Clinical trial NCT04358432: A Study of PCSK9 Inhibitor AK102 in Patients With Hypercholesterolemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Lead sponsor: Akeso
Sponsor class: INDUSTRY
Collaborators: name: AD Pharmaceuticals Co., Ltd.
First posted: 2020-04-24
Enrollment: 262
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 .


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).

Primary outcomes:
measure: Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12
timeFrame: At baseline and week 12
Secondary outcomes:
measure: Percent change from baseline in low-density lipoprotein cholesterol (LDL-C)
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in high-density lipoprotein cholesterol (HDL-C)
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in non High-density lipoprotein (non-HDL) cholesterol
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in serum Triglyceride (TG) cholesterol
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in Apolipoprotein B (Apo B)
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in Apolipoprotein A-I (ApoA-I)
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in Lipoprotein(a) [Lp-(a)]
timeFrame: From baseline through 12 weeks
measure: Percent change from baseline in Total Cholesterol(TC)
timeFrame: From baseline through 12 weeks
measure: Incidence of treatment-emergent adverse events
timeFrame: From baseline through 12 weeks
measure: Serum concentrations of AK102
timeFrame: From baseline through 12 weeks
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From baseline through 12 weeks
measure: Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9)
timeFrame: From baseline through 12 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhong Shan Hosipital Fu Dan University
city: Zhanjiang
country: China
facility: Affiliated hospital of Guangdong medical university
Study officials:
affiliation: Zhong Shan Hospital Fu Dan University
name: Junbo Ge, MD
role: PRINCIPAL_INVESTIGATOR
References: