A Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SYH2053

A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SYH2053 in Subjects With Normal or Elevated Low-Density Lipoprotein Cholesterol

This is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) study of SYH2053 when administered subcutaneously to subjects with normal and elevated LDL-C.

Study Overview

• Status: Completed
• Conditions: Hyperlipemia
• Intervention / Treatment: Drug: Placebo; Drug: SYH2053

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • 10 Chedaogou Rd.,Haidian District, Beijing, China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Subjects must give informed consent before the trial, fully understand the content, procedures and possible adverse reactions, and voluntarily sign a written informed consent.
2. Sex: male or female subjects.
3. Age of 18 - 60 years (inclusive).
4. BMI: 18.6-28.5 kg/m^2 (inclusive), with a minimum weight of 50 kg (inclusive) for male and 45 kg (inclusive) for female.
5. During screening and baseline, LDL-C ≥100 mg/dL (2.6 mmol/L) and < 190 mg/dL (4.9 mmol/L); TG ≤ 400 mg/dL (4.5 mmol/L); TC < 278 mg/dL (7.2 mmol/L) in serum under fasting state;
6. Subjects have no history of chronic or serious diseases or family history of early-onset coronary heart disease, including cardiovascular, liver, kidney, blood and lymphatic, endocrine, immune, psychiatric, neurological, and gastrointestinal systems, and are generally in good health.
7. The subjects can communicate well with the investigators and complete the trial according to the protocol.

Exclusion Criteria:

1. Allergic constitution or known history of allergy to the components of the study drug or similar drugs.
2. Antibody drugs targeting PCSK9 have been used within 6 months prior to screening, oligonucleotides targeting PCSK9 have been used within 12 months prior to screening.
3. There are currently medical disorders of clinical significance, including but not limited to, circulatory, hematological or hematopoietic diseases, respiratory, endocrine, urinary, digestive, neurological or psychiatric disorders, infections, tumors, severe trauma, or any other diseases that the investigator considers to be excluded or likely to interfere with the interpretation of the findings.
4. Those who underwent major surgery within 6 months prior to initial administration, or who planned to undergo surgery during the study.
5. Clinically significant abnormalities in vital signs, physical examination, electrocardiogram and laboratory examination.
6. The estimated glomerular filtration rate (eGFR) during screening was < 90 mL/min/1.73 m^2 (calculated by simplified MDRD formula).
7. During screening, any item of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), γ-glutamyltransferase (GGT), alkaline phosphatase (ALP) > 1.5×ULN (retest once within 1 week allowed).
8. During screening or baseline, subjects with prolonged QT/QTc interval (QTcF > 450 ms in male, > 470 ms in female).
9. Subjects with non-negative test for any of HBsAg, HCV antibodies, syphilis antibodies, and HIV antibodies.
10. Blood loss or blood donation of more than 200 mL within 3 months prior to administration (except for female menstrual period), and/or platelet donation within 2 weeks prior to administration.
11. Use of any drug, supplement, vitamin or dietary supplement known to affect lipid metabolism within 28 days prior to administration; use of any drug for therapeutic purposes (except topical drugs with local effects) within 14 days prior to administration or within the 7 half-lives of the drug (whichever is longer).
12. A history of drug abuse, and/or drug use within 3 months prior to screening, and/or habitual use of any psychotropic drug, including Chinese herbs.
13. Positive urine drug screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo SAD group; Subjects in SAD placebo groups will receive a single subcutaneous injection of placebo on Day 1.	Drug: Placebo; subcutaneous injection
Experimental: SYH2053 SAD experimental group; Subjects in SAD experimental groups will receive a single subcutaneous injection of SYH2053 on Day 1.	Drug: SYH2053; subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0	The investigator will make an assessment of intensity for each AE and SAE reported during the study according to CTCAE V5.0	Pre-dose and multiple timepoints no less than 57 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The serum LDL-C level after dosing SYH2053	measure the LDL-C level in blood by lab examination and evaluate the effect of SYH2053 on LDL-C Level	Pre-dose and multiple timepoints no less than 57 days
The serum PCSK9 level after dosing SYH2053	measure the PCSK9 level in blood by lab examination and evaluate the effect of SYH2053 on PCSK9 Level	Pre-dose and multiple timepoints no less than 57 days
PK parameters (Cmax)	maximum peak observed plasma SYH2053 concentration in treated subjects	Pre-dose and multiple timepoints up to 4 days
PK parameters (Tmax)	time to reach maximum peak plasma SYH2053 concentration in treated subjects	Pre-dose and multiple timepoints up to 4 days
PK parameters (AUC)	area under the plasma concentration-time curve in SYH2053 treated subjects	Pre-dose and multiple timepoints up to 4 days
PK parameters (T1/2)	the elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve in SYH2053 treated subjects	Pre-dose and multiple timepoints up to 4 days
Immunogenicity of SYH2053	Rate of formation of anti-drug antibodies to SYH2053	Pre-dose and multiple timepoints up to 57 days
The serum TC level after dosing SYH2053	measure the TC level in blood by lab examination and evaluate the effect of SYH2053 on TC Level	Pre-dose and multiple timepoints no less than 57 days
The serum TG level after dosing SYH2053	measure the TG level in blood by lab examination and evaluate the effect of SYH2053 on TG Level	Pre-dose and multiple timepoints no less than 57 days
The serum HDL-C level after dosing SYH2053	measure the HDL-C level in blood by lab examination and evaluate the effect of SYH2053 on HDL-C Level	Pre-dose and multiple timepoints no less than 57 days
The serum Lp(a) level after dosing SYH2053	measure the Lp(a) level in blood by lab examination and evaluate the effect of SYH2053 on Lp(a) Level	Pre-dose and multiple timepoints no less than 57 days
The serum VLDL-C level after dosing SYH2053	measure the VLDL-C level in blood by lab examination and evaluate the effect of SYH2053 on VLDL-C Level	Pre-dose and multiple timepoints no less than 57 days
The serum non-HDL-C level after dosing SYH2053	measure the non-HDL-C level in blood by lab examination and evaluate the effect of SYH2053 on non-HDL-C Level	Pre-dose and multiple timepoints no less than 57 days
The serum ApoA1 level after dosing SYH2053	measure the ApoA1 level in blood by lab examination and evaluate the effect of SYH2053 on ApoA1 Level	Pre-dose and multiple timepoints no less than 57 days
The serum ApoB level after dosing SYH2053	measure the ApoB level in blood by lab examination and evaluate the effect of SYH2053 on ApoB Level	Pre-dose and multiple timepoints no less than 57 days
The serum hsCRP level after dosing SYH2053	measure the hsCRP level in blood by lab examination and evaluate the effect of SYH2053 on hsCRP Level	Pre-dose and multiple timepoints no less than 57 days

Collaborators and Investigators

• Sponsor: CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
• Investigators: Principal Investigator: Dongyang Liu, Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2024
• Primary Completion (Actual): December 23, 2024
• Study Completion (Actual): March 25, 2025

Study Registration Dates

• First Submitted: December 20, 2023
• First Submitted That Met QC Criteria: January 19, 2024
• First Posted (Actual): January 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: April 2, 2025
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Dyslipidemias; Lipid Metabolism Disorders; Hyperlipidemias
• Other Study ID Numbers: SYH2053-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No