A Study of PCSK9 Inhibitor AK102 in Patients With Hypercholesterolemia

A Double-blind, Randomized, Placebo-controlled, Multicenter Phase II Study of AK102 in the Treatment of Hypercholesterolemia Patients at Very High or High Risk of Cardiovascular Disease

This is a double-blind, randomized, placebo-controlled, multicenter study to evaluate the safety and efficacy of AK102 in patients with Hypercholesterolemia Patients at Very High or High Risk of Cardiovascular Disease .

The primary objective of this study is to evaluate the efficacy of AK102 in patients with Hypercholesterolemia Patients at Very High or High Risk of Cardiovascular Disease .

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Phase 2

Contacts and Locations

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

Study Locations

• China
  • Shanghai, China, 200032
    • Zhong Shan Hosipital Fu Dan University
  • Zhanjiang, China, 524000
    • Affiliated Hospital of Guangdong Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntarily sign the informed consent form (ICF), and be able to comply with the treatment plan, visit, laboratory examination and other requirements specified in the study;
2. Age ≥ 18, male or female;
3. According to the guidelines for the prevention and treatment of dyslipidemia in Chinese adults (revised in 2016), subjects assessed as very high risk or high risk of cardiovascular disease;
4. Subjects received stable and optimal dose of statins for at least 4 weeks before randomization, either in combination with or without ezetimibe;
5. The blood lipid level of the patients with stable 4-week basic lipid-lowering drug treatment met one of the following conditions by the central laboratory test: LDL-C level in very high risk subjects > 1.8 mmol / L (70 mg / dl) or LDL-C level of high-risk subjects > 2.6 mmol / L (100 mg / dl)
6. TG ≤ 4.5 mmol / L (400 mg / dl) measured by central laboratory at screening；

Exclusion Criteria:

1. Has received cholesterol ester transfer protein (CETP) inhibitor within12 months prior to randomization;
2. Has received PCSK9 inhibitors or are known to be allergic to PCSK9 inhibitors or their components;
3. Has received other investigational drugs within 4 weeks or within 5 half lives (whichever was longer) prior to screening.
4. Has previously received biological agent treatment, organ transplantation or gene therapy;
5. Abnormal laboratories prior to the first study drug administration: ALT or AST> 3 × ULN; Creatine kinase > 5 × ULN; eGFR <= 30 ml/min/1.73m2 by Cockcroft Gault method;
6. Uncontrolled hypothyroidism or hyperthyroidism defined as TSH < 1.0 ×LLN or > 1.5 × ULN, respectively;
7. Myocardial infarction, unstable angina pectoris, percutaneous coronary intervention (PCI), coronary bypass grafting (CABG), stroke, severe deep vein thrombosis or pulmonary embolism, or severe arrhythmia occurred within three months prior to randomization ;
8. Grade III or IV according to NYHA assessment;
9. Planned to have heart-related surgery within 3 months after randomization;
10. Type 1 diabetes or poorly controlled type 2 diabetes [HbA1c > 8.5% within 1 month];
11. Subjects with hypertension that could not be controlled by drugs;
12. Known concomitant diseases that may lead to secondary hyperlipidemia, including nephrotic syndrome, cholestatic liver failure, etc;
13. Positive HBsAg or HCV antibody;
14. Known history of primary immunodeficiency virus infection or positive human immunodeficiency virus (HIV) test;
15. History of drug or alcohol abuse prior to screening;
16. Has taken the following drugs within 6 weeks prior to screening: red koji rice > 200 mg/day; niacin > 1000 mg/day; omega-3 fatty acids; steroids or prescription lipid regulating drugs ; cholesterol lowering drugs, health care products, Chinese patent medicines or other food additives other than statins and ezetimibe;
17. Has taken the following drugs within 3 months prior to screening: systemic cyclosporine, systemic steroids, vitamin A derivatives and retinol derivatives for the treatment of skin diseases (such as retinoic acid).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

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: Statins and/or Ezetimibe; Lipid-lowering therapies; Drug: Placebos; Administered by subcutaneous injection
Placebo Comparator: Placebo Q2W; Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks	Drug: Statins and/or Ezetimibe; Lipid-lowering therapies; Drug: Placebos; Administered by subcutaneous injection
Experimental: AK102 75 mg; Participants received AK102 75 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

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.

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2020
• Primary Completion (Actual): February 25, 2021
• Study Completion (Actual): February 25, 2021

Study Registration Dates

• First Submitted: April 21, 2020
• First Submitted That Met QC Criteria: April 21, 2020
• First Posted (Actual): April 24, 2020

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

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe
• Other Study ID Numbers: AK102-203

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