Evolocumab Compared to LDL-C Apheresis in Patients Receiving LDL-C Apheresis Prior to Study Enrollment

Phase 3

Completed

Interventions: Biological: Evolocumab
Procedure: Low-density Lipoprotein Cholesterol (LDL-C) Apheresis

Brief Summary: To evaluate the efficacy of subcutaneous (SC) evolocumab, compared to regularly scheduled low-density lipoprotein cholesterol (LDL-C) apheresis, on reducing the need for future apheresis.

Recruitment & Eligibility

Inclusion Criteria

Male or female, ≥ 18 years of age
Subject has been receiving regular apheresis for LDL-C lowering for at least 3 months immediately prior to lipid screening and has a treatment goal of LDL-C < 100 mg/dL (2.6 mmol/L), and has been receiving LDL-C apheresis during the last ≥ 4 weeks prior to lipid screening at regular QW or Q2W schedule and with no changes in apheresis type
Subject is receiving lipid-lowering pharmacological background therapy which includes a high-intensity statin dose (moderate-intensity statin dose with attestation that a higher dose is not appropriate for the subject) unless the subject has a history of statin intolerance
Lipid-lowering therapy status (ie, any therapy for lowering lipids, including apheresis type and frequency) must be unchanged for ≥ 4 weeks prior to LDL-C screening
Pre-apheresis LDL-C is ≥ 100 mg/dL (≥ 2.6 mmol/L) and ≤ 190 mg/dL (≤ 4.9 mmol/L) at screening
Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L) at screening.

Exclusion criteria:

Known homozygous familial hypercholesterolemia
Missing any apheresis session is medically contraindicated or inappropriate
Stopping apheresis would be inappropriate in the opinion of the investigator even if LDL-C is controlled to < 100 mg/dL with other therapies
Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization.
Uncontrolled hypertension

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Evolocumab	Evolocumab	Participants received 140 mg evolocumab every 2 weeks (Q2W) administered by subcutaneous injection for 6 weeks during the primary period of the study. Starting at week 6 (beginning of the post-primary period), participants received 140 mg evolocumab Q2W up to week 24.
Low Density Lipoprotein Cholesterol (LDL-C) Apheresis	Low-density Lipoprotein Cholesterol (LDL-C) Apheresis	Participants continued apheresis at the same schedule, every week (QW) or every two weeks (Q2W), as prior to study entry, for the first 6 weeks. Starting at week 6 (beginning of the post-primary period), participants received 140 mg evolocumab Q2W up to week 24.
Low Density Lipoprotein Cholesterol (LDL-C) Apheresis	Evolocumab	Participants continued apheresis at the same schedule, every week (QW) or every two weeks (Q2W), as prior to study entry, for the first 6 weeks. Starting at week 6 (beginning of the post-primary period), participants received 140 mg evolocumab Q2W up to week 24.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Apheresis Avoidance at the End of Randomized Therapy	Week 5 and week 6	Avoidance of apheresis at end of randomized therapy was defined as no apheresis at week 5 and week 6. Aperesis at weeks 5 or 6 was based on LDL-C level at week 4: participants with LDL-C ≥ 100 mg/dL at week 4 received apheresis at week 5 (participants who received apheresis QW before study entry) or week 6 (participants who received apheresis Q2W prior to study entry). If LDL-C was \< 100 mg/dL at week 4, no apheresis was performed at week 5 or week 6, irrespective of assigned treatment group. Participants who ended the study prior to week 6 were considered as not achieving apheresis avoidance.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Non-high-density Lipoprotein-Cholesterol	Baseline and Week 4
Percent Change From Baseline in Low-density Lipoprotein Cholesterol	Baseline and week 4
Percent Change From Baseline in Total Cholesterol/High-density Lipoprotein Cholesterol Ratio	Baseline and Week 4