A Study of PCSK9 Inhibitor AK102 in Patients With Hypercholesterolemia

NCT ID: NCT04358432

Last Updated: 2023-03-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 262 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-13
• Study Completion Date: 2021-02-25

Brief Summary

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 .

Conditions

Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

AK102 450 mg

Participants received AK102 450 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks

Group Type: EXPERIMENTAL

AK102

Intervention Type: DRUG

Administered by subcutaneous injection

Statins and/or Ezetimibe

Intervention Type: DRUG

Lipid-lowering therapies

AK102 300 mg

Participants received AK102 300 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks

Group Type: EXPERIMENTAL

AK102

Intervention Type: DRUG

Administered by subcutaneous injection

Statins and/or Ezetimibe

Intervention Type: DRUG

Lipid-lowering therapies

AK102 150 mg

Participants received AK102 150 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks

Group Type: EXPERIMENTAL

AK102

Intervention Type: DRUG

Administered by subcutaneous injection

Statins and/or Ezetimibe

Intervention Type: DRUG

Lipid-lowering therapies

AK102 75 mg

Participants received AK102 75 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks

Group Type: EXPERIMENTAL

AK102

Intervention Type: DRUG

Administered by subcutaneous injection

Statins and/or Ezetimibe

Intervention Type: DRUG

Lipid-lowering therapies

Placebo Q4W

Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Administered by subcutaneous injection

Statins and/or Ezetimibe

Intervention Type: DRUG

Lipid-lowering therapies

Placebo Q2W

Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Administered by subcutaneous injection

Statins and/or Ezetimibe

Intervention Type: DRUG

Lipid-lowering therapies

Interventions

AK102

Administered by subcutaneous injection

Intervention Type: DRUG

Placebos

Administered by subcutaneous injection

Intervention Type: DRUG

Statins and/or Ezetimibe

Lipid-lowering therapies

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AD Pharmaceuticals Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Akeso

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Junbo Ge, MD

Role: PRINCIPAL_INVESTIGATOR

Zhong Shan Hospital Fu Dan University

Locations

Zhong Shan Hosipital Fu Dan University

Shanghai, , China

Affiliated hospital of Guangdong medical university

Zhanjiang, , China

Countries

China

Other Identifiers

AK102-203

Identifier Type: -

Identifier Source: org_study_id