Effect of Evolocumab on Coronary Endothelial Function

NCT03500302 | Completed Phase 2 Results FDA Drug

• 1 other identifier: IRB00127952
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose a pilot study using (1) MRI to assess coronary artery endothelial function, (2) brachial ultrasound to assess systemic endothelial function, (3) serum markers of inflammation and of endothelial cell function and (4) echocardiographic measures of left ventricular diastolic and systolic properties, before and following initiation of PCSK9 antibody in HIV positive subjects.

Conditions

Human Immunodeficiency Virus; Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Coronary Endothelial Function as Assessed by Percent Coronary Artery Area Change With Isometric Handgrip Exercise

  Coronary endothelial function will be assessed by the percent change in cross sectional coronary artery area (measured on MRI) from rest to isometric handgrip stress exercise at week 1 and week 6. The percent change from week 1 to week 6 is presented below.

  1 week and 6 weeks

Secondary Outcomes (1)

• LDL Cholesterol Level

  At 6 weeks

Study Arms (1)

Evolocumab

EXPERIMENTAL

All enrolled patients will receive evolocumab sq once a month for a total of two doses

Drug: Evolocumab

Interventions

Evolocumab DRUG

Evolocumab sq once a month for a total of two doses

Also known as: Repatha

Evolocumab

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants of either gender who are \>21 years of age (no upper age limit)
• HIV (Human Immunodeficiency Virus) positive and taking stable Anti-Retroviral Therapy (ART), no change in regimen in last 3 months)
• Undetectable HIV viral load (plasma HIV RNA concentration, RNA=Ribonucleic Adic)
• Abnormal coronary endothelial function on MRI (Magnetic Resonance Imaging) at baseline (\<5% change in coronary cross sectional area during isometric handgrip exercise as compared to resting value).
• Lipids at screening visit: Fasting LDL-C \>70 mg/dL (LDL-C=Low Density Lipoprotein Cholesterol); fasting TG\<500 mg/dL (TG=Triglycerides)
• Permission of treating physician

You may not qualify if:

• Patients unable to understand the risks, benefits, and alternatives of participation and give meaningful consent.
• Patients with contraindications to MRI such as implanted metallic objects (pre-existing cardiac pacemakers, cerebral clips),
• History of a recent cardiovascular or cerebrovascular events or procedure (e.g. myocardial infarction, stroke, transient ischemic attack, angioplasty, Coronary artery bypass surgery) during the past 90 days.
• Subjects with prior exposure to evolocumab or another PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitor.
• Pregnant women or breastfeeding women. Women of childbearing potential (even if using oral contraceptive agents) or intention to breastfeed.
• History of alcoholism or drug addiction according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria within 12 months prior to screening. Use of any recreational drugs within 6 months prior to screening.
• Renal impairment defined by estimated glomerular filtration rate \<45 ml/min.
• Moderate-severe hepatic disease (elevation in hepatic transaminases \>3x upper limit of normal, ULN) or direct bilirubin \>3.0 X ULN at screening.
• Cluster of differentiation 4 (CD4)\<200 cell/mm3
• History of allergic or anaphylactic reaction to any therapeutic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibodies
• Active phase hepatitis. Stable patients with hepatitis B or C infection \>3 years before randomization are eligible.

Sponsors & Collaborators

• Johns Hopkins University: lead
• American Heart Association: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• Leucker TM, Gerstenblith G, Schar M, Brown TT, Jones SR, Afework Y, Weiss RG, Hays AG. Evolocumab, a PCSK9-Monoclonal Antibody, Rapidly Reverses Coronary Artery Endothelial Dysfunction in People Living With HIV and People With Dyslipidemia. J Am Heart Assoc. 2020 Jul 21;9(14):e016263. doi: 10.1161/JAHA.120.016263. Epub 2020 Jul 17.

  PMID: 32674634 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Coronary Artery Disease

Interventions

evolocumab

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Results Point of Contact

• Title: Allison Hays
• Organization: Johns Hopkins University

ahays2@jhmi.edu

443-287-6827

Study Officials

• Allison Hays, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pilot clinical trial to study HIV+ patients with baseline coronary endothelial dysfunction and assess changes in that function from the baseline measure to 1 and 6 weeks following initiation of therapy with evolocumab so as to test the hypotheses that PCSK9 inhibition with evolocumab improves coronary endothelial function (CEF) measured directly and non-invasively with MRI at 1 week and 6 weeks after initiation of evolocumab.

Study Record Dates

• First Submitted: November 27, 2017
• First Posted: April 18, 2018
• Study Start: May 4, 2018
• Primary Completion: November 30, 2019
• Study Completion: November 30, 2019
• Last Updated: July 24, 2020
• Results First Posted: July 24, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)