Homozygous familial hypercholesterolaemia MedDRA version: 14.1 Level: LLT Classification code 10057100 Term: Homozygous familial hypercholesterolaemia System Organ Class: 100000004850
Conditions
Interventions
Product Name: AMG 145
Product Code: AMG 145
Pharmaceutical Form: Solution for injection in pre-filled pen
Current Sponsor code: AMG 145
Other descriptive name: AMG 145
Concentration unit: mg/ml millig
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Subject has provided informed consent. • Male or female = 12 to = 80 years of age • 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. • On a stable on a low-fat diet and taking pre-existing lipid-lowering therapies (such as statins, cholesterol-absorption inhibitors, bile-acid sequestrants or nicotinic acid, or combinations thereof) for at least 4 weeks, with fasting central lab LDL cholesterol concentration > 130 (3.4 mmol/L) • Fasting triglycerides = 400 mg/dL (4.5 mmol/L) by central laboratory at screening • Bodyweight of 40 kg or greater at screening Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 34 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: • LDL or plasma apheresis within 8 weeks prior to enrollment • Use of Mipomersen or Lomitapide within 5 months of screening • NYHA III or IV heart failure, or last known left ventricular ejection fraction 180 mmHg or diastolic BP (DBP) > 110 mmHg, confirmed with repeat measurement • Subject requires uptitration of their current statin dose within 4 weeks of screening (these subjects can be uptitrated and rescreened 1 month later) • Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) 3 times the ULN as determined by central laboratory analysis at screening • Unexplained CK > 5 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 enrollment • 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 1 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; • Subject is pregnant or breast feeding, or planning to become pregnant during treatment and/or within 15 weeks after the end of treatment • Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years • Subject has previously received AMG 145 or any other investigational therapy to inhibit inhibiting PCSK9 • Known sensitivity to any of the products to be administered during dosing • Subject will not be available for protocol-required study visits or procedures, to the best of the subject and investigator’s knowledge. • Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: To characterize the effect of 12 weeks of subcutaneous (SC) AMG 145 on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in subjects with homozygous familial hypercholesterolemia (HoFH) Part B: To evaluate the effect of 12 weeks of subcutaneous (SC) AMG 145 compared with placebo on percent change from baseline in LDL-C in subjects with HoFH;Secondary Objective: Part A: - To evaluate the safety and tolerability of AMG 145 SC in subjects with HoFH - To assess the effects of 12 weeks of AMG 145 SC on absolute change in LDL-C, and percent change in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol/HDL-C ratio, and ApoB/Apolipoprotein A-1 (ApoA1) ratio in subjects with HoFH - To evaluate AMG 145 pharmacokinetics and absolute change in PCSK9 in subjects with HoFH Part B: -To assess the effects of 12 weeks of AMG 145 SC, compared with placebo, on percent change from baseline in apolipoprotein B (ApoB) and lipoprotein (a) [Lp(a)] in subjects with homozygous familial hypercholesterolemia - Please refer to page 17 of the protocol for the exploratory objectives for Part B;Primary end point(s): Part A: The percent change LDL-C from baseline to week 12. Part B: Co-Primary Endpoints: - Mean percent change from baseline in LDL-C at weeks 6 and 12 - Mean percent change from baseline in LDL-C at weeks 8 and 12;Timepoint(s) of evaluation of this end point: Part A: From baseline to week 12 Part B: Baseline, weeks 6 and 12 Baseline, weeks 6 and 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A: - 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 - Response rate of subjects with 15% or greater reduction in LDL-C from baseline to Week 12 - Change from baseline in PCSK9 at week 12 Part B: Co-Secondary Endpoints: The co-secondary endpoints are the mean percent change from baseline at weeks 6 and 12 and weeks 8 and 12 for: -ApoB -Lp(a) ;Timepoint(s) of evaluation of this end point: Part A: - 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 - Response rate of subjects with 15% or greater reduction in LDL-C from baseline to Week 12 (Part A only): from baseline to week 12 - Change in PCSK9 at week 12 (Part A and Part B) Part B: - Baseline, weeks 6, 8 and 12 | — |
Countries
Belgium, Brazil, Canada, Czech Republic, France, Hong Kong, Italy, Lebanon, Malaysia, Netherlands, New Zealand, South Africa, Spain, Turkey, United States
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed