Clinical trial NCT04173793: A Study of PCSK9 Inhibitor AK102 in Patients With Heterozygous Familial Hypercholesterolemia (HeFH)
Official title: A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of AK102 in Patients With Heterozygous Familial Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heterozygous Familial Hypercholesterolemia
Keywords: HeFH
LDL-C
Lead sponsor: Akeso
Sponsor class: INDUSTRY
Collaborators: name: AD Pharmaceuticals Co., Ltd.
First posted: 2019-11-22
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12
timeFrame: At baseline and week 12
Secondary outcomes:
measure: Percent change from baseline in low-density lipoprotein cholesterol (LDL-C)
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in high-density lipoprotein cholesterol (HDL-C)
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in non High-density lipoprotein (non-HDL) cholesterol
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in serum Triglyceride (TG) cholesterol
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in Apolipoprotein B (Apo B)
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in Apolipoprotein A-I (ApoA-I)
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in Lipoprotein(a) [Lp-(a)]
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in Total Cholesterol(TC)
timeFrame: From baseline through 12 weeks
measure: Incidence of treatment-emergent adverse events
timeFrame: From baseline through 12 weeks
measure: Serum concentrations of AK102
timeFrame: From baseline through 12 weeks
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From baseline through 12 weeks
measure: Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9)
timeFrame: From baseline through 12 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Anzhen Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
affiliation: Peking Union Medical College Hospital
name: Shuyang Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Anzhen Hospital
name: Yujie Zhou, MD
role: PRINCIPAL_INVESTIGATOR
References: