A Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of JS401

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetcs and pharmacodynamics of single-dose of JS401 in healthy volunteers with normal or mildly elevated triglycerides.

Official Title
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A Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Kinetic Effects in Healthy Volunteers With Normal or Mildly Elevated Triglycerides

Conditions
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Hyperlipidemia

Intervention / Treatment
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* Drug: JS401
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects aged 18 60 (inclusive) at the time of signing the ICF, with no less than 1/3 of either gender; Fasting TG≥1.1mmol/L (100 mg/dL) and ≤ 5.0mmol/L (450mg/dL) at screening; (3) Fasting LDL-C at screening> 1.8 mmol/L (70 mg/dL). Exclusion Criteria: Have a medical history or clinical evidence that the subject has obvious concomitant diseases (including but not limited to: cardiovascular, respiratory, digestive, urinary, neurological, blood, immunological, endocrine and metabolic, infection, etc.), or any clinically significant abnormalities found in physical examination, laboratory examination, and ECG examination, which are judged by the investigator to not meet the standards of clinical health or are not suitable for participating in clinical trials; Acute or chronic infection requiring hospitalization or undergoing systemic parenteral therapy (antiviral/bacterial/fungal/parasitic, etc.) within 60 days prior to randomization; Positive for syphilis antibodies, or positive for human immunodeficiency virus (HIV) antibodies, or positive for hepatitis C virus (HCV) antibodies, or positive for hepatitis B virus surface antigen (HBsAg) at screening; History of substance abuse within 12 months prior to screening, or positive urine drug screening at screening; History of alcohol dependence within 6 months prior to screening, or positive breath test for alcohol at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: JS401 injection<br> | Drug: JS401<br>* Single dose of JS401 by subcutaneous (sc) injections<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Calculated volume to match active treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) | Number of Participants with Adverse Events (AEs) | Up to 112 days post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | Peak Plasma Concentration of JS401 | Up to 48 hours post-dose | 
| Time to Maximum Plasma Concentration (Tmax) | Time to Maximum Plasma Concentration of JS401 | Up to 48 hours post-dose | 
| Terminal Elimination Half-Life (t1/2) | Terminal Elimination Half-Life (t1/2) of JS401 | Up to 48 hours post-dose | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) | Area Under the Plasma Concentration Versus Time Curve of JS401 | Up to 48 hours post-dose | 
| Angiopoietin-like 3 (ANGPTL3) | Reduction in Fasting Serum ANGPTL3 from Pre-Dose Baseline | Up to 112 days post-dose | 
| Triglycerides | Reduction in Fasting Serum LDL-C from Pre-Dose Baseline | Up to 112 days post-dose | 
| immunogenic characteristics ADA of JS401 | The number and percentage of subjects who were positive for anti-JS401 anti-drug antibody (ADA) after administration of JS401 injection were counted, and the titer of ADA-positive samples was analyzed. | Up to 112 days post-dose | 
| Low-density lipoprotein cholesterol (LDL-C) | Reduction in Fasting Serum LDL-C from Pre-Dose Baseline | Up to 112 days post-dose | 
| Non-high-density lipoprotein cholesterol (non-HDL-C) | Reduction in Fasting Serum non-HDL-C from Pre-Dose Baseline | Up to 112 days post-dose | 
| Very low-density lipoprotein cholesterol (VLDL-C) | Reduction in Fasting Serum VLDL-C from Pre-Dose Baseline | Up to 112 days post-dose | 
| High-density lipoprotein cholesterol (HDL-C) | Reduction in Fasting SerumHDL-C from Pre-Dose Baseline | Up to 112 days post-dose | 
| Lipoprotein (a) (Lp(a)) | Reduction in Fasting Lp(a) from Pre-Dose Baseline | Up to 112 days post-dose | 
| Apolipoprotein B (ApoB) | Reduction in Fasting ApoB from Pre-Dose Baseline | Up to 112 days post-dose | 
| Apolipoprotein A1 (ApoA1) | Reduction in Fasting ApoA1 from Pre-Dose Baseline | Up to 112 days post-dose | 
| Q-T interval | Change in QTc from baseline | Up to 112 days post-dose |