A Study to Evaluate the Safety and Efficacy of the PCSK9 Inhibitor AK102 in Patients With HoFH

Study Overview
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Brief Summary
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AK102 is being developed for the treatment of HoFH. The study will be conducted in 2 parts, part 1 is open label, single arm study to evaluate the safety, tolerability and efficacy of PCSK9 inhibitor AK102, and part 2 is double blind, randomized, placebo controlled study to evaluate the efficacy and safety of PCSK9 inhibitor AK102. The treatment period will last 12 week.

Official Title
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A Phase 2 Study to Evaluate the Safety and Efficacy of PCSK9 Inhibitor AK102 in Patients With Homozygous Familial Hypercholesterolemia (HoFH)

Conditions
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Homozygous Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: AK102
* Drug: Statins
* Drug: Ezetimibe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, ≥18 years of age with a diagnosis of homozygous familial hypercholesterolemia by genetic confirmation or a clinical diagnosis based on a history of an untreated low-density lipoprotein cholesterol (LDL-C) concentration >500 mg/deciliter (dL) [13 millimoles/liter (mmol/L)] together with either xanthoma before 10 years of age or evidence of heterozygous familial hypercholesterolemia in both parents Stable on pre-existing, lipid-lowering therapies (statins in combination with ezetimibe) for at least 4 weeks with no planned medication or dose change for the duration of study participation Fasting central lab LDL-C concentration >130 mg/dL (3.4 mmol/L) and triglyceride concentration <400 mg/dL (4.5 mmol/L). Body weight of 40 kilograms (kg) or greater at screening Exclusion Criteria: Received LDL plasma replacement therapy within 8 weeks before Investigational product administration Received Lomitapide or Mipomersen within 5 months before Investigational product administration Received prior treatment with PCSK9 inhibitors or AK102. Unexplained creatine kinase (CK) ≥ 5 times the upper limit of normal (ULN) Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA exceeding 500 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects with non-active HBsAg carriers, treated and stable hepatitis B (HBV DNA <500 IU/ mL) , and cured hepatitis C can be enrolled. Subjects with positive HCV antibodies are eligible only if the HCV RNA test results are negative. Known allergic reactions to any ingredients of AK102 Any other condition(s) that would compromise the safety of the patient or compromise the quality of the clinical study as judged by the Investigator and/or Medical Monitor.

Ages Eligible for Study
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Minimum Age: 18 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<br>450mg AK102, Q4W, subcutaneous injection | Drug: AK102<br>* 450mg, Q4W, subcutaneous injection<br>Drug: Statins<br>* Lipid-lowering therapies<br>Drug: Ezetimibe<br>* Lipid-lowering therapies<br>|
| Placebo Comparator: placebo<br>Placebo, Q4W, subcutaneous injection | Drug: Statins<br>* Lipid-lowering therapies<br>Drug: 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 |  | Week 12 | 
| Incidence of treatment-emergent adverse events as assessed by CTCAE V5.0（only for part 1） |  | From baseline through 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in High-density lipoprotein (HDL) cholesterol |  | 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) |  | 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 (Apo A-I) |  | From baseline through 12 weeks | 
| Percent Change From Baseline in Total Cholesterol(TC) |  | From baseline through 12 weeks | 
| Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) |  | From baseline through 12 weeks | 
| Concentrations of AK102 in Serum |  | Part 1: Day 1,Day 2, Day 4, Day 8, Day 15, Day 22, D29, D57. Part 2: Day 1, Day 29, Day 57 | 
| Number of subjects who develop detectable anti-drug antibodies (ADAs) |  | From baseline through 12 weeks | 

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