A Study of PCSK9 Inhibitor AK102 in Patients With Heterozygous Familial Hypercholesterolemia (HeFH)

Akeso

Status and phase: Completed; Phase 2

Conditions: Heterozygous Familial Hypercholesterolemia

Treatments: Drug: Placebo; Drug: Statins and/or Ezetimibe; Drug: AK102

Study type: Interventional

Funder types: Industry

Identifiers

NCT04173793

AK102-201

Details and patient eligibility

About

This is a double-blind, randomized, placebo-controlled, multicenter study to evaluate the safety and efficacy of AK102 in patients with heterozygous familial hypercholesterolemia (HeFH).The primary objective of this study is to evaluate the efficacy of AK102 in patients with HeFH.

Enrollment: 109 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Subjects with heterozygous familial hypercholesterolemia diagnosed by genetic confirmation or clinical diagnosis criteria.
• Stable on pre-existing, lipid-lowering therapies (statins with or without ezetimibe) for at least 4 weeks with no planned medication or dose change for the duration of study participation.
• Fasting Low-Density Lipoprotein Cholesterol (LDL-C) ≥ 70 mg/dL in patients with history of Atherosclerotic Cardiovascular Disease (ASCVD) or Fasting Low-Density Lipoprotein Cholesterol (LDL-C) ≥ 100 mg/dL in patients without history of Atherosclerotic Cardiovascular Disease (ASCVD).
• Fasting triglycerides ≤ 400 mg/dL.
• Body weight ≥ 40kg.

Key Exclusion Criteria:

• Subjects with homozygous FH (clinically or by genotyping).
• Receipt of LDL apheresis within 12 months prior to the first dose of Investigational product.
• Receipt of Lomitapide or Mipomersen within 5 months prior to the first dose of Investigational product.
• Prior use of PCSK9 inhibitors.
• Creatine kinase (CK) >3 times of the upper limit of normal (ULN).
• Aspartate Aminotransferase (AST) ≥ 2 x ULN.
• Estimated Glomerular Filtration Rate (eGFR)≤ 30 mL/min/1.73m^2.
• Thyroid-Stimulating Hormone (TSH)> 1.5 x ULN or <1 x LLN.
• Type 1 diabetes, or type 2 diabetes that is or poorly controlled（HbA1c> 8.5%).
• Subjects with untreated or active chronic hepatitis B or active hepatitis C virus infections.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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109 participants in 5 patient groups, including a placebo group

AK102 450 mg

Experimental group

Description:

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

Treatment:

Drug: Statins and/or Ezetimibe

Drug: AK102

AK102 300 mg

Experimental group

Description:

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

Treatment:

Drug: Statins and/or Ezetimibe

Drug: AK102

AK102 150 mg

Experimental group

Description:

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

Treatment:

Drug: Statins and/or Ezetimibe

Drug: AK102

Placebo Q4W

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Statins and/or Ezetimibe

Placebo Q2W

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Statins and/or Ezetimibe