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

Homozygous Familial Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03933293
• Other study ID #: AK102-202
• Status: Completed
• Phase: Phase 2
• Start date: May 13, 2019
• Est. completion date: March 15, 2021

Study information

• Verified date: March 2023
• Source: Akeso
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 15, 2021
• Est. primary completion date: March 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Homozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• AK102
450mg, Q4W, subcutaneous injection
• Statins
Lipid-lowering therapies
• Ezetimibe
Lipid-lowering therapies

Locations

Country	Name	City	State
China	Beijing Anzhen Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Akeso	AD Pharmaceuticals Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12		Week 12
Primary	Incidence of treatment-emergent adverse events as assessed by CTCAE V5.0(only for part 1)		From baseline through 12 weeks
Secondary	Percent Change From Baseline in High-density lipoprotein (HDL) cholesterol		From baseline through 12 weeks
Secondary	Percent Change From Baseline in non High-density lipoprotein (non-HDL) cholesterol		From baseline through 12 weeks
Secondary	Percent Change From Baseline in Serum Triglyceride (TG)		From baseline through 12 weeks
Secondary	Percent Change From Baseline in Apolipoprotein B (Apo B)		From baseline through 12 weeks
Secondary	Percent Change From Baseline in Apolipoprotein A-I (Apo A-I)		From baseline through 12 weeks
Secondary	Percent Change From Baseline in Total Cholesterol(TC)		From baseline through 12 weeks
Secondary	Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)		From baseline through 12 weeks
Secondary	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
Secondary	Number of subjects who develop detectable anti-drug antibodies (ADAs)		From baseline through 12 weeks