A Study of PCSK9 Inhibitor AK102 in Patients With Hypercholesterolemia

Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04358432
• Other study ID #: AK102-203
• Status: Completed
• Phase: Phase 2
• Start date: May 13, 2020
• Est. completion date: February 25, 2021

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 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 .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 262
• Est. completion date: February 25, 2021
• Est. primary completion date: February 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

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

Locations

Country	Name	City	State
China	Zhong Shan Hosipital Fu Dan University	Shanghai
China	Affiliated hospital of Guangdong medical university	Zhanjiang

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