Open Label Study of Long Term Evaluation Against LDL-C Trial

Study Overview
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Brief Summary
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The primary clinical hypothesis is that long-term exposure of evolocumab (AMG 145) will be safe and well tolerated in adults with hypercholesterolemia.

Official Title
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A Multicenter, Controlled, Open-label Extension (OLE) Study to Assess the Long-term Safety and Efficacy of AMG 145 (Evolocumab)

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Biological: Evolocumab
* Other: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Complete a qualifying evolocumab (AMG 145) parent study protocol, including: 20101154 (NCT01375777), 20101155 (NCT01380730), 20090158 (NCT01375751), 20090159 (NCT01375764), and 20110231 (NCT01652703) Exclusion Criteria: Experienced a treatment-related serious adverse event that led to investigational product (IP) 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care<br>Participants received standard of care (SOC) treatment for the first year of the study (SOC-controlled period). At week 52 participants began treatment with evolocumab 420 mg once a month (QM) for 4 years during the all-investigational product [all-IP] period. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;Other: Standard of care<br>* Standard of care therapy as per local practices. This could include prescribed therapies and/or dietary/exercise regimes<br>|
| Experimental: Evolocumab + SOC<br>Participants received evolocumab 420 mg once a month plus standard of care for the first year of the study (SOC-controlled period). At week 52 participants continued treatment with evolocumab 420 mg QM for another 4 years during the all-IP period. | Biological: Evolocumab<br>* Administered by subcutaneous injection<br>* Other names: Repatha;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 4.03, 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. | 52 weeks in the SOC-controlled period and up to 4 years in the All-IP period; actual median duration of treatment in the All-IP period was 46.9 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Low-density Lipoprotein Cholesterol (LDL-C) Level at Week 24 and Week 52 |  | Baseline of parent study and extension study weeks 24 and 52 | 
| Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Level at Week 24 and Week 52 |  | Baseline of parent study and extension study weeks 24 and 52 | 
| Apolipoprotein B Level at Week 24 and Week 52 |  | Baseline of parent study and extension study weeks 24 and 52 | 
| Total Cholesterol/HDL-C Ratio at Week 24 and Week 52 |  | Baseline of parent study and extension study weeks 24 and 52 | 
| Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24 and Week 52 |  | Baseline of parent study and extension study weeks 24 and 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High cholesterol, Raised cholesterol, Cholesterol, Elevated Cholesterol