Heterozygous Familial Hypercholesterolemia MedDRA version: 15.0 Level: LLT Classification code 10057079 Term: Heterozygous familial hypercholesterolemia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: AMG 145
Pharmaceutical Form: Solution for injection
Current Sponsor code: AMG 145
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-
Ph
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subject has provided informed consent - Male or female => 18 to 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 =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 4 months prior to randomization NYHA III or IV heart failure, or last known left ventricular ejection fraction 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) 1.5 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 - 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 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 has either (1) not used at least 1 highly effective method of birth control for at least 1 month prior to screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of 12 weeks of subcutaneous (SC) AMG 145 every-2-weeks (Q2W) and every-4-weeks (Q4W), compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in subjects with heterozygous familial hypercholesterolemia.;Secondary Objective: - To evaluate the safety and tolerability of SC AMG 145 Q2W and Q4W, compared with placebo, in subjects with heterozygous familial hypercholesterolemia - To assess the effects of 12 weeks of SC AMG 145 Q2W and Q4W, compared with placebo, on change from baseline in LDL-C, and percent change from baseline in nonhigh-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol/HDL-C ratio, ApoB/Apolipoprotein A-1 (ApoA1) ratio, Lipoprotein (a) [Lp(a)], triglycerides and HDL-C in subjects with heterozygous familial hypercholesterolemia - To assess the effects of 12 weeks of SC AMG 145 Q2W and Q4W, compared with placebo, on percent of subjects attaining LDL-C < 70 mg/dL (1.8 mmol/L) in subjects with heterozygous familial hypercholesterolemia;Primary end point(s): The primary endpoint is the percent change from baseline in LDL-C at week 12.;Timepoint(s) of evaluation of this end point: At week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Tier 1 endpoints - Change from baseline in LDL-C at week 12 - LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) 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 Tier 2 endpoints - Percent change from baseline in Lp(a) at week 12 - Percent change from baseline in triglycerides at week 12 - Percent change from baseline in HDL-C at week 12;Timepoint(s) of evaluation of this end point: Tier 1 endpoints - Change from baseline in LDL-C at week 12 - LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) 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 Tier 2 endpoints - Percent change from baseline in Lp(a) at week 12 - Percent change from baseline in triglycerides at week 12 - Percent change from baseline in HDL-C at week 12 | — |
Countries
Australia, Canada, France, Germany, Hong Kong, Japan, Netherlands, New Zealand, Norway, Singapore, South Africa, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed