Acute Ischemic Stroke Interventional Study

• Status: Completed
• Trial end date: 2021-09-27
• Target enrollment: 0
• Participant gender: All

Summary

To assess safety of single IV (bolus + infusion) doses of ACT017 in patients with an acute ischemic stroke in addition to best emergency standard of care (including fibrinolysis by rtPA with or without added thrombectomy), with a specific focus on hemorrhage, whether clinically symptomatic (NIHSS score + 4 points or death, without other explanation), or seen (excluding other diagnoses) on 24-hour (hr) CT scan, serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs), and medically important events and other safety items including biological and immunological tolerability.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Acticor Biotech
• Collaborators: Axial Biotech, Inc; Orion Corporation, Orion Pharma; QPS
• Treatments: Tissue Plasminogen Activator

Criteria

Inclusion Criteria:

1. Adult male or female patients ≥ 18 years (i.e., at least 18 years old at time of randomization). Extreme caution should be exercised in patients over 80 years of age with regards their general health, neurological status and any concomitant diseases and treatments that are likely to be more common;

2. Patients who have given written consent, legal representative consent or emergency consent (including e-consent) in accordance with local legal and IECs/IRBs requirements;

3. 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;

4. Patients presenting at least a NIHSS ≥ 6 prior to thrombolysis with tPA;

5. Patients eligible for, or administered thrombolysis treatment with tPA;

6. Patients who can undergo mechanical thrombectomy if eligible;

7. Patients affiliated to social security insurance (if applicable, in accordance to local regulations);

8. Effective birth control method should be used for at least the next 2 months by women, and 4 months by men after IMP administration; birth control methods considered to be highly effective include:

• intrauterine device

• intrauterine hormone-releasing system

• bilateral tubal occlusion

• vasectomized partner

• sexual abstinence (if applicable in accordance to local regulations)

9. Women of child-bearing potential must undergo a urinary or plasma pregnancy test with negative results;

Exclusion Criteria:

1. Coma, and/or NIHSS >25;

2. Patients < 18 years of age;

3. Prior ischemic stroke within the past 3 months with pre-stroke mRS known to be > 2;

4. Baseline CT-scan evaluation: more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline imaging;

5. Significant mass effect with midline shift;

6. Stroke of hemorrhagic origin;

7. Contra-indications to thrombolysis with tPA:

1. Patients with known hypersensitivity to the active substance alteplase or to any of its excipients;

2. Patients with a high risk of hemorrhages:

• significant bleeding disorder at present or within the past 6 months;

• known haemorrhagic diathesis (episodes within past 6 months);

• patients receiving effective oral anticoagulant treatment, e.g. warfarin sodium;

• manifest or recent severe or dangerous bleeding;

• known history of or suspected intra-cranial haemorrhage;

• any history of central nervous system lesion (i.e. trauma, intra-parenchymal neoplasm, unsecured aneurysm, intracranial or spinal surgery, vascular malformation etc..);

• recent (< 10 days) traumatic external heart massage, obstetrical delivery, or puncture of a non-compressible blood-vessel (e.g. subclavian or jugular vein puncture);

• bacterial endocarditis, pericarditis;

• acute pancreatitis;

• documented ulcerative gastrointestinal disease during the past 3 months, oesophageal varices, arterial-aneurysm, arterial/venous malformations;

• neoplasm involving an increased risk of bleeding;

• severe liver disease, including hepatic failure, cirrhosis, portal hypertension (esophageal varices) and active hepatitis;

• major surgery or significant trauma during the past 3 months;

• patients receiving anti-coagulants prior to study: the inclusion may however be considered when the dose or time since the last intake of anticoagulant treatment makes residual efficacy unlikely. This should be confirmed by the appropriate tests of anticoagulant activity for the product(s) concerned to show no clinically relevant activity on the coagulation system defined as follows :

• INR ≤ 1.5 for vitamin K antagonists; .

• Low Molecular Weight Heparin (LMWH) and Unfractionated Heparin (UFH):

aPPT/ACT/KCT ≤ 39 sec or their patient/witness ratio ≤ 1.2 and/or PT ≤ 16 sec (heparin at sub-therapeutic doses (≤ 50 IU/kg) during the mechanical thrombectomy procedure is authorized);

• Non-Vitamin-K or Direct Oral Anti-Coagulants (NOACs- DOACs) ≤ 50 ng/mL in patients with normal renal function;

• need for carotid stenting together with a dual anti-platelet treatment (on top of glenzocimab); this can be carried out 24 hrs after the initiation of treatment with glenzocimab;

• platelets count <100 × 103/μL (<100 000/ mm3)

• prior hemorrhagic stroke.

3. Systolic blood pressure ≥ 185 mm Hg despite appropriate acute therapy to lower blood pressure therapy;

4. Diastolic blood pressure ≥ 110 mm Hg; despite appropriate acute therapy to lower blood pressure therapy;

5. Glucose >400 mg/dL (>4 g/L) despite treatment;

6. Glycemia <50 mg/dL (<0,5 g/L);

8. Patients receiving a dual antiplatelet treatment;

9. Cardiopulmonary resuscitation within the past 10 days;

10. Childbirth within the past 10 days,

11. Epileptic seizure at the onset of symptoms;

12. Life expectancy < 3 months

13. Pregnant or breastfeeding;

14. Females of childbearing potential not using effective birth control methods;

15. Known severe (grade 3 and above) renal impairment or Glomerular Filtration Rate < 30 ml/min/1.73 m2 or Serum Creatinine > 2X ULN (1.2 mg/dL for men and 1.0 mg/dL for women) at screening;

16. Known current participation