A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Study to Evaluate the Safety and Efficacy of Recombinant Fully Human Anti-PCSK9 Monoclonal Antibody Injection (SAL003) Combined With Atorvastatin in Subjects With Hypercholesterolemia and Mixed Dyslipidemia
Overview
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 214
- Locations
- 1
- Primary Endpoint
- Percent change of Low-Density Lipoprotein Cholesterol (LDL-C)
Overview
Brief Summary
This is a Phase II, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of SAL003, a recombinant fully human anti-PCSK9 monoclonal antibody, in combination with a stable dose of atorvastatin in patients with hypercholesterolemia and mixed dyslipidemia.
Detailed Description
This is a Phase II, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and pharmacokinetics of SAL003, a recombinant fully human anti-PCSK9 monoclonal antibody, when used in combination with stable, background atorvastatin therapy in adult patients with hypercholesterolemia and mixed dyslipidemia.
The study is structured into four distinct periods to ensure patient eligibility, standardize background therapy, and assess both short-term and longer-term effects of the investigational product.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects aged 18 to 75 years.
- •Diagnosis of hypercholesterolemia and/or mixed dyslipidemia per the 2016 Chinese guidelines.
- •On a stable statin regimen as defined by the two pathways:
- •Pathway 1: On other statins or irregular atorvastatin, willing to switch to/stabilize on atorvastatin.
- •Pathway 2: On stable, regular atorvastatin (Lipitor) for ≥4 weeks.
- •Fasting LDL-C must be above target:
- •With ASCVD history: ≥1.8 mmol/L (70 mg/dL)
- •Without ASCVD history: ≥2.6 mmol/L (100 mg/dL)
- •Fasting triglycerides (TG) ≤ 5.6 mmol/L (500 mg/dL) at screening.
- •Provide signed informed consent.
Exclusion Criteria
- •Suffering from homozygous familial hypercholesterolemia (HoFH); Other diseases that may cause secondary increase of LDL-C: Cushing's syndrome, nephrotic syndrome, myeloma, glycogen storage disease, systemic lupus erythematosus, acute intermittent porphyria;
- •Route 1: The medication compliance of atorvastatin during the induction period is less than 80% or more than 120%; Route 2: The medication compliance of atorvastatin within 28 days before screening is less than 80% or more than 120%;
- •Within 3 months before screening, there is heart failure (NYHA cardiac function classification of grade III and IV), acute coronary syndrome, percutaneous coronary intervention, or other serious heart diseases \[such as cardiogenic shock, grade II-III atrioventricular block, bradycardia (heart rate \< 50 beats/minute), other serious arrhythmias, etc.\];
- •Within 3 months before screening, there is a serious cerebrovascular disease (hypertensive encephalopathy, cerebral vascular injury, stroke, transient ischemic attack, etc.), or there is a serious aortic or peripheral vascular lesion, or there are indications for surgical intervention;
- •Within 3 months before screening, there is a major surgical history or plans to undergo major surgery during the study period;
- •Patients with poorly controlled hypertension (SBP ≥ 160 mm Hg or DBP ≥ 100 mm Hg);
- •Diabetic patients with the following conditions known: 1) Type 1 diabetic patients; 2) Type 2 diabetic patients with poor blood sugar control (HbA1c \> 8.0%);
- •Patients with active viral hepatitis (including hepatitis B and hepatitis C), other severe liver diseases, or liver dysfunction (ALT or AST \> 2.5 times the upper limit of normal, TBIL \> 2 times the upper limit of normal);
- •Glomerular filtration rate (eGFR) \< 30 ml/min/1.73m2 during the screening period;
- •Patients with abnormal thyroid function (thyroid stimulating hormone TSH exceeds the normal range of the center);
Arms & Interventions
Test Group Q4W
Intervention: SAL003 140mg+Atorvastatin (Drug)
Test Group Q8W
Intervention: SAL003 420mg+Atorvastatin (Drug)
Reference Group Q4W
Intervention: Placebo 140mg+Atorvastatin (Drug)
Reference Group Q8W
Intervention: Placebo 420mg+Atorvastatin (Drug)
Outcomes
Primary Outcomes
Percent change of Low-Density Lipoprotein Cholesterol (LDL-C)
Time Frame: at Week 24
Percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24.
Secondary Outcomes
No secondary outcomes reported