A Double-Blind, Placebo-Controlled, Randomized, Phase Ib/IIa Clinical Study of ApTOLL for the Treatment of Acute Ischemic Stroke
Overview
- Phase
- Phase 1
- Intervention
- ApTOLL
- Conditions
- Stroke
- Sponsor
- aptaTargets S.L.
- Enrollment
- 151
- Locations
- 16
- Primary Endpoint
- Safety of ApTOLL
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a prospective, multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to assess the administration of ApTOLL together with endovascular therapy in acute ischemic stroke patients who are candidates to receive reperfusion therapies.
Detailed Description
This is a prospective, multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to assess the administration of ApTOLL together with endovascular therapy in acute ischemic stroke (AIS) patients with confirmed Large Vessel Occlusion (LVO) who are candidates to receive reperfusion therapies including endovascular treatment with or without i.v. rt-PA (recombinant tissue Plasminogen Activator). The study will be a Phase Ib/IIa trial where 2 doses selected, based on safety criteria, on Phase Ib will be administered in the following Phase IIa.The objective of the study is to evaluate if administration of ApTOLL at different doses is safe and well tolerated compared to placebo when administered with endovascular therapy (EVT), with or without i.v. rt-PA, in the AIS target population.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 and ≤90 years.
- •Informed consent obtained from subject or acceptable subject surrogate (i.e. next of kin, or legal representative).
- •A new focal disabling neurologic deficit consistent with acute cerebral ischemia.
- •Baseline NIHSS obtained prior to randomization ≥ 8 points and ≤ 25 points.
- •Pre-stroke mRS score of 0 -
- •Treatable as soon as possible and at least within 6 hours of symptom onset, defined as point in time when the subject was last seen well (at baseline).
- •Patients should be candidates to receive EVT treatment with or without i.v. rt-PA.
- •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 embolectomy, confirmed on Computed Tomography Angiography.
- •The following imaging criteria should also be met on admission neuroimaging:
- •MRI criterion: volume of DWI (Diffusion-weighted Imaging) restriction ≥5 mL and ≤70 mL OR
Exclusion Criteria
- •Subject has suffered a stroke in the past 1 year.
- •Occlusion (TICI 0 or TICI 1 flow) of the basilar or vertebral or posterior or anterior cerebral arteries.
- •Clinical symptoms suggestive of bilateral stroke or stroke in multiple territories.
- •Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR (international normalized ratio)\>3.
- •Baseline platelet count \<50,000/μL.
- •Baseline blood glucose of \<50 mg/dL or \>400 mg/dL.
- •Severe, sustained hypertension (systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg).
- •Serious, advanced, or terminal illness with anticipated life expectancy of less than 1 year.
- •Subjects with identifiable intracranial tumors.
- •History of life-threatening allergy (more than rash) to contrast medium.
Arms & Interventions
Phase Ib ApTOLL
ApTOLL is administered intravenously in a single ascending dose pattern in four dose levels (0.025mg/kg - 0.2mg/kg). All levels include six patients.
Intervention: ApTOLL
Phase Ib Placebo
Placebo is administered intravenously in a single ascending dose pattern in four dose levels (0.025mg/kg - 0.2mg/kg). All levels include two patients.
Intervention: Placebo
Phase IIa ApTOLL
ApTOLL is administered intravenously (two doses selected in Phase Ib). The two dose levels include 35 patients each one.
Intervention: ApTOLL
Phase IIa Placebo
Placebo is administered intravenously in one arm which includes 49 patients.
Intervention: Placebo
Outcomes
Primary Outcomes
Safety of ApTOLL
Time Frame: From dosing to follow-up (day 90 after dosing)
To assess if ApTOLL is safe when combined with EVT therapy as determined by: 1. Death. 2. Adverse events that occur during the study. 3. Physical examination. 4. Laboratory tests. 5. Recurrent stroke. 6. Symptomatic intracranial hemorrhage (sICH).
Secondary Outcomes
- Mean infarct volume(72 hours)
- Early clinical course(72 hours post-dose)
- Effect in inflammatory response(Predose and up to 72 hours post-dose)
- Long-term outcome(Day 90 post-dose)