Evolocumab in Acute Coronary Syndrome

NCT03515304 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB00156313
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Vascular and myocardial inflammation are significantly increased in Acute Coronary Syndrome (ACS) patients, are closely correlated to LDL-C levels, and are associated with these adverse consequences in the post-ACS patient population. Serum proprotein convertase subtilisin/kerin type 9 (PCSK9) levels are also increased in ACS, may raise LDL-C, and the investigators' pre-clinical studies indicate that PCSK9 is also a potent inducer of vascular inflammation. The addition of the PCSK9 antibody evolocumab, currently approved to lower LDL-C in certain patient populations, to current medical therapies would appear to be of particular benefit in an important subset of ACS patients, those with non-ST elevation myocardial infarction (NSTEMI) by markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting inflammation-associated myocardial cell loss and resultant dysfunction.

Conditions

Acute Coronary Syndrome

Outcome Measures

Primary Outcomes (2)

• Percent Change in LDL-Cholesterol

  Baseline to 30 days

• Change From Baseline in Target to Background Ratio Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Scans

  PET Imaging for Inflammation: Change from baseline in target to background ratio Fluorodeoxyglucose (FDG) PET scans in the myocardium.

  Baseline to 30 days

Secondary Outcomes (7)

• Left Ventricular Volume as Assessed by Echocardiography

  Baseline, day 30 and 6 months

• Ejection Fraction as Assessed by Echocardiography

  Baseline, day 30 and 6 months

• Plasma Proprotein Convertase Subtilisin Kexin-9 (PCSK9) Levels (ng/ml)

  Baseline, day 30 and 6 months

• PET-FDG Assessed Vascular Inflammation as Assessed by Standardized Uptake Value (SUV)

  Baseline to day 30

• High Sensitivity C-reactive Protein (Hs-CRP) Serum Levels

  Baseline, day 30 and 6 months

Study Arms (2)

Evolocumab

EXPERIMENTAL

420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.

Drug: Evolocumab

Placebo

PLACEBO COMPARATOR

Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.

Drug: Placebo

Interventions

Evolocumab DRUG

420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.

Also known as: Repatha

Evolocumab

Placebo DRUG

Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.

Placebo

Eligibility Criteria

• Age: 25 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non ST segment elevation myocardial infarction
• Troponin I \>/ 5.0 ng/dL
• Permission of attending physician

You may not qualify if:

• ST elevation myocardial infarction
• Patients requiring invasive hemodynamic support
• Scheduled for cardiac surgery
• Current or prior treatment with a PCSK9 antibody
• Current participation in an intervention clinical trial
• Female of childbearing potential who has not used acceptable method(s) of birth control for at least one month prior to screening
• Contraindication to statin therapy
• Subject likely not able to complete protocol related visits or procedures
• Latex allergy
• History of hypersensitivity to any monoclonal antibody

Sponsors & Collaborators

• Johns Hopkins University: lead
• Amgen: collaborator

Study Sites (1)

Steven Paul Schulman

Baltimore, Maryland, 21136, United States

Location

Related Publications (1)

• Vavuranakis MA, Jones SR, Ziogos E, Blaha MJ, Williams MS, Foran P, Schindler TH, Lai S, Schulman SP, Gerstenblith G, Leucker TM. The Trajectory of Lipoprotein(a) During the Peri- and Early Postinfarction Period and the Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition. Am J Cardiol. 2022 May 15;171:1-6. doi: 10.1016/j.amjcard.2022.01.058. Epub 2022 Mar 21.

  PMID: 35314069 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Results Point of Contact

• Title: Dr. Thorsten Leucker
• Organization: Johns Hopkins University - Baltimore, MD

tleucke1@jhmi.edu

4105020469

Study Officials

• Thorsten M Leucker, MD, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Persons performing the PET imaging, laboratory technicians are all masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, placebo controlled trial

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: May 3, 2018
• Study Start: May 20, 2018
• Primary Completion: October 25, 2024
• Study Completion: March 25, 2025
• Last Updated: May 1, 2026
• Results First Posted: November 24, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)