Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2

NCT01763827 | Completed Phase 3 Results DMC

• 1 other identifier: 20110114
• Study Type: interventional
• Target: 615
• Locations: 10 countries
• Sites: 83

Brief Summary

The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneous (SC) monotherapy every 2 weeks (Q2W) and monthly (QM), compared with placebo and ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with a 10-year Framingham risk score of 10% or less.

Conditions

Hyperlipidemia

Keywords

High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12

  Baseline and Week 12

• Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

  Baseline and Weeks 10 and 12

Secondary Outcomes (20)

• Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

  Baseline and Weeks 10 and 12

• Change From Baseline in LDL-C at Week 12

  Baseline and Week 12

• Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL

  Weeks 10 and 12

• Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12

  Week 12

• Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12

  Baseline and Weeks 10 and 12

Study Arms (6)

Placebo Q2W

PLACEBO COMPARATOR

Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.

Biological: Placebo to Evolocumab; Other: Placebo to Ezetimibe

Placebo QM

PLACEBO COMPARATOR

Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.

Biological: Placebo to Evolocumab; Other: Placebo to Ezetimibe

Ezetimibe (Q2W)

ACTIVE COMPARATOR

Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.

Drug: Ezetimibe; Biological: Placebo to Evolocumab

Ezetimibe (QM)

ACTIVE COMPARATOR

Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.

Drug: Ezetimibe; Biological: Placebo to Evolocumab

Evolocumab Q2W

EXPERIMENTAL

Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.

Biological: Evolocumab; Other: Placebo to Ezetimibe

Evolocumab QM

EXPERIMENTAL

Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.

Biological: Evolocumab; Other: Placebo to Ezetimibe

Interventions

Evolocumab BIOLOGICAL

Administered by subcutaneous injection

Also known as: AMG 145, Repatha

Evolocumab Q2W; Evolocumab QM

Ezetimibe DRUG

Administered orally once a day

Also known as: Zetia

Ezetimibe (Q2W); Ezetimibe (QM)

Placebo to Evolocumab BIOLOGICAL

Administered by subcutaneous injection

Ezetimibe (Q2W); Ezetimibe (QM); Placebo Q2W; Placebo QM

Placebo to Ezetimibe OTHER

Administered orally once daily

Evolocumab Q2W; Evolocumab QM; Placebo Q2W; Placebo QM

Eligibility Criteria

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

You may qualify if:

• Male or female ≥ 18 to ≤ 80 years of age
• National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) Framingham risk score of 10% or less
• Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L) and \<190 mg/dL
• Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

You may not qualify if:

• History of coronary heart disease
• New York Heart Association (NYHA) III or IV heart failure
• Uncontrolled cardiac arrhythmia
• Uncontrolled hypertension
• Diabetes mellitus (Type 1 diabetes, poorly controlled type 2 diabetes)
• Uncontrolled hypothyroidism or hyperthyroidism

Sponsors & Collaborators

• Amgen: lead

Study Sites (83)

Research Site

Birmingham, Alabama, 35216, United States

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Chandler, Arizona, 85224, United States

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Little Rock, Arkansas, 72205, United States

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Carmichael, California, 95608, United States

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Encinitas, California, 92024, United States

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San Diego, California, 92111, United States

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Tustin, California, 92780, United States

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Jacksonville, Florida, 32204, United States

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Jacksonville, Florida, 32216, United States

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Miami, Florida, 33144, United States

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Ponte Vedra, Florida, 32081, United States

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Sanford, Florida, 32771, United States

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Boise, Idaho, 83704, United States

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Chicago, Illinois, 60654, United States

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Indianapolis, Indiana, 46260, United States

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Overland Park, Kansas, 66202, United States

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Louisville, Kentucky, 40213, United States

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Bethesda, Maryland, 20817, United States

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Brockton, Massachusetts, 02301, United States

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Edina, Minnesota, 55435, 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, 45212, United States

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Cincinnati, Ohio, 45236, United States

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Cincinnati, Ohio, 45246, United States

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Cleveland, Ohio, 44122, United States

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Norman, Oklahoma, 73069, United States

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Oklahoma City, Oklahoma, 73103, United States

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Duncansville, Pennsylvania, 16635, United States

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Anderson, South Carolina, 29621, 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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Jackson, Tennessee, 38305, United States

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Boerne, Texas, 78006, United States

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Dallas, Texas, 75230, United States

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San Antonio, Texas, 78205, United States

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Salt Lake City, Utah, 84124, United States

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Norfolk, Virginia, 23502, 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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Darlinghurst, New South Wales, 2010, Australia

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Maroubra, New South Wales, 2035, Australia

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Carina Heights, Queensland, 4152, Australia

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Sherwood, Queensland, 4075, Australia

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Anthée, 5520, Belgium

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Brussels, 1080, Belgium

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Gozée, 6534, Belgium

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Gribomont, 6887, Belgium

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Halen, 3545, Belgium

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Ham, 3945, Belgium

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Linkebeek, 1630, Belgium

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Retie, 2470, Belgium

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Tessenderlo, 3980, Belgium

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

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Mount Pearl, Newfoundland and Labrador, A1N 1W7, Canada

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Toronto, Ontario, M9W 4L6, Canada

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Granby, Quebec, J2G 8Z9, Canada

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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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Gières, 38610, France

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Grenoble, 38043, France

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Alberton, Gauteng, 1449, South Africa

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Johannesburg, Gauteng, 2196, 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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Worcester, Western Cape, 6850, South Africa

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Bloemfontein, 9301, South Africa

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Seoul, 120-752, South Korea

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Seoul, 135-710, South Korea

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Seoul, 138-736, South Korea

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Kaohsiung City, 807, Taiwan

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Kaohsiung City, 83301, Taiwan

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Taipei, 100, Taiwan

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Istanbul, 34093, Turkey (Türkiye)

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Istanbul, 34662, Turkey (Türkiye)

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Related Publications (11)

• Koren MJ, Lundqvist P, Bolognese M, Neutel JM, Monsalvo ML, Yang J, Kim JB, Scott R, Wasserman SM, Bays H; MENDEL-2 Investigators. Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2531-2540. doi: 10.1016/j.jacc.2014.03.018. Epub 2014 Mar 29.

  PMID: 24691094 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

• Koren MJ, Jones PH, Robinson JG, Sullivan D, Cho L, Hucko T, Lopez JAG, Fleishman AN, Somaratne R, Stroes E. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther. 2020 Dec;9(2):447-465. doi: 10.1007/s40119-020-00181-8. Epub 2020 Jun 20.

  PMID: 32564340 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

• Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, Fazio S. Relationship Between Low-Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab. J Am Heart Assoc. 2019 Feb 19;8(4):e010932. doi: 10.1161/JAHA.118.010932.

  PMID: 30755061 BACKGROUND

• Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, Ma Y, Wasserman SM, Koren MJ. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21.

  PMID: 30120772 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

• May HT, Muhlestein JB, Ma Y, Lopez JAG, Coll B, Nelson J. Effects of Evolocumab on the ApoA1 Remnant Ratio: A Pooled Analysis of Phase 3 Studies. Cardiol Ther. 2019 Jun;8(1):91-102. doi: 10.1007/s40119-019-0133-6. Epub 2019 Mar 9.

  PMID: 30852766 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperlipidemias; Hypercholesterolemia

Interventions

evolocumab; Ezetimibe

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

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 7, 2013
• First Posted: January 9, 2013
• Study Start: January 21, 2013
• Primary Completion: October 10, 2013
• Study Completion: October 29, 2013
• Last Updated: November 8, 2022
• Results First Posted: December 30, 2015

Record last verified: 2022-11

Locations

DK (3); TW (3); AU (4); KR (3); CA (4); BE (9); FR (2); TU (2); US (47); ZA (6)