Ongericimab Injection Reducing Recurrence of Ischemic Stroke (ORIS)

Capital Medical University

Status and phase: Not yet enrolling; Phase 3

Conditions: Ischemic Cerebral Infarction

Treatments: Combination Product: High target group; Combination Product: Low target group

Study type: Interventional

Funder types: Other

Identifiers

NCT07242599

ORIS-2025-10

Details and patient eligibility

About

The Oris trial aims to evaluate whether the use of Ongericimab injection in patients with atherosclerotic ischemic cerebrovascular disease within 3 months of onset can reduce the risk of recurrent major cardiovascular events by achieving lower lipid-lowering target values (LDL-C < 1.4 mmol/L).

Enrollment: 4,398 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Obtaining informed consent；
• Age ≥18 years；
• Patients with ischemic stroke within 3 months( NIHSS<15 before randomization);
• Presence of ≥50% stenosis in major intracranial or extracranial arteries, and related to the symptoms of the current episode or the location of infarction；
• LDL-C ≥ 70 mg/dL (1.8 mmol/L) at screening.

Exclusion criteria

• History of cerebral hemorrhage at any time (microhemorrhages present only on SWI are not an exclusion criterion)
• Hemorrhage or other pathological neurological conditions on baseline brain CT/MRI (e.g., vascular malformations, tumors, abscesses, or common non-ischemic brain diseases like multiple sclerosis);
• Presence of isolated sensory symptoms (e.g., numbness), isolated visual changes, or isolated dizziness or vertigo, but no evidence of recent infarction on baseline head CT or MRI;
• Unable to complete the assessment of intracranial and extracranial arterial stenosis before randomization
• mRS score≥2 before onset (based on assessment of medical history);
• Stroke caused by angioplasty/vascular surgery;
• Cardioembolic stroke caused by atrial fibrillation, artificial heart valves, endocarditis, mitral stenosis, sinus node dysfunction, etc.
• Most recent fasting triglycerides >400 mg/dL (4.5 mmol/L) prior to randomization;
• Uncontrolled hypertension (SBP >180 mmHg or DBP >110 mmHg);
• Hypothyroidism diagnosed within 1 month before randomization.
• Severe renal impairment (eGFR <30 mL/min/1.73m²);
• Active liver disease or dysfunction (AST/ALT >3×ULN within 30 days pre-randomization);
• NYHA Class III/IV heart failure within 1 year prior to randomization;
• Life-limiting non-cardiovascular diseases (life expectancy <1 years);
• Malignancy within 10 years (excluding adequately treated basal cell carcinoma, cervical CIS, DCIS, or stage 1 prostate cancer);
• Active phase of infection (including respiratory tract infection, urinary tract infection, or gastroenteritis), or currently using or planning to use oral or intravenous anti-infective treatment due to infection;
• Known hypersensitivity to monoclonal antibody therapies;
• PCSK9 inhibitor use within 3 months before randomization.
• Participation in other drug/device trials within 30 days;
• History of severe drug or alcohol abuse within the past year.
• Women of childbearing potential without contraception, pregnancy, or lactation;
• Inability to understand or comply with the study due to mental illness, cognitive, or emotional disorders, or other reasons deemed unsuitable for participation in the study by the investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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4,398 participants in 2 patient groups

Control group (High target group)

Active Comparator group

Description:

Standardized lipid-lowering therapy according to the Chinese Stroke Association Guidelines for Clinical Management of Cerebrovascular Diseases to achieve an LDL-C target below 70 mg/dL (1.8 mmol/L).

Treatment:

Combination Product: High target group

Intervention group (Low target group)

Experimental group

Description:

Ongericimab subcutaneous injection once every two weeks (150mg) or every four weeks(300mg) combined with standardized lipid-lowering therapy to achieve an LDL-C target below 55 mg/dL (1.4 mmol/L)

Treatment:

Combination Product: Low target group