A Study to Evaluate the Safety and Efficacy of the PCSK9 Inhibitor AK102 in Patients With HoFH

A Phase 2 Study to Evaluate the Safety and Efficacy of PCSK9 Inhibitor AK102 in Patients With Homozygous Familial Hypercholesterolemia (HoFH)

AK102 is being developed for the treatment of HoFH. The study will be conducted in 2 parts, part 1 is open label, single arm study to evaluate the safety, tolerability and efficacy of PCSK9 inhibitor AK102, and part 2 is double blind, randomized, placebo controlled study to evaluate the efficacy and safety of PCSK9 inhibitor AK102. The treatment period will last 12 week.

Study Overview

• Status: Completed
• Conditions: Homozygous Familial Hypercholesterolemia
• Intervention / Treatment: Drug: AK102; Drug: Statins; Drug: Ezetimibe

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaoping Jin, PhD; Phone Number: +86 (0760) 8987 3999; Email: clinicaltrials@akesobio.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100029
      • Beijing Anzhen Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females, ≥18 years of age with a diagnosis of homozygous familial hypercholesterolemia by genetic confirmation or a clinical diagnosis based on a history of an untreated low-density lipoprotein cholesterol (LDL-C) concentration >500 mg/deciliter (dL) [13 millimoles/liter (mmol/L)] together with either xanthoma before 10 years of age or evidence of heterozygous familial hypercholesterolemia in both parents
• Stable on pre-existing, lipid-lowering therapies (statins in combination with ezetimibe) for at least 4 weeks with no planned medication or dose change for the duration of study participation
• Fasting central lab LDL-C concentration >130 mg/dL (3.4 mmol/L) and triglyceride concentration <400 mg/dL (4.5 mmol/L).
• Body weight of 40 kilograms (kg) or greater at screening

Exclusion Criteria:

• Received LDL plasma replacement therapy within 8 weeks before Investigational product administration
• Received Lomitapide or Mipomersen within 5 months before Investigational product administration
• Received prior treatment with PCSK9 inhibitors or AK102.
• Unexplained creatine kinase (CK) ≥ 5 times the upper limit of normal (ULN)
• Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA exceeding 500 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects with non-active HBsAg carriers, treated and stable hepatitis B (HBV DNA <500 IU/ mL) , and cured hepatitis C can be enrolled. Subjects with positive HCV antibodies are eligible only if the HCV RNA test results are negative.
• Known allergic reactions to any ingredients of AK102
• Any other condition(s) that would compromise the safety of the patient or compromise the quality of the clinical study as judged by the Investigator and/or Medical Monitor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK102; 450mg AK102, Q4W, subcutaneous injection	Drug: AK102; 450mg, Q4W, subcutaneous injection; Drug: Statins; Lipid-lowering therapies; Drug: Ezetimibe; Lipid-lowering therapies
Placebo Comparator: placebo; Placebo, Q4W, subcutaneous injection	Drug: Statins; Lipid-lowering therapies; Drug: Ezetimibe; Lipid-lowering therapies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12	Week 12
Incidence of treatment-emergent adverse events as assessed by CTCAE V5.0（only for part 1）	From baseline through 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in High-density lipoprotein (HDL) cholesterol	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)	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 (Apo A-I)	From baseline through 12 weeks
Percent Change From Baseline in Total Cholesterol(TC)	From baseline through 12 weeks
Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)	From baseline through 12 weeks
Concentrations of AK102 in Serum	Part 1: Day 1,Day 2, Day 4, Day 8, Day 15, Day 22, D29, D57. Part 2: Day 1, Day 29, Day 57
Number of subjects who develop detectable anti-drug antibodies (ADAs)	From baseline through 12 weeks

Collaborators and Investigators

• Sponsor: Akeso
• Collaborators: AD Pharmaceuticals Co., Ltd.
• Investigators: Principal Investigator: Shuyang Zhang, MD, Peking Union Medical College Hospital; Principal Investigator: Lvya Wang, Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2019
• Primary Completion (Actual): March 15, 2021
• Study Completion (Actual): March 15, 2021

Study Registration Dates

• First Submitted: April 28, 2019
• First Submitted That Met QC Criteria: April 30, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: LDL-C; HoFH
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe
• Other Study ID Numbers: AK102-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No