Back to resultsA Study of PCSK9 Inhibitor AK102 in Patients With Heterozygous Familial Hypercholesterolemia (HeFH)
Primary Purpose
Heterozygous Familial Hypercholesterolemia
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
AK102
Placebo
Statins and/or Ezetimibe
Sponsored by
About this trial
This is an interventional treatment trial for Heterozygous Familial Hypercholesterolemia focused on measuring HeFH, LDL-C
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.
Sites / Locations
- Beijing Anzhen Hospital
- Peking Union Medical College Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Arm Label
AK102 450 mg
AK102 300 mg
AK102 150 mg
Placebo Q4W
Placebo Q2W
Arm Description
Participants received AK102 450 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
Participants received AK102 300 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
Participants received AK102 150 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
Outcomes
Primary Outcome Measures
Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12
Secondary Outcome Measures
Percent change from baseline in low-density lipoprotein cholesterol (LDL-C)
Percent change from baseline in high-density lipoprotein cholesterol (HDL-C)
Percent change from baseline in non High-density lipoprotein (non-HDL) cholesterol
Percent change from baseline in serum Triglyceride (TG) cholesterol
Percent change from baseline in Apolipoprotein B (Apo B)
Percent change from baseline in Apolipoprotein A-I (ApoA-I)
Percent change from baseline in Lipoprotein(a) [Lp-(a)]
Percent change from baseline in Total Cholesterol(TC)
Incidence of treatment-emergent adverse events
Serum concentrations of AK102
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.
Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9)
Full Information
NCT ID
NCT04173793
First Posted
November 17, 2019
Last Updated
March 1, 2023
Sponsor
Akeso
Collaborators
AD Pharmaceuticals Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04173793
Brief Title
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
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
November 18, 2019 (Actual)
Primary Completion Date
September 26, 2022 (Actual)
Study Completion Date
September 26, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akeso
Collaborators
AD Pharmaceuticals Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heterozygous Familial Hypercholesterolemia
Keywords
HeFH, LDL-C
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
109 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AK102 450 mg
Arm Type
Experimental
Arm Description
Participants received AK102 450 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
Arm Title
AK102 300 mg
Arm Type
Experimental
Arm Description
Participants received AK102 300 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
Arm Title
AK102 150 mg
Arm Type
Experimental
Arm Description
Participants received AK102 150 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
Arm Title
Placebo Q4W
Arm Type
Placebo Comparator
Arm Description
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
Arm Title
Placebo Q2W
Arm Type
Placebo Comparator
Arm Description
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
Intervention Type
Drug
Intervention Name(s)
AK102
Intervention Description
Administered by subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered by subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Statins and/or Ezetimibe
Intervention Description
Lipid-lowering therapies
Primary Outcome Measure Information:
Title
Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12
Time Frame
At baseline and week 12
Secondary Outcome Measure Information:
Title
Percent change from baseline in low-density lipoprotein cholesterol (LDL-C)
Time Frame
From baseline through 12 weeks
Title
Percent change from baseline in high-density lipoprotein cholesterol (HDL-C)
Time Frame
From baseline through 12 weeks
Title
Percent change from baseline in non High-density lipoprotein (non-HDL) cholesterol
Time Frame
From baseline through 12 weeks
Title
Percent change from baseline in serum Triglyceride (TG) cholesterol
Time Frame
From baseline through 12 weeks
Title
Percent change from baseline in Apolipoprotein B (Apo B)
Time Frame
From baseline through 12 weeks
Title
Percent change from baseline in Apolipoprotein A-I (ApoA-I)
Time Frame
From baseline through 12 weeks
Title
Percent change from baseline in Lipoprotein(a) [Lp-(a)]
Time Frame
From baseline through 12 weeks
Title
Percent change from baseline in Total Cholesterol(TC)
Time Frame
From baseline through 12 weeks
Title
Incidence of treatment-emergent adverse events
Time Frame
From baseline through 12 weeks
Title
Serum concentrations of AK102
Time Frame
From baseline through 12 weeks
Title
Number of subjects who develop detectable anti-drug antibodies (ADAs)
Description
The immunogenicity of AK102 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies.
Time Frame
From baseline through 12 weeks
Title
Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9)
Time Frame
From baseline through 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shuyang Zhang, MD
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yujie Zhou, MD
Organizational Affiliation
Beijing Anzhen Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Anzhen Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100029
Country
China
Facility Name
Peking Union Medical College Hospital
City
Beijing
ZIP/Postal Code
100000
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of PCSK9 Inhibitor AK102 in Patients With Heterozygous Familial Hypercholesterolemia (HeFH)
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