Effect of Evolocumab on Coronary Plaque Characteristics

NCT04710368 | Completed Phase 4 Results FDA Drug

• 1 other identifier: GCO 20-2935
• Study Type: interventional
• Target: 137
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to assess the effect of evolocumab on coronary plaque morphology using intravascular imaging and gene expression analysis of peripheral blood mononuclear cells (PBMC) in patients with stable CAD on maximally tolerated statin therapy. The study combines multi-modality intravascular imaging approaches and transcriptomic based machine learning algorithms to uncover molecular mechanisms responsible for the beneficial changes in atherosclerotic lesions of patients treated with evolocumab. The primary end-points are the changes from baseline to follow-up in (1) the minimal fibrous cap thickness (FCT) assessed by optical coherence tomography (OCT) and (2) maxLCBI4mm assessed by near-infrared spectroscopy (NIRS) after 26 weeks of evolocumab. The secondary endpoints are the changes in (1) the maximal lipid arc, lipid length, lipid volume index, macrophage accumulation and calcification by OCT; (2) PAV and TAV defined by intravascular ultrasound (IVUS) and (3) Changes in PBMC gene expression.

Conditions

Coronary Artery Disease

Keywords

Coronary Artery Disease; Coronary Plaque; Optical Coherence Tomography; Near-Infrared Spectroscopy; Evolocumab; Statin

Outcome Measures

Primary Outcomes (5)

• Change in Minimal Fibrous Cap Thickness (FCT)

  Changes in the minimal Minimal Fibrous Cap Thickness (FCT) is assessed by Optical Coherence Tomography (OCT) imaging and measured in microns. FCT describes plaque morphology composition.

  Baseline and 26 Weeks

• Number of Participants With FCT <65 µm

  Baseline and 26 Weeks

• Number of Participants With Increased Fibrous Cap

  26 weeks

• Change in maxNIRS4mm

  Changes in maximal lipid-core burden index within 4 mm (maxLCBI4mm). LCBI4mm is assessed by NIRS and calculated as the fraction of yellow pixels on a chemogram multiplied by 1000. Each pixel on the chemogram represents a probability of lipid presence in the given region; pixels are color-coded on a red-to-yellow color scale, with the low probability of lipid shown as red and the high probability of lipid shown as yellow. Maximal lipid-core burden index is calculated as a fraction of yellow pixels (representing lipid) obtained from the NIRS chemogram multiplied by 1000. It ranges is from 0 to 1000 and represents the amount of lipid in the investigated segment with "0" corresponding to no lipid and "1000" representing all lipid lesion.

  Baseline and 26 Weeks

• Number of Participants With Decreased maxLCBI4mm

  26 Weeks

Secondary Outcomes (11)

• Change in Maximal Lipid Arc

  Baseline and 26 Weeks

• Change in Lipid Length

  Baseline and 26 weeks

• Change in Lipid Volume Index (LVI)

  Baseline and 26 Weeks

• Change in Macrophage Accumulation

  Baseline and 26 Weeks

• Change in Macrophage Volume Index

  Baseline and 26 Weeks

Study Arms (1)

Treatment

EXPERIMENTAL

Evolocumab subcutaneously administered 140 mg every 2 weeks for 26 weeks

Drug: Evolocumab Injections

Interventions

Evolocumab Injections DRUG

Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.

Also known as: Repatha

Treatment

Eligibility Criteria

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

You may qualify if:

• Men or women aged 18 years or older at screening who signed written Informed Consent
• Patients with coronary artery disease undergoing cardiac catheterization and PCI for a target lesion and also have a non-obstructive lesion (30-50% stenosis) identified by angiography
• Patients who are not candidates for PCI or CABG currently or over the next 12 months, in the opinion of the investigator
• Patients treated with statins for at least 4 weeks with LDL-C level ≥ 80 mg/dL for low- or moderate -intensity statin use and ≥ 60 mg/dL for high-dose statin. Patients with history of statin intolerance and LDL-C ≥ 100 mg/dL.
• Angiographic criteria: 30-50% reduction of lumen diameter in addition to the target lesion accessible by the OCT catheter. The target segment should not have a history of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), and may not be a bypass graft.
• OCT criteria: target segment should have a lipid-rich plaque with lipid arc \>90° and fibrous cap thickness ≤120 µm.
• Women of childbearing potential must agree to be on an acceptable method of birth control/contraceptive

You may not qualify if:

• Patients who have acute myocardial infarction (Q wave or non-Q wave with CK-MB \> 5 times above the upper normal (31.5 ng/ml) within 72 hours)
• Patients who are in cardiogenic shock
• Patients with left main disease, in-stent restenotic lesions or patients requiring coronary artery bypass graft surgery
• Patients with elevated CK-MB (\>6.3 ng/ml) or Tnl (\>0.5 ng/ml)
• Patients with platelet count \< 100,000 cell/mm3
• Patients who have co-morbidity which reduces life expectancy to one year
• Patients who are currently participating in another investigational drug/device study
• Patients with liver disease
• Patient with creatinine \> 2.0 mg/dL
• Pregnant women and women of childbearing potential who intend to have children during the duration of the trial
• Patients having undergone heart transplantation, or those that may undergo heart transplantation during the study period
• Patients with active autoimmune disease

Sponsors & Collaborators

• Annapoorna Kini: lead

Study Sites (1)

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Related Publications (5)

• Nissen SE, Stroes E, Dent-Acosta RE, Rosenson RS, Lehman SJ, Sattar N, Preiss D, Bruckert E, Ceska R, Lepor N, Ballantyne CM, Gouni-Berthold I, Elliott M, Brennan DM, Wasserman SM, Somaratne R, Scott R, Stein EA; GAUSS-3 Investigators. Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial. JAMA. 2016 Apr 19;315(15):1580-90. doi: 10.1001/jama.2016.3608.

  PMID: 27039291 BACKGROUND

• Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR; FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 May 4;376(18):1713-1722. doi: 10.1056/NEJMoa1615664. Epub 2017 Mar 17.

  PMID: 28304224 BACKGROUND

• Connolly CK. Lung function testing. Respir Med. 1994 Nov;88(10):795-6. doi: 10.1016/s0954-6111(05)80207-0. No abstract available.

  PMID: 7846344 BACKGROUND

• Kini AS, Vengrenyuk Y, Shameer K, Maehara A, Purushothaman M, Yoshimura T, Matsumura M, Aquino M, Haider N, Johnson KW, Readhead B, Kidd BA, Feig JE, Krishnan P, Sweeny J, Milind M, Moreno P, Mehran R, Kovacic JC, Baber U, Dudley JT, Narula J, Sharma S. Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment: The YELLOW II Study. J Am Coll Cardiol. 2017 Feb 14;69(6):628-640. doi: 10.1016/j.jacc.2016.10.029. Epub 2016 Oct 29.

  PMID: 27989886 BACKGROUND

• Johnson KW, Glicksberg BS, Shameer K, Vengrenyuk Y, Krittanawong C, Russak AJ, Sharma SK, Narula JN, Dudley JT, Kini AS. A transcriptomic model to predict increase in fibrous cap thickness in response to high-dose statin treatment: Validation by serial intracoronary OCT imaging. EBioMedicine. 2019 Jun;44:41-49. doi: 10.1016/j.ebiom.2019.05.007. Epub 2019 May 22.

  PMID: 31126891 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Results Point of Contact

• Title: Annapoorna S Kini, M.D.
• Organization: Mount Sinai Hospital

annapoorna.kini@mountsinai.org

(212) 241-4181

Study Officials

• Annapoorna Kini, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine, Cardiology

Model Details: The study team will screen patients scheduled for elective PCI, who are receiving statin therapy for at least 4 weeks with acceptable LDL-C levels. Patients with non-obstructive lesion (30-50% stenosis) by angiography and lipid-rich plaque with lipid arc \>90° and minimal fibrous cap thickness ≤ 120 µm detected by OCT will comprise the final study population. Serial NIRS/IVUS and OCT imaging will be performed in a non-target lesions, first during PCI and subsequently after 26 weeks.

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: January 14, 2021
• Study Start: May 4, 2021
• Primary Completion: October 28, 2022
• Study Completion: November 6, 2023
• Last Updated: November 18, 2023
• Results First Posted: May 3, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)