Evaluating HST101 for lowering cholesterol in Chinese patients

A Randomized, Double-blind, Placebo-controlled Phase 3 Clinical Study to Evaluate the Efficacy and Safety of HST101 in Chinese Patients with Hypercholesterolemia

This study is testing if a new drug called HST101 can lower cholesterol levels in Chinese patients who have high cholesterol and are at risk for heart disease.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 210 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hasten Biopharmaceutical Co., Ltd. (industry)
• Locations: 18 sites (Beijing, Beijing Municipality and 17 other locations)
• Trial ID: NCT06568471 on ClinicalTrials.gov

What this trial studies

This Phase 3 clinical trial aims to assess the efficacy and safety of HST101 (lerodalcibep), a PCSK9 inhibitor, in reducing LDL cholesterol levels in Chinese patients with hypercholesterolemia, particularly those at high risk for atherosclerotic cardiovascular disease. The study involves a randomized, double-blind, placebo-controlled design over a total duration of 55 weeks, including a 12-week initial treatment phase followed by a 36-week open-label phase. Participants will receive either HST101 or a placebo during the initial phase, with all transitioning to HST101 in the open-label phase. The study will take place across multiple centers in mainland China.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with hypercholesterolemia who are on stable lipid-lowering therapy and meet specific LDL-C and triglyceride levels.

Not a fit: Patients who are not on stable lipid-lowering therapy or have significantly different cholesterol levels may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly lower cholesterol levels in patients at high risk for cardiovascular diseases, potentially reducing their risk of heart-related complications.

How similar studies have performed: Previous studies involving PCSK9 inhibitors have shown promising results in lowering cholesterol levels, indicating a potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

* Provision of written and signed informed consent form prior to any study-specific procedure;
* Male or female participants ≥18 years of age at the screening visit;
* Body weight ≥ 40 kg and body mass index (BMI) ≥18 and ≤35 kg/m2;
* On a stable diet and lipid-lowering oral drugs (such as statins, ezetimibe or Hybutimibe, omega-3 compounds, fenofibrate, nicotinic acid, etc.) for at least 4 weeks prior to the first drug administration
* LDL-C≥1.8 mmol/L (70 mg/dL) and TG≤4.52 mmol/L (400 mg/dL) at screening for ASCVD patients or those at very (ultra)-high risk for ASCVD, including patients with HeFH; LDL-C ≥ 2.6 mmol/L (100 mg/dL) and TG ≤ 4.52 mmol/L (400 mg/dL) at screening for patients at high-risk for ASCVD including patients with HeFH;
* Patients on a PCSK9 mAb at a dose of 75 mg, 140 mg, or 150 mg Q2W must undergo a washout period of ≥6 weeks after the last dose; for those on 300 mg or 420 mg Q4W, the washout period is ≥10 weeks following last dose;
* Female of childbearing potential must have a negative pregnancy test at the last screening visit and consent to use highly effective contraceptives during the trial and 3 months after the last dose of investigational drug.

Exclusion Criteria:

* Documented history of homozygous familial hypercholesterolemia (HoFH);
* Estimated glomerular filtration rate (eGFR)\<30 mL/min/1.73m2;
* Active liver disease or hepatic dysfunction, history of liver transplant, and/or ALT or AST \>2.5 × ULN at screening;
* Poorly controlled thyroid disorder including hypothyroidism or hyperthyroidism;
* Poorly controlled Type 1 or Type 2 diabetes mellitus defined as fasting blood glucose ≥11.0 mmol/L (200 mg/dL) and glycosylated hemoglobin (HbA1c) ≥ 9%;
* Serious arrhythmia, MI, unstable angina pectoris, PCI, CABG, implantable cardioverter defibrillator, aortic valve surgery or stroke within 3 months prior to the first dose;
* Planned cardiac surgery or revascularization during the study period;
* New York Heart Association (NYHA) Class III-IV heart failure;
* Pregnant or lactating women;
* Poorly controlled hypertension (SBP≥160 mmHg or DBP≥100 mmHg in a sitting position)
* Unexplained creatine kinase (CK) \> 5 x ULN (retested once is needed if suspected to be related to excessive exercise or abnormal activity);
* LDL apheresis or plasma exchange within 2 months prior to the first dose;
* HIV, Treponema pallidum, or HCV antibody test positive, or HBV-DNA \>ULN at screening;
* History of prescription drug abuse, illicit drug use or alcohol abuse within 6 months prior to screening;
* History of any major drug allergy, including allergy to protein biologics;
* Participate another clinical trial within 30 days or less than 5 half-lifes (drug) before screening, whichever is longer

Where this trial is running

Beijing, Beijing Municipality and 17 other locations

• Beijing Anzhen Hospital of Capital Medical University — Beijing, Beijing Municipality, China (RECRUITING)
• Beijing Luhe Hospital, Capital Medical Univeristy — Beijing, Beijing Municipality, China (RECRUITING)
• Beijing Tsinghua Changgeng Hospital — Beijing, Beijing Municipality, China (RECRUITING)
• Fuwai Hospital, CAMS & PUMC — Beijing, Beijing Municipality, China (RECRUITING)
• Guangdong Provincial People's Hospital — Guangzhou, Guangdong, China (RECRUITING)
• Shijiazhuang People's Hospital — Shijiazhuang, Hebei, China (RECRUITING)
• Daqingshi People's Hospital — Daqing, Heilingjiang, China (RECRUITING)
• The 2nd Xiangya Hospital of Central South University — Changsha, Hunan, China (RECRUITING)
• The Third Xiangya Hospital of Central South University — Changsha, Hunan, China (RECRUITING)
• Nanchang People's Hospital — Nanchang, Jiangxi, China (RECRUITING)
• Binzhou Medical University Hospital — Binzhou, Shandong, China (RECRUITING)
• Heze Municipal Hospital — Heze, Shandong, China (RECRUITING)
• Qilu Hospital of Shandong University — Jinan, Shandong, China (RECRUITING)
• Zibo Municipal Hospital — Zibo, Shandong, China (RECRUITING)
• West China Hospital of Sichuan University — Chengdu, Sichuan, China (RECRUITING)
• Tianjin People's Hospital — Tianjin, Tianjin Municipality, China (RECRUITING)
• The First Affiliated Hospital of Wenzhou Medical Univesity — Wenzhou, Zhejiang, China (RECRUITING)
• Peking University First Hospital — Beijing, China (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Yong Huo — Peking University First Hospital
• Study coordinator: Yong Huo

Conditions: Hypercholesterolemia, Dyslipidemias, Primary Hypercholesterolemia, Heterozygous Familial Hypercholesterolemia, Hyperlipidemia, Mixed, Metabolic Disease, ASCVD