A Study to Evaluate the Safety, Efficacy of SYH2053 in Chinese Participants With Non-familial Hypercholesterolemia and Mixed Hyperlipidemia on a Background of Lipid-lowering Therapy

Official title

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

Overview

The purpose of this study is to compare the effectiveness, safety of SYH2053 in participants with primary hypercholesterolemia (non-familial) or mixed dyslipidemia on a background of lipid-lowering therapy. This trial plans to enroll 900 Participants.

Interventions

• Drug SYH2053/placebo injection
  Participants receive SYH2053/placebo injection by subcutaneous administration.

Primary outcome measures

• Percentage change in LDL-C relative to baseline [Time frame: Day 330]

Secondary outcome measures (4)

• The value of change in LDL-C relative to baseline [Time frame: Day 330]
• Time adjusted percent change in LDL-C levels from baseline between Day 90 and Day 360 levels [Time frame: Day 90-360]
• Incidence and severity of adverse events (AE), serious adverse events (SAE), etc. Description: [Time frame: Days 1-360]
• Number of ADA and Nab [Time frame: Day 30-360]

Eligibility criteria

Inclusion criteria

• Age of 18 - 75 years (inclusive);
• Participants with primary hypercholesterolemia or mixed dyslipidemia who have maintained stable dose of lipid-lowering therapy (statin with other lipid-lowering therapy) ≥4 weeks;
• 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):

With a history of ASCVD:

• Very high risk: 55 mg/dL (1.4 mmol/L) ≤ LDL-C < 188 mg/dL (4.9 mmol/L);
• Extremely high risk: LDL-C ≥ 70 mg/dL (1.8 mmol/L);

Without a history of ASCVD:

• Moderate to high risk: LDL-C ≥ 100 mg/dL (2.6 mmol/L);
• Low risk: LDL-C ≥ 130 mg/dL (3.4 mmol/L); 4.Participants are able to establish good communication with the investigator and complete the trial in accordance with the protocol.

Exclusion criteria

• 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；
• Treatment with PCSK9 monoclonal antibodies or oral PCSK9 inhibitors within the past 180 days before screening or treatment with incisiran or any other RNA-based lipid-lowering therapy within the past 2 years before screening;
• 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;
• Systolic blood pressure (SBP) > 180 mmHg or diastolic blood pressure (DBP) > 110 mmHg during the Screening Period or prior to Randomization;
• History of heart failure with NYHA Class III-IV within 180days before screening or prior to Randomization, or LVEF < 40% within 180 days before screening;
• eGFR < 30 mL/min/1.73 m² during the Screening Period or prior to Randomization;
• Creatine Kinase (CK) > 3 × ULN at Screening Period;
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × ULN or Total Bilirubin (TBIL), > 1.5 × ULN at Screening Period or prior to Randomization;
• Prolonged QT/QTcF interval at Screening Period or prior to Randomization (QTcF > 450 ms for males, > 470 ms for females)
• Positive result for any one of hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody, syphilis antibody, or Human Immunodeficiency Virus (HIV) antibody;
• HbA1c > 8.0% at screening Period or prior to Randomization; or Type 1 diabetes , gestational diabetes ;
• 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;
• History of alcohol abuse within 1 year (defined as consuming more than 14 units of alcohol per week \[1 unit = 360 mL of beer with 5% alcohol content, or 45 mL of spirits with 40% alcohol content, or 150 mL of wine with 12% alcohol content\]);
• 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;
• 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;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Affiliation: Peking University Third Hospital — Beijing

Identifiers

NCT: NCT07421284 · SYH2053-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗