A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability, and Efficacy of TAK-755 in Acute Ischemic Stroke
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 222
- 试验地点
- 60
- 主要终点
- Part A and B: Percentage of Participants who Develop Symptomatic Intracranial Hemorrhage (sICH) as Defined by the Heidelberg Bleeding Classification System
研究概览
简要总结
Acute ischemic stroke (AIS) is a medical emergency that happens because of a sudden stop of blood flow to a part of the brain. This happens when a blood clot forms within the vessel (known as thrombotic occlusion) or a clot originating from somewhere else blocks a blood vessel (known as embolic occlusion). Strokes can cause serious health problems, death, and affect one's quality of life. To reduce long-term damage, it is important to restore blood flow to the brain as soon as possible.
The main aim of this study is to check how safe TAK-755 is, and how well adults with AIS tolerate it. Other aims are to check how well TAK-755 helps participants to manage their everyday activities and to understand whether it helps reduce the seriousness of their stroke symptoms when compared to placebo. A placebo looks like TAK-755, but does not have any medicine in it, to make sure participants do not know which treatment they are taking.
The participants will receive TAK-755 or placebo once; afterwards, their health will be monitored for about 3 months (90 days). All participants, regardless of their assignment to either TAK-755 or placebo, will receive the usual treatment for AIS as per the hospital's normal practice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed Consent:
- •The participant or legally authorized representative has provided informed consent or deferred consent eligibility confirmed before the initiation of any trial procedures.
- •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:
- •Clinical diagnosis of AIS.
- •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.
- •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).
- •Estimated Modified Rankin Scale score less than (<) 2 prior to AIS presentation, signifying no significant disability.
- •Persistent neurological signs and symptoms consistent with unilateral supratentorial circulation stroke.
- •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]).
- •Evidence of salvageable brain tissue on CT or MR imaging.
排除标准
- •Medical History:
- •Weight >130 kilograms (kg) or <40 kg.
- •History of severe traumatic brain injury in the past 90 days.
- •History of intracranial hemorrhage.
- •History of intracranial neoplasm except for small meningioma.
- •History of prior stroke in the past 90 days.
- •History of intracranial or intraspinal surgery within the past 90 days.
- •Major surgery or severe trauma in the past 14 days.
- •History of cerebral amyloid angiopathy.
- •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.
- •Diagnosis of serious, advanced, or terminal illness with anticipated life expectancy of less than 1 year.
- •Participation in other interventional clinical trials within the previous 90 days.
- •Known life-threatening hypersensitivity reaction to TAK-755 or its components.
- •Any prior administration of TAK-
- •Administration of caplacizumab in the past 30 days.
- •Administration of von Willebrand factor-containing products in the past 14 days.
- •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:
- •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.
- •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.
- •Intent to proceed with endovascular thrombectomy (EVT) for the index AIS event based on eligibility and direct availability.
- •Seizure at time of index AIS event onset, only if it precludes accurate assessment of baseline NIHSS.
- •Persistent blood pressure elevation (systolic >=185 millimeters of mercury [mmHg] or diastolic >=110 mm Hg) prior to randomization.
- •Blood glucose <50 milligrams per deciliter (mg/dL) or >400 mg/dL.
- •Current Medical Conditions:
- •Active, uncontrolled bleeding.
- •Bleeding diathesis or any other conditions that would pose significant bleeding risk.
- •Inability to undergo MRI or CT.
- •Chronic causative intracranial occlusion.
- •Causative total occlusion of the extracranial ICA.
- •Evidence of septic emboli or bacterial endocarditis.
- •Another clinically significant concomitant disease that may pose additional risks for the participant in the opinion of the investigator.
- •Pregnancy, lactation, or unable to comply with birth control methods or abstinence as specified in the protocol in the opinion of the investigator.
- •Poor quality imaging that precludes interpretation according to trial protocol.
- •Evidence of significant intracranial mass effect or midline shift.
- •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.
- •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).
- •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.
- •Evidence of intracranial tumor (except incidental, small meningioma), cerebral aneurysm, or arteriovenous malformation.
- •Laboratory:
- •Platelet count <50,000/ cubic millimeters (mm^3).
- •Identification by the investigator as being potentially unable or unwilling to cooperate with trial procedures.
研究组 & 干预措施
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.
干预措施: TAK-755 (Biological)
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.
干预措施: TAK-755 (Biological)
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.
干预措施: Placebo (Other)
结局指标
主要结局
Part A and B: Percentage of Participants who Develop Symptomatic Intracranial Hemorrhage (sICH) as Defined by the Heidelberg Bleeding Classification System
时间窗: 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.
次要结局
- Part A and B: Percentage of Participants With Reperfusion(At 24 Hours)
- Part A: Percentage of Participants With AEs of Special Interest (AESIs)(From start of study drug administration up to 168 hours)
- Part A: Percentage of Participants With Clinically Relevant Changes in Vital Signs(From screening up to 90 days)
- Part A: Percentage of Participants With Clinically Relevant Changes in Clinical Chemistry and Hematology(From screening up to 90 days)
- Part A: Number of Participants With Treatment-induced Binding Antibodies to ADAMTS13(From Day 30 to Day 90)
- Part A: Number of Participants With Treatment-induced Neutralizing Antibodies to ADAMTS13(From Day 30 to Day 90)
- Part A and B: Final Infarct Volume(At 72 hours or earlier at hospital discharge)
- Part A: Percentage of Participants With Treatment-Related and Unrelated Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From start of study drug administration up to follow-up (up to 90 days))
- Part A: Percentage of Participants With Severe TEAEs(From start of study drug administration up to follow-up (up to 90 days))
- Part A: Percentage of Participants With Life-Threatening Adverse Events (AEs)(From start of study drug administration up to follow-up (up to 90 days))
- Part A: Percentage of Participants With AEs of Special Interest (AESIs)(From start of study drug administration up to follow-up (up to 90 days))
- Part A: Percentage of Participants With Clinically Relevant Changes in Vital Signs(From screening up to discharge (up to approximately 8 days))
- Part A: Percentage of Participants With Clinically Relevant Changes in Clinical Chemistry and Hematology(From screening up to discharge (up to approximately 8 days))
- Part A: Number of Participants With Binding Antibodies to ADAMTS13(From Day 30 to Day 90)
- Part A: Number of Participants With Neutralizing Antibodies to ADAMTS13(From Day 30 to Day 90)
- Part A: Percentage of Participants With All-cause Mortality(From start of study drug administration up to follow-up (up to 90 days))
- Part A and B: Percentage of Participants With Modified Rankin Scale (mRS) Score of 0-1(At Day 90)
- Part A and B: Percentage of Participants With mRS Score of 0-2(At Day 90)
- Part A and B: Ordinal Distribution of mRS at Day 90(At Day 90)
- Part A and B: Change From Baseline in National Institutes of Health Stroke Scale (NIHSS) Score at 24 Hours(Baseline up to 24 hours)
- Part A and B: Percentage of Participants With Recanalization According to Arterial Occlusive Lesion (AOL) Score of 3(At 24 Hours)
- Part A and B: Final Infarct Volume(At 72 Hours)