Clinical trial NCT06990867: Optimizing Reperfusion to Improve Outcomes and Neurologic Function
Official title: Optimizing Reperfusion to Improve Outcomes and Neurologic Function (ORION): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group, Phase 2/3 Study to Evaluate the Efficacy and Safety of JX10 in Acute Ischemic Stroke With Late Presentations
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Acute Ischemic Stroke
Keywords: reperfusion
ORION
Acute Ischemic Stroke
Late Presentation
JX10
thrombolytic
Lead sponsor: Corxel Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2025-05-25
Enrollment: 740
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to evaluate the safety and efficacy of JX10 versus placebo in participants with Acute Ischemic Stroke (AIS) who present for care within 4.5 to 24 hours.

The main question the study aims to answer are:

1. JX10 improves functional outcomes as measured by the modified Rankin Scale score when compared with placebo following AIS.
2. Risk of symptomatic intracranial hemorrhage of JX10 in participants with AIS.

During Part 1, participants will be randomized to JX 10 (1mg/kg, 3 mg/kg) or placebo. During Part 2, participants will receive JX10 (optimal dose chosen from Part 1) or placebo.


Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 and ≤ 90 years old.
2. Acute ischemic stroke with compatible clinical presentation and symptomatic high grade or complete occlusion of the intracranial internal carotid, M1, M2 or distal branches of the middle cerebral artery (MCA), anterior cerebral artery (ACA), or posterior cerebral artery (PCA).
3. Radiographic evidence of salvageable tissue.
4. Pre-treatment score of NIHSS ≥ 5.

Exclusion Criteria:

1. Radiographic findings pre-randomization of any of the following:

   1. Large core infarction, or
   2. Occlusion in more than 1 vascular territory, or
   3. Significant mass effect or clinically significant cerebral edema, or
   4. Evidence of acute intracranial or extracranial hemorrhage, intracranial tumor (except small meningioma), neoplasm, or arteriovenous malformation), or
   5. Clinical history, past imaging, or clinical judgement suggests that the intracranial occlusion is chronic.
2. Medical history or active clinically significant bleeding, lesions, or conditions (at the investigator's judgement) considered to be of significant risk for major bleeding.
3. Severe, uncontrolled hypertension (systolic blood pressure ≥ 185 mmHg or diastolic blood pressure ≥ 110 mmHg) that cannot be controlled with antihypertensive therapy.
4. Known bleeding diathesis (hereditary or acquired) or any significant coagulopathy. Specifically, platelet count \< 100,000/μL, international normalized ratio \> 1.7, aPTT \> 40 seconds, or prothrombin time \> 15 seconds.
5. Major trauma, surgery, or invasive procedures.
6. Pre-existing medical, neurological, or psychiatric disease that would confound the neurological or functional evaluations of this study.
7. Pre-treatment blood glucose \> 400 mg/dL (22.20 mmol/L) or Pre-treatment blood glucose \< 50 mg/dL (2.78 mmol/L) unless it is corrected prior to study treatment administration. Participants with subsequently normalized blood glucose levels may be considered for inclusion, per Investigator judgement.

Primary outcomes:
measure: Efficacy: Proportion of participants with no or minimal symptoms (mRS score 0-1) at 90 days
timeFrame: 90 days
measure: Safety: Incidence of symptomatic intracranial hemorrhage within 36 hours post-randomization
timeFrame: Within 36 hours post-randomization
Secondary outcomes:
measure: Ordinal mRS score (0-6), based on a 6-point ordinal scale at 90 days
timeFrame: 90 days
measure: Proportion of participants with functional independence at 90 days
timeFrame: 90 days
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 90 days
measure: Incidence of major bleeding within 24 hours and 14 days of study treatment
timeFrame: Within 24 hours and 14 days of study treatment
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Corxel Investigational Site
state: Illinois
city: Beijing
country: China
facility: Corxel Investigational Site
Study officials:
affiliation: Corxel Pharmaceuticals
name: Senior Director, Clinical Operations
role: STUDY_DIRECTOR
References: