Evaluating HRS-5346 for high-risk adults with elevated lipoprotein(a)

A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of Oral HRS-5346 in Adult Patients at High Risk of Cardiovascular Events With Elevated Lipoprotein(a)

This study is testing a new drug called HRS-5346 to see if it can help high-risk adults with high lipoprotein(a) levels lower their chances of heart problems.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shandong Suncadia Medicine Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT06816264 on ClinicalTrials.gov

What this trial studies

This study aims to assess the efficacy and safety of HRS-5346 in adult participants who have elevated levels of lipoprotein(a) and are at high risk for cardiovascular events. Participants will be randomly assigned to receive either the investigational drug HRS-5346 or a placebo. The study will involve monitoring participants for cardiovascular outcomes and potential side effects over a specified period. The goal is to determine if HRS-5346 can effectively reduce cardiovascular risks in this population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with elevated lipoprotein(a) and a diagnosis of atherosclerotic cardiovascular disease or those at high risk for such disease.

Not a fit: Patients without elevated lipoprotein(a) or those not at high risk for cardiovascular events may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly lower the risk of cardiovascular events for patients with elevated lipoprotein(a).

How similar studies have performed: While there may be limited data on HRS-5346 specifically, similar approaches targeting lipoprotein(a) have shown promise in other studies.

Eligibility criteria

Inclusion Criteria:

1. Understanding the specific procedures of the trial, voluntarily participating in this trial, and providing written informed consent;
2. Being at least 18 years of age on the day of signing the informed consent form;
3. Body Mass Index (BMI) within the range of 18.5 to 40 kg/m² (inclusive of boundary values);
4. Participants must be at high risk of cardiovascular events, defined as individuals diagnosed with Atherosclerotic Cardiovascular Disease (ASCVD) and those at high risk for ASCVD.
5. Participants (including their partners) are willing to voluntarily use highly effective contraceptive measures from the time of signing the informed consent form until 6 months after the last administration of the study drug; female participants must have a negative blood pregnancy test and must not be breastfeeding;
6. Willing and able to comply with all the provisions of the protocol, including demonstrating the ability to adhere to study procedures prior to random assignment.

Exclusion Criteria:

- Medical History and Concomitant Medications

1. Occurrence of any of the following events within 3 months prior to screening, or between screening and randomization, or any other event deemed by the investigator to indicate clinical instability: major cardiac or non-cardiac surgery, coronary, carotid, or peripheral artery revascularization, stroke or transient ischemic attack, myocardial infarction or unstable angina, acute limb ischemia;
2. Planned or anticipated cardiac, cerebrovascular, or peripheral artery surgery or coronary revascularization or other major surgery after randomization;
3. History of hemorrhagic stroke or other significant bleeding events;
4. History of malignancy in any organ system (except well-treated basal cell carcinoma of the skin);
5. History of diseases that significantly affect lipid levels, such as nephrotic syndrome, severe liver disease, Cushing's syndrome, etc.;
6. Uncontrolled type 1 or type 2 diabetes within 6 months prior to screening (including diabetic ketoacidosis or hyperosmolar hyperglycemic state or HbA1c \> 8.5% at screening);
7. History of acute kidney injury within 12 months prior to screening;
8. Uncontrolled hyperthyroidism or hypothyroidism;
9. Active infection requiring systemic antiviral or antibiotic therapy prior to randomization;
10. New York Heart Association (NYHA) class III-IV heart function or most recent left ventricular ejection fraction (LVEF) \< 30% at screening or prior to randomization;
11. Use of weight-loss medications or surgery leading to weight instability within 2 months prior to screening;
12. Long-term continuous or repeated use of systemic corticosteroids within 3 months prior to screening (excluding local use, such as intra-articular, nasal, inhaled, topical, etc.; long-term continuous means ≥7 days; repeated means cumulative use ≥3 times);
13. Lipoprotein apheresis treatment within 3 months prior to screening, or planned to undergo this treatment during the study;
14. Use of PCSK9 inhibitors within 12 months prior to screening;
15. Allergy to the active ingredient of HRS-5346 or any excipient.

    Laboratory and Other Tests
16. Uncontrolled hypertension at screening (sitting systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg);
17. Severe renal insufficiency, defined as eGFR \< 30 ml/min/1.73 m² (calculated using the CKD-EPI formula) at screening, or undergoing dialysis;
18. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or γ-glutamyl transferase (GGT) more than 3 times the upper limit of normal (ULN), or total bilirubin more than 2 times the ULN;
19. Positive test results for any of the following: human immunodeficiency virus antibody (HIV-Ab), hepatitis C virus antibody (HCV-Ab), Treponema pallidum antibody; positive hepatitis B virus surface antigen (HBsAg) with HBV-DNA ≥1000 copies/ml (or ≥200 IU/ml, if the lower limit of detection is higher than 1000 copies/ml or 200 IU/ml, then HBV-DNA ≥ the lower limit of detection);
20. Creatine kinase (CK) more than 3 times the ULN;
21. Thyroid-stimulating hormone (TSH) below the lower limit of normal (LLN) or more than 1.5 times the ULN;

    Other Conditions
22. History of drug or alcohol abuse or dependence within the past 1 year;
23. Pregnant or breastfeeding women;
24. Participants in any drug or medical device clinical trial within 3 months prior to screening (defined by the participant receiving the trial drug/device treatment), or within 5 half-lives of the trial drug prior to screening, whichever is longer;
25. Participants deemed by the investigator to have poor compliance or any factors that make them unsuitable for this trial, including but not limited to participation posing unacceptable risk to the participant or potentially interfering with study results.

Where this trial is running

Beijing, Beijing

• Peking University Third Hospital — Beijing, Beijing, China (Recruiting)

Study contacts

• Study coordinator: Ruxia Xu

Conditions Treatment of Lipoprotein Disorder