Study to assess the tolerability and efficacy of AMG 145 in patients with heterozygous familial hypercholesterolemia
- Conditions
- Heterozygous familial hypercholesterolaemiaMedDRA version: 14.0Level: LLTClassification code 10057099Term: Heterozygous familial hypercholesterolaemiaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2011-001528-39-SE
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 150
- 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 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 an approved statin, with stable dose(s) for all allowed (eg, ezetimibe,
bile-acid sequestering resin, stanols, or regulatory-approved and
marketed niacin (eg, Niaspan or Niacor)) lipid-regulating 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/liter) by central laboratory at screening
- Fasting triglycerides = 400 mg/dL (4.5 mmol/liter)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 90
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 12 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 within 20 weeks of
screening
- Type 1 diabetes or newly diagnosed (within 3 months of randomization) type 2 diabetes, or poorly controlled type 2 diabetes (HbA1c > 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 in the last 6 weeks prior to LDL-C screening red
yeast rice, omega-3 fatty acids ([eg, DHA and EPA] [> 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)
- Treatment in the last 3 months prior to LDL-C screening with any of the following drugs: systemic 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 thyroid stimulating
hormone (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) < 30 ml/min/1.73m2 at screening
- Active 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, 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 (Note: anti-platelet agents [eg, aspirin, clopidogrel, prasugrel, ticagrelor, dipyridamole] are permitted).
- 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 who is not willing to use at least one highly effective method of birth contr
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