PCSK9 Inhibition in Patients With Symptomatic Intracranial Atherosclerosis (PINNACLE)

Utah System of Higher Education (USHE)

Status and phase: Terminated; Early Phase 1

Conditions: Intraplaque Hemorrhage; Intracranial Atherosclerosis; Stroke

Treatments: Drug: Alirocumab; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03507374

00104839

Details and patient eligibility

About

This will be a randomized double blind placebo-controlled pilot study using a repeated measures design in which participants with acute ischemic stroke and intracranial atherosclerotic disease are randomized to either drug or placebo.

Full description

The purpose of this study will be a dataset that lays the foundation for a randomized controlled trial of PCSK9 inhibition in intracranial atherosclerotic disease (ICAD) patients, designed to show a reduction in the primary endpoint of ischemic stroke recurrence. Such a trial would provide evidence for the utility of alirocumab to prevent recurrent stroke in ICAD. While we are proposing future studies to reduce recurrent ICAD stroke risk, it should be noted that, in the long term, our research may lead to effective primary ICAD stroke risk reduction through PCSK9 inhibition in patients at high risk of stroke identified through asymptomatic stenosis, post-contrast plaque enhancement (PPE) or intraplaque hemorrhage (IPH) on vwMRI.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients, ≥ 18 years of age
• Ischemic stroke (≤ 1 month from onset) in one major vascular territory on diffusion-weighted MRI
• ICAD plaque of a "major intracranial artery," causing >25% and <99% stenosis
• Eligible arteries: vertebral (V4), basilar, PCA (P1, P2), MCA (M1, M2), terminal ICA, and ACA (A1)
• Able to tolerate high-dose statin (atorvastatin 40-80 mg)

Exclusion criteria

• Stroke mechanism other than ICAD, including history of atrial fibrillation, hypercoagulability, ipsilateral arterial dissection or carotid stenosis >50%, and rare causes of stroke such as vasculitis or CADASIL
• Bihemispheric stroke or simultaneous stroke in the anterior and posterior circulation
• Positive pregnancy test
• Gadolinium or PCSK9 inhibitor allergy
• Acute or chronic kidney disease with eGFR<30 ml/min/1.73m2
• Pacemaker or other MRI contraindications per American College of Radiology guidelines33
• Inability to return for 1-year follow-up clinic visit and vwMRI

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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20 participants in 2 patient groups, including a placebo group

Placebo Comparator

Placebo Comparator group

Description:

After review of eligibility criteria, 20 patients will be randomized to the placebo arm of the study where patient will administer one subcutaneous injection of placebo every two weeks for a total of 52 weeks. Additionally, per standard-of-care, patient will also be treated with atorvastatin 40-80 mg.

Treatment:

Drug: Placebo

Active Comparator

Active Comparator group

Description:

After review of eligibility criteria, 20 patients will be randomized to receive the investigational treatment of alirocumab 150mg which will be administered subcutaneously with a single-dose pre-filled pen syringe every 2 weeks for a total of 52 weeks. Additionally, per standard-of-care, patient will also be treated with atorvastatin 40-80 mg

Treatment:

Drug: Alirocumab