Dyslipidemia
Conditions
Brief summary
This is a multicenter, open-label extension (OLE) study designed to assess the extended long-term safety of evolocumab in subjects who have completed the FOURIER trial (Study 20110118). Approximately 1600 subjects will be enrolled in this study. This study will continue for 260 weeks (approximately 5 years).
Detailed description
This is a multicenter, open-label extension (OLE) study designed to assess the extended long-term safety of evolocumab in subjects who have completed the FOURIER trial (Study 20110118). FOURIER is a randomized placebo-controlled study of evolocumab, in patients with clinically evident atherosclerotic CVD on stable effective statin therapy. Subjects at sites participating in FOURIER OLE (Study 20160250) who are eligible and have signed the FOURIER OLE informed consent will be enrolled after completion of FOURIER. The FOURIER OLE study requires laboratory assessments at day 1, week 12, and thereafter approximately every 6 months from day 1; the corresponding blood samples will be processed using a central laboratory. Upon enrollment in FOURIER OLE study, subjects will receive evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) according to their preference. Frequency and corresponding dose of administration can be changed at any scheduled time point where evolocumab is supplied to the subject, provided the appropriate supply is available. It is recommended that subjects continue the same background lipid-lowering therapy (LLT), including statin, as taken during FOURIER. This study will continue for 260 weeks (approximately 5 years). Subjects ending administration of evolocumab should continue study assessments until the end of study. All subjects will be followed and complete procedures/assessments from enrollment through the date of study termination unless the subject has withdrawn consent, irrespective of whether the subject is continuing to receive treatment. All deaths and cardiovascular events of interest will be reviewed by an independent external Clinical Events Committee (CEC), using standardized definitions.
Interventions
DRUGEvolocumab
Subjects will receive Evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM), according to the subject's preference.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent prior to initiation of any study-specific activities/procedures. * Subject had completed FOURIER (Study 20110118) while still receiving assigned Investigational Product.
Exclusion criteria
* Permanent discontinuation of Investigational Product during FOURIER for any reason including an adverse event or serious adverse event. * Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. * Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge. * History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. * Subject has known sensitivity to any of the active substances or excipients (eg, sodium acetate) to be administered during dosing. * Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment with evolocumab and for an additional 15 weeks after treatment with evolocumab discontinues. * Female subjects of childbearing potential unwilling to use an acceptable method of effective contraception during treatment and for an additional 15 weeks after the last dose of protocol-required therapies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event | Up to 5 years | All adverse event summaries for the primary analysis of the primary endpoint (OLE study period only) included all treatment-emergent events reported on the Event electronic case report form (eCRF), including CEC positively reviewed events and disease-related events. |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260 |
| Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260 |
Countries
Belgium, Denmark, France, Germany, Italy, Portugal, Sweden
Participant flow
Recruitment details
This was an open-label extension of study 20110118 (NCT01764633). Eligible participants were enrolled after the completion of the 20110118 study. 1600 participants were enrolled at 86 centers in Belgium, Germany, Denmark, France, Italy, Portugal, and Sweden from 13 March 2017 to 04 March 2022.
Pre-assignment details
1600 participants were enrolled and 1599 of those participants received study drug.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study Participants in the parent study who received placebo subcutaneous injections either Q2W or QM, and received evolocumab 140 mg Q2W or 420 mg QM in the open label extension, according to the participant's preference. | 745 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study Participants in the parent study who received evolocumab either Q2W or QM, and received evolocumab 140 mg Q2W or 420 mg QM in the open label extension according to the participants preference. | 854 |
| Total | 1,599 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 34 | 50 |
| Overall Study | Lost to Follow-up | 5 | 4 |
| Overall Study | Withdrawal by Subject | 11 | 15 |
Baseline characteristics
| Characteristic | Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Total | Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study |
|---|---|---|---|
| Age, Continuous | 62.6 Years STANDARD_DEVIATION 8.9 | 62.6 Years STANDARD_DEVIATION 9 | 62.7 Years STANDARD_DEVIATION 9.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 41 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 830 Participants | 1558 Participants | 728 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 53 Participants | 91 Participants | 38 Participants |
| Race/Ethnicity, Customized White | 797 Participants | 1503 Participants | 706 Participants |
| Sex: Female, Male Female | 151 Participants | 289 Participants | 138 Participants |
| Sex: Female, Male Male | 703 Participants | 1310 Participants | 607 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 35 / 745 | 51 / 855 |
| other Total, other adverse events | 451 / 745 | 528 / 854 |
| serious Total, serious adverse events | 323 / 745 | 410 / 854 |
Outcome results
Primary
Number of Participants Who Experienced an Adverse Event
All adverse event summaries for the primary analysis of the primary endpoint (OLE study period only) included all treatment-emergent events reported on the Event electronic case report form (eCRF), including CEC positively reviewed events and disease-related events.
Time frame: Up to 5 years
Population: OLE Safety Analysis Set which included all participants who received at least 1 dose of open-label evolocumab in the OLE study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Number of Participants Who Experienced an Adverse Event | 686 Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Number of Participants Who Experienced an Adverse Event | 810 Participants |
Secondary
Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL
Time frame: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260
Population: OLE Safety Analysis Set which included all participants who received at least 1 dose of open-label evolocumab in the OLE study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 120 | 70.9 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 144 | 75.3 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 168 | 72.3 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Baseline in parent study | 0 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 12 | 72.8 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 24 | 72.9 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 48 | 66.5 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 72 | 73.2 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 96 | 71.1 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 192 | 71.6 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 216 | 72.1 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 260 | 76.1 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 216 | 67.3 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 120 | 68.6 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 48 | 68.0 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 144 | 72.2 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 192 | 66.3 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 168 | 69.3 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 72 | 72.3 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Baseline in parent study | 0 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 260 | 68.8 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 12 | 72.5 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 96 | 69.2 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 24 | 73.4 Percentage of Participants |
Secondary
Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit
Time frame: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260
Population: OLE Safety Analysis Set which included all participants who received at least 1 dose of open-label evolocumab in the OLE study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 48 | -62.61 Percent Change | Standard Deviation 26.6 |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 144 | -66.79 Percent Change | Standard Deviation 29.22 |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 96 | -64.58 Percent Change | Standard Deviation 27.01 |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 168 | -65.28 Percent Change | Standard Deviation 27.55 |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 24 | -66.48 Percent Change | Standard Deviation 27.52 |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 192 | -65.02 Percent Change | Standard Deviation 27.93 |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 72 | -65.58 Percent Change | Standard Deviation 28.13 |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 216 | -64.92 Percent Change | Standard Deviation 27.93 |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 120 | -64.26 Percent Change | Standard Deviation 28.31 |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 260 | -66.45 Percent Change | Standard Deviation 29.84 |
| Placebo Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 12 | -66.32 Percent Change | Standard Deviation 26.88 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 260 | -64.72 Percent Change | Standard Deviation 29.5 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 12 | -67.24 Percent Change | Standard Deviation 25.23 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 48 | -63.45 Percent Change | Standard Deviation 26.03 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 72 | -65.33 Percent Change | Standard Deviation 28.42 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 24 | -66.47 Percent Change | Standard Deviation 28.11 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 96 | -63.43 Percent Change | Standard Deviation 28.8 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 120 | -63.10 Percent Change | Standard Deviation 29.56 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 144 | -65.13 Percent Change | Standard Deviation 31.96 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 168 | -63.55 Percent Change | Standard Deviation 29.6 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 192 | -62.46 Percent Change | Standard Deviation 26.39 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once Every Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 216 | -62.46 Percent Change | Standard Deviation 28.32 |