A Study to Assess the Efficacy, Safety, and Pharmacokinetics of TB006 in Participants With Acute Ischemic Stroke

Study Overview
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Brief Summary
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This multi-center, randomized, parallel-group, double-blind, placebo-controlled study will evaluate the efficacy and safety of TB006 in participants with an Acute Ischemic Stroke (AIS) event with 57 days of treatment.

Official Title
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A Phase 2 Double-blind, Randomized, Multi-center, Parallel-group Study to Assess the Efficacy, Safety, and Pharmacokinetics of TB006 in Patients With Acute Ischemic Stroke

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: TB006
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) between 18 and 40 kilograms per meters squared (kg/m^2), inclusive Clinical diagnosis of AIS in anterior circulation, supported by evidence of a new stroke on acute brain computed tomography (CT) or magnetic resonance imaging (MRI) consistent with the clinical diagnosis. Able to be randomized and dosed within 7 days of index stroke event. The last known awake time will be used for participants whose stoke occurred during sleep. National Institute of Health Stroke Scale total score of 7 to 21, inclusive Participants may have received standard of care therapy including recombinant tissue plasminogen activator (r-tPA), thrombectomy, mannitol, hypertonic saline, and other treatments per local guidelines as determined by the Investigator. Participants who have received r-tPA within the first day of their stroke event are eligible. However, study drug administration must begin more than 24 hours following r-tPA administration. Exclusion Criteria: Evidence of severe stroke on imaging (e.g., sulcal effacement or blurring of gray-white junction in greater than 1/3 of middle cerebral artery [MCA] territory, Alberta Stroke Program Early CT [ASPECT] score of 0 to 4 based on head CT, acute infarct volume on MRI diffusion weighed imaging ≥70 mL based on acute imaging studies performed under the standard of care Lacunar or isolated brainstem or cerebellar stroke based on clinical assessment and available acute imaging studies performed under the standard of care Evidence of seizure at the onset of index stroke Evidence of acute myocardial infarction (MI) at Baseline, including any of the following: Acute ST elevation MI; Acute decompensated heart failure, or New York Heart Association Class III/IV heart failure; Admission for an acute coronary syndrome, MI, cardiac arrest, or non-voluntary coronary intervention (percutaneous coronary intervention or coronary artery surgery) within the past 3 months. QT interval corrected using Bazett's formula (QTcB) >520 milliseconds (msec). Evidence of acute intracranial or subarachnoid hemorrhage or evidence of active bleeding based on acute brain CT or MRI performed under the standard of care. However, petechial hemorrhages of ≤ 1 centimeter (cm) are not exclusionary. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TB006<br>Participants will receive intravenous (IV) 3 infusions of 4000 milligrams (mg) TB006, one every 28 days (Q28D). | Drug: TB006<br>* TB006 diluted in normal saline, administered through IV infusion over an hour<br>|
| Placebo Comparator: Placebo<br>Participants will receive an IV infusion of normal saline 500 milliliters (mL) Q28D. | Drug: Placebo<br>* Normal saline administered through IV infusion over an hour<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Recovery Success Measured by modified Rankin Scale (mRS) score of 0-1 on the final mRS assessment. | The Modified Rankin Scale (mRS) measures neurological disability or dependence of participants with stroke on a scale of 0 to 6 and scores indicate the following: 0 - No symptoms; 1 - No significant disability; 2 - Slight disability; 3 - Moderate disability; 4 - Moderately severe disability; 5 - Severe disability; 6 - Dead. Higher score indicates worse condition. | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Clinically Significant Improvement on the National Institutes of Health Stroke Scale (NIHSS) | Clinically significant improvement is defined as a 4-point decrease on the NIHSS | At Days 29, 57 and 85 | 
| Change from Baseline in Neurological Function on the NIHSS | The NIHSS is composed of 11 items, each of which rates a specific parameter of ability or function. Each item is rated on a scale of 0 to 4. A score of 0 indicates normal function, with higher scores indicating greater degree of impairment. The individual item scores are added to calculate the NIHSS total score. The minimum score being a 0 (no impairment) and maximum possible score is 42 (death). Higher scores indicate worse condition. | Baseline and through Day 85 | 
| Percentage of Participants with Clinically Significant Improvement on the mRS | Clinically Significant Improvement is defined as 1-point decrease on the mRS | At Days 29, 57 and 85 | 
| Change from Baseline in the Montreal Cognitive Assessment (MoCA) Total Score | The MoCA is a brief screening instrument designed to assess mild cognitive impairment in a variety of participant conditions. The MoCA assesses eight cognitive domains: visuospatial ability, executive function, short-term memory recall, attention, concentration, working memory, language, and orientation to time and space. Scores on the MoCA range from 0 to 30, with lower scores indicating greater impairment. | Baseline and at Days 29, 57, and 85 | 
| Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Up to Day 141 | 
| Number of Participants with Clinically Significant Clinical Laboratory Parameter Values |  | Up to Day 141 | 
| Number of Participants with Clinically Significant Vital Sign Values |  | Up to Day 141 | 
| Number of Participants with Clinically Significant 12-Lead Electrocardiogram Findings |  | Up to Day 141 | 
| Number of participants with Columbia Suicide Severity Rating Scale (C-SSRS) Score | The C-SSRS is a suicidal ideation and behavior rating scale with yes/no responses. For each of the 5 items of the C-SSRS related to suicidal ideation intensity, an individual's degree of suicidal ideation is rated on a 0-5 scale with 0: no suicidal behavior and 5: active suicidal ideation. The total score is the sum of the 5 intensity item scores (total score ranges from 0 to 25). Higher scores in the scale indicate greater disease severity. | Up to Day 141 | 
| Number of Participants with Clinically Significant Physical Examination Findings |  | Up to Day 141 | 
| Number of Participants with Anti-drug Antibodies |  | Up to Day 141 | 
| Plasma concentration of TB006 |  | Pre-dose and post-dose on Days 1, 29, 57, 85 and 141 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TB006, Acute Ischemic Stroke (AIS), stroke, efficacy, safety, pharmacokinetics, ischemia