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
Overview
- Phase
- Phase 2
- Intervention
- Statins and/or Ezetimibe
- Conditions
- Hypercholesterolemia
- Sponsor
- Akeso
- Enrollment
- 262
- Locations
- 2
- Primary Endpoint
- Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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 .
Investigators
Eligibility Criteria
Inclusion Criteria
- •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;
- •Age ≥ 18, male or female;
- •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;
- •Subjects received stable and optimal dose of statins for at least 4 weeks before randomization, either in combination with or without ezetimibe;
- •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)
- •TG ≤ 4.5 mmol / L (400 mg / dl) measured by central laboratory at screening；
Exclusion Criteria
- •Has received cholesterol ester transfer protein (CETP) inhibitor within12 months prior to randomization;
- •Has received PCSK9 inhibitors or are known to be allergic to PCSK9 inhibitors or their components;
- •Has received other investigational drugs within 4 weeks or within 5 half lives (whichever was longer) prior to screening.
- •Has previously received biological agent treatment, organ transplantation or gene therapy;
- •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;
- •Uncontrolled hypothyroidism or hyperthyroidism defined as TSH \< 1.0 ×LLN or \> 1.5 × ULN, respectively;
- •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 ;
- •Grade III or IV according to NYHA assessment;
- •Planned to have heart-related surgery within 3 months after randomization;
- •Type 1 diabetes or poorly controlled type 2 diabetes \[HbA1c \> 8.5% within 1 month\];
Arms & Interventions
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
Intervention: Statins and/or Ezetimibe
AK102 450 mg
Participants received AK102 450 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
Intervention: AK102
AK102 450 mg
Participants received AK102 450 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
Intervention: Statins and/or Ezetimibe
AK102 300 mg
Participants received AK102 300 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
Intervention: AK102
AK102 300 mg
Participants received AK102 300 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
Intervention: Statins and/or Ezetimibe
AK102 150 mg
Participants received AK102 150 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
Intervention: AK102
AK102 150 mg
Participants received AK102 150 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
Intervention: Statins and/or Ezetimibe
AK102 75 mg
Participants received AK102 75 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
Intervention: AK102
AK102 75 mg
Participants received AK102 75 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
Intervention: Statins and/or Ezetimibe
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
Intervention: Placebos
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
Intervention: Placebos
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
Intervention: Statins and/or Ezetimibe
Outcomes
Primary Outcomes
Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12
Time Frame: At baseline and week 12
Secondary Outcomes
- 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)
- Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9)(From baseline through 12 weeks)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From baseline through 12 weeks)