A Study of SYH2070 Injection in Participants With Mixed Hyperlipidemia

Official title

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial to Evaluate the Efficacy and Safety of SYH2070 Injection in Participants With Mixed Hyperlipidemia

Overview

This is a randomized, double-blind, placebo-parallel, multicenter phase II clinical trial to evaluate the efficacy and safety of SYH2070 injection in participants with mixed hyperlipidemia.

Interventions

• Drug SYH2070
  SYH2070 injection, 150 mg, 300 mg, 400 mg, SC, administration duration: 24 weeks
• Drug Placebo
  Placebo, SC, administration duration: 24 weeks

Primary outcome measures

• The percentage change in serum TG levels from baseline at week 24 [Time frame: Baseline through Week 24]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years old, no gender limitation;
• 1.7 mmol/L (150 mg/dL) ≤ fasting TG ≤ 5.6 mmol/L (499 mg/dL) at screening;
• fasting LDL-C ≥ 2.6 mmol/L (100 mg/dL) at screening;
• Participants must have been continuously taking stable medium-intensity or higher statin drugs for at least 4 weeks, accompanied or not by cholesterol absorption inhibitors or fibrates, and maintain the same drug, dosage, frequency and brand throughout the trial period;
• Weight index range: 18.5 kg/m2 ≤ BMI ≤ 40.0 kg/m2 at screening;
• Understand the trial procedures and methods, voluntarily participate in this trial and sign the ICF in person;
• Male participants with reproductive capacity and their partners who are reproductive-aged women must agree to use highly effective contraceptive measures during the trial period and 24 weeks after the last administration of the trial drug; serum pregnancy tests before medication, serum or urine pregnancy tests during the trial period must be negative, and not be in the lactation period; participants are not allowed to donate sperm or eggs during the trial period and 24 weeks after the last administration of the trial drug.

Exclusion criteria

• Genetic diagnosis or clinical diagnosis indicates homozygous familial hypercholesterolemia;
• During the screening or before randomization, there is NYHA-defined heart function grade Ⅲ-Ⅳ or known left ventricular ejection fraction < 30%;
• Within 3 months before the screening, there has been a new major cardiovascular adverse event, including acute coronary syndrome (such as myocardial infarction, unstable angina pectoris), cerebrovascular disease history (such as acute stroke or transient ischemic attack), or acute pulmonary embolism;
• Within 3 months before the screening, there are clinically significant arrhythmias, such as recurrent and symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular rate, atrial flutter with rapid ventricular rate, third-degree atrioventricular block, sinus arrest, etc.), drug or ablation-induced arrhythmias that cannot be controlled;
• Within 1 month before the screening, there is a history of percutaneous coronary intervention or peripheral artery revascularization surgery;
• At screening, there is poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg);
• Previously diseases that significantly affect lipid levels, such as nephrotic syndrome, severe liver diseases, Cushing's syndrome, etc.;
• Previously diagnosed with type 1 diabetes, or type 2 diabetes HbA1c > 8.5% at screening ;
• Within 1 year before the screening, there is a history of acute or chronic pancreatitis;
• Within 5 years before the screening, there is a history of malignant tumor (excluding well-treated basal cell skin cancer and cervical carcinoma in situ);
• Within 3 months before the screening, there is a history of major surgery (including coronary artery bypass grafting surgery) or planned major surgery during the trial;
• Plan to undergo percutaneous coronary intervention, coronary artery bypass grafting, carotid or peripheral artery revascularization, pacemaker implantation, cardiac resynchronization therapy, implantation of implantable cardioverter-defibrillator, etc. during the trial;
• At the time of screening or before randomization, there is an active infectious disease that the investigator deems not suitable for participation in the trial;
• Previously had a history of drug abuse, alcohol abuse, or drug addiction;
• Known to be allergic to the test drugs or have a severe allergic reaction to other small nucleic acid drugs;
• Within 6 months before the screening has used other ANGPTL3 inhibitor lipid-lowering drugs;
• Within 3 months before the screening has used PCSK9 monoclonal antibody lipid-lowering drugs;
• Within 1 year before the screening has used other siRNA lipid-lowering drugs;
• Within 2 months before the screening has received or plans to receive plasma exchange treatment;
• Within 3 months before the screening has used drugs with weight loss effects or undergone surgeries that cause unstable weight;
• Within 3 months before the screening has long-term continuous or repeated use of cyclosporine, systemic corticosteroids (excluding local use, such as intra-articular, nasal, inhalation, topical use, etc.; long-term continuous refers to ≥ 7 days; repeated refers to cumulative use ≥ 3 times);
• Within 3 months before the screening has participated in any clinical trial (excluding those who failed the screening), or is within 5 half-lives of the trial drug at the time of screening, with the longer time being the criterion;
• Any of the indicators meet the following criteria:

1\) Alanine aminotransferase or aspartate aminotransferase or γ-glutamyl transferase exceeds 2.0 times the upper limit of normal (ULN), or total bilirubin exceeds 1.5 times of the ULN; 2) QTcF interval: for males, > 450 ms; for females, > 470 ms; 3) HBsAg positive and HBV-DNA positive; or HCV antibody positive and HCV RNA positive; or positive for HIV antibody or anti- Treponema pallidum antibody; 4) Creatine kinase exceeds 3 times of the ULN; 5) Thyroid stimulating hormone is lower than the lower limit of normal or exceeds 1.5 times of the ULN (except for those who have been using thyroid hormone replacement therapy for 12 weeks or more before LDL-C testing in the screening period); 6) eGFR < 30 mL/min/1.73m2 (calculated using the MDRD formula); 24. General criteria:

• Researchers evaluate those whose lifestyle has undergone significant changes within the previous 4 weeks, or those who cannot maintain it during the trial;
• Researchers determine that they are not suitable for subcutaneous injection;
• Pregnant or lactating women;
• Researchers judge that the participants have poor compliance or any factors that are not suitable for participating in this trial, including but not limited to participating in the trial would expose the participants to unacceptable risks or may interfere with the trial results.

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

• The Second Affiliated Hospital Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT07695597 · SYH2070-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗