A Study to Determine the Safety, Tolerability, and Efficacy of SHR-1209 in Patients With Familial Hypercholesterolemia

Study Overview
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Brief Summary
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The study is being conducted to evaluate the efficacy, safety and tolerability of SHR-1209 in subjects with familial hypercholesterolemia. 8 eligible patients (aged ≥18 years) with familial hypercholesterolemia, on stable maximum tolerable dose lipid-regulating therapy for at least 28 days, to receive subcutaneous SHR-1209, follow up 8 weeks. The primary endpoint was percentage change in LDL cholesterol from baseline at week 12 .

Official Title
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Open-label, Single-arm, Multicentre Study to Evaluate Efficacy and Safety of SHR-1209 in Subjects With Homozygous Familial Hypercholesterolemia

Conditions
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Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: SHR-1209


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years of age Diagnosis of homozygous familial hypercholesterolemia Stable lipid-lowering therapies for at least 28 days LDL cholesterol ≥ 130 mg/dl (3.4 mmol/L) Triglyceride ≤ 400 mg/dL (4.5 mmol/L) Bodyweight of ≥ 40 kg at screening. Exclusion Criteria: LDL or plasma apheresis within 8 weeks prior to randomization New York Heart Association (NYHA) class III or IV or last known left ventricular ejection fraction < 30% Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke within 3 months of randomization, Planned cardiac surgery or revascularization, Uncontrolled cardiac arrhythmia Liver transplant history. Uncontrolled hypertension. Moderate to severe renal dysfunction. Active liver disease or hepatic dysfunction. Known sensitivity to any of the products to be administered during dosing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>SHR-1209 administered by subcutaneous injection Atorvastatin or Rosuvastatin combined with Ezetimibe oral | Drug: SHR-1209<br>* SHR-1209 administered by subcutaneous injection Atorvastatin or Rosuvastatin combined with Ezetimibe oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in LDL-C at Week 12 |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in LDL-C at Week 12 |  | Week 12 | 
| Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 |  | Weeks 10 and 12 | 
| Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 |  | Weeks 10 and 12 | 
| Percent Change From Baseline in the Total Cholesterol at the Mean of Weeks 10 and 12 |  | Weeks 10 and 12 | 
| Percent Change From Baseline in the Total Cholesterol at Week 12 |  | Week 12 | 
| Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 |  | Weeks 10 and 12 | 
| Percent Change From Baseline in HDL-C at Week 12 |  | Week 12 | 
| Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 |  | Weeks 10 and 12 | 
| Percent Change From Baseline in Non-HDL-C at Week 12 |  | Week 12 | 
| Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 |  | Weeks 10 and 12 | 
| Percent Change From Baseline in Triglycerides at Week 12 |  | Week 12 | 
| Percent Change From Baseline in Apo B at the Mean of Weeks 10 and 12 |  | Weeks 10 and 12 | 
| Percent Change From Baseline in ApoB at Week 12 |  | Week 12 | 
| Percent Change From Baseline in Apo A1 at the Mean of Weeks 10 and 12 |  | Weeks 10 and 12 | 
| Percent Change From Baseline in Apo A1 at Week 12 |  | Week 12 | 
| Percent Change From Baseline in Lipo(a) at the Mean of Weeks 10 and 12 |  | Weeks 10 and 12 | 
| Percent Change From Baseline in Lipo(a) at Week 12 |  | Week 12 | 
| Number of investigational product-related adverse events |  | Weeks 12 and 20 | 
| Number of ADA and Nab |  | Week 20 |