Hyperlipidemia and Mixed Dyslipidemia
Conditions
Keywords
High cholesterol, Raised cholesterol, Cholesterol, Elevated Cholesterol
Brief summary
This study will contribute to the evaluation of long-term safety, tolerability and efficacy of evolocumab (AMG 145) in adults with hyperlipidemia and adults with mixed dyslipidemia.
Interventions
BIOLOGICALEvolocumab
Administered by subcutaneous injection either every 2 weeks or once a month (patient preference) using a prefilled autoinjector pen
DRUGStandard of Care
Standard of care therapy as per local practices. This could include prescribed therapies and/or dietary/exercise regimes
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
\- Complete a qualifying evolocumab (AMG 145) parent study (ie, Study 20110114 \[NCT01763827\], 20110115 \[NCT01763866\], 20110116 \[NCT01763905\], 20110117 \[NCT01763918\], 20110109 \[NCT01516879\], 20120122 \[NCT01953328\], 20120332 \[NCT01984424\], 20120348 \[NCT01849497\], or 20120356 \[NCT01879319\]).
Exclusion criteria
* Experienced a treatment-related serious adverse event that led to study drug discontinuation in the 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 | 48 weeks in the SOC-controlled period and up to 2 years in the All-IP period | Adverse event (AE) severity assessments were made using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grading, version 4.0, where grade 1 = mild AE, grade 2 = moderate AE, Grade 3 = severe AE, grade 4 = life-threatening AE and Grade 5 = death due to AE. |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in LDL-C at Weeks 48 and 104 | Baseline of the parent study and weeks 48 amd 104 |
| Change From Baseline in LDL-C at Weeks 48 and 104 | Baseline of the parent study and weeks 48 amd 104 |
Countries
Australia, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Hong Kong, Hungary, Italy, Japan, Netherlands, New Zealand, Norway, Poland, Russia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 365 study centers in 24 countries in Europe, North America, and Asia Pacific from 23 April 2013 to 31 August 2015.
Pre-assignment details
Participants were randomized in a 2:1 ratio to receive evolocumab plus standard of care (SOC) or SOC alone for the first year. In years 2 and 3 all participants received evolocumab. Randomization was stratified by the parent study and parent study dose frequency (every 2 weeks \[Q2W\] or once monthly \[QM\]).
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Participants received standard of care (SOC) treatment for the first year of the study (SOC-controlled period). At week 48, participants began treatment with evolocumab at a dose of either 140 mg every 2 weeks (Q2W) or 420 mg every month (QM), based on participant choice, for approximately 2 years during the all-investigational product \[all-IP\] period. | 1,227 |
| Evolocumab + Standard of Care Participants received subcutaneous evolocumab plus standard of care during the first year of the study (SOC-controlled period) and for approximately 2 years during the all-IP period. Evolocumab was administered at a dose of 140 mg every 2 weeks (Q2W) or 420 mg every month (QM) based on participant choice. | 2,454 |
| Total | 3,681 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| All-IP Period (Years 2 and 3) | Death | 5 | 16 |
| All-IP Period (Years 2 and 3) | Decision by Sponsor | 8 | 11 |
| All-IP Period (Years 2 and 3) | Lost to Follow-up | 27 | 51 |
| All-IP Period (Years 2 and 3) | Withdrawal by Subject | 78 | 117 |
| SOC-controlled Period (Year 1) | Death | 5 | 5 |
| SOC-controlled Period (Year 1) | Decision by Sponsor | 2 | 1 |
| SOC-controlled Period (Year 1) | Lost to Follow-up | 3 | 8 |
| SOC-controlled Period (Year 1) | Withdrawal by Subject | 20 | 49 |
Baseline characteristics
| Characteristic | Standard of Care | Evolocumab + Standard of Care | Total |
|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 10.7 | 58.6 years STANDARD_DEVIATION 10.7 | 58.7 years STANDARD_DEVIATION 10.7 |
| Age, Customized < 65 years | 823 Participants | 1665 Participants | 2488 Participants |
| Age, Customized ≥ 65 years | 404 Participants | 789 Participants | 1193 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 58 Participants | 109 Participants | 167 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1169 Participants | 2345 Participants | 3514 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Parent Study Baseline Low-density Lipoprotein Cholesterol (LDL-C) Concentration | 125.8 mg/dL STANDARD_DEVIATION 49.3 | 127.4 mg/dL STANDARD_DEVIATION 51.7 | 126.9 mg/dL STANDARD_DEVIATION 50.9 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 5 Participants | 7 Participants |
| Race/Ethnicity, Customized Asian | 152 Participants | 288 Participants | 440 Participants |
| Race/Ethnicity, Customized Black or African American | 49 Participants | 84 Participants | 133 Participants |
| Race/Ethnicity, Customized Mixed Race | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 16 Participants | 30 Participants | 46 Participants |
| Race/Ethnicity, Customized White | 1003 Participants | 2041 Participants | 3044 Participants |
| Region Asia Pacific | 209 Participants | 435 Participants | 644 Participants |
| Region Europe | 504 Participants | 1018 Participants | 1522 Participants |
| Region North America | 514 Participants | 1001 Participants | 1515 Participants |
| Sex: Female, Male Female | 560 Participants | 1176 Participants | 1736 Participants |
| Sex: Female, Male Male | 667 Participants | 1278 Participants | 1945 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 1,227 | 5 / 2,454 | 5 / 1,197 | 16 / 2,391 | 21 / 3,588 |
| other Total, other adverse events | 334 / 1,227 | 681 / 2,454 | 498 / 1,197 | 928 / 2,391 | 1,426 / 3,588 |
| serious Total, serious adverse events | 104 / 1,227 | 195 / 2,454 | 181 / 1,197 | 344 / 2,391 | 525 / 3,588 |
Outcome results
Primary
Number of Participants With Adverse Events
Adverse event (AE) severity assessments were made using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grading, version 4.0, where grade 1 = mild AE, grade 2 = moderate AE, Grade 3 = severe AE, grade 4 = life-threatening AE and Grade 5 = death due to AE.
Time frame: 48 weeks in the SOC-controlled period and up to 2 years in the All-IP period
Population: All randomized participants (year 1) and randomized participants on study and who received at least 1 dose of evolocumab in the all-IP period (years 2-3).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Year 1: Standard of Care | Number of Participants With Adverse Events | All adverse events | 796 Participants |
| Year 1: Standard of Care | Number of Participants With Adverse Events | Adverse events ≥ grade 2 | 519 Participants |
| Year 1: Standard of Care | Number of Participants With Adverse Events | Adverse events ≥ grade 3 | 124 Participants |
| Year 1: Standard of Care | Number of Participants With Adverse Events | Adverse events ≥ grade 4 | 7 Participants |
| Year 1: Standard of Care | Number of Participants With Adverse Events | Serious adverse events | 104 Participants |
| Year 1: Standard of Care | Number of Participants With Adverse Events | AEs leading to discontinuation of evolocumab | 0 Participants |
| Year 1: Standard of Care | Number of Participants With Adverse Events | Fatal adverse events | 5 Participants |
| Year 1: Standard of Care | Number of Participants With Adverse Events | Device related adverse events | 0 Participants |
| Year 1: Evolocumab + Standard of Care | Number of Participants With Adverse Events | AEs leading to discontinuation of evolocumab | 55 Participants |
| Year 1: Evolocumab + Standard of Care | Number of Participants With Adverse Events | Serious adverse events | 195 Participants |
| Year 1: Evolocumab + Standard of Care | Number of Participants With Adverse Events | Adverse events ≥ grade 2 | 1070 Participants |
| Year 1: Evolocumab + Standard of Care | Number of Participants With Adverse Events | Device related adverse events | 57 Participants |
| Year 1: Evolocumab + Standard of Care | Number of Participants With Adverse Events | Fatal adverse events | 5 Participants |
| Year 1: Evolocumab + Standard of Care | Number of Participants With Adverse Events | Adverse events ≥ grade 4 | 17 Participants |
| Year 1: Evolocumab + Standard of Care | Number of Participants With Adverse Events | Adverse events ≥ grade 3 | 225 Participants |
| Year 1: Evolocumab + Standard of Care | Number of Participants With Adverse Events | All adverse events | 1655 Participants |
| Years 2-3: SOC / Evolocumab + SOC | Number of Participants With Adverse Events | Fatal adverse events | 3 Participants |
| Years 2-3: SOC / Evolocumab + SOC | Number of Participants With Adverse Events | Adverse events ≥ grade 3 | 214 Participants |
| Years 2-3: SOC / Evolocumab + SOC | Number of Participants With Adverse Events | Adverse events ≥ grade 4 | 11 Participants |
| Years 2-3: SOC / Evolocumab + SOC | Number of Participants With Adverse Events | Serious adverse events | 178 Participants |
| Years 2-3: SOC / Evolocumab + SOC | Number of Participants With Adverse Events | AEs leading to discontinuation of evolocumab | 26 Participants |
| Years 2-3: SOC / Evolocumab + SOC | Number of Participants With Adverse Events | Device related adverse events | 25 Participants |
| Years 2-3: SOC / Evolocumab + SOC | Number of Participants With Adverse Events | All adverse events | 929 Participants |
| Years 2-3: SOC / Evolocumab + SOC | Number of Participants With Adverse Events | Adverse events ≥ grade 2 | 700 Participants |
| Years 2-3: Evolocumab + SOC / Evolocumab + SOC | Number of Participants With Adverse Events | Adverse events ≥ grade 3 | 379 Participants |
| Years 2-3: Evolocumab + SOC / Evolocumab + SOC | Number of Participants With Adverse Events | Adverse events ≥ grade 4 | 35 Participants |
| Years 2-3: Evolocumab + SOC / Evolocumab + SOC | Number of Participants With Adverse Events | Adverse events ≥ grade 2 | 1339 Participants |
| Years 2-3: Evolocumab + SOC / Evolocumab + SOC | Number of Participants With Adverse Events | All adverse events | 1789 Participants |
| Years 2-3: Evolocumab + SOC / Evolocumab + SOC | Number of Participants With Adverse Events | Serious adverse events | 332 Participants |
| Years 2-3: Evolocumab + SOC / Evolocumab + SOC | Number of Participants With Adverse Events | Device related adverse events | 45 Participants |
| Years 2-3: Evolocumab + SOC / Evolocumab + SOC | Number of Participants With Adverse Events | Fatal adverse events | 16 Participants |
| Years 2-3: Evolocumab + SOC / Evolocumab + SOC | Number of Participants With Adverse Events | AEs leading to discontinuation of evolocumab | 42 Participants |
Secondary
Change From Baseline in LDL-C at Weeks 48 and 104
Time frame: Baseline of the parent study and weeks 48 amd 104
Population: Participants who were randomized in 20120138 and on-study and with known dosing information in the All-IP period, and with non-missing data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Year 1: Standard of Care | Change From Baseline in LDL-C at Weeks 48 and 104 | Week 48 | 0.4 mg/dL | Standard Deviation 43.9 |
| Year 1: Standard of Care | Change From Baseline in LDL-C at Weeks 48 and 104 | Week 104 | -66.4 mg/dL | Standard Deviation 50.1 |
| Year 1: Evolocumab + Standard of Care | Change From Baseline in LDL-C at Weeks 48 and 104 | Week 48 | -68.8 mg/dL | Standard Deviation 46.6 |
| Year 1: Evolocumab + Standard of Care | Change From Baseline in LDL-C at Weeks 48 and 104 | Week 104 | -67.2 mg/dL | Standard Deviation 46.6 |
Secondary
Percent Change From Baseline in LDL-C at Weeks 48 and 104
Time frame: Baseline of the parent study and weeks 48 amd 104
Population: Participants who were randomized in 20120138 and on-study and with known dosing information in the All-IP period, and with non-missing data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Year 1: Standard of Care | Percent Change From Baseline in LDL-C at Weeks 48 and 104 | Week 48 | 7.43 percent change | Standard Deviation 38.93 |
| Year 1: Standard of Care | Percent Change From Baseline in LDL-C at Weeks 48 and 104 | Week 104 | -49.96 percent change | Standard Deviation 33.29 |
| Year 1: Evolocumab + Standard of Care | Percent Change From Baseline in LDL-C at Weeks 48 and 104 | Week 48 | -51.59 percent change | Standard Deviation 28.88 |
| Year 1: Evolocumab + Standard of Care | Percent Change From Baseline in LDL-C at Weeks 48 and 104 | Week 104 | -50.31 percent change | Standard Deviation 30.34 |