Heterozygous Familial Hypercholesterolemia
Conditions
Keywords
HeFH, LDL-C
Brief summary
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.
Interventions
DRUGPlacebo
Administered by subcutaneous injection
Lipid-lowering therapies
DRUGAK102
Administered by subcutaneous injection
Sponsors
AD Pharmaceuticals Co., Ltd.
Akeso
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12 | At baseline and week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 low-density lipoprotein cholesterol (LDL-C) | 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) | From baseline through 12 weeks | The immunogenicity of AK102 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies. |
| Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9) | From baseline through 12 weeks | — |
| Percent change from baseline in Lipoprotein(a) [Lp-(a)] | From baseline through 12 weeks | — |
Countries
China
Outcome results
None listed