A clinical study to assess the safety, tolerability and efficacy of AMG 145 in subjects with homozygous familial hypercholesterolemia

• Register: EUCTR
• Last refreshed on: 5 August 2013
• Main ID: EUCTR2011-005399-40-ES
• Date of registration: 09/04/2013
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: A clinical study to assess the safety, tolerability and efficacy of AMG 145 in subjects with homozygous familial hypercholesterolemia
• Scientific title: A two part, Phase 2/3 Study to Assess the Safety, Tolerability and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia Part A - Open-label, Single-arm, Multicenter Pilot Study to Evaluate Safety, Tolerability, and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia Part B - Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia
• Date of first enrolment: 24/06/2013
• Target sample size: 67
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005399-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Part A - Open label, single blind; Part B - double blind, parallel group If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Austria, Belgium, Brazil, Canada, Czech Republic, France, Hong Kong, Malaysia, New Zealand, South Africa, Spain, Turkey, United States

Contacts

• Name: IHQ Medical Info - Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ Medical Info - Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
? Subject has provided informed consent.
? Male or female ? 12 to ? 65 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: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 51
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
? LDL or plasma apheresis within 8 weeks prior to enrollment
? Use of Mipomersen within 5 months of screening
? 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 enrollment
? Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to enrollment
? Planned cardiac surgery or revascularization within 20 weeks of screening
? Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 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) < 30 ml/min/1.73m2 at screening
? Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Homozygous familial hypercholesterolaemia
MedDRA version: 14.1 Level: LLT Classification code 10057100 Term: Homozygous familial hypercholesterolaemia System Organ Class: 100000004850

Intervention(s)

Product Name: AMG 145
Product Code: AMG 145
Pharmaceutical Form: Solution for injection
INN or Proposed INN: n/a
CAS Number: n/a
Current Sponsor code: AMG 145
Other descriptive name: AMG 145
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Part A & Part B: The percent change LDL-C from baseline to week 12.

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 evaluate the safety and tolerability of AMG 145 SC compared with placebo in subjects with HoFH
- To assess the effects of 12 weeks of AMG 145 SC, compared with placebo, 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

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

Timepoint(s) of evaluation of this end point: From baseline to week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - 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)Subject incidence of treatment emergent adverse events: from baseline to week 12

Secondary end point(s): ? Change in LDL-C at week 12 (Part A and Part B)
? Percent change in non-HDL-C at week 12 (Part A and Part B)
? Percent change in ApoB at week 12 (Part A and Part B)
? Percent change in the total cholesterol/HDL-C ratio at week 12 (Part A and Part B)
? Percent change in ApoB/ApoA1 ratio at week 12 (Part A and Part B)
? Response rate of subjects with 15% or greater reduction in LDL-C from baseline to Week 12 (Part A only)
? Change in PCSK9 at week 12 (Part A and Part B)Subject incidence of treatment emergent adverse events

Secondary ID(s)

2011-005399-40-BE

20110233

Source(s) of Monetary Support

Amgen Inc