Hypercholesterolemia
Conditions
Brief summary
The purpose of this study was to characterize the safety and tolerability of long-term administration of evolocumab in adults with known coronary artery disease and hypercholesterolemia.
Interventions
BIOLOGICALEvolocumab
Administered by subcutaneous injection once a month
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Completed week 80 of study 20120153 (NCT01813422).
Exclusion criteria
* Did not complete investigational product in the 20120153 parent study * Have an unstable medical condition, in the judgment of the investigator * Known sensitivity to any of the products to be administered during dosing * Currently enrolled in another investigational device or drug study (excluding evolocumab (AMG 145) parent study), or less than 30 days since ending another investigational device or drug study(s),or receiving other investigational agent(s)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From first dose of evolocumab up to 30 days after the last dose, or end of study, whichever was earlier, up to 108 weeks. | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Baseline (of study 20120153) and weeks 0, 4, 12, 24, 36, 48, 52, 76, and 104 of study 20140128 |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Czechia, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Malaysia, Mexico, Netherlands, Norway, Poland, Russia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Evolocumab Participants received 420 mg evolocumab once a month for up to 2 years. | 770 |
| Total | 770 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 9 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 14 |
Baseline characteristics
| Characteristic | Evolocumab |
|---|---|
| Age, Continuous | 59.5 years STANDARD_DEVIATION 8.8 |
| Age, Customized 18 - 64 years | 536 Participants |
| Age, Customized ≥ 65 years | 234 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 732 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Low-density Lipoprotein Cholesterol (LDL-C) Concentration | 92.2 mg/dL STANDARD_DEVIATION 27.3 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian | 19 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants |
| Race/Ethnicity, Customized Multiple | 11 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 4 Participants |
| Race/Ethnicity, Customized White | 729 Participants |
| Sex: Female, Male Female | 202 Participants |
| Sex: Female, Male Male | 568 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 770 |
| other Total, other adverse events | 49 / 770 |
| serious Total, serious adverse events | 153 / 770 |
Outcome results
Primary
Number of Participants With Adverse Events
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.
Population: All enrolled participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Evolocumab | Number of Participants With Adverse Events | Any adverse event | 526 Participants |
| Evolocumab | Number of Participants With Adverse Events | Adverse events ≥ Grade 2 | 415 Participants |
| Evolocumab | Number of Participants With Adverse Events | Adverse events ≥ Grade 3 | 206 Participants |
| Evolocumab | Number of Participants With Adverse Events | Adverse events ≥ Grade 4 | 38 Participants |
| Evolocumab | Number of Participants With Adverse Events | Serious adverse events | 153 Participants |
| Evolocumab | Number of Participants With Adverse Events | AEs leading to discontinuation of evolocumab | 14 Participants |
| Evolocumab | Number of Participants With Adverse Events | Fatal adverse events | 6 Participants |
| Evolocumab | Number of Participants With Adverse Events | Device-related adverse events | 12 Participants |
| Evolocumab | Number of Participants With Adverse Events | Device-related adverse events ≥ Grade 2 | 2 Participants |
| Evolocumab | Number of Participants With Adverse Events | Device-related adverse events ≥ Grade 3 | 1 Participants |
| Evolocumab | Number of Participants With Adverse Events | Device-related adverse events ≥ Grade 4 | 0 Participants |
| Evolocumab | Number of Participants With Adverse Events | Serious device-related adverse events | 0 Participants |
Secondary
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
Time frame: Baseline (of study 20120153) and weeks 0, 4, 12, 24, 36, 48, 52, 76, and 104 of study 20140128
Population: Enrolled participants with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Percent change from baseline to week 0 | -21.52 percent change | Standard Deviation 40.49 |
| Evolocumab | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Percent change from baseline to week 4 | -57.23 percent change | Standard Deviation 22.19 |
| Evolocumab | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Percent change from baseline to week 12 | -58.54 percent change | Standard Deviation 25.6 |
| Evolocumab | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Percent change from baseline to week 24 | -55.26 percent change | Standard Deviation 28.51 |
| Evolocumab | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Percent change from baseline to week 36 | -51.72 percent change | Standard Deviation 30.34 |
| Evolocumab | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Percent change from baseline to week 48 | -53.65 percent change | Standard Deviation 28.72 |
| Evolocumab | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Percent change from baseline to week 52 | -51.30 percent change | Standard Deviation 28.48 |
| Evolocumab | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Percent change from baseline to week 76 | -51.73 percent change | Standard Deviation 32.49 |
| Evolocumab | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Percent change from baseline to week 104 | -47.94 percent change | Standard Deviation 36.49 |