A 2-Part, Phase 2/3 Study to Assess the Safety, Tolerability and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia Part A - Open-label, Single-arm, Multicenter Pilot Study to Evaluate Safety, Tolerability, and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia Part B - Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 in Subjects

Phase 2

Completed

Conditions: hypercholesterolemia
elevated cholesterol
10027424

Registration Number: NL-OMON38555

Lead Sponsor: Amgen

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 3

Inclusion Criteria

Males and females, * 12 to * 80 years of age with a 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.
For enrollment, subjects have to be stable on a low-fat diet and their pre-existing, lipid-lowering
therapies (such as statins, cholesterol-absorption inhibitors, bile-acid sequestrants, nicotinic acid,
or combinations thereof) for at least 4 weeks, with fasting central lab LDL cholesterol
concentration >130 mg/dL (3.4 mmol/L), central lab triglyceride concentration < 400 mg/dL
(4.5 mmol/L), and bodyweight of 40 kg or greater at screening. Patients are should not change
their background lipid-lowering drug during the trial.

Exclusion Criteria

LDL or plasma apheresis within 8 weeks prior to enrollment; use of
Mipomersen within 5 months of screening; New York Heart Failure Association (NYHA) class III
or IV or last known left ventricular ejection fraction < 30%; cardiac arrhythmia within past
3 months that is not controlled by medication; myocardial infarction, unstable angina,
percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within
3 months of enrollment; planned cardiac surgery or revascularization; systolic blood pressure
(SBP) > 180 mmHg or diastolic BP (DBP) > 110 mmHg; requiring statin up-titration within
4 weeks of screening; estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2; persistent
aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x ULN, creatine kinase
(CK) > 5x ULN without a known source; known major active infection, or major hematologic,
renal, metabolic, gastrointestinal or endocrine dysfunction; deep vein thrombosis or pulmonary
embolism within 3 months prior to enrollment.