Back to results

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

Primary Purpose

Homozygous Familial Hypercholesterolemia

Status

Completed

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

AK102

Statins

Ezetimibe

About this trial

This is an interventional treatment trial for Homozygous Familial Hypercholesterolemia focused on measuring HoFH, LDL-C

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Peking Union Medical College Hospital
Beijing Anzhen Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AK102

placebo

Arm Description

450mg AK102, Q4W, subcutaneous injection

Placebo, Q4W, subcutaneous injection

Outcomes

Primary Outcome Measures

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

Incidence of treatment-emergent adverse events as assessed by CTCAE V5.0（only for part 1）

Secondary Outcome Measures

Percent Change From Baseline in High-density lipoprotein (HDL) cholesterol

Percent Change From Baseline in non High-density lipoprotein (non-HDL) cholesterol

Percent Change From Baseline in Serum Triglyceride (TG)

Percent Change From Baseline in Apolipoprotein B (Apo B)

Percent Change From Baseline in Apolipoprotein A-I (Apo A-I)

Percent Change From Baseline in Total Cholesterol(TC)

Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)

Concentrations of AK102 in Serum

Number of subjects who develop detectable anti-drug antibodies (ADAs)

Full Information

NCT ID

NCT03933293

First Posted

April 28, 2019

Last Updated

March 1, 2023

Sponsor

Akeso

Collaborators

AD Pharmaceuticals Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03933293

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

May 13, 2019 (Actual)

Primary Completion Date

March 15, 2021 (Actual)

Study Completion Date

March 15, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Akeso

Collaborators

AD Pharmaceuticals Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Homozygous Familial Hypercholesterolemia

Keywords

HoFH, LDL-C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AK102

Arm Type

Experimental

Arm Description

450mg AK102, Q4W, subcutaneous injection

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

Placebo, Q4W, subcutaneous injection

Intervention Type

Drug

Intervention Name(s)

AK102

Intervention Description

450mg, Q4W, subcutaneous injection

Intervention Type

Drug

Intervention Name(s)

Statins

Intervention Description

Lipid-lowering therapies

Intervention Type

Drug

Intervention Name(s)

Ezetimibe

Intervention Description

Lipid-lowering therapies

Primary Outcome Measure Information:

Title

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

Time Frame

Week 12

Title

Incidence of treatment-emergent adverse events as assessed by CTCAE V5.0（only for part 1）

Time Frame

From baseline through 12 weeks

Secondary Outcome Measure Information:

Title

Percent Change From Baseline in High-density lipoprotein (HDL) cholesterol

Time Frame

From baseline through 12 weeks

Title

Percent Change From Baseline in non High-density lipoprotein (non-HDL) cholesterol

Time Frame

From baseline through 12 weeks

Title

Percent Change From Baseline in Serum Triglyceride (TG)

Time Frame

From baseline through 12 weeks

Title

Percent Change From Baseline in Apolipoprotein B (Apo B)

Time Frame

From baseline through 12 weeks

Title

Percent Change From Baseline in Apolipoprotein A-I (Apo A-I)

Time Frame

From baseline through 12 weeks

Title

Percent Change From Baseline in Total Cholesterol(TC)

Time Frame

From baseline through 12 weeks

Title

Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)

Time Frame

From baseline through 12 weeks

Title

Concentrations of AK102 in Serum

Time Frame

Part 1: Day 1,Day 2, Day 4, Day 8, Day 15, Day 22, D29, D57. Part 2: Day 1, Day 29, Day 57

Title

Number of subjects who develop detectable anti-drug antibodies (ADAs)

Time Frame

From baseline through 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shuyang Zhang, MD

Organizational Affiliation

Peking Union Medical College Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Lvya Wang

Organizational Affiliation

Beijing Anzhen Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Peking Union Medical College Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100000

Country

China

Facility Name

Beijing Anzhen Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100029

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs