LAPLACE-TIMI 57: Low-density Lipoprotein Cholesterol (LDL-C) Assessment With PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy (LAPLACE)

• ClinicalTrials.gov Identifier: NCT01380730
• Recruitment Status: Completed
• First Posted: June 27, 2011
• Results First Posted: October 1, 2015
• Last Update Posted: January 5, 2021
• Sponsor: Amgen
• Collaborator: TIMI Study Group
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: June 23, 2011
• First Posted Date: June 27, 2011
• Results First Submitted Date: September 1, 2015
• Results First Posted Date: October 1, 2015
• Last Update Posted Date: January 5, 2021
• Actual Study Start Date: July 1, 2011
• Actual Primary Completion Date: April 5, 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 1, 2015)

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]

LDL-C was measured using ultracentrifugation.

• Original Primary Outcome Measures (submitted: June 23, 2011): The primary endpoint is the percent change from baseline in LDL-C at week 12 [ Time Frame: 12 weeks ]

Current Secondary Outcome Measures (submitted: September 1, 2015)

• Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
  LDL-C was measured using ultracentrifugation.
• Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]
• Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]

Original Secondary Outcome Measures (submitted: June 23, 2011)

• Percent change from baseline in non-HDL-C at week 12 [ Time Frame: 12 weeks ]
• Percent change from baseline in ApoB at week 12 [ Time Frame: 12 weeks ]
• Percent change from baseline in the total cholesterol/HDL-C ratio at week 12 [ Time Frame: 12 weeks ]
• Percent change from baseline in ApoB/ApoA1 ratio at week 12 [ Time Frame: 12 weeks ]
• Absolute change from baseline in LDL-C at week 12 [ Time Frame: 12 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: LAPLACE-TIMI 57: Low-density Lipoprotein Cholesterol (LDL-C) Assessment With PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy
• Official Title: LAPLACE TIMI 57 - A Double-blind, Randomized, Placebo-controlled, Multicenter, Dose-ranging Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Combination With HMG-CoA Reductase Inhibitors in Hypercholesterolemic Subjects
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hyperlipidemia

Intervention

• Biological: Evolocumab
  Administered by subcutaneous injection
  Other Names:

  • AMG 145
  • Repatha
• Other: Placebo to Evolocumab
  Administered by subcutaneous injection

Study Arms

• Placebo Comparator: Placebo Q2W
  Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
  Intervention: Other: Placebo to Evolocumab
• Placebo Comparator: Placebo Q4W
  Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
  Intervention: Other: Placebo to Evolocumab
• Experimental: Evolocumab 70 mg Q2W
  Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
  Intervention: Biological: Evolocumab
• Experimental: Evolocumab 105 mg Q2W
  Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
  Intervention: Biological: Evolocumab
• Experimental: Evolocumab 140 mg Q2W
  Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
  Intervention: Biological: Evolocumab
• Experimental: Evolocumab 280 mg Q4W
  Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
  Intervention: Biological: Evolocumab
• Experimental: Evolocumab 350 mg Q4W
  Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
  Intervention: Biological: Evolocumab
• Experimental: Evolocumab 420 mg Q4W
  Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
  Intervention: Biological: Evolocumab

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 14, 2012): 631
• Original Estimated Enrollment (submitted: June 23, 2011): 600
• Actual Study Completion Date: April 5, 2012
• Actual Primary Completion Date: April 5, 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Czechia, Denmark, Hungary, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01380730
• Other Study ID Numbers: 20101155
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Amgen
• Study Sponsor: Amgen
• Collaborators: TIMI Study Group

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: January 2021