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

• Register: ClinicalTrials.gov
• Last refreshed on: 13 March 2023
• Main ID: NCT03933293
• Date of registration: 28/04/2019
• Prospective Registration: Yes
• Primary sponsor: Akeso
• Public title: A Study to Evaluate the Safety and Efficacy of the PCSK9 Inhibitor AK102 in Patients With HoFH
• Scientific title: A Phase 2 Study to Evaluate the Safety and Efficacy of PCSK9 Inhibitor AK102 in Patients With Homozygous Familial Hypercholesterolemia (HoFH)
• Date of first enrolment: May 13, 2019
• Target sample size: 10
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03933293
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

China

Contacts

• Name: Lvya Wang
• Affiliation: Beijing Anzhen Hospital

• Name: Shuyang Zhang, MD
• Affiliation: Peking Union Medical College Hospital

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Homozygous Familial Hypercholesterolemia

Intervention(s)

Drug: Statins

Drug: AK102

Drug: Ezetimibe

Primary Outcome(s)

Incidence of treatment-emergent adverse events as assessed by CTCAE V5.0(only for part 1) [Time Frame: From baseline through 12 weeks]

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 [Time Frame: Week 12]

Secondary Outcome(s)

Percent Change From Baseline in non High-density lipoprotein (non-HDL) cholesterol [Time Frame: From baseline through 12 weeks]

Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) [Time Frame: From baseline through 12 weeks]

Percent Change From Baseline in High-density lipoprotein (HDL) cholesterol [Time Frame: From baseline through 12 weeks]

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]

Number of subjects who develop detectable anti-drug antibodies (ADAs) [Time Frame: From baseline through 12 weeks]

Percent Change From Baseline in Apolipoprotein B (Apo B) [Time Frame: From baseline through 12 weeks]

Percent Change From Baseline in Total Cholesterol(TC) [Time Frame: From baseline through 12 weeks]

Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) [Time Frame: From baseline through 12 weeks]

Percent Change From Baseline in Serum Triglyceride (TG) [Time Frame: From baseline through 12 weeks]

Secondary ID(s)

AK102-202

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

AD Pharmaceuticals Co., Ltd.