A Study of PCSK9 Inhibitor AK102 in Patients With Hypercholesterolemia

NCT04358432 | Completed Phase 2

• 1 other identifier: AK102-203
• Study Type: interventional
• Target: 262
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12

  At baseline and week 12

Secondary Outcomes (12)

• 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

Study Arms (6)

AK102 450 mg

EXPERIMENTAL

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

Drug: AK102; Drug: Statins and/or Ezetimibe

AK102 300 mg

EXPERIMENTAL

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

Drug: AK102; Drug: Statins and/or Ezetimibe

AK102 150 mg

EXPERIMENTAL

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

Drug: AK102; Drug: Statins and/or Ezetimibe

AK102 75 mg

EXPERIMENTAL

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

Drug: AK102; Drug: Statins and/or Ezetimibe

Placebo Q4W

PLACEBO COMPARATOR

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

Drug: Placebos; Drug: Statins and/or Ezetimibe

Placebo Q2W

PLACEBO COMPARATOR

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

Drug: Placebos; Drug: Statins and/or Ezetimibe

Interventions

AK102 DRUG

Administered by subcutaneous injection

AK102 150 mg; AK102 300 mg; AK102 450 mg; AK102 75 mg

Placebos DRUG

Administered by subcutaneous injection

Placebo Q2W; Placebo Q4W

Statins and/or Ezetimibe DRUG

Lipid-lowering therapies

AK102 150 mg; AK102 300 mg; AK102 450 mg; AK102 75 mg; Placebo Q2W; Placebo Q4W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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；

You may not qualify if:

• 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 \[HbA1c \> 8.5% within 1 month\];
• Subjects with hypertension that could not be controlled by drugs;
• Known concomitant diseases that may lead to secondary hyperlipidemia, including nephrotic syndrome, cholestatic liver failure, etc;
• Positive HBsAg or HCV antibody;
• Known history of primary immunodeficiency virus infection or positive human immunodeficiency virus (HIV) test;
• History of drug or alcohol abuse prior to screening;

Sponsors & Collaborators

• Akeso: lead
• AD Pharmaceuticals Co., Ltd.: collaborator

Study Sites (2)

Zhong Shan Hosipital Fu Dan University

Shanghai, 200032, China

Location

Affiliated hospital of Guangdong medical university

Zhanjiang, 524000, China

Location

MeSH Terms

Conditions

Hypercholesterolemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Junbo Ge, MD

  Zhong Shan Hospital Fu Dan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2020
• First Posted: April 24, 2020
• Study Start: May 13, 2020
• Primary Completion: February 25, 2021
• Study Completion: February 25, 2021
• Last Updated: March 2, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)