Acute Ischemic Stroke stroke
Conditions
Interventions
Dose Escalation (Phase 1b):
During this phase, patients are unevenly randomized between groups, to obtain a
total of 60 patients, 12 at each dose level, providing escalation is complete.
This phase
* Thrombolysis with tPA AND mechanical thrombectomy.
A total of 100 new patients should be recruited, 50 under active treatment and
50 under placebo to complete up to 160 patients. Each treatment arm
Sponsors
ACTICOR BIOTECH
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1 Patients presenting with an acute disabling ischemic stroke in either the anterior or posterior circulation.The time of onset is known or if unknown, the last time the patient was seen well, was at most 4.5 hrs before confirmation of the diagnosis enabling the initiation of alteplase administration within this time-frame; 2. Patients presenting at least a NIHSS * 6 prior to thrombolysis with tPA; 3. Patients eligible for, or administered thrombolysis treatment with tPA; 4. Patients who can undergo mechanical thrombectomy if eligible;
Exclusion criteria
Exclusion criteria: 1.Coma, and/or NIHSS >25; 2.Prior ischemic stroke within the past 3 months with pre-stroke mRS known to be > 2; 3. Baseline CT-scan evaluation: more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline imaging; 4. Significant mass effect with midline shift; 5. Stroke of hemorrhagic origin; 6. Contra-indications to thrombolysis with tPA: 7. Patients receiving a dual antiplatelet treatment; 8. Cardiopulmonary resuscitation within the past 10 days; 9. Epileptic seizure at the onset of symptoms; 10. Known severe (grade 3 and above) renal impairment or Glomerular Filtration Rate 2X ULN (1.2 mg/dL for men and 1.0 mg/dL for women) at screening;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: Safety: Incidence of intra-cranial hemorrhages (ICH, symptomatic, total, fatal): symptomatic hemorrhages being those defined by a secondary increase in the NIHSS (National Institute of Health Stroke Scale) score of 4 points or more, or death, in the absence of any other causative factor. Non-symptomatic hemorrhages are those seen on the 24-hr CT scan and not present at the initial assessment, once other diagnoses have been excluded. ICH detected by brain imaging should be classified according to the Heidelberg classification. Incidence, nature and severity of Adverse Events (AEs), SAEs, bleeding-related adverse events, including mortality, and TreatmentEmergent Adverse Events (TEAEs). Safety results will be displayed by treatment group. For glenzocimab, results by dose levels will also be summarized. SAE and TEAE will be graded using CTCAE version 5.0. Pre-defined bleeding-related events will be compared across groups and dose-levels. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: Safety: * Changes to vital signs over the study course duration versus screening; * Changes to clinical laboratory assessments (hematology, biochemistry, urinalysis) over the study duration versus screening; * ECG over the study duration versus screening; Efficacy: * Neurological recovery as assessed by: - NIHSS score at 24 hrs versus that measured at screening (pre-thrombolysis) in each group. - Dramatic improvements (defined by a reduction in the NIHSS score of > 8 points) or recovery (NIHSS = 0) will be assessed in each group. - Patients with a favorable outcome as defined by a Day 90 mRS score of 0-2. * Impact on brain lesions as measured by diffusion T2 weighted MRI and recanalization assessed by angiogram in,eligible patients to determine the infarct size (volume). Other Biological parameters: * PK: glenzocimab plasma concentration will be assayed. * Immunogenicity: search for anti-ACT017 antibodies (ADA) | — |
Countries
Netherlands
Outcome results
None listed