A Study to Evaluate the Efficacy and Safety of AK102 Q6W 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 # clinical study evaluating the efficacy and safety of AK102 Q6W 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 Q6W, 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 Q6W 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


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.

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 450 mg by subcutaneous injection every 6 weeks Drug: Statins and/or Ezetimibe lipid-lowering therapies<br>|
| Experimental: AK102 regimen 2<br> | Biological: AK102<br>* Administered AK102 600 mg by subcutaneous injection every 6 weeks Drug: Statins and/or Ezetimibe lipid-lowering therapies<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Administered placebo by subcutaneous injection every 6 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 |  | At week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline of serum LDL-C, TC, HDL-C, TG, ApoB, ApoA-I, non HDL-C and Lp(a) levels |  | Week 0-24 | 
| The incidence and severity of adverse events (AE) |  | Week 0-24 | 
| Evaluate the changes of AK102 PK parameters(t1/2) |  | Week 0-24 | 
| Evaluate the changes of AK102 PK parameters(AUC） |  | Week 0-24 | 
| Evaluate the changes of AK102 PK parameters(Vd) |  | Week 0-24 | 
| Evaluate the changes of AK102 PK parameters(Tmax) |  | Week 0-24 | 
| Evaluate the changes of free PCSK9 concentration |  | Week 0-24 | 
| Evaluate the changes of AK102 PK parameters(Cmax) |  | Week 0-24 | 
| Evaluate the changes of AK102 PK parameters(CL) |  | Week 0-24 | 
| Evaluate the changes of AK102 PK parameters(MRT) |  | Week 0-24 | 
| The number and percentage of anti AK102 antibody (ADA)positive subjects |  | Week 0-24 | 
| The number and percentage of anti AK102 neutralizing antibody (NAB) positive subjects |  | Week 0-24 | 
| the time of ADA positive |  | Week 0-24 | 
| the time of nab positive |  | Week 0-24 |