Ongericimab Injection Reducing Recurrence of Ischemic Stroke

Official title

A Multicenter, Randomized, Open-label, Parallel-controlled, Event-driven, Blinded-endpoint Trial Evaluating the Efficacy and Safety of Ongericimab Injection in High-risk Stroke Patients With Intracranial or Extracranial Atherosclerotic Stenosis.

Overview

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).

Interventions

• Combination product High target group
  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)
• Combination product Low target group
  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)

Primary outcome measures

• The major cardiovascular events [Time frame: A median of 2 years follow-up]

Secondary outcome measures (7)

• New ischemic stroke [Time frame: A median follow-up of 2 years]
• Myocardial infarction [Time frame: A median of 2 year follow-up]
• Vascular death [Time frame: A median of 2 years follow-up]
• Poor functional prognosis (mRS score > 1) at 1 year [Time frame: A median of 2 years follow-up]
• Severity of new stroke [Time frame: A median of 2 years follow-up]
• Absolute and percent changes in LDL-C levels [Time frame: A median of 2 years follow-up]
• Treatment-emergent serious adverse events (SAEs) and adverse events (AEs) [Time frame: A median of 2 years follow-up]

Eligibility criteria

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);
• Known hypersensitivity to monoclonal antibody therapies;
• PCSK9 inhibitor use within 3 months before randomization.
• Participation in other drug/device trials within 30 days;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 199 centers

• Fuyang People's Hospital — Fuyang
• The First Affiliated Hospital of Wannan Medical College — Wuhu
• The First Hospital of Fangshan District, Beijing — Beijing
• Chongqing Sanbo Changan Hospital — Chongqing
• The Fifth People's Hospital of Chongqing — Chongqing
• The First Affiliated Hospital of Chongqing Medical and Pharmaceutical College — Chongqing
• Ningde People's Hospital — Ningde
• Minxian County Hospital of Traditional Chinese Medicine — Dingxi
• … and 191 more centers

Publications

• Cholesterol Treatment Trialists' (CTT) Collaboration; Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010 Nov 13;376(9753):1670-81. doi: 10.1016/S0140-6736(10)61350-5. Epub 2010 Nov 8 PMID 21067804
• 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
• Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97. doi: 10.1056/NEJMoa1410489 PMID 26039521
• Turan TN, Nizam A, Lynn MJ, Egan BM, Le NA, Lopes-Virella MF, Hermayer KL, Harrell J, Derdeyn CP, Fiorella D, Janis LS, Lane B, Montgomery J, Chimowitz MI. Relationship between risk factor control and vascular events in the SAMMPRIS trial. Neurology. 2017 Jan 24;88(4):379-385. doi: 10.1212/WNL.0000000000003534. Epub 2016 Dec 21. PMID 28003500
• Shao C, Zhang S, Cheng Z, Yang K, Wang G, Shi X, Yang H, Ji Y, Li H, Zhang S, Ma J, Pei Z, Zhang Y, Li Y, Li L, Zheng Y, Shao C, Zhang M, Hao Y, Tang YD. Efficacy and safety of ongericimab in Chinese statin-intolerant patients with primary hypercholesterolemia or mixed dyslipidemia: a randomized, placebo-controlled phase 3 trial. Atherosclerosis. 2025 Aug;407:120408. doi: 10.1016/j.atherosclerosis PMID 40543299
• Lin J, Ji Y, Wang G, Ma X, Yao Z, Han X, Chen J, Chen J, Huang W, Xu G, Peng D, Yan P, Qiao P, He Y, Tang Y, Wang M, Zhang M, Yu J, Hao Y, Ma C. Efficacy and safety of ongericimab in Chinese patients with heterozygous familial hypercholesterolemia: A randomized, double-blind, placebo-controlled phase 3 trial. Atherosclerosis. 2025 Apr;403:119120. doi: 10.1016/j.atherosclerosis.2025.119120. Epub 20 PMID 39999660
• Xu YY, Chen WQ, Wang MX, Pan YS, Li ZX, Liu LP, Zhao XQ, Wang YL, Li H, Wang YJ, Meng X; CNSR-III Investigators. Lipid management in ischaemic stroke or transient ischaemic attack in China: result from China National Stroke Registry III. BMJ Open. 2023 Mar 8;13(3):e069465. doi: 10.1136/bmjopen-2022-069465. PMID 36889830
• 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 PMID 21899409

Identifiers

NCT: NCT07242599 · ORIS-2025-10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗