NCT01380730

Brief Summary

To evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab (AMG 145) administered every 2 weeks (Q2W) or every 4 weeks (Q4W), compared with placebo, on percent change from baseline in LDL-C when used in addition to a statin in adults with hypercholesterolemia.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
631

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jul 2011

Shorter than P25 for phase_2

Geographic Reach
5 countries

100 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 23, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 27, 2011

Completed
4 days until next milestone

Study Start

First participant enrolled

July 1, 2011

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 5, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 5, 2012

Completed
3.5 years until next milestone

Results Posted

Study results publicly available

October 1, 2015

Completed
Last Updated

November 15, 2022

Status Verified

November 1, 2022

Enrollment Period

9 months

First QC Date

June 23, 2011

Results QC Date

September 1, 2015

Last Update Submit

November 10, 2022

Conditions

Keywords

HypercholesterolemiaProprotein convertase subtilisin/kexin type 9 (PCSK9)

Outcome Measures

Primary Outcomes (1)

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

    LDL-C was measured using ultracentrifugation.

    Baseline and Week 12

Secondary Outcomes (5)

  • Change From Baseline in LDL-C at Week 12

    Baseline and Week 12

  • Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12

    Baseline and Week 12

  • Percent Change From Baseline in Apolipoprotein B at Week 12

    Baseline and Week 12

  • Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12

    Baseline and Week 12

  • Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12

    Baseline and Week 12

Study Arms (8)

Placebo Q2W

PLACEBO COMPARATOR

Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.

Other: Placebo to Evolocumab

Placebo Q4W

PLACEBO COMPARATOR

Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.

Other: Placebo to Evolocumab

Evolocumab 70 mg Q2W

EXPERIMENTAL

Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.

Biological: Evolocumab

Evolocumab 105 mg Q2W

EXPERIMENTAL

Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.

Biological: Evolocumab

Evolocumab 140 mg Q2W

EXPERIMENTAL

Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.

Biological: Evolocumab

Evolocumab 280 mg Q4W

EXPERIMENTAL

Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Biological: Evolocumab

Evolocumab 350 mg Q4W

EXPERIMENTAL

Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Biological: Evolocumab

Evolocumab 420 mg Q4W

EXPERIMENTAL

Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Biological: Evolocumab

Interventions

EvolocumabBIOLOGICAL

Administered by subcutaneous injection

Also known as: AMG 145, Repatha
Evolocumab 105 mg Q2WEvolocumab 140 mg Q2WEvolocumab 280 mg Q4WEvolocumab 350 mg Q4WEvolocumab 420 mg Q4WEvolocumab 70 mg Q2W

Administered by subcutaneous injection

Placebo Q2WPlacebo Q4W

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female ≥ 18 to ≤ 80 years of age
  • On an approved statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks
  • Fasting LDL-C ≥ 85 mg/dL
  • Fasting triglycerides ≤ 400 mg/dL

You may not qualify if:

  • 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 (Glycosyated Hemoglobin (HbA1c) \> 8.5%)
  • Uncontrolled hypertension
  • New York Heart Association (NYHA) III or IV heart failure, or known left ventricular ejection fraction \< 30%
  • Uncontrolled cardiac arrhythmia

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (100)

Research Site

Birmingham, Alabama, 35294, United States

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Tucson, Arizona, 85710, United States

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Malvern, Arkansas, 72104, United States

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Anaheim, California, 92801, United States

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Carmichael, California, 95608, United States

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Newport Beach, California, 92663, United States

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Roseville, California, 95747, United States

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Westlake Village, California, 91361, United States

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Colorado Springs, Colorado, 80909, United States

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Littleton, Colorado, 80120, United States

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Daytona Beach, Florida, 32117, United States

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Green Cove Springs, Florida, 32043, United States

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Melbourne, Florida, 32901, United States

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Miami, Florida, 33143, United States

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Miami, Florida, 33173, United States

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Port Charlotte, Florida, 33952, United States

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Peoria, Illinois, 61614, United States

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Hammond, Indiana, 46320, United States

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Indianapolis, Indiana, 46237, United States

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Valparaiso, Indiana, 46383, United States

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Iowa City, Iowa, 52242, United States

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Lexington, Kentucky, 40536, United States

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Auburn, Maine, 04210, United States

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Bangor, Maine, 04401, United States

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Portland, Maine, 04101, United States

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Kalamazoo, Michigan, 49048, United States

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Marquette, Michigan, 49855, United States

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Ypsilanti, Michigan, 48197, United States

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Tupelo, Mississippi, 38801, United States

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Great Falls, Montana, 59405, United States

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Voorhees Township, New Jersey, 08043, United States

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Cortlandt Manor, New York, 10567, United States

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Williamsville, New York, 14221, United States

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Smithfield, North Carolina, 27577, United States

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Winston-Salem, North Carolina, 27103, United States

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Canton, Ohio, 44708, United States

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Cincinnati, Ohio, 45212, United States

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Cincinnati, Ohio, 45219, United States

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Dayton, Ohio, 45414, United States

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Mansfield, Ohio, 44906, United States

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Marion, Ohio, 43302, United States

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Sandusky, Ohio, 44870, United States

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Camp Hill, Pennsylvania, 17011, United States

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Philadelphia, Pennsylvania, 19104, United States

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Pittsburgh, Pennsylvania, 15216, United States

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York, Pennsylvania, 17405, United States

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Florence, South Carolina, 29501, United States

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Spartanburg, South Carolina, 29302, United States

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Rapid City, South Dakota, 57701, United States

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Jackson, Tennessee, 38301, United States

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Jackson, Tennessee, 38305, United States

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Houston, Texas, 77002, United States

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Houston, Texas, 77074, United States

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Tacoma, Washington, 98405, United States

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Madison, Wisconsin, 53713, United States

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Burnaby, British Columbia, V5G 1T4, Canada

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Kelowna, British Columbia, V1Y 1V6, Canada

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Vancouver, British Columbia, V6Z 1Y6, Canada

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Victoria, British Columbia, V8T 5G1, Canada

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Cambridge, Ontario, N1R 6V6, Canada

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Greater Sudbury, Ontario, P3C 5K7, Canada

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Hamilton, Ontario, L8L 2X2, Canada

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London, Ontario, N5W 6A2, Canada

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London, Ontario, N6A 5K8, Canada

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Newmarket, Ontario, L3Y 5G8, Canada

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Oshawa, Ontario, L1J 2J9, Canada

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Oshawa, Ontario, L1J 2K1, Canada

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Sarnia, Ontario, N7T 4X3, Canada

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Scarborough Village, Ontario, M1P 2T7, Canada

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Toronto, Ontario, M8V 3X8, Canada

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Toronto, Ontario, M9V 4B4, Canada

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Woodstock, Ontario, N4S 5P5, Canada

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Gatineau, Quebec, J8Y 6S9, Canada

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Lachine, Quebec, H8S 2E4, Canada

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Longueuil, Quebec, J4N 0C9, 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, 603 00, Czechia

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Brno, 625 00, Czechia

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Brno, 656 91, Czechia

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Olomouc, 775 20, Czechia

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Prague, 120 00, Czechia

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Prague, 140 21, Czechia

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Slaný, 274 01, Czechia

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Svitavy, 568 25, Czechia

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Ústí nad Orlicí, 562 18, Czechia

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Znojmo, 669 02, 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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Budapest, 1096, Hungary

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Debrecen, 4032, Hungary

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Dunaújváros, 2400, Hungary

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Eger, 3300, Hungary

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Gyula, 5700, Hungary

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Kecskemét, 6000, Hungary

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Komárom, 2991, Hungary

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Mosonmagyaróvár, 9200, Hungary

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Szolnok, 5004, Hungary

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Zalaegerszeg, 8900, Hungary

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Related Publications (3)

  • Giugliano RP, Desai NR, Kohli P, Rogers WJ, Somaratne R, Huang F, Liu T, Mohanavelu S, Hoffman EB, McDonald ST, Abrahamsen TE, Wasserman SM, Scott R, Sabatine MS; LAPLACE-TIMI 57 Investigators. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet. 2012 Dec 8;380(9858):2007-17. doi: 10.1016/S0140-6736(12)61770-X. Epub 2012 Nov 6.

    PMID: 23141813BACKGROUND
  • Kohli P, Desai NR, Giugliano RP, Kim JB, Somaratne R, Huang F, Knusel B, McDonald S, Abrahamsen T, Wasserman SM, Scott R, Sabatine MS. Design and rationale of the LAPLACE-TIMI 57 trial: a phase II, double-blind, placebo-controlled study of the efficacy and tolerability of a monoclonal antibody inhibitor of PCSK9 in subjects with hypercholesterolemia on background statin therapy. Clin Cardiol. 2012;35(7):385-91. doi: 10.1002/clc.22014. Epub 2012 Jun 19.

    PMID: 22714699BACKGROUND
  • Desai NR, Kohli P, Giugliano RP, O'Donoghue ML, Somaratne R, Zhou J, Hoffman EB, Huang F, Rogers WJ, Wasserman SM, Scott R, Sabatine MS. AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9, significantly reduces lipoprotein(a) in hypercholesterolemic patients receiving statin therapy: an analysis from the LDL-C Assessment with Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined with Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 trial. Circulation. 2013 Aug 27;128(9):962-9. doi: 10.1161/CIRCULATIONAHA.113.001969. Epub 2013 Jul 24.

Related Links

MeSH Terms

Conditions

HyperlipidemiasHypercholesterolemiaHypercholesterolemia, Autosomal Dominant, 3

Interventions

evolocumab

Condition Hierarchy (Ancestors)

DyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Results Point of Contact

Title
Study Director
Organization
Amgen Inc.

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 2
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

June 23, 2011

First Posted

June 27, 2011

Study Start

July 1, 2011

Primary Completion

April 5, 2012

Study Completion

April 5, 2012

Last Updated

November 15, 2022

Results First Posted

October 1, 2015

Record last verified: 2022-11

Locations