A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Oral SAL0137 in Adults With Elevated Lp(a) and Increased Risk of Cardiovascular Events

Official title

A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of Oral SAL0137 Tablets in Adult Patients With Elevated Lipoprotein(a) and Increased Risk of Cardiovascular Events

Overview

This is a randomized, double-blind, placebo-controlled Phase II trial evaluating the efficacy and safety of oral SAL0137 in adults with elevated Lp(a) and high cardiovascular risk. Participants will be randomized 1:1:1:1 to receive low-dose SAL0137, medium-dose SAL0137, high-dose SAL0137, or placebo for a treatment period of 12 weeks. The study assesses changes in Lp(a) levels and safety parameters.

Interventions

• Drug SAL0137 Dose 1
  SAL0137 Tablets
• Drug SAL0137 Dose 2
  SAL0137 Tablets
• Drug SAL0137 Dose 3
  SAL0137 Tablets
• Drug Placebo
  Placebo

Primary outcome measures

• Percent Change from Baseline in Lipoprotein (a) Lp(a) [Time frame: Baseline to Week 12]

Eligibility criteria

Inclusion criteria

• Aged ≥ 18 years on the date of signing the informed consent form, male or female;
• Body mass index (BMI) within the range of 18.5 to 40.0 kg/m² (inclusive);
• Participants must be at elevated risk for cardiovascular events;
• Lp(a) ≥ 150 nmol/L (or ≥ 60 mg/dL) at screening or prior to randomization;
• Participants receiving the following medications at screening must have been on a stable regimen for the specified duration prior to screening and prior to randomization, and are expected to remain on a stable regimen throughout the study
• Compliance with study drug administration during the run-in period prior to randomization must be between 80% and 120%;
• Participants (including their partners) must be willing to voluntarily adopt highly effective contraceptive measures from the time of signing the informed consent form until 3 months after the last dose of study drug (see Appendix 2); female participants of childbearing potential must have a negative pregnancy test (serum) and must not be breastfeeding;
• Fully understand the objectives and requirements of this study, voluntarily participate in the clinical trial and sign the written informed consent form, and be willing and able to comply with the visit, treatment, and examination procedures specified in the protocol.

Exclusion criteria

• Experienced any of the following within 3 months prior to screening or prior to randomization: myocardial infarction or unstable angina, stroke or transient ischemic attack, acute limb ischemia, hemorrhagic stroke or other major bleeding history, major cardiac or non-cardiac surgery, coronary, carotid, or peripheral artery revascularization; or other events that, in the investigator's opinion, indicate clinical instability;
• Planned cardiac, cerebrovascular, or peripheral artery surgery, or coronary revascularization, or other major surgery after randomization;
• Active malignancy, or history of malignancy within 5 years prior to screening (except for basal cell carcinoma of the skin or carcinoma in situ of the cervix that have been radically resected);
• Previous history of diseases that significantly affect lipid levels, such as nephrotic syndrome, severe liver disease, Cushing's syndrome, etc.;
• History of acute kidney injury within 12 months prior to screening;
• Uncontrolled hyperthyroidism or hypothyroidism;
• Uncontrolled type 1 or type 2 diabetes mellitus within 6 months prior to screening (including diabetic ketoacidosis or hyperglycemic hyperosmolar state, or HbA1c > 8.5% at screening);
• Active infection requiring systemic anti-infective therapy (oral or intravenous) prior to randomization, and the infection has not clinically resolved or still requires continued anti-infective treatment prior to randomization;
• New York Heart Association (NYHA) Class III or IV cardiac function prior to screening;
• Lipoprotein apheresis within 3 months prior to screening, or planned during the study period;
• Use of weight-loss medications (see Appendix 3) or undergone surgery causing weight instability within 2 months prior to screening;
• Long-term continuous or repeated use of systemic glucocorticoids within 3 months prior to screening;
• Known allergy to the active ingredient or any excipients of SAL0137;
• Uncontrolled hypertension at screening or prior to randomization (office sitting systolic blood pressure ≥ 160 mmHg and/or office sitting diastolic blood pressure ≥ 100 mmHg);
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² at screening or prior to randomization (calculated using the CKD-EPI 2021 formula, see Appendix 4), or undergoing dialysis;
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT) > 3 × upper limit of normal (ULN), or total bilirubin > 2 × ULN at screening or prior to randomization;
• Fasting triglycerides ≥ 5.6 mmol/L at screening or prior to randomization;
• Creatine kinase (CK) > 3 × ULN at screening or prior to randomization;
• Thyroid-stimulating hormone (TSH) < lower limit of normal (LLN) or > 1.5 × ULN at screening or prior to randomization;
• History of drug or alcohol abuse or dependence within 6 months prior to screening (average weekly alcohol intake > 14 standard units; 1 unit = 285 mL beer, or 25 mL spirits, or 100 mL wine);
• Positive virology test results at screening, including hepatitis B surface antigen (if positive, the investigator may decide whether to perform HBV-DNA quantification), HCV antibody, HIV antibody, and Treponema pallidum-specific antibody;
• Participation in any drug clinical trial and use of investigational drug within 3 months prior to screening (or within 5 half-lives of the investigational drug, whichever is longer), or participation in any medical device clinical trial and use of a medical device;
• Any other reasons that, in the investigator's opinion, may affect the evaluation of efficacy and/or safety of this study, or make the participant unsuitable for participation in this clinical trial (including but not limited to poor compliance as judged by the investigator, or remote residence precluding scheduled follow-up visits).

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

• Peking University First Hospital — Beijing

Identifiers

NCT: NCT07729475 · SAL0137A201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗