Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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21 August 2017 |
Main ID: |
EUCTR2011-005399-40-BE |
Date of registration:
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07/02/2012 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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A clinical study to assess the safety, tolerability and efficacy of AMG 145 in subjects with homozygous familial hypercholesterolemia
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Scientific title:
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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
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Date of first enrolment:
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09/03/2012 |
Target sample size:
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59 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005399-40 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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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
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Belgium
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Brazil
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Canada
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Czech Republic
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France
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Hong Kong
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Italy
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Lebanon
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Malaysia
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Netherlands
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New Zealand
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South Africa
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Spain
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Turkey
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United States
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Contacts
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Name:
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IHQ Medical Info - Clinical Trials
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Address:
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Dammstrasse 23, P.O. Box 1557
(CH-)6300
Zug
Switzerland |
Telephone:
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N/A |
Email:
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MedinfoInternational@amgen.com |
Affiliation:
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Amgen (EUROPE) GmbH |
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Name:
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IHQ Medical Info - Clinical Trials
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Address:
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Dammstrasse 23, P.O. Box 1557
(CH-)6300
Zug
Switzerland |
Telephone:
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N/A |
Email:
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MedinfoInternational@amgen.com |
Affiliation:
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Amgen (EUROPE) GmbH |
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Key inclusion & exclusion criteria
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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: • 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 < 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
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Health Condition(s) or Problem(s) studied
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Homozygous familial hypercholesterolaemia MedDRA version: 14.1
Level: LLT
Classification code 10057100
Term: Homozygous familial hypercholesterolaemia
System Organ Class: 100000004850
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Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
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Intervention(s)
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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 milligram(s)/millilitre Concentration type: equal Concentration number: 140- Pharmaceutical form of the placebo: Solution for injection in pre-filled pen Route of administration of the placebo: Subcutaneous use
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Primary Outcome(s)
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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
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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
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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
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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
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Secondary Outcome(s)
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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
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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)
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Source(s) of Monetary Support
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Amgen Inc
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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