Clinical Trials List
Protocol NumberDS1040-A-U103
NCT Number(ClinicalTrials.gov Identfier)NCT02586233
2017-09-04 - 2020-01-31
Phase I/II
Terminated4
ICD-10I63.9
Cerebral infarction, unspecified
A Phase 1b/2, Multi-Center, Double-Blind (Principal Investigators and Study Subjects Blinded, Sponsor Unblinded), Placebo-Controlled, Randomized, Single-Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of DS-1040b in Subjects With Acute Ischemic Stroke
-
Trial Applicant
Syneos Health
-
Sponsor
Daiichi Sankyo Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Tsong-Hai Lee Division of Neurology
- Chi-Hung Liu Division of Neurology
- KuoLun Huang Division of Neurology
- 張寓智 Division of Neurology
- 鄭之光 Division of Neurology
- 張俊偉 Division of Neurology
- 張國軒 Division of Neurology
- Yu-Jhih Chang Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chih-Hung Chen Division of Neurology
- 蘇慧真 Division of Neurology
- Pi-Shan Sung Division of Neurology
- 謝函潔 Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- Ming-Kuei Lu Division of Neurology
- Hui-Chun Huang Division of Neurology
- Ching-Hua Lu Lu Division of Neurology
- Chung-Hsiang Liu Division of Neurology
- Yuh-Cherng Guo Division of Neurology
- Jui-Cheng Chen Division of Neurology
- Chon-Haw Tsai Division of Neurology
- Kuan-Fei Chen Division of Neurology
- Fu-Yu Lin Division of Neurology
- Yu-Wan Yang Division of Neurology
- Kang-Hsu Lin Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- SHIN-JOE YEH Division of Neurology
- LI-KAI TSAI Division of Neurology
- SUNG-CHUN TANG Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Acute Ischemic Stroke
Objectives
The primary objective of the study is to assess the safety and tolerability of DS-1040b (intravenous [IV] infusion over 6 hours) in subjects with AIS within 4.5 to 12 hours after stroke symptoms onset.Secondary Objectives:1. To assess plasma and urinary pharmacokinetics (PK) of DS-1040b in subjects with AIS.2. To assess the effect of DS-1040b on fibrinolysis biomarkers in subjects with AIS.3. To assess the effect of DS-1040b on recanalization at 24 hours in subjects with AIS and a visible occlusion demonstrated on brain imaging atpredose.4. To assess the effect of DS-1040b on neurological outcome by using the National Institute of Health Stroke Scale (NIHSS) and functional outcome by using the modified Rankin Scale (mRS) in subjects with AIS.
Test Drug
DS-1040b
Active Ingredient
DS-1040b
Dosage Form
Injection
Dosage
10mg/10mL
Endpoints
Safety Parameters:
Safety parameters will include; adverse events occurrence,
physical examination findings, vital sign measurements,
standard clinical laboratory parameters (including serum
chemistry, hematology, urinalysis, and coagulation
parameters), and electrocardiogram (ECG) parameters.
Other safety parameters will include bleeding events and
neurologic function. Bleeding events will be assessed and
categorized as symptomatic intracranial hemorrhage
(sICH), any intracranial hemorrhage (ICH), or non-ICH
major bleeding. Neurologic function will be measured
using the NIHSS.
Pharmacokinetic Parameters:
The PK parameters that will be calculated from the plasma
concentrations of DS-1040a using non-compartmental
analysis are the area under the concentration-versus-time
curve, from time 0 to the last quantifiable concentration
sampling point (AUClast), maximum (peak) observed
plasma concentration (Cmax), and time of maximum
observed concentration (tmax). If data permit, the following
parameters will be estimated: the area under the
concentration-versus-time curve from time 0 extrapolated
to infinity (AUC0-inf), half-life (t1/2), clearance, and the
volume of distribution at terminal elimination phase.
The PK parameters that will be calculated from urinary
concentrations of DS-1040a are the amount of drug
excreted in urine from 0 to 24 hours (Ae0-24), the renal
clearance (CLR), and the percentage of the dose
administered excreted in urine from 0 to 24 hours
(%Fe0-24).
Pharmacodynamic Parameters:
Pharmacodynamic analysis for thrombin-activatable
fibrinolysis inhibitor (TAFI) antigen, clot lysis (an
exploratory biomarker), D-dimer, and total TAFIa activity
will be performed. Remaining blood samples will be used
for post-hoc TAFIa inhibition-related coagulation
biomarker assessments.
Recanalization will be assessed by CT (or MR)
angiography at predose baseline and 24 hours after the start
of treatment using modified Arterial Occlusive Lesion
(mAOL) scores in the subjects with visible occlusion at
predose.
Functional Outcome Parameter:
Functional outcome will be assessed using mRS.
Safety parameters will include; adverse events occurrence,
physical examination findings, vital sign measurements,
standard clinical laboratory parameters (including serum
chemistry, hematology, urinalysis, and coagulation
parameters), and electrocardiogram (ECG) parameters.
Other safety parameters will include bleeding events and
neurologic function. Bleeding events will be assessed and
categorized as symptomatic intracranial hemorrhage
(sICH), any intracranial hemorrhage (ICH), or non-ICH
major bleeding. Neurologic function will be measured
using the NIHSS.
Pharmacokinetic Parameters:
The PK parameters that will be calculated from the plasma
concentrations of DS-1040a using non-compartmental
analysis are the area under the concentration-versus-time
curve, from time 0 to the last quantifiable concentration
sampling point (AUClast), maximum (peak) observed
plasma concentration (Cmax), and time of maximum
observed concentration (tmax). If data permit, the following
parameters will be estimated: the area under the
concentration-versus-time curve from time 0 extrapolated
to infinity (AUC0-inf), half-life (t1/2), clearance, and the
volume of distribution at terminal elimination phase.
The PK parameters that will be calculated from urinary
concentrations of DS-1040a are the amount of drug
excreted in urine from 0 to 24 hours (Ae0-24), the renal
clearance (CLR), and the percentage of the dose
administered excreted in urine from 0 to 24 hours
(%Fe0-24).
Pharmacodynamic Parameters:
Pharmacodynamic analysis for thrombin-activatable
fibrinolysis inhibitor (TAFI) antigen, clot lysis (an
exploratory biomarker), D-dimer, and total TAFIa activity
will be performed. Remaining blood samples will be used
for post-hoc TAFIa inhibition-related coagulation
biomarker assessments.
Recanalization will be assessed by CT (or MR)
angiography at predose baseline and 24 hours after the start
of treatment using modified Arterial Occlusive Lesion
(mAOL) scores in the subjects with visible occlusion at
predose.
Functional Outcome Parameter:
Functional outcome will be assessed using mRS.
Inclution Criteria
Subjects must satisfy all of the following criteria to be
included in the study:
1. Men and women 18 years of age and older.
2. Subjects have a clinical diagnosis of acute ischemic
stroke (including lacunar stroke) supported by
computed topography or magnetic resonance
imaging.
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.
5. Subjects (or their legally authorized representativewhere 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.
included in the study:
1. Men and women 18 years of age and older.
2. Subjects have a clinical diagnosis of acute ischemic
stroke (including lacunar stroke) supported by
computed topography or magnetic resonance
imaging.
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.
5. Subjects (or their legally authorized representativewhere 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.
Exclusion Criteria
Subjects who meet any of the following criteria will be
disqualified from entering the study:
1. 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.
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
hemorrhage (excluding microhemorrahages
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 of randomization. Low dose heparin or low
molecular weight heparin at a preventive dose are
allowed from 24 hours after treatment start and after
confirmation of no intracranial bleeding on the
24-hours repeat brain imaging.
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 month.
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 hemoglobin < 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 or an immediate family
member of an employee of the Sponsor, the CRO
(INC Research), or the Site.
25. Any other reason, in the opinion of the Investigator,
which precludes subject participation in the study.
disqualified from entering the study:
1. 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.
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
hemorrhage (excluding microhemorrahages
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 of randomization. Low dose heparin or low
molecular weight heparin at a preventive dose are
allowed from 24 hours after treatment start and after
confirmation of no intracranial bleeding on the
24-hours repeat brain imaging.
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 month.
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 hemoglobin < 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 or an immediate family
member of an employee of the Sponsor, the CRO
(INC Research), or the Site.
25. Any other reason, in the opinion of the Investigator,
which precludes subject participation in the study.
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
150 participants
