HeFH Adult Patient Recruitment | Phase III Clinical Trial of SYH2053 Injection for HeFH
Dear patients with heterozygous familial hypercholesterolemia (HeFH),
Hello everyone!
On March 9, 2026, a"Multicenter, randomized, double-blind, placebo-controlled phase III clinical trial of SYH2053 injection for the treatment of heterozygous familial hypercholesterolemia"was publicly announced.This clinical trialwas applied forby CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd. / CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd., aiming toevaluate the efficacy of SYH2053 injection in reducing LDL-C in participants with heterozygous familial hypercholesterolemia.
Image source: "Drug Clinical Trial Registration and Information Disclosure Platform"
To help everyone understand the specific details of this clinical trial, we have organized the key information as follows. The following is the specific information of this clinical trial:
Registration number:CTR20260676
Trial title:Multicenter, randomized, double-blind, placebo-controlled phase III clinical trial of SYH2053 injection for the treatment of heterozygous familial hypercholesterolemia
Investigational drug:SYH2053 injection
Mechanism of action:The active ingredient of SYH2053 injection is a chemically modified and GalNAc-conjugated siRNA drug targeting PCSK9 mRNA, with a registration classification of chemical drug category 1. The mechanism of action is that the GalNAc-siRNA conjugate compound rapidly enters the liver through the circulatory system; upon entering the liver, it is rapidly internalized by hepatocytes via asialoglycoprotein receptor-mediated endocytosis, accumulates in lysosomes, is slowly released, and is continuously loaded onto the RNA-induced silencing complex, achieving long-lasting inhibition of PCSK9 mRNA translation, thereby reducing serum LDL-C levels in patients.
Route of administration:Subcutaneous injection. After the first dose, a second subcutaneous injection is given 3 months later, followed by injection once every 6 months.
Drug development progress:Phase 2 results of this drug showed that monotherapy/combination therapy effectively reduced LDL-C with good overall safety and tolerability. The product received the drug clinical trial approval notice from the National Medical Products Administration on November 24, 2023, and monotherapy and combination hyperlipidemia projects are currently being conducted in parallel.
Target enrollment:Planned recruitment of 135 patients with HeFH.
1. Aged ≥18 years at the time of signing the ICF (Informed Consent Form), regardless of gender;
2. Genetically diagnosed with HeFH; or clinically diagnosed with HeFH (DLCN criteria >8 points);
3. Received stable-dose maintenance treatment with moderate-to-high intensity statins with or without other lipid-lowering drugs (e.g., cholesterol absorption inhibitors) for ≥4 weeks prior to signing the ICF, with no planned dose changes during the study period;
Note: Statin types and daily doses include: 10 mg ≤ atorvastatin ≤ 80 mg; 5 mg ≤ rosuvastatin ≤ 20 mg; fluvastatin 80 mg; lovastatin 40 mg; pitavastatin ≥1 mg; pravastatin 40 mg; simvastatin ≥20 mg;
4. Low-fat diet for ≥4 weeks prior to signing the ICF;
5. Fasting LDL-C at screening meeting any one of the following criteria:
1) Without ASCVD: LDL-C ≥ 2.6 mmol/L;
2) With ASCVD (very high risk): LDL-C ≥ 1.4 mmol/L;
Note: ASCVD refers to a definite diagnosis of atherosclerotic cardiovascular disease, including acute coronary syndrome, stable coronary artery disease, ischemic cardiomyopathy, post-revascularization, ischemic stroke, transient ischemic attack, peripheral atherosclerotic disease, etc. This also includes significant plaques (stenosis >50%) shown on imaging examinations such as CAG, coronary CT, or carotid/femoral artery ultrasound, and CAC >300 points.
6. Fasting TG ≤ 5.6 mmol/L at screening;
7. Participants who can understand and cooperate with the completion of this trial, voluntarily participate in this trial, and sign the ICF.
1. Genetically diagnosed withHoFH; or clinically suspected or confirmedHoFH (withLDL-C ≥ 8 mmol/L at screening or LDL-C ≥ 13 mmol/L if previously untreated);
2. At screening, in the investigator's judgment, use of medications that significantly affect LDL-C levels (e.g., long-term oral or intravenous glucocorticoids, tacrolimus, cyclosporine, estrogens, vitamin A derivatives, antidepressants, etc.) or uncontrolled other diseases (e.g., nephrotic syndrome, hypothyroidism, renal insufficiency, liver disease, glycogen storage disease, systemic lupus erythematosus, Cushing's syndrome, etc.);
3. Use of any of the following treatments within the specified timeframes prior to signing the ICF:
1) Other PCSK9 inhibitors (monoclonal antibodies or oral small molecule drugs within 90 days; Leqvio® or other RNA-based drugs within 2 years);
2) Evinacumab (within 12 weeks);
3) Lomitapide (within 6 weeks);
4) Mipomersen (within 5 months);
5) Bempedoic acid (within 4 weeks);
6) Lipid apheresis (within 8 weeks);
7) Liver transplantation or CRISPR-based gene editing therapy (at any time);
4. Allergy or suspected allergy to oligonucleotide drugs or excipients of the investigational product;
5. Major adverse cardiovascular events (e.g., myocardial infarction, stroke or cerebrovascular events, unstable angina, worsening heart failure, or hospitalization) within 180 days prior to signing the ICF; or a history of hemorrhagic stroke; or meeting very high risk criteria for ASCVD at screening;
6. Uncontrolled (after drug or ablation treatment) or severe arrhythmias (e.g., atrial fibrillation, recurrent/persistent supraventricular or ventricular tachycardia, QT interval prolongation) within 180 days prior to signing the ICF;
7. NYHA class III-IV heart failure or LVEF <40% within 1 year prior to signing the ICF or at screening;
8. Type 1 diabetes mellitus at screening;
9. Uncontrolled serious diseases or diseases that may affect study results or increase risk (e.g., active liver disease) at screening, as judged by the investigator;
10. History of malignancy (except cured basal cell carcinoma of the skin, etc.) within 5 years prior to signing the ICF or at screening, or potential malignancy;
11. Major surgery (including PCI or CABG, etc.) performed within 180 days prior to signing the ICF or planned during the study period;
12. History of drug abuse or alcohol abuse within 5 years prior to signing the ICF;
13. Received or planned to receive other clinical study treatments (drugs or devices) within 90 days or 5 half-lives (whichever is longer) prior to signing the ICF, or planned during the study period;
14. Any of the following at screening examinations:
1) SBP ≥ 160 mmHg, or DBP ≥ 100 mmHg (untreated or after stable drug treatment);
2) ALT or AST >3×ULN, or total bilirubin >1.5×ULN;
3) CK >2.5×ULN;
4) QTcF interval: male >450 ms, female >470 ms;
5) eGFR <30 mL/min/1.73 m2 (CKD-EPI formula);
6) HBsAg positive and HBV DNA positive; or any one of HCV antibody, syphilis antibody, and HIV antibody positive;
7) TSH
8) HbA1c >8.5%;
15. Female participants of childbearing potential who are pregnant or lactating at screening, or have a positive pregnancy test from screening to before randomization; or female and male participants of childbearing potential with plans for reproduction (including sperm donation and egg donation) during the study period and within 3 months after the end of treatment, and/or inability to take effective contraceptive measures;
16. Other conditions that the investigator considers inappropriate for participation in this study (including poor compliance, etc.).
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Information source: "Drug Clinical Trial Registration and Information Disclosure Platform"
Website:
https://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml
If you or your family members are interested in participating in this clinical study, please contact the research centers listed in the table above for specific consultation.
