, liver disease, diabetes,
 hypothyroidism, etc.) or any clinically significant abnormalities found in physical
 examinations, laboratory tests, and electrocardiograms, which would make the subject
 unsuitable for this study.

 8. The medical history or clinical evidence indicates that the subject had severe acute
 or chronic disease (including not limited to: heart, kidney, nerves, endocrine, blood,
 immunity, infection, metabolic disorders, etc.), and the disease has not been
 controlled, which may confuse the outcome of the study or put the subject at risk
 judged by the investigator, The following situations need to be excluded:

 -  had major surgery in the last 6 months, or

 -  has been hospitalized (e.g. infection) in the last 3 months, or

 -  donated blood or blood loss ≥500 mL in the past 3 months, or

 -  has used any prescription or over-the-counter drugs in the past 1 month.

 9. Transplantation History of organs (such as heart, lung, liver, kidney, etc.) Malignant
 tumors history, except for cervical carcinoma in situ or surgically resected skin
 cancer (basal cells and squamous epithelial cells) for more than 5 years.

 10. Drug abuse or alcohol dependence in the past 1 year.

 11. HIV infection, or HIV antibody positive at screening visit.

 12. Syphilis infection, or serotonin antibody (TPPA) positive at screening visit.

 13. Hepatitis B surface antigen (HBsAg) was positive at screening visit.

 14. Hepatitis C virus (HCV) antibody was positive at screening visit.

 15. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2 times the
 upper limit of normal (ULN); alkaline phosphatase and bilirubin ≥ 1.5 times the upper
 limit of normal (ULN).

 16. Allergy history to mammalian-derived biological agents, including monoclonal
 antibodies.

 17. Women during pregnancy and lactation.

 18. Any other investigator believes that the subject is not suitable for the study, such
 as the subject has potential compliance issues, cannot complete all tests and
 assessments according to the protocol requirements.