PCSK9 Inhibitor With Statin Therapy for Asymptomatic Intracranial Atherosclerosis

NCT06902740 | Recruiting Phase 4 DMC

• 3 other identifiers: I-24PJ26012024ZD052160582025013
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 19

Brief Summary

This is a prospective, multicenter, open-label, blinded-endpoint, randomized controlled trial designed to evaluate the efficacy and safety of PCSK9 inhibitor combined with statin therapy compared to statin monotherapy in reversing asymptomatic intracranial atherosclerosis, assessed using high-resolution magnetic resonance imaging of the intracranial vessel walls.

Conditions

Intracranial Atherosclerosis; Intracranial Artery Stenosis; Atherosclerotic Plaque

Keywords

Intracranial Atherosclerosis; intracranial artery stenosis; atherosclerotic plaque; high-resolution magnetic resonance imaging; PCSK9 inhibitor; statin; Recaticimab

Outcome Measures

Primary Outcomes (1)

• Change in plaque burden from baseline to week 24

  Intracranial plaque burden was assessed at maximum stenosis site by high-resolution magnetic resonance imaging, performed at baseline and the end of the treatment period (24 \[±1\] week) on the same machine. The plaque burden is calculated according to the following formula: plaque burden = \[(vessel wall cross-sectional area - lumen cross-sectional area ) / vessel wall cross-sectional area\] ×100%. The outcome will be centrally assessed by an independent core imaging laboratory blinded to treatment allocation according to a predefined imaging analysis protocol.

  From baselie to the end of treatment at 24 weeks

Secondary Outcomes (9)

• Change in stenosis degree from baseline to week 24

  From baseline to the end of treatment at 24 weeks

• Time from randomization to the first-ever ischemic stroke or transient ischemic attack

  From baseline to the end of treatment at 24 weeks

• Change in plasma marker glial fibrillary acidic protein(GFAP)

  From baseline to the end of treatment at 24 weeks

• Change in plasma marker neurofilament light(NfL)

  From baseline to the end of treatment at 24 weeks

• Time from randomization to the occurrence of major adverse cardiovascular events

  From baseline to the end of treatment at 24 weeks

Other Outcomes (26)

• Time from randomization to the time of the first occurrence of transient ischemic attack

  From baseline to the end of treatment at 24 weeks

• Time from randomization to the time of the first occurrence of ischemic stroke

  From baseline to the end of treatment at 24 weeks

• Time from randomization to the time of the occurrence of any stroke

  From baseline to the end of treatment at 24 weeks

Study Arms (2)

Recaticimab plus Statin Group

EXPERIMENTAL

Recaticimab (450mg every 12 weeks subcutaneously) combined with rosuvastatin 10mg qn or atorvastatin 20mg qn

Drug: Recaticimab and Statin

Statin Group

ACTIVE COMPARATOR

Rosuvastatin 10mg qn or atorvastatin 20mg qn

Drug: Statin

Interventions

Recaticimab and Statin DRUG

Recaticimab (450mg every 12 weeks subcutaneously) combined with rosuvastatin 10mg qn or atorvastatin 20mg qn

Recaticimab plus Statin Group

Statin DRUG

Rosuvastatin 10mg qn or atorvastatin 20mg qn

Statin Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤80, male or female;
• Asymptomatic intracranial artery stenosis (50%-99%) in the internal carotid artery (C6-7 segments), middle cerebral artery (M1 segment), vertebral artery (V4 segment), or basilar artery, confirmed by angiography (MRA, CTA, or DSA);
• Atherosclerosis identified as the cause of intracranial artery stenosis by high-resolution magnetic resonance imaging;
• No previous ischemic cerebrovascular events (including ischemic stroke or transient ischemic attack).
• Baseline low-density lipoprotein cholesterol ≥ 1.8 mmol/L;
• Informed consent signed.

You may not qualify if:

• Non-atherosclerotic intracranial artery stenosis, including arterial dissection; moya moya disease; systemic vasculitis and primary central nervous system vasculitis; varicella-zoster vasculopathy or other viral vasculopathy; neurosyphilis and other intracranial infections, radiation vasculopathy; fibromuscular dysplasia, sickle cell disease, neurofibromatosis; reversible cerebral vasoconstriction syndrome; postpartum vasculopathy; suspected vasospasm, suspected reperfusion after vessel occlusion.
• Upstream tandem extracranial vessel stenosis (≥50%) adjacent to the target intracranial stenotic vessel.
• Previous treatment of target intracranial lesion with endovascular intervention or plan to perform endovascular intervention within 6 months, including intracranial stenting, endovascular angioplasty, and thrombectomy.
• Any intracranial hemorrhage (parenchymal, subarachnoid, subdural, extradural, intraventricular) within 90 days prior to enrollment.
• Presence of intracranial tumors.
• Presence of cerebral aneurysms or arteriovenous malformations with indications for interventional therapy.
• Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days or planned in the next 6 months after enrollment.
• Presence of any of the following unequivocal cardiac sources of embolism: mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within 3 months, dilated cardiomyopathy, chronic or paroxysmal atrial fibrillation.
• New York Heart Association (NYHA) class III or IV, or known left ventricular ejection fraction \< 30%.
• Severe liver dysfunction or severe kidney dysfunction: AST and/or ALT \> 3 times the ULN; creatinine clearance \< 0.6 mL/s and/or serum creatinine \> 265 μmol/L (\>3.0 mg/dL); CK \>5 times the ULN at screening.
• Active bleeding diathesis or coagulopathy (e.g., active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets count \< 125,000 / uL, hematocrit \< 30%, Hgb \< 10 g/dl, international normalized ratio \>1.5, bleeding time \> 1 minute beyond normal value upper limit).
• Presence of systemic autoimmune diseases: systemic sclerosis, systemic lupus erythematosus, Sjögren's syndrome, Behçet's disease, mixed connective tissue disease, IgG4-related disease.
• Dementia or psychiatric problem that hinder their ability to consistently adhere to an outpatient program. Co-morbid conditions that may limit the life expectancy to less than 3 years.
• Relative/absolute contraindications to magnetic resonance imaging (MRI) (such as presence of internal metallic objects, claustrophobia, contrast agent allergy, severe renal impairment, epilepsy, hypotension, asthma, and other hypersensitivity respiratory diseases).
• Uncontrolled hypertension during the screening period, defined as seated systolic blood pressure (SBP) \> 180 mmHg or diastolic blood pressure (DBP) \> 110 mmHg.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Chinese PLA General Hospital: collaborator
• Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator
• The Affiliated Hospital of Qingdao University: collaborator
• Zhongnan Hospital: collaborator
• Huashan Hospital: collaborator
• First Affiliated Hospital of Harbin Medical University: collaborator
• Hebei General Hospital: collaborator
• Taihe Hospital: collaborator
• Weifang People's Hospital: collaborator
• Nanjing First Hospital, Nanjing Medical University: collaborator
• Baotou Central Hospital: collaborator
• Jining First People's Hospital: collaborator
• Liaocheng People's Hospital: collaborator
• Tangshan Worker's Hospital: collaborator
• Chongqing General Hospital: collaborator

Study Sites (19)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100730, China

RECRUITING

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

NOT YET RECRUITING

The Third Affiliated Hospital of Sun Yat-sen University, Yuedong Hospital

Meizhou, Guangdong, China

NOT YET RECRUITING

Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine

Cangzhou, Hebei, China

NOT YET RECRUITING

Peking University Third Hospital Qinhuangdao Hospital

Qinhuangdao, Hebei, China

NOT YET RECRUITING

Hebei Provincial People's Hospital

Shijiazhuang, Hebei, 050051, China

RECRUITING

Tangshan Worker's Hospital

Tangshan, Hebei, 063000, China

NOT YET RECRUITING

First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, China

NOT YET RECRUITING

The first affiliated hospital of zhengzhou university

Zhengzhou, Henan, China

NOT YET RECRUITING

Taihe Hospital

Shiyan, Hubei, 442000, China

NOT YET RECRUITING

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

NOT YET RECRUITING

Baotou Central Hospital

Baotou, Inner Mongolia, 014000, China

NOT YET RECRUITING

Nanjing First Hospital

Nanjing, Jiangsu, 210000, China

NOT YET RECRUITING

Jining First People's Hospital

Jining, Shandong, 272000, China

NOT YET RECRUITING

Liaocheng People's Hospital

Liaocheng, Shandong, 252000, China

NOT YET RECRUITING

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

NOT YET RECRUITING

Weifang People's Hospital

Weifang, Shandong, 261000, China

NOT YET RECRUITING

Chongqing General Hospital

Chongqing, China

NOT YET RECRUITING

Huashan Hospital, Fudan University

Shanghai, China

NOT YET RECRUITING

Related Publications (13)

• Perez de Isla L, Diaz-Diaz JL, Romero MJ, Muniz-Grijalvo O, Mediavilla JD, Argueso R, Sanchez Munoz-Torrero JF, Rubio P, Alvarez-Banos P, Ponte P, Manas D, Suarez Gutierrez L, Cepeda JM, Casanas M, Fuentes F, Guijarro C, Angel Barba M, Saltijeral Cerezo A, Padro T, Mata P; SAFEHEART Study Group. Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study. Circulation. 2023 May 9;147(19):1436-1443. doi: 10.1161/CIRCULATIONAHA.122.062557. Epub 2023 Apr 3.

  PMID: 37009731 RESULT

• 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 RESULT

• Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJ, Koenig W, Somaratne R, Kassahun H, Yang J, Wasserman SM, Scott R, Ungi I, Podolec J, Ophuis AO, Cornel JH, Borgman M, Brennan DM, Nissen SE. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial. JAMA. 2016 Dec 13;316(22):2373-2384. doi: 10.1001/jama.2016.16951.

  PMID: 27846344 RESULT

• Kim BS, Lim JS, Jeong JU, Mun JH, Kim SH. Regression of asymptomatic intracranial arterial stenosis by aggressive medical management with a lipid-lowering agent. J Cerebrovasc Endovasc Neurosurg. 2019 Sep;21(3):144-151. doi: 10.7461/jcen.2019.21.3.144. Epub 2019 Sep 30.

  PMID: 31886149 RESULT

• Miao H, Yang Y, Wang H, Huo L, Wang M, Zhou Y, Hua Y, Ren M, Ren C, Ji X, Yang Q, Guo X. Intensive Lipid-Lowering Therapy Ameliorates Asymptomatic Intracranial Atherosclerosis. Aging Dis. 2019 Apr 1;10(2):258-266. doi: 10.14336/AD.2018.0526. eCollection 2019 Apr.

  PMID: 31011477 RESULT

• Zhu J, Wang Y, Li J, Deng J, Zhou H. Intracranial artery stenosis and progression from mild cognitive impairment to Alzheimer disease. Neurology. 2014 Mar 11;82(10):842-9. doi: 10.1212/WNL.0000000000000185. Epub 2014 Jan 31.

  PMID: 24489130 RESULT

• Zhao D, Guallar E, Qiao Y, Knopman DS, Palatino M, Gottesman RF, Mosley TH Jr, Wasserman BA. Intracranial Atherosclerotic Disease and Incident Dementia: The ARIC Study (Atherosclerosis Risk in Communities). Circulation. 2024 Sep 10;150(11):838-847. doi: 10.1161/CIRCULATIONAHA.123.067003. Epub 2024 Aug 1.

  PMID: 39087353 RESULT

• Gao P, Wang T, Wang D, Liebeskind DS, Shi H, Li T, Zhao Z, Cai Y, Wu W, He W, Yu J, Zheng B, Wang H, Wu Y, Dmytriw AA, Krings T, Derdeyn CP, Jiao L; CASSISS Trial Investigators. Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis: The CASSISS Randomized Clinical Trial. JAMA. 2022 Aug 9;328(6):534-542. doi: 10.1001/jama.2022.12000.

  PMID: 35943472 RESULT

• Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF, Janis LS, Lutsep HL, Barnwell SL, Waters MF, Hoh BL, Hourihane JM, Levy EI, Alexandrov AV, Harrigan MR, Chiu D, Klucznik RP, Clark JM, McDougall CG, Johnson MD, Pride GL Jr, Torbey MT, Zaidat OO, Rumboldt Z, Cloft HJ; SAMMPRIS Trial Investigators. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011 Sep 15;365(11):993-1003. doi: 10.1056/NEJMoa1105335. Epub 2011 Sep 7.

  PMID: 21899409 RESULT

• Li S, Tang M, Zhang D, Han F, Zhou L, Yao M, Li M, Cui L, Zhang S, Peng B, Jin Z, Zhu Y, Ni J. The prevalence and prognosis of asymptomatic intracranial atherosclerosis in a community-based population: Results based on high-resolution magnetic resonance imaging. Eur J Neurol. 2023 Dec;30(12):3761-3771. doi: 10.1111/ene.16057. Epub 2023 Sep 22.

  PMID: 37738517 RESULT

• Gutierrez J, Khasiyev F, Liu M, DeRosa JT, Tom SE, Rundek T, Cheung K, Wright CB, Sacco RL, Elkind MSV. Determinants and Outcomes of Asymptomatic Intracranial Atherosclerotic Stenosis. J Am Coll Cardiol. 2021 Aug 10;78(6):562-571. doi: 10.1016/j.jacc.2021.05.041.

  PMID: 34353533 RESULT

• Wong KS, Ng PW, Tang A, Liu R, Yeung V, Tomlinson B. Prevalence of asymptomatic intracranial atherosclerosis in high-risk patients. Neurology. 2007 Jun 5;68(23):2035-8. doi: 10.1212/01.wnl.0000264427.09191.89.

  PMID: 17548555 RESULT

• Wong KS, Huang YN, Yang HB, Gao S, Li H, Liu JY, Liu Y, Tang A. A door-to-door survey of intracranial atherosclerosis in Liangbei County, China. Neurology. 2007 Jun 5;68(23):2031-4. doi: 10.1212/01.wnl.0000264426.63544.ee.

  PMID: 17548554 RESULT

MeSH Terms

Conditions

Intracranial Arteriosclerosis; Plaque, Atherosclerotic

Interventions

Hydroxymethylglutaryl-CoA Reductase Inhibitors

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; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

Central Study Contacts

Weihai Xu, MD

CONTACT

86+13651147766; xuwh@pumch.cn

Yiyang Liu, PhD

CONTACT

86+13938912070; liuyydoct@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD & PhD

Study Record Dates

• First Submitted: March 16, 2025
• First Posted: March 30, 2025
• Study Start: November 7, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 12, 2026

Record last verified: 2026-06

Locations

CN (19)