Heterozygous familial hypercholesterolemia MedDRA version: 13.1 Level: LLT Classification code 10057099 Term: Heterozygous familial hypercholesterolaemia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subject has provided informed consent - Male or female = 18 to = 75 years of age - Diagnosis of heterozygous familial hypercholesterolemia by having met the diagnostic criteria outlined by the Simon Broome Register Group (Scientific Steering Committee 1991) as defined by the documentation of one of the following in the patient's past medical record: 1. A total cholesterol concentration > 290 mg/dL (> 7.5 mmol/liter) in adulthood or a total cholesterol concentration > 260 mg/dL (> 6.7 mmol/liter) in childhood at an age of less than 16 years, or a LDL-C concentration > 190 mg/dL (> 4.9 mmol/liter) in adulthood or > 155 mg/dL (> 4.0 mmol/liter) in childhood AND Tendinous xanthomas in the patient or first- or second-degree relative 2. Deoxyribonucleic acid (DNA)-based evidence of mutation in the LDLR, ApoB, or PCSK9 gene 3. A total cholesterol concentration > 290 mg/dL (> 7.5 mmol/liter) in adulthood or a total cholesterol concentration > 260 mg/dL (> 6.7 mmol/liter) in childhood at an age of less than 16 years, or a LDL-C concentration > 190 mg/dL (> 4.9 mmol/liter) in adulthood or > 155 mg/dL (> 4.0 mmol/liter) in childhood AND family history of myocardial infarction before age 50 years in a second-degree relative or before age 60 years in a first-degree relative 4. A total cholesterol concentration > 290 mg/dL (> 7.5 mmol/liter) in adulthood or a total cholesterol concentration > 260 mg/dL (> 6.7 mmol/liter) in childhood at an age of less than 16 years, or a LDLC concentration > 190 mg/dL (> 4.9 mmol/liter) in adulthood or > 155 mg/dL (> 4.0 mmol/liter) in childhood AND family history of raised total cholesterol concentration > 290 mg/dL (> 7.5 mmol/liter) in a first or second-degree adult relative or > 260 mg/dL (> 6.7 mmol/liter) in child, brother, or sister aged younger than 16 years - On an approved statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks before LDL-C screening and, in the opinion of the investigator, not requiring uptitration - Fasting LDL-C = 100 mg/dL by central laboratory at screening - Fasting triglycerides = 400 mg/dL by central laboratory at screening Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: - Homozygous familial hypercholesterolemia - LDL or plasma apheresis within 12 months prior to randomization - NYHA III or IV heart failure, or known left ventricular ejection fraction 8.5%) - Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 160 mmHg or diastolic BP (DBP) > 100 mmHg, confirmed with repeat measurement - Subject requires uptitration of their current statin dose (these subjects can be uptitrated and rescreened one month later). - Subject has taken during > 2 weeks in the last 3 months prior to LDL-C screening: prescription lipid-regulating drugs other than statins or ezetimibe, such as fibrates and derivatives, bile-acid sequestering resins; red yeast rice, niacin (> 200 mg/day), or omega-3 fatty acids (>1000 mg/day) - Treatment in the last 3 months prior to LDL-C screening with any of the following drugs: cyclosporine, systemic steroids (IV, intramuscular [IM], or PO), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (eg, Accutane); (Note: vitamin A in a multivitamin preparation is permitted) - Hyperthyroidism or hypothyroidism as defined by TSH below the lower limit of normal (LLN) or >1.5 times the upper limit of normal (ULN), respectively, at screening - Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) 2 times the ULN as determined by central laboratory analysis at screening - CK > 3 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 randomization - Current therapeutic anticoagulation with vitamin K antagonist (eg, warfarin), heparin, low-molecular weight heparin, direct thrombin inhibitor, or Factor Xa inhibitor - 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 is not willing to use at least one highly effective method of birth control during treatment and for an additional 15 weeks after the end of treatment unless subject is sterilized or postmenopausal; postmenopausal is defined as 12 continuous months of spontaneous ame
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of 12 weeks of subcutaneous (SC) AMG 145, compared with placebo SC, on percent change from baseline in lowdensity lipoprotein cholesterol (LDL-C) in subjects with heterozygous familial hypercholesterolemia;Secondary Objective: - To evaluate the safety and tolerability of 2 doses of AMG 145 SC, compared with placebo SC, in subjects with heterozygous familial hypercholesterolemia - To assess the effects of 12 weeks of AMG 145 SC, compared with placebo SC, on absolute change in LDL-C, and percent change in nonhigh-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol/HDL-C ratio, and ApoB/Apolipoprotein A-1 (ApoA1) ratio in subjects with heterozygous familial hypercholesterolemia - To characterize pharmacokinetics of AMG 145 following SC injection in subjects with heterozygous familial hypercholesterolemia;Primary end point(s): The percent change from baseline in LDL-C at week 12.;Timepoint(s) of evaluation of this end point: From baseline to week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Absolute change from baseline in LDL-C at week 12 - Percent change from baseline in non-HDL-C at week 12 - Percent change from baseline in ApoB at week 12 - Percent change from baseline in the total cholesterol/HDL-C ratio at week 12 - Percent change from baseline in ApoB/ApoA1 ratio at week 12;Timepoint(s) of evaluation of this end point: - Absolute change from baseline in LDL-C at week 12: from baseline to week 12 - Percent change from baseline in non-HDL-C at week 12: from baseline to week 12 - Percent change from baseline in ApoB at week 12: from baseline to week 12 - Percent change from baseline in the total cholesterol/HDL-C ratio at week 12: from baseline to week 12 - Percent change from baseline in ApoB/ApoA1 ratio at week 12: from baseline to week 12 | — |
Countries
Canada, Germany, Hong Kong, Netherlands, Norway, Singapore, South Africa, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) Gmbh
Outcome results
None listed