INtensive liPid-lowering Therapy for Acute High-risk IntracRanial or Extracranial atheroSclerosis -II (INSPIRES-2)

NCT07341958 | Not Yet Recruiting DMC

• 1 other identifier: HX-A-2025103
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 1

Brief Summary

The research team is conducting a randomized, double-blind, placebo-controlled, multicenter clinical study aimed at evaluating the impact of adding Tolecilimab (a PCSK9 inhibitor) to standard lipid-lowering therapy (statins ± ezetimibe) on serum lipoprotein(a) \[Lp(a)\] levels and the risk of stroke recurrence within 90 days in patients with ischemic stroke or high-risk TIA (ABCD² ≥ 4) accompanied by elevated lipoprotein(a) levels (≥50 mg/dL).

Conditions

Ischemic Stroke or High-risk TIA (ABCD² ≥ 4)

Keywords

PCSK9 inhibitor; lipid-lowering therapy; ischemic stroke

Outcome Measures

Primary Outcomes (1)

• The percentage reduction in Lp(a) from baseline at 90 days.

  From baseline to 90 days after randomization

Secondary Outcomes (17)

• Incidence of new stroke (including hemorrhagic and ischemic stroke) within 90 days.

  From baseline to 90 days after randomization

• Incidence of composite clinical endpoint events within 90 days

  From baseline to 90 days after randomization

• Incidence of myocardial infarction within 90 days.

  From baseline to 90 days after randomization

• Incidence of vascular death within 90 days.

  From baseline to 90 days after randomization

• Incidence of all-cause death within 90 days.

  From baseline to 90 days after randomization

Study Arms (2)

Standard lipid-lowering therapy(statin therapy with or without ezetimibe) + Tafolecimab

EXPERIMENTAL

Drug: Tafolecimab

Standard lipid-lowering therapy (statin therapy with or without ezetimibe)+Tafolecimab placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tafolecimab DRUG

Treatment should be initiated as soon as possible after randomization, with Tafolecimab administered subcutaneously once every two weeks for a total duration of 90 days. All patients received standard lipid-lowering therapy as recommended by stroke secondary prevention guidelines, including intensive statin treatment with or without ezetimibe, administered at maximally tolerated doses.

Standard lipid-lowering therapy(statin therapy with or without ezetimibe) + Tafolecimab

Placebo DRUG

Treatment should be initiated as soon as possible after randomization, with Tafolecimab placebo administered subcutaneously once every two weeks for a total duration of 90 days. All patients received standard lipid-lowering therapy as recommended by stroke secondary prevention guidelines, including intensive statin treatment with or without ezetimibe, administered at maximally tolerated doses.

Standard lipid-lowering therapy (statin therapy with or without ezetimibe)+Tafolecimab placebo

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 35 and 80 years, regardless of gender.
• For patients with prior lipid-lowering treatment: screening LDL-C ≥1.8 mmol/L; for treatment-naïve patients: screening LDL-C ≥2.6 mmol/L.
• Lp(a) ≥50 mg/dL.
• Onset of symptoms within 3 to 7 days.
• Diagnosis of ischemic stroke (NIHSS score ≤20) or high-risk TIA with ABCD² score ≥4; and meeting at least one of the following imaging criteria:
• (1) Large-artery atherosclerosis (LAA) subtype per TOAST classification: vascular imaging confirms ≥50% atherosclerotic stenosis of the intracranial or extracranial culprit artery.
• (2) Head CT or MRI demonstrates acute multiple infarcts, with etiology consistent with large-artery atherosclerosis (including nonstenotic vulnerable plaques).
• The patient or their legally authorized representative has provided written informed consent.

You may not qualify if:

• Patients who have undergone or are scheduled to undergo thrombolysis or thrombectomy therapy.
• Definite cardiogenic ischemic cerebrovascular disease (e.g., accompanied by atrial fibrillation, prosthetic heart valves, atrial myxoma, infective endocarditis, etc.).
• Other clearly identified etiologies of ischemic cerebrovascular disease (e.g., aortic dissection, cervical/cerebral arterial dissection, vasculitis, vascular malformations, moyamoya disease/syndrome, fibromuscular dysplasia, etc.).
• Non-vascular intracranial diseases (e.g., intracranial tumors, multiple sclerosis, etc.).
• Imaging findings indicating that the current cerebral infarction area exceeds 1/2 of a single brain lobe.
• Imaging findings indicating hemorrhagic transformation of the current cerebral infarction.
• Pre-stroke mRS score \> 2.
• Patients with known allergies to Tafolecimab or other contraindications for its use.
• Use of immunosuppressive drugs, antifungal drugs, or fibrates (which affect statin metabolism) within 14 days prior to randomization.
• Creatine kinase levels exceeding 5 times the upper limit of normal after the onset of the event.
• Severe hepatic or renal insufficiency prior to randomization (Note: Severe hepatic insufficiency is defined as ALT \>2×ULN or AST \>2×ULN; severe renal insufficiency is defined as serum creatinine \>1.5×ULN or GFR \<40 ml/min/1.73m²).
• History of intracranial hemorrhage (e.g., ICH, SAH).
• History of intracranial or extracranial vascular angioplasty.
• History of gastrointestinal bleeding or major surgery within 90 days prior to enrollment.
• Planned surgical or interventional procedures within the next 90 days that may necessitate discontinuation of the investigational drug.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hopital, Capital Medical University

Beijing, China

Location

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Yuesong Pan

CONTACT

0086-010-59975807; yuesongpan@aliyun.com

Yilong Wang

CONTACT

0086-010-67092222; yilong528@aliyun.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The active drug and placebo are identical in appearance, packaging, labeling, and administration. Standard background lipid-lowering therapy (statin ± ezetimibe) is administered to both groups and does not affect blinding. Routine tests and imaging at study sites contain no group allocation information, preventing unintentional unblinding. Investigators and subjects must remain blinded to treatment assignment. Unblinding of randomization codes is prohibited unless required for managing a serious adverse event (SAE). All unblinding events must be fully documented and reported to the sponsor and the independent Data Safety Monitoring Board (DSMB).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: A multicenter, randomized, double-blind, placebo-controlled clinical trial

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 15, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): August 30, 2027
• Last Updated: January 15, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)