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

Hyperlipemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06229548
• Other study ID #: SYH2053-001
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: January 26, 2024
• Est. completion date: December 30, 2024

Study information

• Verified date: December 2023
• Source: CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
• Contact: Clinical Trials Information Group officer
• Phone: +86-0311-69085587
• Email: ctr-contact[@]cspc.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 39
• Est. completion date: December 30, 2024
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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), ?-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.

Related Conditions & MeSH terms

• Hyperlipemia
• Hyperlipidemias

Intervention

Drug:
• SYH2053
subcutaneous injection
• Placebo
subcutaneous injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	PK parameters (Cmax)	maximum peak observed plasma SYH2053 concentration in treated subjects	Pre-dose and multiple timepoints up to 4 days
Secondary	PK parameters (Tmax)	time to reach maximum peak plasma SYH2053 concentration in treated subjects	Pre-dose and multiple timepoints up to 4 days
Secondary	PK parameters (AUC)	area under the plasma concentration-time curve in SYH2053 treated subjects	Pre-dose and multiple timepoints up to 4 days
Secondary	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
Secondary	Immunogenicity of SYH2053	Rate of formation of anti-drug antibodies to SYH2053	Pre-dose and multiple timepoints up to 57 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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