A Study to Evaluate the Efficacy and Safety of AK102 in Patients With Hyperlipidemia

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled phase Ⅲ clinical study evaluating the efficacy and safety of AK102 in patients with primary hypercholesterolemia and mixed hyperlipidemia.

Detailed Description
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This is a Phase 3 clinical study to evaluate the efficacy and safety of AK102, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), in subjects with primary hypercholesterolemia and mixed hyperlipidemia.

Official Title
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A Phase 3 Clinical Study Evaluating the Efficacy and Safety of AK102 in Patients With Primary Hypercholesterolemia and Mixed Hyperlipidemia

Conditions
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Hyperlipidemia

Intervention / Treatment
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* Biological: AK102
* Biological: AK102
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject understand and voluntarily sign the written Inform Consent Form (ICF). Male or female ≥ 18 to ≤ 80 years of age. The fasting serum LDL-C level of subjects did not meet the treatment goal after at least 4 weeks of stable lipid-lowering background treatment. TG ≤ 4.5 mmol/L (400 mg/dl). Exclusion Criteria: Known homozygous familial hypercholesterolemia. Received PCSK9 inhibitors within 6 months before randomization. Known sensitivity to PCSK9 inhibitors and any substances to be administered. Severe renal dysfunction. Previously received organ transplantation. Uncontrolled hypothyroidism or hyperthyroidism. Uncontrolled hypertension. Known hyperlipidemia secondary to comorbidity, including nephrotic syndrome, cholestatic liver failure, etc. History of malignancy of any organ system within the past 5 years. Pregnant or lactating women.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK102 regimen 1<br> | Biological: AK102<br>* Administered AK102 by subcutaneous injection every 2 weeks Drug: Statins and/or Ezetimibe lipid-lowering therapies<br>|
| Experimental: AK102 regimen 2<br> | Biological: AK102<br>* Administered AK102 by subcutaneous injection every 4 weeks Drug: Statins and/or Ezetimibe lipid-lowering therapies<br>|
| Placebo Comparator: Placebo 1<br> | Drug: Placebo<br>* Administered placebo by subcutaneous injection every 2 weeks Drug: Statins and/or Ezetimibe lipid-lowering therapies<br>|
| Placebo Comparator: Placebo 2<br> | Drug: Placebo<br>* Administered placebo by subcutaneous injection every 4 weeks Drug: Statins and/or Ezetimibe lipid-lowering therapies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline of serum LDL-C level | Percentage change from baseline of serum LDL-C level | At week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline of serum TC, HDL-C, TG, ApoB, ApoA-I, non HDL-C and Lp(a) levels | Percentage change from baseline of serum TC, HDL-C, TG, ApoB, ApoA-I, non HDL- | Week 0-12 | 
| The incidence and severity of adverse events (AE) | The incidence and severity of adverse events (AE) | Week 0-12 | 
| To evaluate the population pharmacokinetic (PK) characteristics of AK102，such as AK102 concentration | To evaluate the population pharmacokinetic (PK) characteristics of AK102，such as AK102 concentration | Week 0-12 | 
| Number and percentage of subjects with positive anti-ak102 antibody (ADA) / neutralizing antibody (NAB) and the time of ADA / nab positivity | Number and percentage of subjects with positive anti-ak102 antibody (ADA) / neutralizing antibody (NAB) and the time of ADA / nab positivity | Week 0-12 |