Study to assess the tolerability and efficacy of AMG 145 in patients with heterozygous familial hypercholesterolemia
- Conditions
- Heterozygous Familial HypercholesterolemiaMedDRA version: 20.0 Level: LLT Classification code 10057079 Term: Heterozygous familial hypercholesterolemia System Organ Class: 100000004850Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2012-001365-32-GB
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 331
•Subject has provided informed consent.
•Male or female = 18 to = 80 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 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 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 a stable dose of an approved statin, and on stable dose(s) for all allowed (eg, ezetimibe, bile-acid sequestering resin, stanols, or regulatory-approved and marketed niacin (eg, Niaspan or Niacor)) lipidregulating drugs 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 (2.6 mmol/L) by central laboratory at screening
•Fasting triglycerides = 400 mg/dL (4.5 mmol/L) by central laboratory at screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 240
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60
•Homozygous familial hypercholesterolemia
•LDL or plasma apheresis within 4 months prior to randomization
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 randomization
•Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization
•Planned cardiac surgery or revascularization
•Type 1 diabetes, poorly controlled type 2 diabetes (HbA1c > 8.5%), newly diagnosed type 2 diabetes (within 6 months of randomization), or laboratory evidence of diabetes during screening (fasting plasma glucose = 126 mg/dL [7.0 mmol/L] or HbA1c = 6.5%) without prior diagnosis of diabetes
•Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 160 mmHg or diastolic BP (DBP) > 100 mmHg
•Subject requires uptitration of their current statin dose (these subjects can be uptitrated and rescreened one month later)
•Subject has taken in the last 6 weeks prior to LDL-C screening red yeast rice, omega-3 fatty acids ([eg, DHA and EPA combined] [> 1000 mg/day]) or prescription lipid-regulating drugs (eg, fibrates and derivatives) other than statins, ezetimibe, bile-acid sequestering resin, stanols, or regulatory approved and marketed niacin (eg, Niaspan or Niacor)
•Subject has taken a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to LDL-C screening, such as: anacetrapib, dalcetrapib or evacetrapib.Treatment in the last 3 months prior to LDL-C screening with any of the following drugs: systemic cyclosporine, systemic steroids (eg, IV, intramuscular [IM], or PO) (Note: hormone replacement therapy is permitted), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (eg, Accutane); (Note: vitamin A in a multivitamin preparation is permitted)
•Uncontrolled hypothyroidism or hyperthyroidism as defined by thyroid stimulating hormone (TSH) < 1.0 time 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) < 30 ml/min/1.73m2 at screeningActive liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times the ULN as determined by central laboratory analysis at screening
•CK > 3 times the ULN at screening
•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
•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 d
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