NCT03933293CompletedPhase 2
A Phase 2 Study to Evaluate the Safety and Efficacy of PCSK9 Inhibitor AK102 in Patients With Homozygous Familial Hypercholesterolemia (HoFH)
Akeso2 sites in 1 country10 target enrollmentStarted: May 13, 2019Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 10
- Locations
- 2
- Primary Endpoint
- Incidence of treatment-emergent adverse events as assessed by CTCAE V5.0（only for part 1）
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 AK
- •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.
Arms & Interventions
AK102
Experimental
450mg AK102, Q4W, subcutaneous injection
Intervention: Statins (Drug)
AK102
Experimental
450mg AK102, Q4W, subcutaneous injection
Intervention: AK102 (Drug)
AK102
Experimental
450mg AK102, Q4W, subcutaneous injection
Intervention: Ezetimibe (Drug)
placebo
Placebo Comparator
Placebo, Q4W, subcutaneous injection
Intervention: Statins (Drug)
placebo
Placebo Comparator
Placebo, Q4W, subcutaneous injection
Intervention: Ezetimibe (Drug)
Outcomes
Primary Outcomes
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 Outcomes
- Percent Change From Baseline in High-density lipoprotein (HDL) cholesterol(From baseline through 12 weeks)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From baseline through 12 weeks)
- Percent Change From Baseline in non High-density lipoprotein (non-HDL) cholesterol(From baseline through 12 weeks)
- Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)(From baseline through 12 weeks)
- Percent Change From Baseline in Serum Triglyceride (TG)(From baseline through 12 weeks)
- Percent Change From Baseline in Apolipoprotein B (Apo B)(From baseline through 12 weeks)
- Percent Change From Baseline in Apolipoprotein A-I (Apo A-I)(From baseline through 12 weeks)
- Percent Change From Baseline in Total Cholesterol(TC)(From baseline through 12 weeks)
- Concentrations of AK102 in Serum(Part 1: Day 1,Day 2, Day 4, Day 8, Day 15, Day 22, D29, D57. Part 2: Day 1, Day 29, Day 57)
Investigators
Study Sites (2)
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