Trial of PCSK9 Inhibition in Patients with Acute Stroke and Symptomatic Intracranial Atherosclerosis

NCT05001984 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: TOPICAL-MRIMOST 110-2314-B-182A-072
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate whether low-density lipoprotein (LDL-C) lowering with alirocumab results in greater change from baseline in intracranial atherosclerotic plaque at week 26 than control in adults with acute ischemic stroke from intracranial atherosclerosis taking lipid lowering therapy.

Conditions

Intracranial Atherosclerosis; Acute Ischemic Stroke; ICAS - Intracranial Atherosclerosis

Keywords

Intracranial Atherosclerosis; Acute Ischemic Stroke; PCSK9 inhibitor

Outcome Measures

Primary Outcomes (3)

• The changes of intracranial atherosclerotic plaque: stenosis degree

  The changes of intracranial atherosclerotic plaque in vessel-wall MRI before and after 6-month treatment, measured as stenosis degree. The degree of stenosis was calculated as: (1-lumen area of stenotic lesion/reference lumen area)×100%.

  26 weeks

• The changes of intracranial atherosclerotic plaque: percent atheroma volume

  The changes of intracranial atherosclerotic plaque in vessel-wall MRI before and after 6-month treatment, measured as percent atheroma volume (PAV). The PAV was calculated using the following equation: PAV = Σ(EEM area - Lumen area) / ΣEEM area × 100, where EEM area is the cross-sectional area of the external elastic membrane and Lumen area is the cross-sectional area of the lumen.

  26 weeks

• The changes of intracranial atherosclerotic plaque: enhancement volume

  The changes of intracranial atherosclerotic plaque in vessel-wall MRI before and after 6-month treatment, measured as enhancement volume. The enhancement volume was measured as post-contrast plaque enhancement for intracranial arteries and intraplaque hemorrhage.

  26 weeks

Secondary Outcomes (8)

• Percentage of patients with major cardiovascular events

  26 weeks

• Percentage of patients with myocardial infarction

  26 weeks

• Percentage of patients with cardiovascular death

  26 weeks

• Percentage of patients with stroke

  26 weeks

• Percentage of patients with ischemic stroke or transient ischemic attack.

  26 weeks

Study Arms (2)

Intervention group

ACTIVE COMPARATOR

In addition to high-intensity statin and antiplatelet treatment, patients will receive treatment of alirocumab 75mg subcutaneously every 2 weeks for a total of 26 weeks

Drug: Alirocumab

Control group

NO INTERVENTION

Patient will have high-intensity statin and antiplatelet treatment.

Interventions

Alirocumab DRUG

Alirocumab 75mg subcutaneously every 2 weeks for a total of 26 weeks.

Also known as: Praluent

Intervention group

Eligibility Criteria

• Age: 20 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) score of 1-15
• Ischemic lesions on diffuse-weighted imaging located in the territory of symptomatic intracranial atherosclerosis (ICAS).
• Symptomatic ICAS (above 30%) at the M1 or M2 of the middle cerebral artery, basilar artery or at the intracranial portion of the internal carotid artery or vertebral artery.
• Serum LDL-C ≥70 mg/dL for subjects on lipid-lowering therapies (such as a statin and/or ezetimibe) or LDL-C ≥100 mg/dL for subjects without lipid-lowering therapies.
• Ability to randomize within 7 days of time last known free of new ischemic symptoms.
• Ability to receive alirocumab or statin treatment within 7 days of stroke onset.
• Head CT or MRI ruling out hemorrhage or other pathology, such as vascular malformation, tumor, or abscess, that could explain symptoms or contraindicate therapy.
• Pre-stroke modified Rankin Scale (mRS)≦2

You may not qualify if:

• Age \<20 years.
• Judged by clinical physician.
• After endovascular intervention or endarterectomy for the symptomatic ICAS.
• Patients with more than 50% stenosis of extra-cranial arteries the relevant arteries on magnetic resonance angiography (MRA), including extra-cranial carotid artery or vertebral arteries.
• Patients with high risk of cardioembolic source, such as atrial fibrillation, acute myocardial infarction, severe heart failure or valvular heart disease.
• Other determined stroke etiology, such as vasculitis, shock, antiphospholipid antibody syndrome, arterial dissection, CADASIL and etc.
• Qualifying ischemic event induced by angiography or surgery.
• Severe non-cardiovascular comorbidity with life expectancy \<6 months.
• Contraindication or allergy to alirocumab or Gadolinium
• Severe renal (serum creatinine \>2 mg/dL) or calculated glomerular filtration rate \<30 mL/min/ 1.73 m2 by estimated glomerular filtration rate (eGFR) using Cockcroft Gault methodology.
• Hepatic insufficiency (INR\>1.2; ALT\>40 U/L or any resultant complication, such as variceal bleeding, encephalopathy, or jaundice)
• Hemostatic disorder or systemic bleeding in the past 3 months
• Current thrombocytopenia (platelet count \<100 x109/L) or leukopenia (\<2 x109/L)
• Anemia（\<10 mg/dL）
• History of drug-induced hematologic or hepatic abnormalities

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead
• Chang Gung University: collaborator

Study Sites (1)

Yenchu Huang

Chiayi City, Taiwan, 613, Taiwan

Location

Related Publications (23)

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• Huang YC, Chang CH, Tsai YH, Weng HH, Lin LC, Lee JD. PCSK9 inhibition in patients with acute stroke and symptomatic intracranial atherosclerosis: protocol for a prospective, randomised, open-label, blinded end-point trial with vessel-wall MR imaging. BMJ Open. 2022 Apr 29;12(4):e060068. doi: 10.1136/bmjopen-2021-060068.

  PMID: 35487727 DERIVED

MeSH Terms

Conditions

Intracranial Arteriosclerosis; Ischemic Stroke

Interventions

alirocumab

Condition Hierarchy (Ancestors)

Intracranial Arterial Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke

Study Officials

• Yenchu Huang, MD

  Chang Gung Memorial Hospital, Chiayi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized, open-label, blinded end-point study

Study Record Dates

• First Submitted: July 22, 2021
• First Posted: August 12, 2021
• Study Start: August 1, 2021
• Primary Completion: April 15, 2025
• Study Completion: April 15, 2025
• Last Updated: March 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)