A Study of PCSK9 Inhibitor AK102 in Patients With Heterozygous Familial Hypercholesterolemia (HeFH)

Heterozygous Familial Hypercholesterolemia Clinical Trial

Official title:

A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of AK102 in Patients With Heterozygous Familial Hypercholesterolemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04173793
• Other study ID #: AK102-201
• Status: Completed
• Phase: Phase 2
• Start date: November 18, 2019
• Est. completion date: September 26, 2022

Study information

• Verified date: March 2023
• Source: Akeso
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: September 26, 2022
• Est. primary completion date: September 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heterozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• AK102
Administered by subcutaneous injection
• Placebo
Administered by subcutaneous injection
• Statins and/or Ezetimibe
Lipid-lowering therapies

Locations

Country	Name	City	State
China	Beijing Anzhen Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Akeso	AD Pharmaceuticals Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12		At baseline and week 12
Secondary	Percent change from baseline in low-density lipoprotein cholesterol (LDL-C)		From baseline through 12 weeks
Secondary	Percent change from baseline in high-density lipoprotein cholesterol (HDL-C)		From baseline through 12 weeks
Secondary	Percent change from baseline in non High-density lipoprotein (non-HDL) cholesterol		From baseline through 12 weeks
Secondary	Percent change from baseline in serum Triglyceride (TG) cholesterol		From baseline through 12 weeks
Secondary	Percent change from baseline in Apolipoprotein B (Apo B)		From baseline through 12 weeks
Secondary	Percent change from baseline in Apolipoprotein A-I (ApoA-I)		From baseline through 12 weeks
Secondary	Percent change from baseline in Lipoprotein(a) [Lp-(a)]		From baseline through 12 weeks
Secondary	Percent change from baseline in Total Cholesterol(TC)		From baseline through 12 weeks
Secondary	Incidence of treatment-emergent adverse events		From baseline through 12 weeks
Secondary	Serum concentrations of AK102		From baseline through 12 weeks
Secondary	Number of subjects who develop detectable anti-drug antibodies (ADAs)	The immunogenicity of AK102 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies.	From baseline through 12 weeks
Secondary	Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9)		From baseline through 12 weeks