Assessment of Atherosclerotic Plaque Characteristics Change by DCE-MRI With Alirocumab

NCT02992301 | Unknown Phase 4 DMC

• 1 other identifier: WMALA-99-032
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Aim 1: To determine whether therapy with Alirocumab, compared to pre-treatment, will effectively improve carotid atherosclerotic plaque characteristics by reducing Ktrans and LRNC size. To achieve this goal, we will (a) enroll 30 subjects who are intolerant to high intensity statin therapy and only able to tolerate low potency statin or low weekly dose of high potency statin and have LDL-C ≥70 mg/dl; (b) initiate alirocumab at 150mg subcutaneously injection every 2 weeks; (c) perform carotid DCE-MRI scans at baseline, 3, 6 and 12 months; (d) perform quantitative analysis for vascular inflammation and plaque LRNC volume and other plaque characteristics; (e) compare vascular inflammation and LRNC volume between pre- and post-alirocumab at 3, 6 and 12 months. Aim 2: To examine associations between reductions in atherogenic lipids (LDL-C, Lp(a), non-HDL-C) and changes in atherosclerotic plaque characteristics. To achieve this goal, we will (a) perform laboratory assessments of lipids, lipoproteins and apo-lipoproteins at baseline and during the study; (b) compare lipids, lipoproteins and apo-lipoproteins levels between pre- and post-alirocumab; (c) correlate reductions in atherogenic lipids with changes atherosclerotic plaque characteristics.

Conditions

Atherosclerosis; Hyperlipidemia

Outcome Measures

Primary Outcomes (1)

• Changes in carotid atherosclerotic plaque characteristics as evidenced by effect on the volume transfer constant( Ktrans) and lipid-rich necrotic core (LRNC) size.

  To determine whether therapy with Alirocumab, compared to pre-treatment, will effectively improve carotid atherosclerotic plaque characteristics by reducing Ktrans and LRNC size. To achieve this goal, we will (a) enroll 30 subjects who are intolerant to high intensity statin therpay and only able to tolerate low potency statin or low weekly dose of high potency statin and have LDL-C ≥100 mg/dl; (b) initiate alirocumab at 150mg subcutaneously injection every 2 weeks; (c) perform carotid DCE-MRI scans at baseline, 3, 6 and 12 months; (d) perform quantitative analysis for vascular inflammation (Ktrans) and plaque LRNC volume and other plaque characteristics; (e) compare Ktrans and LRNC volume between pre- and post-alirocumab at 3, 6 and 12 months.

  52 weeks

Secondary Outcomes (1)

• Associations between reductions in atherogenic lipids and changes in atherosclerotic plaque characteristics

  52 weeks

Study Arms (1)

Open Label

EXPERIMENTAL

All enrolled patients will receive open label Praluent (Alirocumab).

Drug: Alirocumab

Interventions

Alirocumab DRUG

Injectable prescription medicine called a PCSK9 inhibitor.

Also known as: Praluent

Open Label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women ≥18 years of age.
• Subjects with documented inability to consistently take or tolerate high intensity statin therapy and LDL-C ≥70 mg/dL.
• Subjects are only able or allowed to take lower potency statin or low weekly dose of high potency statin due to concern of drug-to-drug interactions or lack of tolerance (pravastatin ≤140 mg, pitavastatin ≤14 mg, simvastatin ≤140 mg, atorvastatin ≤70 mg, or rosuvastatin ≤70 mg, weekly) or intolerant of all statin doses and with fasting LDL-C ≥100 mg/dL.
• Subjects must have significant carotid artery plaque with maximum wall thickness ≥2 mm on ultrasound performed within twelve months of screening.
• Subject must present with a LRNC on baseline MRI scan.
• Subjects must show an adequate image quality for MRI analysis.
• Medically stable.
• Willing to participate and sign informed consent.

You may not qualify if:

• Contraindication to MRI.
• Have immediate plans for bilateral carotid endarterectomy.
• Had received 2 or more doses of treatment with a PCSK9 inhibitor in the past 4 months.
• GFR ≤45 mL/min/1.73 m2 prior to MRI scan.
• Claustrophobia.
• Pregnant women; breastfeeding women; men and women of childbearing potential who are unwilling or unable to use a highly effective method of contraception.
• TIA or stroke within the preceding twelve months
• Severe carotid stenosis in an asymptomatic patient defined as any one of the following:
• Greater than or equal to 70% luminal narrowing on any imaging modality
• Peak systolic velocity greater than or equal to 250 cm/second
• End diastolic velocity greater than or equal to 100 cm/second
• Systolic volume ratio greater than or equal to 3.5

Sponsors & Collaborators

• Westside Medical Associates of Los Angeles: lead
• University of Washington: collaborator
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Westside Medical Associates of Los Angeles

Beverly Hills, California, 90211, United States

Location

MeSH Terms

Conditions

Atherosclerosis; Hyperlipidemias

Interventions

alirocumab

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Norman Lepor, MD

  Westside Medical Associates of Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: December 14, 2016
• Study Start: November 1, 2016
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2019
• Last Updated: April 26, 2019

Record last verified: 2019-04

Locations

US (1)