A Phase 1b/2 study to assess the safety, pharmacokinetics, and pharmacodynamics of DS-1040B in subjects with acute ischemic stroke.

Phase 1

• Conditions: DS-1040b is an inhibitor of the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa) intended to be used for the treatment of thrombotic diseases including acute ischemic stroke (AIS).; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2015-001824-43-DE
• Lead Sponsor: Daiichi Sankyo, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-06-29
• Study Completion: 2019-08-13
• Last Update Posted: 31 August 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 106

Inclusion Criteria

1. Subjects have a clinical diagnosis of acute ischemic stroke (including lacunar stroke) supported by computed topography or magnetic resonance imaging to rule out alternative cause for presenting symptoms.
2. Men and women 18 years of age and older.
3. Subjects have stroke symptoms onset within 4.5 to 12 hours before initiation of study drug administration. For subjects with a wake-up stroke, symptoms onset time refers to the last time the subject was known to be well.
4. Subjects have a NIHSS score of >2 (Cohort 1-5).
4a. NIHSS score = 5 (Cohort 6).
5. In Cohort 6, subjects who have been treated or are anticipated to be treated with IAT for index stroke, at the time of randomization, can be enrolled in the IAT subgroup.
6. Subjects (or their legally authorized representative-where applicable
and based on country-specific practice), must give written informed consent to participate in the study prior to participating in any study-related procedures. A separate written informed consent is required for collecting a blood sample for genotyping.

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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 76

Exclusion Criteria

1. Cohort 1-5: Subjects have been treated or are anticipated to be treated with tissue plasminogen activator and / or endovascular thrombectomy during current stroke. Eligible subjects declining these treatments can be enrolled to this study.
1a. Cohort 6: subjects have been treated and/or are anticipated to be
treated with tPA during current stroke. Eligible subjects declining tPA
treatment can be enrolled to this study. Subjects have been treated or
anticipated to be treated with IAT can be enrolled.
2. Subjects have evidence of intracranial hemorrhage on non-contrast computed tomography (CT) (or magnetic resonance [MR])
3. Subjects have symptoms of subarachnoid hemorrhage, even with normal CT.
4. Subjects have an Alberta Stroke Program Early CT Score (ASPECTS) <6.
5. Subjects have prior non-traumatic intracranial haemorrhage (excluding microhemorraghes observed in imaging).
6. Subjects have known arteriovenous malformation or aneurysm.
7. Subjects have evidence of active bleeding.
8. Subjects have platelet count < 100,000.
9. Subjects have International Normalized Ratio > 1.7.
10. Subjects have used unfractionated heparin within 24 hours prior to treatment and have an elevated partial thromboplastin time.
11. Subjects have used a nonvitamin K antagonist oral anticoagulant such as dabigatran, rivaroxaban, apixaban, or other factor Xa inhibitors within 24 hours prior to treatment.
12. Subjects have used fondaparinux or low molecular weight heparin at an anticoagulation dose within 24 hours prior to treatment.
13. Subjects with anticipated use of an anticoagulation dose of heparin, or fondaparinux or low molecular weight heparin, or nonvitamin K antagonist oral anticoagulant such as dabigatran, rivaroxaban, apixaban, or other factor Xa inhibitors within 48 hours after completion of study drug treatment. Low dose heparin or low molecular weight heparin at a preventive dose are allowed from 24 hours after treatment completion and after confirmation of no intracranial bleeding on the 24 hours repeat brain imaging. In Cohort 6, heparin treatment associated with IAT is allowed.
14. Subjects have blood pressure > 185/110 mmHg, or require aggressive medication to maintain blood pressure below this limit (routine medical treatment is allowed to lower the blood pressure below this limit).
15. Subjects have had intracranial surgery, clinically significant head trauma (in the opinion of Principal Investigator), Alteplase treatment, or a previous stroke within 1 months.
16. Subjects have had major surgery within 14 days.
17. Subjects have had gastrointestinal or genitourinary bleeding in the last 21 days.
18. Subjects have had a lumbar puncture (or epidural steroid injection) within 14 days.
19. Subjects have a preexisting disability classified by mRS > 2.
20. Subjects have an estimated glomerular filtration rate (using Modification of Diet in Renal Disease equation) < 60 mL/min/1.73 m2.
21. Subjects have baseline haemoglobin < 10.5 g/dL.
22. Subjects have a positive pregnancy test. Serum or urine pregnancy tests will be performed (according to site-specific practice) in women of childbearing potential (childbearing potential is assumed in women up to 55 years of age).
23. Subject is currently participating in another investigational study or has participated in an investigational drug study within 30 days or 5 half lives of that investigational drug prior to administration of the study drug.
24. Subject is an employee

Study & Design

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