Acute Ischemic Stroke
Conditions
Brief summary
The goal of this clinical trial is to learn if AB126, an investigational treatment made from neural exosomes, is safe and well tolerated when given to adults with moderate to severe acute ischemic stroke (AIS) who have undergone endovascular thrombectomy (EVT) but have had limited neurological improvement after the procedure. The study will also evaluate different doses of AB126 to help determine the highest dose that can be given safely. The main questions it aims to answer are: 1. Is AB126 safe and well tolerated when given to participants with AIS following EVT? 2. What dose of AB126 can be given safely? 3. Does treatment with AB126 provide preliminary evidence of improved neurological recovery following stroke? Researchers will compare participants who receive AB126 with participants who receive placebo to evaluate the safety and tolerability of AB126 and to collect preliminary information about recovery following stroke. Participants will: 1. Be randomly assigned to receive either AB126 or placebo. Neither participants nor the study team will know which treatment is assigned. 2. Receive 3 intravenous (IV) doses of AB126 or placebo. The first dose will be given as soon as possible after EVT, but no later than 6 hours after blood flow has been restored. The second and third doses will be given approximately 24 and 48 hours after EVT. 3. Undergo medical examinations, laboratory tests, neurological assessments, and brain imaging during the study. 4. Remain under observation at a comprehensive stroke center until hospital discharge. 5. Complete follow-up assessments by telephone and in person for approximately 1 year after treatment, including assessments at approximately 10, 30, 90, 180, 270, and 360 days after treatment.
Interventions
BIOLOGICALAB126 Neural Exosomes Intravenous Injection
Three (3) intravenous injections of the active ingredient will be administered on Day 0, 1, and 2 after stroke.
OTHERAB126 Placebo
AB126 Placebo, comprised of non-active ingredients, will be administered on Day 0, 1, and 2 after stroke.
Sponsors
Aruna Bio, Inc.
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female patients 18 to 85 years of age, inclusive. 2. Provision of written informed consent obtained from participant or an acceptable legally authorized representative. 3. Pre-stroke modified Rankin Scale score of 0 or 1. 4. Diagnosis of AIS due to large vessel occlusion in the anterior circulation, confirmed by neuroimaging (NCCT, CTA). 5. Diagnosis of moderate to severe cerebral ischemic stroke, defined by the presence of a measurable motor and/or speech-language deficit at pre-randomization, as assessed by the Investigator. 6. Baseline National Institutes of Health Stroke Scale (NIHSS) score ≥12 prior to EVT to ensure sufficient stroke severity. 7. Baseline imaging characteristics predictive of poor prognosis post-EVT defined by ASPECTS between 3 and 7 on NCCT. 8. Has undergone EVT, specifically mechanical thrombectomy, for the treatment of the current AIS. 9. Post-EVT NIHSS score, performed within 4 hours of EVT completion, must be between 12 and 25, inclusive, prior to randomization. 10. Participants must demonstrate a change in NIHSS score of no more than ±30% from Baseline (pre-EVT) to Pre-Randomization (post-EVT). 11. Patient must be capable of undergoing Magnetic Resonance Imaging (MRI). 12. If male, participant must agree to use adequate contraceptive methods. If female, participant must be of non-childbearing potential or, if of childbearing potential, must agree to use adequate contraceptive methods. 13. Patient must agree not to donate whole blood, blood components (including plasma and leukocytes), tissue, breast milk, ova, and sperm for one year following final administration of study drug.
Exclusion criteria
1. Known sensitivity to bovine serum albumin or other components likely to be present in AB126; 2. Posterior circulation stroke, including infarcts involving brainstem or cerebellum; 3. Pre-existing significant neurological deficits that would confound outcome assessments, including: * A pre-stroke modified Rankin Scale (mRS) score greater than 1 * A history of prior stroke with persistent neurological deficits; 4. Clinically significant hemorrhagic transformation post-EVT, including: * PH-2 classification intracerebral hemorrhage (≥30% of infarcted area with significant mass effect) * sICH, as determined by the Investigator; 5. A \> ±30% change in NIHSS from Baseline to Pre-Randomization (i.e., 30% change in either direction) 6. Comatose patients or those with severely reduced consciousness, defined as a score ≥2 on NIHSS Item 1a (Level of Consciousness) at the time of post-EVT assessment; 7. Patients with uncontrolled systemic medical conditions that may confound assessments or increase risk, including but not limited to: * Severe or unstable cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmias) * Severe hepatic or renal disfunction (e.g., ALT/AST \>2x ULN, bilirubin \>1.5x ULN, or eGFR ≤30mL/min/1.73m2); 8. Current clinically significant infection, including sepsis, meningitis, or active central nervous system infection; 9. Recent history of seizures at stroke onset or a diagnosis of epilepsy; 10. Planned withdrawal of care or comfort measures only at the time of Screening; 11. Known or suspected life expectancy less than 90 days due to non-stroke related comorbidities (e.g., advanced malignancy, end-stage organ failure); 12. Clinically significant stroke or head trauma within the previous 3 months, or residual neurological deficits from prior events that, in the opinion of the Investigator, would interfere with the assessment of clinical outcomes in the current study; 13. Severe hyperglycemia or hypoglycemia at Screening, defined as blood glucose levels \<50 mg/dL or \>350 mg/dL. Participant may be eligible if glucose levels are stabilized during hospitalization prior to randomization, as assessed by the Investigator. 14. Women who are pregnant or nursing; 15. Comorbidities that, in the judgment of the Investigator, would interfere with the ability to assess safety of the investigational product or the interpretation of study results. Such comorbidities may include, but are not limited to: * Active hepatic disease * Unstable angina or severe cardiovascular instability * Ongoing systemic infection * Allergy to human tissue * Restrictive pulmonary disease * Chronic lung infection 16. Prior participation in a clinical interventional trial within the last 6 months; 17. Weight of ≥ 220 lbs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent adverse events | Through Day 90 | The primary objective of this study is to evaluate the safety and tolerability of escalating doses of AB126 in patients with moderate to severe AIS who have undergone EVT and demonstrate limited neurological improvement post-procedure. The primary safety study endpoints will be assessed through Day 90. These study endpoints will also be assessed through Day 360 or end of study. |
| Changes in physical and clinical examination findings | Through Day 90 | — |
| Rates of death | Through Day 90 | — |
| Recurrent stroke | Through Day 90 | — |
| Symptomatic intracranial hemorrhage (sICH) | Through Day 90 | — |
Countries
United States
Contacts
CONTACTDr. Savitz, Principal Investigator
Outcome results
None listed