A Double-Blind, Placebo-Controlled, Randomized, Phase Ib/IIa Clinical Study of ApTOLL for the Treatment of Acute Ischemic Stroke

Phase 2

• Conditions: Stroke

• Registration Number: DRKS00025976
• Lead Sponsor: AptaTargets S. L.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-08-03
• Study Completion: 2022-04-22
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 151

Inclusion Criteria

1. Age =18 and =90 years.

2. Informed consent obtained from subject or acceptable
subject surrogate (i.e. next of kin, or legal representative).

3. A new focal disabling neurologic deficit consistent with
acute cerebral ischemia.

4. Baseline NIHSS obtained prior to randomization = 8 points and = 25 points.
5. Pre-stroke mRS score of 0 - 2.

6. Treatable as soon as possible and at least within 6 h of symptom onset, defined as point in time when the subject was last seen well (at baseline).
(Treatment start is defined as
study drug administration.)

7. Patients should be candidates to receive EVT treatment with or without i.v. rt-PA. For such patients candidates to i.v. rt-PA therapy, rt-PA should be initiated as recommended by the European Stroke Organization for the early management of patients with AIS, it means, as soon as possible and within 4.5h of stroke onset (onset time is defined as the last time when the patient was witnessed to be well at baseline), with investigator verification that the subject has received/is receiving the correct i.v. rt-PA dose for the estimated weight. Should for any reason i.v. rt-PA is prematurely halted the cause and the total administered dose will be recorded. On the other hand, once the patient is included in the study, if it is observed and documented that recanalization has occurred, the patient will continue in the trial and no protocol deviation will be recorded.

8. Occlusion
(TICI 0 or TICI 1 flow), of the terminal internal carotid artery
(TICA), M1 or M2 segments of the middle cerebral artery, suitable for mechanical thrombectomy, confirmed on CTA (CT Angiography). Tandem extra- intracranial lesions may be included.

9. The following imaging criteria should also be met on admission neuroimaging:
a) MRI criterion: volume of DWI (Diffusion-weighted Imaging) restriction =5 mL and =70 mL determined by RAPID® software OR

b) CT criterion: Alberta Stroke program early CT score (ASPECTS ) 6 to 10 on baseline CT AND infarct core determined on admission CTPerfusion by CBF<30%: =5 mL and =70 mL determined by RAPID® software.
NOTE: ASPECTS will be stablished following the investigator criterium.

10. The subject has an indication and is planned to receive endovascular treatment of stroke according to the ESO Guidelines.

Exclusion Criteria

1. Subject has suffered a stroke in the past 1 year.

2. Occlusion (TICI 0 or TICI 1 flow) of the basilar or vertebral or posterior or anterior cerebral arteries.

3. Clinical symptoms suggestive of bilateral stroke or stroke in multiple territories.

4. Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR >3.0.

5. Baseline platelet count <50,000/µL.

6. Baseline blood glucose of <50 mg/dL or >400 mg/dL.

7. Severe, sustained hypertension (systolic blood pressure>185 mmHg or diastolic blood pressure >110 mmHg). NOTE: If the blood pressure can be successfully reduced and maintained at an acceptable level using European Stroke Organization (ESO ) guidelines recommended medication (including i.v. antihypertensive drips), the patient can be enrolled.

8. Serious, advanced, or terminal illness with anticipated life expectancy of less than 1 year.

9. Subjects with identifiable intracerebral tumors (meningioma is considered extracerebral tumor, so it is not included in this exclusion criterium).

10. History of life-threatening allergy (more than rash ) to contrast medium.

11. Known renal insufficiency with creatinine =3 mg/dL or Glomerular Filtration Rate (GFR) <30 mL/min.

12. Cerebral vasculitis.

13. Evidence of active systemic infection.

14. Known current use of cocaine at time of treatment.

15. Patient participating in a study i drug or device that would impact this study.

16. Patients that are unlikely to be available for a 90-day follow-up (e.g. no fixed home address, visitor from overseas).

17. Female who is pregnant or lactating or has a positive pregnancy test at time of admission.

18. CT or MRI evidence of hemorrhage (the presence of microbleeds is allowed).

19. Significant mass effect with midline shift.

20. Suspicion of aortic dissection presumed septic embolus, or suspicion of bacterial endocarditis.nvolving an investigational

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess if ApTOLL is safe when combined with EVT therapy

Secondary Outcome Measures

Name	Time	Method
Secondary endpoints:<br>1. Mean final infarct volumes measured at 72+/-24h (MRI; Magnetic Resonance Image). In those cases where the MRI at 72+/-24h is missed, the last CT (Computed Tomography) data available after ApTOLL administration should be considered.<br>2. Proinflammatory markers in blood between study groups.<br>3. Early clinical course (NIHSS, 72h).<br>4. Long-term outcome (mRS, 90d). In those cases where the mRS 90 days is missed, the worst score (mRS of 6) will be assigned in case the living status of the patient is not known. For patients known to be alive at 3 months post randomization in whom follow-up evaluations will not be possible the discharge mRS will be carried forward.<br>5. Neuroimage proinflammatory biomarkers in MRI at 72h and 90d post-stroke (sub-study).