A Study of PCSK9 Inhibitor AK102 in Patients With Heterozygous Familial Hypercholesterolemia (HeFH)

Study Overview
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Brief Summary
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This is a double-blind, randomized, placebo-controlled, multicenter study to evaluate the safety and efficacy of AK102 in patients with heterozygous familial hypercholesterolemia (HeFH).The primary objective of this study is to evaluate the efficacy of AK102 in patients with HeFH.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of AK102 in Patients With Heterozygous Familial Hypercholesterolemia

Conditions
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Heterozygous Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: AK102
* Drug: Placebo
* Drug: Statins and/or Ezetimibe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with heterozygous familial hypercholesterolemia diagnosed by genetic confirmation or clinical diagnosis criteria. Stable on pre-existing, lipid-lowering therapies (statins with or without ezetimibe) for at least 4 weeks with no planned medication or dose change for the duration of study participation. Fasting Low-Density Lipoprotein Cholesterol (LDL-C) ≥ 70 mg/dL in patients with history of Atherosclerotic Cardiovascular Disease (ASCVD) or Fasting Low-Density Lipoprotein Cholesterol (LDL-C) ≥ 100 mg/dL in patients without history of Atherosclerotic Cardiovascular Disease (ASCVD). Fasting triglycerides ≤ 400 mg/dL. Body weight ≥ 40kg. Key Exclusion Criteria: Subjects with homozygous FH (clinically or by genotyping). Receipt of LDL apheresis within 12 months prior to the first dose of Investigational product. Receipt of Lomitapide or Mipomersen within 5 months prior to the first dose of Investigational product. Prior use of PCSK9 inhibitors. Creatine kinase (CK) >3 times of the upper limit of normal (ULN). Aspartate Aminotransferase (AST) ≥ 2 x ULN. Estimated Glomerular Filtration Rate (eGFR)≤ 30 mL/min/1.73m^2. Thyroid-Stimulating Hormone (TSH)> 1.5 x ULN or <1 x LLN. Type 1 diabetes, or type 2 diabetes that is or poorly controlled（HbA1c> 8.5%). Subjects with untreated or active chronic hepatitis B or active hepatitis C virus infections.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK102 450 mg<br>Participants received AK102 450 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks | Drug: AK102<br>* Administered by subcutaneous injection<br>Drug: Statins and/or Ezetimibe<br>* Lipid-lowering therapies<br>|
| Experimental: AK102 300 mg<br>Participants received AK102 300 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks | Drug: AK102<br>* Administered by subcutaneous injection<br>Drug: Statins and/or Ezetimibe<br>* Lipid-lowering therapies<br>|
| Experimental: AK102 150 mg<br>Participants received AK102 150 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks | Drug: AK102<br>* Administered by subcutaneous injection<br>Drug: Statins and/or Ezetimibe<br>* Lipid-lowering therapies<br>|
| Placebo Comparator: Placebo Q4W<br>Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks | Drug: Placebo<br>* Administered by subcutaneous injection<br>Drug: Statins and/or Ezetimibe<br>* Lipid-lowering therapies<br>|
| Placebo Comparator: Placebo Q2W<br>Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks | Drug: Placebo<br>* Administered by subcutaneous injection<br>Drug: Statins and/or Ezetimibe<br>* Lipid-lowering therapies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12 |  | At baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) |  | From baseline through 12 weeks | 
| Percent change from baseline in high-density lipoprotein cholesterol (HDL-C) |  | From baseline through 12 weeks | 
| Percent change from baseline in non High-density lipoprotein (non-HDL) cholesterol |  | From baseline through 12 weeks | 
| Percent change from baseline in serum Triglyceride (TG) cholesterol |  | From baseline through 12 weeks | 
| Percent change from baseline in Apolipoprotein B (Apo B) |  | From baseline through 12 weeks | 
| Percent change from baseline in Apolipoprotein A-I (ApoA-I) |  | From baseline through 12 weeks | 
| Percent change from baseline in Lipoprotein(a) [Lp-(a)] |  | From baseline through 12 weeks | 
| Percent change from baseline in Total Cholesterol(TC) |  | From baseline through 12 weeks | 
| Incidence of treatment-emergent adverse events |  | From baseline through 12 weeks | 
| Serum concentrations of AK102 |  | From baseline through 12 weeks | 
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | The immunogenicity of AK102 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies. | From baseline through 12 weeks | 
| Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9) |  | From baseline through 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HeFH, LDL-C