Study of VSA001 Injection in Chinese Healthy Adult Volunteers

Study Overview
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Brief Summary
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This is a phase 1, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics effects of a single dose of VSA001 injection in Chinese healthy adult volunteers. Eligible enrolled participants will initially receive VSA001 injection at the assigned dose level.

Official Title
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A Phase 1 Clinical Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Effects of a Single Dose of VSA001 Injection in Chinese Healthy Adult Volunteers

Conditions
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Healthy Adult Volunteers

Intervention / Treatment
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* Drug: VSA001 injection
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subjects voluntarily participate in this study who are able to read, understand, and sign the ICF before participation; and have a full understanding of the content, process and possible adverse reactions of the study and are able to complete the study in accordance with the requirements of the protocol. Healthy male and female subjects aged between 18 and 55 years (both inclusive) at the time of informed consent. Body mass index (BMI) = weight (kg)/height (m)2, within the range of 19.0-30.0 kg/m2 (both inclusive), and body weight no less than 50 kg. In good general health and without clinically significant abnormalities as judged by the investigator, based on medical history, physical examination, vital signs, 12-lead ECG, and laboratory results. Negative serum pregnancy test within 72 h prior to initiation of study treatment in all premenopausal females and females who have been amenorrheic for less than 12 months. (Serum pregnancy test is not required for females who have undergone surgical sterilization, such as hysterectomy and/or bilateral oophorectomy, or those who have not experienced menses for 12 consecutive months and are judged to be postmenopausal based on factors such as age and castration therapy). Subjects and their partners must agree to use adequate contraceptive methods prior to initiation of study treatment, during the study, and for at least 3 months after discontinuation of study treatment. Fasting serum TGs >80 mg/dL (>0.903 mmol/L) at screening. Exclusion Criteria: History or presence of significant or clinically significant diseases/abnormality, including but not limited to cardiac/cardiovascular, respiratory, endocrine, gastrointestinal, renal, hepatic, gallbladder, dermatological, hematological, immunological, neurologic, or psychiatric diseases/abnormality, or the disease that, in the judgement of the investigator, present a safety concern or affects the pharmacokinetic evaluation. A family history of congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death. Subjects who are with acute exacerbation of any significant acute or chronic disease as judged by the investigator. AST and ALT >2×upper limit of normal (ULN) , or total bilirubin >ULN at screening. Serum creatinine estimated eGFR < 60 ml/min/1.73 m2 per MDRD formula. Cardiac troponin (troponin I) above ULN at Screening. Fasting serum TGs >300 mg/dL (>3.38 mmol/L) at screening. Presence of other conditions or treatments that may affect the study results and interfere with the subject's participation in the study as assessed by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VSA001 injection<br>A single dose of active drug (VSA001, low or high dose) will be administered by subcutaneous injection on Day 1. | Drug: VSA001 injection<br>* The active drug is VSA001 injection. The active pharmaceutical ingredient (API) contained in VSA001 is a synthetic, double-stranded, hepatocyte targeted NAG-conjugated RNAi.<br>|
| Placebo Comparator: Placebo<br>The placebo is normal saline (0.9%) administered subcutaneously; volume matched to the corresponding VSA001 dose volume. | Drug: Placebo<br>* 0.9% Saline, volume matched<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Incidence, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs), and the relationship with VSA-01001. Clinically significant abnormalities in laboratory tests, vital signs, physical examination, 12-lead electrocardiograms (ECG). | 85 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics parameter: Cmax | Maximum plasma concentration (Cmax) | 48 hours | 
| Pharmacokinetics parameter: Tmax | Time to maximum plasma concentration (Tmax) | 48 hours | 
| Pharmacokinetics parameter: AUC0-t | Area under the plasma concentration-time curve from the time 0 to the last quantifiable time point (AUC0-t). | 48 hours | 
| Pharmacokinetics parameter: t1/2 | Half-life (t1/2). | 48 hours | 
| Pharmacokinetics parameter: CL/F | Apparent clearance (CL/F). | 48 hours | 
| Pharmacokinetics parameter: Vz/F | Apparent volume of distribution (Vz/F). | 48 hours | 
| Pharmacodynamic (PD) parameters | Change from baseline over time in fasting serum APOC3 and triglycerides (TGs). | 85 days |