A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability, and Efficacy of TAK-755 in Acute Ischemic Stroke
A Study of TAK-755 in Adults With Acute Ischemic Stroke
Nonomura Hidenori
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-6-6204-2111
smb.Japanclinicalstudydisclosure@takeda.com
Contact for Clinical Trial Information
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-6-6204-2111
smb.Japanclinicalstudydisclosure@takeda.com
Recruiting
May. 17, 2026
May. 17, 2026
222
Interventional
randomized controlled trial
double blind
placebo control
parallel assignment
treatment purpose
Informed Consent:
1. The participant or legally authorized representative has provided informed consent or deferred consent eligibility confirmed before the initiation of any trial procedures.
Age:
2. greater than and equal to (>=) 18 years of age, inclusive, at the time of signing the Informed Consent Form (ICF) or confirmation of deferred consent eligibility.
Clinical Characteristics:
3. Clinical diagnosis of Acute Ischemic Stroke (AIS).
4. Onset of stroke symptoms within 24 hours of randomization. Wake-up strokes may be included if Last Known Well is within 24 hours of randomization; time of onset will be considered the time of Last Known Well.
5. National Institutes of Health Stroke Scale score of 5 to 25, indicating moderate to severe stroke. Participants with an NIHSS score of 5 are eligible only if at least 1 predefined disabling neurological deficit is present, as defined by one or more of the following NIHSS criteria:
- Complete hemianopia (NIHSS visual score >=2).
- Aphasia impairing meaningful communication (NIHSS language score >=2).
- Motor deficit with inability to sustain effort against gravity (NIHSS left or right motor arm or leg score >=2).
6. Estimated Modified Rankin Scale score less than (<) 2 prior to AIS presentation, signifying no significant disability.
7. Persistent neurological signs and symptoms consistent with unilateral supratentorial circulation stroke.
Imaging:
8. Evidence of causative AIS occlusions affecting supratentorial circulation on imaging (intracranial internal carotid artery [ICA], middle cerebral artery [MCA; M1 - M4], anterior cerebral artery [ACA; A1 - A3], posterior cerebral artery [PCA; P1 - P3]).
9. Evidence of salvageable brain tissue on CT or MR imaging.
Medical History:
1. Weight >130 kilograms (kg) or <40 kg.
2. History of severe traumatic brain injury in the past 90 days.
3. History of intracranial hemorrhage.
4. History of intracranial neoplasm except for small meningioma.
5. History of prior stroke in the past 90 days.
6. History of intracranial or intraspinal surgery within the past 90 days.
7. Major surgery or severe trauma in the past 14 days.
8. History of cerebral amyloid angiopathy.
9. Recent history of active systemic malignancy within the last 5 years, except for locally excised basal cell or squamous cell skin carcinoma with clear margins.
10. Diagnosis of serious, advanced, or terminal illness with anticipated life expectancy of less than 1 year.
11. Participation in other interventional clinical trials within the previous 90 days.
12. Known life-threatening hypersensitivity reaction to TAK-755 or its components.
13. Any prior administration of TAK-755.
14. Administration of caplacizumab in the past 30 days.
15. Administration of von Willebrand factor-containing products in the past 14 days.
16. Baseline conditions (prior to the index AIS event) that prevent an understanding of the nature, scope, and possible consequences of the trial, in the judgment of the investigator.
Current Stroke Management:
17. Any prior administration (intravenous or intra-arterial) of alteplase or tenecteplase for the index AIS event, as well as any prior administration of prourokinase or reteplase for the index AIS event in countries where approved.
18. Eligible for administration of intravenous thrombolysis (alteplase or tenecteplase, as well as prourokinase or reteplase in countries where approved) for the index AIS event, based on the site's standard clinical guidelines and direct availability.
19. Intent to proceed with endovascular thrombectomy (EVT) for the index AIS event based on eligibility and direct availability.
20. Seizure at time of index AIS event onset, only if it precludes accurate assessment of baseline NIHSS.
21. Persistent blood pressure elevation (systolic >=185 millimeters of mercury [mmHg] or diastolic >=110 mm Hg) prior to randomization.
22. Blood glucose <50 milligrams per deciliter (mg/dL) or >400 mg/dL.
Current Medical Conditions:
23. Active, uncontrolled bleeding.
24. Bleeding diathesis or any other conditions that would pose significant bleeding risk.
25. Inability to undergo MRI or CT.
26. Chronic causative intracranial occlusion.
27. Causative total occlusion of the extracranial ICA.
28. Evidence of septic emboli or bacterial endocarditis.
29. Another clinically significant concomitant disease that may pose additional risks for the participant in the opinion of the investigator.
30. Pregnancy, lactation, or unable to comply with birth control methods or abstinence as specified in the protocol in the opinion of the investigator.
Imaging:
31. Poor quality imaging that precludes interpretation according to trial protocol.
32. Evidence of significant intracranial mass effect or midline shift.
33. Evidence of acute occlusion in >1 vascular territory (right/left MCA, right/left ACA, right/left PCA); multiple occlusions within the same vascular territory are allowed.
34. Evidence of acute or chronic intracranial hemorrhage (presence of chronic cerebral microbleeds on magnetic resonance imaging [MRI]) T2*-weighted type sequence (such as gradient recalled echo [GRE] or susceptibility weighted imaging [SWI]) is not exclusionary if total <10 and not consistent with diagnosis of cerebral amyloid angiopathy).
35. Evidence of extensive early ischemic change estimated to be greater than one-third of the middle cerebral artery territory or evidence of well-demarcated hypoattenuation on computed tomography (CT), if performed, consistent with established infarction and judged by the investigator to correspond to the clinical symptoms of the index AIS.
36. Evidence of intracranial tumor (except incidental, small meningioma), cerebral aneurysm, or arteriovenous malformation.
Laboratory:
37. Platelet count <50,000/ cubic millimeters (mm^3).
Other:
38. Identification by the investigator as being potentially unable or unwilling to cooperate with trial procedures.
18age old over
No limit
Both
Acute Ischemic Stroke
Part A: TAK-755
Participants will receive a single intravenous (IV) infusion of TAK-755 on Day 1 of Part A. All participants will be followed for up to 90 days post treatment.
Part B: TAK-755
Participants will receive a single IV infusion of TAK-755 on Day 1 of Part B. All participants will be followed for up to 90 days post treatment.
Part A and B: Placebo
Participants will receive a single IV infusion of TAK-755 matching placebo on Day 1 of Parts A and B. All participants will be followed for up to 90 days post treatment.
1. Part A and B: Percentage of Participants who Develop Symptomatic Intracranial Hemorrhage (sICH) as Defined by the Heidelberg Bleeding Classification System
Time Frame: Up to 120 hours of study drug administration
The Heidelberg Bleeding Classification System is used to determine whether an Intracranial Hemorrhage (ICH) is symptomatic (sICH) or asymptomatic (aICH). It uses a structured 7-step approach that integrates imaging findings with clinical deterioration. This algorithm includes anatomic description of hemorrhage, adjudication of neurological deterioration, and relatedness between ICH and clinical deterioration. Percentage of participants who develop sICH will be reported.
1. Part A: Percentage of Participants With Treatment-Related and Unrelated Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: From start of study drug administration up to follow-up (up to 90 days)
An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of the trial intervention, whether or not the occurrence is considered related to the trial intervention. A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with a trial intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the trial intervention or medicinal product. An SAE is defined as any untoward medical occurrence that results in death or is life-threatening or requires inpatient hospitalization or results in significant disability/incapacity or is a congenital anomaly or meets the definitions of other medically significant events. Percentage of participants with TEAEs and SAEs will be reported.
2. Part A: Percentage of Participants With Severe TEAEs
Time Frame: From start of study drug administration up to follow-up (up to 90 days)
A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with a trial intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the trial intervention or medicinal product. A severe TEAE is a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Percentage of participants with severe TEAEs will be reported.
3. Part A: Percentage of Participants With Life-Threatening Adverse Events (AEs)
Time Frame: From start of study drug administration up to follow-up (up to 90 days)
Percentage of participants with life-threatening AEs will be reported.
4. Part A: Percentage of Participants With AEs of Special Interest (AESIs)
Time Frame: From start of study drug administration up to 168 hours
AESIs include sICH, treatment-related aICH, treatment-related extracranial bleeding SAEs, and recurrent AIS. Percentage of participants with AESIs will be reported.
5. Part A: Percentage of Participants With Clinically Relevant Changes in Vital Signs
Time Frame: From screening up to 90 days
Vital signs will include measurement of body temperature, respiratory rate, blood pressure and pulse rate. Any clinically relevant changes in vital signs will be determined at the investigator's discretion.
6. Part A: Percentage of Participants With Clinically Relevant Changes in Clinical Chemistry and Hematology
Time Frame: From screening up to 90 days
Laboratory parameters will include clinical chemistry and hematology. Any clinically relevant changes in laboratory values will be determined at the investigator's discretion.
7. Part A: Number of Participants With Treatment-induced Binding Antibodies to ADAMTS13
Time Frame: From Day 30 to Day 90
As per planned analysis, blood sample will be collected to monitor the development of binding antibodies to ADAMTS13.
8. Part A: Number of Participants With Treatment-induced Neutralizing Antibodies to ADAMTS13
Time Frame: From Day 30 to Day 90
As per planned analysis, blood sample will be collected to monitor the development of neutralizing antibodies to ADAMTS13.
9. Part A: Percentage of Participants With All-cause Mortality
Time Frame: From start of study drug administration up to follow-up (up to 90 days)
Percentage of participants who died during the entire study period will be reported.
10. Part A and B: Percentage of Participants With Modified Rankin Scale (mRS) Score of 0-1
Time Frame: At Day 90
The mRS assessment will be used to grade the level of functional independence of participants following a stroke. It is a single-item, global outcome rating scale that categorizes functional independence based on pre-stroke activities, with seven grades representing no (0), no significant (1), slight (2), moderate (3), moderately severe (4), severe (5) disability and death (6). Lower scores indicate better functional outcome. Percentage of participants with mRS of 0-1 will be reported.
11. Part A and B: Percentage of Participants With mRS Score of 0-2
Time Frame: At Day 90
The mRS assessment will be used to grade the level of functional independence of participants following a stroke. It is a single-item, global outcome rating scale that categorizes functional independence based on pre-stroke activities, with seven grades representing no (0), no significant (1), slight (2), moderate (3), moderately severe (4), severe (5) disability and death (6). Lower scores indicate better functional outcome. Percentage of participants with mRS of 0-2 will be reported.
12. Part A and B: Ordinal Distribution of mRS at Day 90
Time Frame: At Day 90
The mRS assessment will be used to grade the level of functional independence of participants following a stroke. It is a single-item, global outcome rating scale that categorizes functional independence based on pre-stroke activities, with seven grades representing no (0), no significant (1), slight (2), moderate (3), moderately severe (4), severe (5) disability and death (6). Lower scores indicate better functional outcome.
13. Part A and B: Change From Baseline in National Institutes of Health Stroke Scale (NIHSS) Score at 24 Hours
Time Frame: Baseline up to 24 hours
The NIHSS is a tool to objectively quantify the impairment caused by a stroke. NIHSS assessment is a 15-item impairment scale assessing level of consciousness, extraocular movements, visual fields, facial muscle function, extremity strength, sensory function, coordination (ataxia), language (aphasia), speech (dysarthria), and hemi-inattention (neglect). The total score ranges from 0 to 42 where higher scores indicate greater impairment. A negative change from Baseline indicates improvement.
14. Part A and B: Percentage of Participants With Recanalization According to Arterial Occlusive Lesion (AOL) Score of 3
Time Frame: At 24 Hours
The AOL scale score is a measure of recanalization and ranges from 0 to 3. The grading scale specifically measures the degree of recanalization at the defined target or causative occlusion. A score of 0 is defined as complete occlusion of the target artery. Scores of 1 and 2 account for partial recanalization, with a score of 1 indicating no distal flow while a score of 2 indicates any distal flow. A score of 3 is defined as complete recanalization with any distal flow. Percentage of participants with AOL Score of 3 will be reported.
15. Part A and B: Percentage of Participants With Reperfusion
Time Frame: At 24 Hours
Percentage of participants with reperfusion, defined as >90 percent (%) reduction from baseline in volume of tissue with time-to maximum (Tmax) >6 seconds on perfusion imaging will be reported.
16. Part A and B: Final Infarct Volume
Time Frame: At 72 hours or earlier at hospital discharge
Final infarct volume at 72 hours or hospital discharge (if earlier than 72 hours) will be reported.
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
