Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk Open-label Extension

Study Overview
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Brief Summary
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The primary clinical hypothesis is that long-term exposure of evolocumab will be safe and well tolerated in subjects with clinically evident atherosclerotic cardiovascular disease (CVD).

Detailed Description
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This is a multicenter, open-label extension study designed to assess the long-term safety of evolocumab in subjects who completed the FOURIER study,which is a randomized placebo-controlled study of evolocumab in subjects with clinically evident atherosclerotic CVD on stable effective statin therapy. Eligible subjects at sites participating in FOURIER OLE who have signed the FOURIER OLE informed consent may be enrolled at the completion of FOURIER study.

Official Title
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A Multicenter, Open-label, Single-arm, Extension Study to Assess Long-term Safety of Evolocumab Therapy in Patients With Clinically Evident Cardiovascular Disease

Conditions
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Dyslipidemia

Intervention / Treatment
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* Biological: Evolocumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has provided informed consent before initiation of any study-specific activities/procedures Subject has completed FOURIER (Study 20110118) while still receiving assigned investigational product. Exclusion Criteria: Investigational product was permanently discontinued during FOURIER for any reason, including an adverse event or serious adverse event Subject is currently receiving treatment in another investigational device or drug study, or ended treatment on another investigational device or drug study(ies) within less than 4 weeks. Other investigational procedures while participating in this study are excluded Subject is not likely to be available to complete protocol-required study visits or procedures and/or to comply with required study procedures to the best of the subject's and investigator's knowledge Subject has a 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 a known sensitivity to any of the active substances or excipients (eg, sodium acetate) to be administered during dosing Female subject is pregnant or breastfeeding or is planning to become pregnant or planning to breastfeed during treatment with evolocumab and within 15 weeks after the end of treatment with evolocumab Female subjects of childbearing potential who are not willing to use an acceptable method(s) of effective birth control during treatment with evolocumab and for an additional 15 weeks after the end of treatment with evolocumab are excluded

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: evolocumab (AMG 145)<br>All subjects are randomized to a single arm and will receive evolocumab 140mg every two weeks (Q2W) or 420mg monthly (QM) according to subject's preference. | Biological: Evolocumab<br>* subjects will receive evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM), according to the subject's preference.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit |  | 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 |  | Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High Cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia