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

NCT04173793 | Completed Phase 2 DMC

• 1 other identifier: AK102-201
• Study Type: interventional
• Target: 109
• 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 heterozygous familial hypercholesterolemia (HeFH).The primary objective of this study is to evaluate the efficacy of AK102 in patients with HeFH.

Conditions

Heterozygous Familial Hypercholesterolemia

Keywords

HeFH; LDL-C

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 (5)

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

Placebo Q4W

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Statins and/or Ezetimibe

Placebo Q2W

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Statins and/or Ezetimibe

Interventions

AK102 DRUG

Administered by subcutaneous injection

AK102 150 mg; AK102 300 mg; AK102 450 mg

Placebo 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; Placebo Q2W; Placebo Q4W

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (2)

Beijing Anzhen Hospital

Beijing, Beijing Municipality, 100029, China

Location

Peking Union Medical College Hospital

Beijing, 100000, China

Location

Study Officials

• Shuyang Zhang, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

• Yujie Zhou, MD

  Beijing Anzhen Hospital

  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: November 17, 2019
• First Posted: November 22, 2019
• Study Start: November 18, 2019
• Primary Completion: September 26, 2022
• Study Completion: September 26, 2022
• Last Updated: March 2, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)