Durable Effect of PCSK9 Antibody CompARed wiTh placEbo Study

NCT01516879 | Completed Phase 3 Results DMC

• 1 other identifier: 20110109
• Study Type: interventional
• Target: 905
• Locations: 8 countries
• Sites: 90

Brief Summary

To evaluate the efficacy, safety, and tolerability of 52 weeks of subcutaneous (SC) evolocumab (AMG 145) compared with placebo when added to assigned background lipid-lowering therapy.

Conditions

Hypercholesterolemia

Keywords

Cholesterol; High Cholesterol; Elevated Cholesterol; Raised Cholesterol

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in LDL-C at Week 52

  Cholesterol was measured by means of ultracentrifugation.

  Baseline and Week 52

Secondary Outcomes (14)

• Change From Baseline in LDL-C at Week 52

  Baseline and Week 52

• Percentage of Participants With an LDL-C Response at Week 52

  Week 52

• Percent Change From Baseline in LDL-C at Week 12

  Baseline and Week 12

• Percent Change From Baseline in Total Cholesterol at Week 12

  Baseline and Week 12

• Percent Change From Baseline in Total Cholesterol at Week 52

  Baseline and Week 52

Study Arms (2)

Evolocumab

EXPERIMENTAL

Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.

Biological: Evolocumab; Drug: Atorvastatin; Drug: Ezetimibe; Other: Diet Only

Placebo

PLACEBO COMPARATOR

Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.

Biological: Placebo; Drug: Atorvastatin; Drug: Ezetimibe; Other: Diet Only

Interventions

Evolocumab BIOLOGICAL

Administered by subcutaneous injection once a month

Also known as: AMG 145, Repatha

Evolocumab

Placebo BIOLOGICAL

Administered by subcutaneous injection once a month

Placebo

Atorvastatin DRUG

Background lipid lowering therapy: 10 mg or 80 mg atorvastatin orally once daily.

Evolocumab; Placebo

Ezetimibe DRUG

Background lipid lowering therapy: ezetimibe 10 mg orally once a day

Evolocumab; Placebo

Diet Only OTHER

Diet only, no lipid lowering background drug given

Evolocumab; Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has provided informed consent.
• Fasting LDL-C ≥ 75 mg/dL and meeting the following LDL-C values on background lipid-lowering therapy:
• \< 100 mg/dL for subjects with diagnosed coronary heart disease (CHD) or CHD risk equivalent
• \< 130 mg/dL for subjects without diagnosed CHD or CHD risk equivalent
• OR on maximal background lipid-lowering therapy defined as atorvastatin 80 mg PO QD and ezetimibe 10 mg PO QD
• Fasting triglycerides ≤ 400 mg/dL

You may not qualify if:

• New York Heart Association (NYHA) II-IV heart failure, or last known left ventricular ejection fraction \< 30%
• Uncontrolled cardiac arrhythmia
• Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization, type 1 diabetes, newly diagnosed or poorly controlled type 2 diabetes
• Uncontrolled hypertension

Sponsors & Collaborators

• Amgen: lead

Study Sites (96)

Research Site

Birmingham, Alabama, 35216, United States

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Little Rock, Arkansas, 72205, United States

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Anaheim, California, 92801, United States

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Encinitas, California, 92024, United States

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Spring Valley, California, 91978, United States

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Westlake Village, California, 91361, United States

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DeLand, Florida, 32720, United States

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Jacksonville, Florida, 32204, United States

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Jacksonville, Florida, 32216, United States

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Ponte Vedra, Florida, 32081, United States

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Atlanta, Georgia, 30338, United States

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Atlanta, Georgia, 30342, United States

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Savannah, Georgia, 31406, United States

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Chicago, Illinois, 60610, United States

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Indianapolis, Indiana, 46260, United States

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Louisville, Kentucky, 40213, United States

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Auburn, Maine, 04210, United States

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Bethesda, Maryland, 20817, United States

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Chevy Chase, Maryland, 20815, United States

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Columbia, Maryland, 21045, United States

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Brockton, Massachusetts, 02301, United States

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Saint Paul, Minnesota, 55114, United States

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Olive Branch, Mississippi, 38654, United States

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Las Vegas, Nevada, 89148, United States

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Endwell, New York, 13760, United States

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New Windsor, New York, 12553, United States

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Raleigh, North Carolina, 27609, United States

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Raleigh, North Carolina, 27612, United States

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Fargo, North Dakota, 58103, United States

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Akron, Ohio, 44311, United States

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Cincinnati, Ohio, 45219, United States

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Cincinnati, Ohio, 45227, United States

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Cincinnati, Ohio, 45246, United States

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Norman, Oklahoma, 73069, United States

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Duncansville, Pennsylvania, 16635, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Rapid City, South Dakota, 57702, United States

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Houston, Texas, 77030, United States

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Richmond, Virginia, 23294, United States

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Renton, Washington, 98057, United States

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Seattle, Washington, 98104, United States

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Camperdown, New South Wales, 2015, Australia

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Maroubra, New South Wales, 2035, Australia

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Carina Heights, Queensland, 4152, Australia

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Milton, Queensland, 4064, Australia

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Fitzroy, Victoria, 3065, Australia

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Perth, Western Australia, 6000, Australia

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Feldkirch, 6807, Austria

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Innsbruck, 6020, Austria

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Salzburg, 5020, Austria

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Wels, 4600, Austria

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Anthée, 5520, Belgium

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Gozée, 6534, Belgium

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Ham, 3945, Belgium

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Ostend, 8400, Belgium

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Victoria, British Columbia, V8T 5G4, Canada

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Bay Roberts, Newfoundland and Labrador, A0A 1G0, Canada

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Cambridge, Ontario, N1R 6V6, Canada

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Greater Sudbury, Ontario, P3C 5K7, Canada

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London, Ontario, N5W 6A2, Canada

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Newmarket, Ontario, L3Y 5G8, Canada

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Toronto, Ontario, M9V 4B4, Canada

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Toronto, Ontario, M9W 4L6, Canada

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Pointe-Claire, Quebec, H9R 3J1, Canada

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Québec, Quebec, G1V 4M6, Canada

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Brno, 602 00, Czechia

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Brno, 625 00, Czechia

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Chomutov, 430 02, Czechia

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Hradec Králové, 500 05, Czechia

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Pardubice, 530 02, Czechia

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Pilsen, 305 99, Czechia

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Prague, 120 00, Czechia

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Prague, 140 21, Czechia

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Prague, 150 06, Czechia

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Slaný, 274 01, Czechia

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Aalborg, 9000, Denmark

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Ballerup Municipality, 2750, Denmark

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Vejle, 7100, Denmark

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Baja, 6500, Hungary

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Budapest, 1085, Hungary

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Budapest, 1115, Hungary

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Budapest, 1125, Hungary

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Komárom, 2991, Hungary

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Pécs, 7624, Hungary

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Szeged, 6720, Hungary

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Zalaegerszeg, 8900, Hungary

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Lyttelton, Gauteng, 0140, South Africa

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Chatsworth, Durban, KwaZulu-Natal, 4092, South Africa

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eManzimtoti, KwaZulu-Natal, 4126, South Africa

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Observatory, Western Cape, 7925, South Africa

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Paarl, Western Cape, 7646, South Africa

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Parow, Western Cape, 7505, South Africa

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Somerset West, Western Cape, 7130, South Africa

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Bloemfontein, 9301, South Africa

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Related Publications (12)

• Toth PP, Sattar N, Blom DJ, Martin SS, Jones SR, Monsalvo ML, Elliott M, Davis M, Somaratne R, Preiss D. Effect of Evolocumab on Lipoprotein Particles. Am J Cardiol. 2018 Feb 1;121(3):308-314. doi: 10.1016/j.amjcard.2017.10.028. Epub 2017 Nov 8.

  PMID: 29221604 BACKGROUND

• Blom DJ, Koren MJ, Roth E, Monsalvo ML, Djedjos CS, Nelson P, Elliott M, Wasserman SM, Ballantyne CM, Holman RR. Evaluation of the efficacy, safety and glycaemic effects of evolocumab (AMG 145) in hypercholesterolaemic patients stratified by glycaemic status and metabolic syndrome. Diabetes Obes Metab. 2017 Jan;19(1):98-107. doi: 10.1111/dom.12788. Epub 2016 Oct 14.

  PMID: 27619750 BACKGROUND

• Blom DJ, Djedjos CS, Monsalvo ML, Bridges I, Wasserman SM, Scott R, Roth E. Effects of Evolocumab on Vitamin E and Steroid Hormone Levels: Results From the 52-Week, Phase 3, Double-Blind, Randomized, Placebo-Controlled DESCARTES Study. Circ Res. 2015 Sep 25;117(8):731-41. doi: 10.1161/CIRCRESAHA.115.307071. Epub 2015 Jul 30.

  PMID: 26228031 BACKGROUND

• Blom DJ, Hala T, Bolognese M, Lillestol MJ, Toth PD, Burgess L, Ceska R, Roth E, Koren MJ, Ballantyne CM, Monsalvo ML, Tsirtsonis K, Kim JB, Scott R, Wasserman SM, Stein EA; DESCARTES Investigators. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014 May 8;370(19):1809-19. doi: 10.1056/NEJMoa1316222. Epub 2014 Mar 29.

  PMID: 24678979 BACKGROUND

• Daviglus ML, Ferdinand KC, Lopez JAG, Wu Y, Monsalvo ML, Rodriguez CJ. Effects of Evolocumab on Low-Density Lipoprotein Cholesterol, Non-High Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a) by Race and Ethnicity: A Meta-Analysis of Individual Participant Data From Double-Blind and Open-Label Extension Studies. J Am Heart Assoc. 2021 Jan 5;10(1):e016839. doi: 10.1161/JAHA.120.016839. Epub 2020 Dec 16.

  PMID: 33325247 BACKGROUND

• Kuchimanchi M, Grover A, Emery MG, Somaratne R, Wasserman SM, Gibbs JP, Doshi S. Population pharmacokinetics and exposure-response modeling and simulation for evolocumab in healthy volunteers and patients with hypercholesterolemia. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):505-522. doi: 10.1007/s10928-018-9592-y. Epub 2018 May 7.

  PMID: 29736889 BACKGROUND

• Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.

  PMID: 29353350 BACKGROUND

• Sattar N, Toth PP, Blom DJ, Koren MJ, Soran H, Uhart M, Elliott M, Cyrille M, Somaratne R, Preiss D. Effect of the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Evolocumab on Glycemia, Body Weight, and New-Onset Diabetes Mellitus. Am J Cardiol. 2017 Nov 1;120(9):1521-1527. doi: 10.1016/j.amjcard.2017.07.047. Epub 2017 Jul 31.

  PMID: 28844508 BACKGROUND

• Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1.

  PMID: 28249876 BACKGROUND

• Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, Lopez JAG, Banach M. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies. J Am Heart Assoc. 2020 Mar 3;9(5):e014129. doi: 10.1161/JAHA.119.014129. Epub 2020 Mar 2.

  PMID: 32114889 BACKGROUND

• Wasserman SM, Sabatine MS, Koren MJ, Giugliano RP, Legg JC, Emery MG, Doshi S, Liu T, Somaratne R, Gibbs JP. Comparison of LDL-C Reduction Using Different Evolocumab Doses and Intervals: Biological Insights and Treatment Implications. J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):423-432. doi: 10.1177/1074248418774043. Epub 2018 May 16.

  PMID: 29768954 BACKGROUND

• Schludi B, Giugliano RP, Sabatine MS, Raal FJ, Teramoto T, Koren MJ, Stein EA, Wang H, Monsalvo ML. Time-averaged low-density lipoprotein cholesterol lowering with evolocumab: Pooled analysis of phase 2 trials. J Clin Lipidol. 2022 Jul-Aug;16(4):538-543. doi: 10.1016/j.jacl.2022.05.069. Epub 2022 Jun 6.

  PMID: 35760720 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

evolocumab; Atorvastatin; Ezetimibe

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Azetidines; Azetines

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2012
• First Posted: January 25, 2012
• Study Start: January 5, 2012
• Primary Completion: October 14, 2013
• Study Completion: October 14, 2013
• Last Updated: July 22, 2022
• Results First Posted: September 29, 2015

Record last verified: 2022-07

Locations

US (41); ZA (8); BE (6); CA (10); AU (4); HU (8); CZ (10); DK (3)