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

Phase 1

• Conditions: Acute Ischemic Stroke (AIS); Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2020-002059-38-DE
• Lead Sponsor: APTATARGETS S.L.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-12-30
• Last Update Posted: 12 July 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 151

Inclusion Criteria

1. Age =18 and =85 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.
Neuro Imaging:
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 121

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-thratening 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 involving an investigational 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.
Neuro Imaging:
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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified