Clinical trial NCT03933293: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Homozygous Familial Hypercholesterolemia
Keywords: HoFH
LDL-C
Lead sponsor: Akeso
Sponsor class: INDUSTRY
Collaborators: name: AD Pharmaceuticals Co., Ltd.
First posted: 2019-05-01
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
timeFrame: Week 12
measure: Incidence of treatment-emergent adverse events as assessed by CTCAE V5.0（only for part 1）
timeFrame: From baseline through 12 weeks
Secondary outcomes:
measure: Percent Change From Baseline in High-density lipoprotein (HDL) cholesterol
timeFrame: From baseline through 12 weeks
measure: Percent Change From Baseline in non High-density lipoprotein (non-HDL) cholesterol
timeFrame: From baseline through 12 weeks
measure: Percent Change From Baseline in Serum Triglyceride (TG)
timeFrame: From baseline through 12 weeks
measure: Percent Change From Baseline in Apolipoprotein B (Apo B)
timeFrame: From baseline through 12 weeks
measure: Percent Change From Baseline in Apolipoprotein A-I (Apo A-I)
timeFrame: From baseline through 12 weeks
measure: Percent Change From Baseline in Total Cholesterol(TC)
timeFrame: From baseline through 12 weeks
measure: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)
timeFrame: From baseline through 12 weeks
measure: Concentrations of AK102 in Serum
timeFrame: Part 1: Day 1,Day 2, Day 4, Day 8, Day 15, Day 22, D29, D57. Part 2: Day 1, Day 29, Day 57
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From baseline through 12 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Anzhen Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Shuyang Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Anzhen Hospital
name: Lvya Wang
role: PRINCIPAL_INVESTIGATOR
References: