SYH2053 monotherapy for Chinese adults with non‑familial high cholesterol or mixed hyperlipidemia

A Phase Ⅲ Randomized, Parallel-group, Placebo-controlled Trial to Assess the Efficacy, Safety of the SYH2053 Subcutaneous Injection as Monotherapy in Participants With Primary Hypercholesterolemia (Non-familial) or Mixed Dyslipidemia

This trial will test whether SYH2053 injections alone can safely lower LDL cholesterol in Chinese adults with non‑familial high cholesterol or mixed high lipids.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 760 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd. (Industry-sponsored)
• Locations: 2 sites (Beijing, Beijing Municipality and 1 other locations)
• Trial ID: NCT07421297 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional study will give participants either SYH2053 injection or a matching placebo as monotherapy to determine safety and effectiveness. The trial plans to enroll about 760 adults in China whose LDL‑C remains above guideline targets for their risk category and whose fasting triglycerides are under 500 mg/dL. Key exclusions include prior familial hypercholesterolemia and certain systemic or metabolic diseases such as Cushing's syndrome, nephrotic syndrome, myeloma, glycogen storage disease, systemic lupus erythematosus, and acute intermittent porphyria. Participants will be screened based on local laboratory results and must be able to communicate with investigators and complete study procedures at the study site.

Who should consider this trial

Good fit: Adults aged 18 or older in China with primary (non‑familial) hypercholesterolemia or mixed dyslipidemia whose fasting LDL‑C remains above guideline targets and with fasting triglycerides below 500 mg/dL are the intended participants.

Not a fit: People with confirmed familial hypercholesterolemia or with excluded conditions listed in the protocol (for example Cushing's syndrome, nephrotic syndrome, myeloma, glycogen storage disease, systemic lupus erythematosus, or acute intermittent porphyria) are not expected to be eligible or benefit from this trial.

Why it matters

Potential benefit: If successful, SYH2053 could provide a new injectable option to lower LDL cholesterol for patients who do not meet LDL targets on current therapies.

How similar studies have performed: While other classes of lipid‑lowering drugs have successfully lowered LDL‑C, SYH2053 is a newer agent and its efficacy and safety in this Phase 3 setting remain to be shown.

Eligibility criteria

Inclusion Criteria:

1. 、Age ≥18 years (inclusive);
2. 、Fasting serum low-density lipoprotein cholesterol (LDL-C) levels failing to meet the target criteria at screening and prior to randomization (based on local laboratory results). Any one of the following conditions satisfies the criterion(according to the 2023 Chinese Guidelines for Lipid Management):① Low risk: LDL-C ≥130 mg/dL（3.4 mmol/L）and LDL-C\<188 mg/dL（4.9 mmol/L）; ②Moderate risk: LDL-C ≥ 100 mg/dL (2.6 mmol/L) and LDL-C\<188 mg/dL（4.9 mmol/L）; 3、At screening (based on local laboratory results), Fasting serum Triglyceride (TG)\<500 mg/dL（5.6 mmol/L） 4、Participants are able to establish good communication with the investigator and complete the trial in accordance with the protocol.

Exclusion Criteria:

1. Prior diagnosis of familial hypercholesterolemia; or a history of the following diseases: Cushing's syndrome, nephrotic syndrome, myeloma, glycogen storage disease, systemic lupus erythematosus, acute intermittent porphyria, cirrhosis, severe biliary obstruction, or other diseases known to significantly cause dyslipidemia；
2. A documented history of established atherosclerotic cardiovascular disease (ASCVD), defined as a history of: acute coronary syndrome (myocardial infarction or unstable angina), chronic coronary syndrome, or prior coronary revascularization (e.g., PCI or CABG); ischemic stroke or transient ischemic attack (TIA); or significant peripheral artery disease (PAD). PAD includes conditions such as chronic limb-threatening ischemia, acute limb ischemia, or atherosclerotic disease in other major arteries (e.g., carotid, vertebral, subclavian, renal, or mesenteric arteries)；
3. Treatment with short-acting lipid-lowering therapies (e.g., statins, fibrates, bempedoic acid, ezetimibe, bile acid sequestrants, niacin, omega-3 fatty acids) or any preparation of unknown composition with lipid-lowering intent (including over-the-counter, traditional, or herbal medicines) within 90 days prior to screening; or treatment with PCSK9 monoclonal antibodies or oral PCSK9 inhibitors within the past 180 days before screening or treatment with inclisiran or any other RNA-based lipid-lowering therapy (e.g., siRNA, antisense oligonucleotide) within the past 2 years before screening;
4. History of malignancy within 5 years (excluding treated basal cell carcinoma of the skin), or presence of a suspected malignancy currently being evaluated by the investigator;
5. At screening, Systolic blood pressure (SBP) \> 160 mmHg or diastolic blood pressure (DBP) \> 100 mmHg（either in untreated patients or in those on stable medical therapy） ;
6. History of heart failure with NYHA Class III-IV within 180days before screening or prior to Randomization;
7. At screening, eGFR \< 30 mL/min/1.73 m²（as calculated by the CKD-EPI equation）;
8. At screening, Creatine Kinase (CK) \> 3 × ULN ;
9. At screening, Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × ULN or Total Bilirubin (TBIL), \> 1.5 × ULN （unless attributable to Gilbert's syndrome）;
10. At screening, prolonged QT/QTcF interval at Screening Period or prior to Randomization (QTcF \> 450 ms for males, \> 470 ms for females)
11. Positive result for any one of hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody, syphilis antibody, or Human Immunodeficiency Virus (HIV) antibody;
12. At screening, HbA1c \> 8.0% at screening Period or prior to Randomization; or Type 1 diabetes , gestational diabetes ;
13. History of drug abuse within 5 years, including the recurrent use of dependence-producing drugs or substances unrelated to medical purposes in large quantities, including addictive and habituating drugs that cause physical and psychological dependence;
14. History of alcohol abuse within 1 year (defined as consuming more than 14 units of alcohol per week \[1 unit = 360 mL of beer with 5% alcohol content, or 45 mL of spirits with 40% alcohol content, or 150 mL of wine with 12% alcohol content\]);
15. Participation in any other clinical trial involving the administration of an investigational drug within 3 months prior to Screening or within 5 half-lives of the other investigational drug (whichever is longer), or plans to participate in any other clinical trial during the study period;
16. Any condition that, in the Investigator's opinion, may interfere with the conduct of the study, including but not limited to: a. presence of any disease within 6 months prior to Screening through the study period that may interfere with study results; b. any other reason that would prevent the subject from completing the study or that makes them inappropriate for inclusion;

Where this trial is running

Beijing, Beijing Municipality and 1 other locations

• Affiliation: Peking University Third Hospital — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Affiliation: Peking University Third Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Clinical Trials Information Group officer

Conditions Non-familial Hypercholesterolemia and Mixed Hyperlipidemia