A study to look at the effect of AMG 145 on the build up of a waxy substance (plaque) in the arteries of the heart, using a method to see inside the heart.

• Register: EUCTR
• Last refreshed on: 12 September 2016
• Main ID: EUCTR2012-004208-37-HU
• Date of registration: 22/05/2013
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: A study to look at the effect of AMG 145 on the build up of a waxy substance (plaque) in the arteries of the heart, using a method to see inside the heart.
• Scientific title: A Double-Blind, Randomized, Multi-Center, Placebo-Controlled, Parallel Group Study to Determine the Effects of Evolocumab (AMG-145) Treatment on Atherosclerotic Disease Burden As Measured By Intravascular Ultrasound in Patients Undergoing Coronary Catheterization - GLAGOV
• Date of first enrolment: 27/06/2013
• Target sample size: 970
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004208-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Canada, Chile, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Russian Federation, South Africa, Spain, Sweden, 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 = 18 age at screening
- Clinical indication for coronary angiography
- Subjects already taking statin therapy, regulatory-approved sustained-release niacin (eg Niaspan?currently taking lipid-regulating therapy can be screened but must enter the study via a lipid stabilization period.
OR
- Subjects who are intolerant to statins (limited to no more than approximately 10% of total planned enrollment) must meet statin intolerance entry criteria in Appendix G.
- Subjects must have at least one eligible LDL-C level (as defined below) via local, central laboratory or point of care device at the initial screening visit and, if applicable, at the end of each lipid stabilization period. A pre-existing local LDL-C level may be used as the initial screening LDL-C value as long as it was drawn within 4 weeks of the screening visit and no interim changes to lipid regulating therapy have occurred during that 4 week period.
LDL-C = 80 mg/dL (2.07 mmol/L) with or without additional risk factors
OR
LDL-C = 60 -<80 mg/dL (1.55-2.07 mmol/L) in the presence of one Major or three Minor Risk factors as defined in the study protocol. Enrollment of subjects with LDL-C between = 60 mg/dL (1.55 mmol/L) and < 80 mg/dL (2.07 mmol/L) will be limited to no more than approximately 25% of total planned enrollment.
(For all major and minor risk factors, please see protocol)
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 745
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 225

Exclusion criteria:
- Clinically significant heart disease which in the opinion of the Principal Investigator is likely to require coronary bypass surgery, PCI (does not apply to PCI deemed necessary by the initial screening angiogram), cardiac transplantation, surgical or percutaneous valve repair and/or replacement during the course of the study.
- Coronary artery bypass graft surgery < 6 weeks prior to the qualifying IVUS.
- NYHA III or IV heart failure, or last known left ventricular ejection fraction < 30%
- Uncontrolled 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
- Known hemorrhagic stroke
- Uncontrolled hypertension at Randomization visit, defined as a resting systolic blood pressure of = 180mmHg.
- Personal or family history of hereditary muscular disorders
- Fasting triglycerides = 400 mg/dL (4.5 mmol/L) at screening and at end of lipid stabilization period
- Subject has taken a cholesterol ester transfer protein (CETP) inhibitor, (ie. anacetrapib, dalcetrapib, evacetrapib) or mipomersen or lomitapide in the last 12 months prior to LDL-C screening.
- Type 1 diabetes or poorly controlled type 2 diabetes (HbA1c > 9%) at screening.
- Treatment for more than 2 weeks 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); systemic vitamin A and retinol
derivatives for the treatment of dermatologic conditions (eg, Accutane) (Note: vitamin A in topical and multivitamin preparations
are permitted)
- Thyroid stimulating hormone (TSH) < lower limit of normal (LLN) or TSH > 1.5x upper limit of normal (ULN). A subject taking thyroid replacement therapy may be enrolled with TSH level below LLN if, in
the opinion of the investigator, the subject is in a clinically euthyroid state.
- Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 at screening, confirmed by a repeat measurement at least 1 week apart
- Active liver disease or hepatic dysfunction, defined as aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times the ULN as determined by analysis at screening or at end of lipid stabilization period.
- CK > 3 times the ULN at screening or at end of lipid stabilization period
- Known active infection or major hematologic, renal, metabolic,
gastrointestinal or endocrine dysfunction in the judgment of the
investigator
- Baseline IVUS does not meet IVUS Core Lab technical standards
- 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 not used an acceptable method(s) of birth control for at least 1 month prior to screening, unless the female subject is sterilized or postmenopausal (see protocol)
- Female subject is not willing to inform her partner of her participation in this clinical study and to use an acceptable method(s

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

Health Condition(s) or Problem(s) studied

Coronary Artery Disease
MedDRA version: 17.1 Level: LLT Classification code 10011079 Term: Coronary artery disease NOS System Organ Class: 100000004849

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: Evolocumab
Product Code: AMG 145
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Evolocumab
CAS Number: N/A
Current Sponsor code: AMG145
Other descriptive name: AMG145
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

Product Name: Evolocumab
Product Code: AMG 145
Pharmaceutical Form: Solution for injection in cartridge
INN or Proposed INN: Evolocumab
Current Sponsor code: AMG145
Other descriptive name: AMG145
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Solution for injection in cartridge
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline and week 78

Primary end point(s): The nominal change in percent atheroma volume (PAV) from baseline to 78 weeks post randomization

Secondary Objective: To evaluate the effect of AMG 145 on the change in normalized total atheroma volume (TAV) and the percentage of patients who demonstrate regression of coronary atherosclerosis either by PAV or TAV.

Main Objective: To evaluate the effect of AMG 145 on the change in burden of coronary atherosclerosis as measured by percent atheroma volume (PAV) in patients with coronary artery disease requiring angiography for a clinical indication who are taking statins.

Secondary Outcome(s)

Secondary end point(s): • Nominal change in total atheroma volume (TAV) from baseline to week 78
• Regression (any reduction from baseline) in PAV
• Regression (any reduction from baseline) in TAV

Timepoint(s) of evaluation of this end point: Baseline and week 78 for all secondary endpoints

Secondary ID(s)

2012-004208-37-NL

20120153

Source(s) of Monetary Support

Agmen Inc