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

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

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.

Study Overview

• Status: Completed
• Conditions: Heterozygous Familial Hypercholesterolemia
• Intervention / Treatment: Drug: Placebo; Drug: AK102; Drug: Statins and/or Ezetimibe

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jing Liu; Phone Number: +86 (0760) 8987 3999; Email: clinicaltrials@akesobio.com

Study Locations

• China
  • Beijing, China, 100000
    • Peking Union Medical College Hospital
    • Contact: Peipei Chen, MD
    • Principal Investigator: Shuyang Zhang, MD
  • Beijing
    • Beijing, Beijing, China, 100029
      • Beijing Anzhen Hospital
      • Principal Investigator: Yujie Zhou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK102 450 mg; Participants received AK102 450 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks	Drug: AK102; Administered by subcutaneous injection; Drug: Statins and/or Ezetimibe; Lipid-lowering therapies
Experimental: AK102 300 mg; Participants received AK102 300 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks	Drug: AK102; Administered by subcutaneous injection; Drug: Statins and/or Ezetimibe; Lipid-lowering therapies
Experimental: AK102 150 mg; Participants received AK102 150 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks	Drug: AK102; Administered by subcutaneous injection; Drug: Statins and/or Ezetimibe; Lipid-lowering therapies
Placebo Comparator: Placebo Q4W; Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks	Drug: Placebo; Administered by subcutaneous injection; Drug: Statins and/or Ezetimibe; Lipid-lowering therapies
Placebo Comparator: Placebo Q2W; Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks	Drug: Placebo; Administered by subcutaneous injection; Drug: Statins and/or Ezetimibe; Lipid-lowering therapies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12	At baseline and week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change from baseline in low-density lipoprotein cholesterol (LDL-C)		From baseline through 12 weeks
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 Lipoprotein(a) [Lp-(a)]		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)	The immunogenicity of AK102 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies.	From baseline through 12 weeks
Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9)		From baseline through 12 weeks

Collaborators and Investigators

• Sponsor: Akeso
• Collaborators: AD Pharmaceuticals Co., Ltd.
• Investigators: Principal Investigator: Shuyang Zhang, MD, Peking Union Medical College Hospital; Principal Investigator: Yujie Zhou, MD, Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2019
• Primary Completion (Actual): September 26, 2022
• Study Completion (Actual): September 26, 2022

Study Registration Dates

• First Submitted: November 17, 2019
• First Submitted That Met QC Criteria: November 20, 2019
• First Posted (Actual): November 22, 2019

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: LDL-C; HeFH
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe
• Other Study ID Numbers: AK102-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No