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

• ClinicalTrials.gov Identifier: NCT02585895
• Recruitment Status: Completed
• First Posted: October 26, 2015
• Results First Posted: September 19, 2017
• Last Update Posted: September 19, 2017
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia	Biological: Evolocumab; Procedure: Low-density Lipoprotein Cholesterol (LDL-C) Apheresis	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Actively Controlled, Open-label, Multicenter Study of Efficacy and Safety of Evolocumab Compared With Low Density Lipoprotein Cholesterol (LDL-C) Apheresis, Followed by Single-Arm Evolocumab Administration in Subjects Receiving LDL-C Apheresis Prior to Study Enrollment
• Actual Study Start Date: December 21, 2015
• Actual Primary Completion Date: September 1, 2016
• Actual Study Completion Date: January 20, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Biological: Evolocumab; Administered by subcutaneous injection once every 2 weeks; Other Names: Repatha; AMG 145
Active Comparator: 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.	Biological: Evolocumab; Administered by subcutaneous injection once every 2 weeks; Other Names: Repatha; AMG 145; Procedure: Low-density Lipoprotein Cholesterol (LDL-C) Apheresis; Participants received apheresis for LDL-C according the their physician's prescription and local custom.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Apheresis Avoidance at the End of Randomized Therapy [ Time Frame: 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 :

1. Percent Change From Baseline in Low-density Lipoprotein Cholesterol [ Time Frame: Baseline and week 4 ]
2. Percent Change From Baseline in Non-high-density Lipoprotein-Cholesterol [ Time Frame: Baseline and Week 4 ]
3. Percent Change From Baseline in Total Cholesterol/High-density Lipoprotein Cholesterol Ratio [ Time Frame: Baseline and Week 4 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Florida

Research Site

Boca Raton, Florida, United States, 33434

United States, Kansas

Research Site

Kansas City, Kansas, United States, 66160

United States, Michigan

Research Site

Grandville, Michigan, United States, 49418

United States, Oregon

Research Site

Portland, Oregon, United States, 97239

Australia, Victoria

Research Site

Heidelberg, Victoria, Australia, 3084

Czechia

Research Site

Hradec Kralove, Czechia, 500 05

France

Research Site

Bron, France, 69677

Research Site

Nantes Cedex 1, France, 44093

Germany

Research Site

Berlin, Germany, 13353

Research Site

Dresden, Germany, 01307

Research Site

Düsseldorf, Germany, 40210

Research Site

Flensburg, Germany, 24939

Italy

Research Site

Pisa, Italy, 56124

Research Site

Roma, Italy, 00161

Spain

Research Site

Sevilla, Andalucía, Spain, 41013

United Kingdom

Research Site

Harefield, United Kingdom, UB9 6JH

Research Site

Penarth, United Kingdom, CF64 2XX

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02585895
• Other Study ID Numbers: 20140316; 2015-001343-37 ( EudraCT Number )
• First Posted: October 26, 2015
• Results First Posted: September 19, 2017
• Last Update Posted: September 19, 2017
• Last Verified: August 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amgen:

LDL-C Apheresis; Hypercholesterolemia; Elevated Cholesterol; High Cholesterol; PCSK9 mutations; Severe Familial Hypercholesterolemia; evolocumab; Repatha

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Evolocumab; Antibodies, Monoclonal; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Immunologic Factors; Physiological Effects of Drugs