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

Akeso

Status and phase: Completed; Phase 2

Conditions: Homozygous Familial Hypercholesterolemia

Treatments: Drug: AK102; Drug: Statins; Drug: Ezetimibe

Study type: Interventional

Funder types: Industry

Identifiers

NCT03933293

AK102-202

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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10 participants in 2 patient groups, including a placebo group

AK102

Experimental group

Description:

450mg AK102, Q4W, subcutaneous injection

Treatment:

Drug: Ezetimibe

Drug: AK102

Drug: Statins

placebo

Placebo Comparator group

Description:

Placebo, Q4W, subcutaneous injection

Treatment:

Drug: Ezetimibe

Drug: Statins