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

NCT03933293 | Completed Phase 2 DMC

• 1 other identifier: AK102-202
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Homozygous Familial Hypercholesterolemia

Keywords

HoFH; LDL-C

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• 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

Study Arms (2)

AK102

EXPERIMENTAL

450mg AK102, Q4W, subcutaneous injection

Drug: AK102; Drug: Statins; Drug: Ezetimibe

placebo

PLACEBO COMPARATOR

Placebo, Q4W, subcutaneous injection

Drug: Statins; Drug: Ezetimibe

Interventions

AK102 DRUG

450mg, Q4W, subcutaneous injection

AK102

Statins DRUG

Lipid-lowering therapies

AK102; placebo

Ezetimibe DRUG

Lipid-lowering therapies

AK102; placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (2)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100000, China

Location

Beijing Anzhen Hospital

Beijing, Beijing Municipality, 100029, China

Location

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Interventions

Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ezetimibe

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Shuyang Zhang, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

• Lvya Wang

  Beijing Anzhen Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 28, 2019
• First Posted: May 1, 2019
• Study Start: May 13, 2019
• Primary Completion: March 15, 2021
• Study Completion: March 15, 2021
• Last Updated: March 2, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)