A clinical study to assess the safety, tolerability and efficacy of AMG 145 in subjects with homozygous familial hypercholesterolemia

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 59

Inclusion Criteria

• Subject has provided informed consent.
• Male or female = 12 to = 80 years of age
• Diagnosis of homozygous familial hypercholesterolemia by genetic confirmation or a clinical diagnosis based on a history of an untreated LDL cholesterol concentration greater than 500 mg/dl (13 mmol/L) together with either xanthoma before 10 years of age or evidence of heterozygous familial hypercholesterolemia in both parents.
• On a stable on a low-fat diet and taking pre-existing lipid-lowering therapies (such as statins, cholesterol-absorption inhibitors, bile-acid sequestrants or nicotinic acid, or combinations thereof) for at least 4 weeks, with fasting central lab LDL cholesterol concentration > 130 (3.4 mmol/L)
• Fasting triglycerides = 400 mg/dL (4.5 mmol/L) by central laboratory at screening
• Bodyweight of 40 kg or greater at screening

Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

• LDL or plasma apheresis within 8 weeks prior to enrollment
• Use of Mipomersen or Lomitapide within 5 months of screening
• NYHA III or IV heart failure, or last known left ventricular ejection fraction < 30%
• Uncontrolled serious cardiac arrhythmia defined as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications, in the past 3 months prior to enrollment
• Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to enrollment
• Planned cardiac surgery or revascularization within 20 weeks of screening
• Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 180 mmHg or diastolic BP (DBP) > 110 mmHg, confirmed with repeat measurement
• Subject requires uptitration of their current statin dose within 4 weeks of screening (these subjects can be uptitrated and rescreened 1 month later)
• Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 at screening
• Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the ULN as determined by central laboratory analysis at screening
• Unexplained CK > 5 times the ULN at screening, confirmed by a repeat measurement at least 1 week apart
• Known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction in the judgment of the investigator
• Diagnosis of deep vein thrombosis or pulmonary embolism within 3 months prior to enrollment
• Unreliability as a study participant based on the investigator's (or designee’s) knowledge of the subject (eg, alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis)
• Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)
• Female subject of childbearing potential who is not willing to inform
her sexual partner of her participation in this clinical study and who
is not willing to use an acceptable method(s) of birth control during
treatment with Investigational product (AMG 145 or placebo) and for
an additional 15 weeks after the last dose of Investigational Product
(AMG 145 or placebo) unless subject is sterilized or postmenopausal.
Male subject with a female partner of childbearing potential not wiling to agree to inform his partner of his participation in this clinical study.
• Subject is pregnant or breast feeding, planning to become pregnant or planning to breastfeed during treatment with Investigational Product (AMG 145 or placebo) and/or within 15 weeks after the last dose of Investigational Product (AMG 145 or placebo).
• Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years
• Subject has previously received AMG 145 or any other investigational therapy to inhibit inhibiting PCSK9
• Known sensitivity to any of the products to be administered during dosing
• Subject will not be available for protocol-required study visits or procedures, to the best of the subject and investigator’s knowledge.
• Subject has any kind of disorder that, in th

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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