Clinical trial NCT06229548: A Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SYH2053
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hyperlipemia
Lead sponsor: CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-01-29
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: The Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0
timeFrame: Pre-dose and multiple timepoints no less than 57 days
Secondary outcomes:
measure: The serum LDL-C level after dosing SYH2053
timeFrame: Pre-dose and multiple timepoints no less than 57 days
measure: The serum PCSK9 level after dosing SYH2053
timeFrame: Pre-dose and multiple timepoints no less than 57 days
measure: PK parameters (Cmax)
timeFrame: Pre-dose and multiple timepoints up to 4 days
measure: PK parameters (Tmax)
timeFrame: Pre-dose and multiple timepoints up to 4 days
measure: PK parameters (AUC)
timeFrame: Pre-dose and multiple timepoints up to 4 days
measure: PK parameters (T1/2)
timeFrame: Pre-dose and multiple timepoints up to 4 days
measure: Immunogenicity of SYH2053
timeFrame: Pre-dose and multiple timepoints up to 57 days
measure: The serum TC level after dosing SYH2053
timeFrame: Pre-dose and multiple timepoints no less than 57 days
measure: The serum TG level after dosing SYH2053
timeFrame: Pre-dose and multiple timepoints no less than 57 days
measure: The serum HDL-C level after dosing SYH2053
timeFrame: Pre-dose and multiple timepoints no less than 57 days
measure: The serum Lp(a) level after dosing SYH2053
timeFrame: Pre-dose and multiple timepoints no less than 57 days
measure: The serum VLDL-C level after dosing SYH2053
timeFrame: Pre-dose and multiple timepoints no less than 57 days
measure: The serum non-HDL-C level after dosing SYH2053
timeFrame: Pre-dose and multiple timepoints no less than 57 days
measure: The serum ApoA1 level after dosing SYH2053
timeFrame: Pre-dose and multiple timepoints no less than 57 days
measure: The serum ApoB level after dosing SYH2053
timeFrame: Pre-dose and multiple timepoints no less than 57 days
measure: The serum hsCRP level after dosing SYH2053
timeFrame: Pre-dose and multiple timepoints no less than 57 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: 10 Chedaogou Rd.,Haidian District, Beijing, China
state: Beijing
Study officials:
References: