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Open-label Extension (OLE) Study to Assess Safety and Efficacy of Evolocumab

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ClinicalTrials.gov Identifier: NCT02304484
Recruitment Status : Completed
First Posted : December 2, 2014
Results First Posted : March 19, 2019
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hypercholesterolemia
Intervention Biological: Evolocumab
Enrollment 770
Recruitment Details This study was conducted at 126 centers in 29 countries in the regions of Europe, North America, Asia Pacific, and Latin America. Participants were enrolled from 24 November 2014 to 31 August 2016.
Pre-assignment Details Participants who successfully completed week 80 of the parent Study 20120153 (NCT01813422) and did not discontinue study drug in the parent study for any reason were eligible for this study. All participants received open-label evolocumab.
Arm/Group Title Evolocumab
Hide Arm/Group Description Participants received 420 mg evolocumab once a month for up to 2 years.
Period Title: Overall Study
Started 770
Completed 745
Not Completed 25
Reason Not Completed
Death             9
Withdrawal by Subject             14
Lost to Follow-up             2
Arm/Group Title Evolocumab
Hide Arm/Group Description Participants received 420 mg evolocumab once a month for up to 2 years.
Overall Number of Baseline Participants 770
Hide Baseline Analysis Population Description
All enrolled participants. Baseline is defined as parent study 20120153 baseline.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 770 participants
59.5  (8.8)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 770 participants
18 - 64 years
536
  69.6%
≥ 65 years
234
  30.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 770 participants
Female
202
  26.2%
Male
568
  73.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 770 participants
Hispanic or Latino
38
   4.9%
Not Hispanic or Latino
732
  95.1%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 770 participants
American Indian or Alaska Native
1
   0.1%
Asian
19
   2.5%
Black or African American
5
   0.6%
Native Hawaiian or Other Pacific Islander
1
   0.1%
White
729
  94.7%
Multiple
11
   1.4%
Other
4
   0.5%
Low-density Lipoprotein Cholesterol (LDL-C) Concentration   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 770 participants
92.2  (27.3)
[1]
Measure Description: Baseline is defined as parent study 20120153 baseline.
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description

The severity of each adverse event (AE) was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 criteria, where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe or medically significant AE, Grade 4 = Life-threatening consequences, and Grade 5 = death related to AE.

An adverse device effect was defined as any adverse event related to the use of a medical device (autoinjector/pen or automated mini doser [AMD]), including but not limited to, AEs resulting from insufficient or inadequate Instructions for Use, AEs resulting from any malfunction of the device, or AEs resulting from use error or from intentional misuse of the device.

Time Frame From first dose of evolocumab up to 30 days after the last dose, or end of study, whichever was earlier, up to 108 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants
Arm/Group Title Evolocumab
Hide Arm/Group Description:
Participants received 420 mg evolocumab once a month for up to 2 years.
Overall Number of Participants Analyzed 770
Measure Type: Count of Participants
Unit of Measure: Participants
Any adverse event
526
  68.3%
Adverse events ≥ Grade 2
415
  53.9%
Adverse events ≥ Grade 3
206
  26.8%
Adverse events ≥ Grade 4
38
   4.9%
Serious adverse events
153
  19.9%
AEs leading to discontinuation of evolocumab
14
   1.8%
Fatal adverse events
6
   0.8%
Device-related adverse events
12
   1.6%
Device-related adverse events ≥ Grade 2
2
   0.3%
Device-related adverse events ≥ Grade 3
1
   0.1%
Device-related adverse events ≥ Grade 4
0
   0.0%
Serious device-related adverse events
0
   0.0%
2.Secondary Outcome
Title Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
Hide Description [Not Specified]
Time Frame Baseline (of study 20120153) and weeks 0, 4, 12, 24, 36, 48, 52, 76, and 104 of study 20140128
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants with available data at each time point
Arm/Group Title Evolocumab
Hide Arm/Group Description:
Participants received 420 mg evolocumab once a month for up to 2 years.
Overall Number of Participants Analyzed 770
Mean (Standard Deviation)
Unit of Measure: percent change
Percent change from baseline to week 0 Number Analyzed 751 participants
-21.52  (40.49)
Percent change from baseline to week 4 Number Analyzed 752 participants
-57.23  (22.19)
Percent change from baseline to week 12 Number Analyzed 746 participants
-58.54  (25.60)
Percent change from baseline to week 24 Number Analyzed 747 participants
-55.26  (28.51)
Percent change from baseline to week 36 Number Analyzed 738 participants
-51.72  (30.34)
Percent change from baseline to week 48 Number Analyzed 709 participants
-53.65  (28.72)
Percent change from baseline to week 52 Number Analyzed 725 participants
-51.30  (28.48)
Percent change from baseline to week 76 Number Analyzed 722 participants
-51.73  (32.49)
Percent change from baseline to week 104 Number Analyzed 607 participants
-47.94  (36.49)
Time Frame Total deaths are reported from the 1st dose of evolocumab up to the end of study; adverse events are reported from the 1st dose of evolocumab up to 30 days after the last dose of study drug or end of study, whichever was earlier. The median (minimum, maximum) duration of treatment was 23.7 (0.4, 24.6) months.
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Evolocumab
Hide Arm/Group Description Participants received 420 mg evolocumab once a month for up to 2 years.
All-Cause Mortality
Evolocumab
Affected / at Risk (%)
Total   9/770 (1.17%) 
Show Serious Adverse Events Hide Serious Adverse Events
Evolocumab
Affected / at Risk (%)
Total   153/770 (19.87%) 
Blood and lymphatic system disorders   
Haemorrhagic anaemia  1  1/770 (0.13%) 
Cardiac disorders   
Acute coronary syndrome  1  2/770 (0.26%) 
Acute myocardial infarction  1  4/770 (0.52%) 
Angina pectoris  1  13/770 (1.69%) 
Angina unstable  1  5/770 (0.65%) 
Arteriospasm coronary  1  1/770 (0.13%) 
Atrial fibrillation  1  5/770 (0.65%) 
Atrial flutter  1  1/770 (0.13%) 
Atrioventricular block complete  1  1/770 (0.13%) 
Cardiac arrest  1  2/770 (0.26%) 
Cardiac failure  1  2/770 (0.26%) 
Cardiac failure acute  1  1/770 (0.13%) 
Cardiac failure chronic  1  1/770 (0.13%) 
Cardiac failure congestive  1  3/770 (0.39%) 
Cardiac ventricular thrombosis  1  1/770 (0.13%) 
Congestive cardiomyopathy  1  1/770 (0.13%) 
Coronary artery disease  1  4/770 (0.52%) 
Coronary artery stenosis  1  1/770 (0.13%) 
Left ventricular failure  1  1/770 (0.13%) 
Myocardial infarction  1  1/770 (0.13%) 
Myocardial ischaemia  1  1/770 (0.13%) 
Palpitations  1  1/770 (0.13%) 
Pericarditis  1  1/770 (0.13%) 
Sinus bradycardia  1  1/770 (0.13%) 
Sinus tachycardia  1  1/770 (0.13%) 
Supraventricular tachycardia  1  1/770 (0.13%) 
Ventricular tachycardia  1  2/770 (0.26%) 
Ear and labyrinth disorders   
Tinnitus  1  1/770 (0.13%) 
Vertigo  1  2/770 (0.26%) 
Eye disorders   
Cataract  1  2/770 (0.26%) 
Diplopia  1  1/770 (0.13%) 
Gastrointestinal disorders   
Abdominal adhesions  1  1/770 (0.13%) 
Abdominal pain  1  1/770 (0.13%) 
Abdominal pain upper  1  1/770 (0.13%) 
Colitis  1  1/770 (0.13%) 
Duodenal perforation  1  1/770 (0.13%) 
Dyspepsia  1  1/770 (0.13%) 
Gastritis erosive  1  1/770 (0.13%) 
Incarcerated umbilical hernia  1  1/770 (0.13%) 
Inguinal hernia  1  1/770 (0.13%) 
Intestinal haemorrhage  1  1/770 (0.13%) 
Large intestine polyp  1  1/770 (0.13%) 
Pancreatitis  1  1/770 (0.13%) 
Pancreatitis acute  1  1/770 (0.13%) 
Pancreatitis chronic  1  1/770 (0.13%) 
Peptic ulcer  1  1/770 (0.13%) 
Umbilical hernia  1  1/770 (0.13%) 
Upper gastrointestinal haemorrhage  1  1/770 (0.13%) 
Vomiting  1  1/770 (0.13%) 
General disorders   
Chest discomfort  1  1/770 (0.13%) 
Chest pain  1  4/770 (0.52%) 
Fatigue  1  1/770 (0.13%) 
Malaise  1  1/770 (0.13%) 
Non-cardiac chest pain  1  6/770 (0.78%) 
Sudden death  1  1/770 (0.13%) 
Vascular stent occlusion  1  1/770 (0.13%) 
Hepatobiliary disorders   
Bile duct stone  1  1/770 (0.13%) 
Cholangitis  1  2/770 (0.26%) 
Cholecystitis acute  1  3/770 (0.39%) 
Cholecystitis chronic  1  1/770 (0.13%) 
Cholelithiasis  1  2/770 (0.26%) 
Portal vein thrombosis  1  1/770 (0.13%) 
Immune system disorders   
Contrast media reaction  1  1/770 (0.13%) 
Infections and infestations   
Appendicitis  1  2/770 (0.26%) 
Bacterial colitis  1  1/770 (0.13%) 
Cellulitis  1  1/770 (0.13%) 
Chronic sinusitis  1  1/770 (0.13%) 
Dengue fever  1  1/770 (0.13%) 
Diabetic foot infection  1  1/770 (0.13%) 
Diverticulitis  1  1/770 (0.13%) 
Gastroenteritis  1  1/770 (0.13%) 
Lung abscess  1  1/770 (0.13%) 
Lymph gland infection  1  1/770 (0.13%) 
Pertussis  1  1/770 (0.13%) 
Pneumonia  1  4/770 (0.52%) 
Pneumonia bacterial  1  2/770 (0.26%) 
Sepsis  1  1/770 (0.13%) 
Staphylococcal osteomyelitis  1  1/770 (0.13%) 
Injury, poisoning and procedural complications   
Anastomotic leak  1  1/770 (0.13%) 
Ankle fracture  1  1/770 (0.13%) 
Concussion  1  1/770 (0.13%) 
Contusion  1  1/770 (0.13%) 
Epicondylitis  1  1/770 (0.13%) 
Fall  1  3/770 (0.39%) 
Femoral neck fracture  1  1/770 (0.13%) 
Hip fracture  1  1/770 (0.13%) 
Intentional overdose  1  1/770 (0.13%) 
Meniscus injury  1  2/770 (0.26%) 
Muscle strain  1  1/770 (0.13%) 
Pelvic fracture  1  1/770 (0.13%) 
Post procedural haemorrhage  1  1/770 (0.13%) 
Radius fracture  1  1/770 (0.13%) 
Spinal compression fracture  1  1/770 (0.13%) 
Subarachnoid haematoma  1  1/770 (0.13%) 
Thoracic vertebral fracture  1  1/770 (0.13%) 
Toxicity to various agents  1  1/770 (0.13%) 
Investigations   
Anticoagulation drug level above therapeutic  1  1/770 (0.13%) 
Metabolism and nutrition disorders   
Dehydration  1  2/770 (0.26%) 
Gout  1  1/770 (0.13%) 
Hypertriglyceridaemia  1  1/770 (0.13%) 
Hypoglycaemia  1  1/770 (0.13%) 
Type 1 diabetes mellitus  1  1/770 (0.13%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  2/770 (0.26%) 
Arthritis  1  1/770 (0.13%) 
Lumbar spinal stenosis  1  2/770 (0.26%) 
Musculoskeletal chest pain  1  2/770 (0.26%) 
Osteoarthritis  1  5/770 (0.65%) 
Pain in extremity  1  1/770 (0.13%) 
Periarthritis  1  1/770 (0.13%) 
Synovial cyst  1  1/770 (0.13%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Benign salivary gland neoplasm  1  1/770 (0.13%) 
Bladder transitional cell carcinoma metastatic  1  1/770 (0.13%) 
Colon adenoma  1  2/770 (0.26%) 
Gastric cancer  1  2/770 (0.26%) 
Lung cancer metastatic  1  1/770 (0.13%) 
Lung neoplasm malignant  1  2/770 (0.26%) 
Metastases to stomach  1  1/770 (0.13%) 
Metastases to urinary tract  1  1/770 (0.13%) 
Metastatic gastric cancer  1  1/770 (0.13%) 
Metastatic malignant melanoma  1  1/770 (0.13%) 
Oesophageal carcinoma  1  1/770 (0.13%) 
Prostate cancer  1  2/770 (0.26%) 
Squamous cell carcinoma  1  1/770 (0.13%) 
Nervous system disorders   
Carotid artery stenosis  1  1/770 (0.13%) 
Carpal tunnel syndrome  1  2/770 (0.26%) 
Cervical radiculopathy  1  1/770 (0.13%) 
Dizziness  1  1/770 (0.13%) 
Generalised tonic-clonic seizure  1  1/770 (0.13%) 
Ischaemic stroke  1  1/770 (0.13%) 
Parkinsonism  1  1/770 (0.13%) 
Sciatica  1  1/770 (0.13%) 
Syncope  1  3/770 (0.39%) 
Transient ischaemic attack  1  2/770 (0.26%) 
Product Issues   
Device loosening  1  1/770 (0.13%) 
Psychiatric disorders   
Suicidal ideation  1  1/770 (0.13%) 
Renal and urinary disorders   
Acute kidney injury  1  1/770 (0.13%) 
Haematuria  1  1/770 (0.13%) 
Renal cyst  1  2/770 (0.26%) 
Reproductive system and breast disorders   
Benign prostatic hyperplasia  1  1/770 (0.13%) 
Respiratory, thoracic and mediastinal disorders   
Acute respiratory failure  1  2/770 (0.26%) 
Chronic obstructive pulmonary disease  1  4/770 (0.52%) 
Dyspnoea  1  1/770 (0.13%) 
Hypoxia  1  1/770 (0.13%) 
Idiopathic pulmonary fibrosis  1  1/770 (0.13%) 
Pneumonitis  1  1/770 (0.13%) 
Pulmonary embolism  1  1/770 (0.13%) 
Skin and subcutaneous tissue disorders   
Angioedema  1  1/770 (0.13%) 
Diabetic foot  1  1/770 (0.13%) 
Skin haemorrhage  1  1/770 (0.13%) 
Skin ulcer  1  1/770 (0.13%) 
Vascular disorders   
Hypotension  1  1/770 (0.13%) 
Venous thrombosis  1  1/770 (0.13%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Evolocumab
Affected / at Risk (%)
Total   49/770 (6.36%) 
Vascular disorders   
Hypertension  1  49/770 (6.36%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02304484     History of Changes
Other Study ID Numbers: 20140128
2014-001524-30 ( EudraCT Number )
First Submitted: October 7, 2014
First Posted: December 2, 2014
Results First Submitted: February 27, 2019
Results First Posted: March 19, 2019
Last Update Posted: March 19, 2019