Acute Ischemic Stroke
Conditions
Keywords
Acute Ischemic Stroke (AIS), TB006, stroke, efficacy, safety, pharmacokinetics, ischemia
Brief summary
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.
Interventions
DRUGTB006
TB006 diluted in normal saline, administered through IV infusion over an hour
DRUGPlacebo
Normal saline administered through IV infusion over an hour
Sponsors
TrueBinding, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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: 1. Acute ST elevation MI; 2. Acute decompensated heart failure, or New York Heart Association Class III/IV heart failure; 3. 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. 4. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Recovery Success Measured by modified Rankin Scale (mRS) score of 0-1 on the final mRS assessment. | Day 90 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Neurological Function on the NIHSS | Baseline and through Day 85 | 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. |
| Percentage of Participants with Clinically Significant Improvement on the mRS | At Days 29, 57 and 85 | Clinically Significant Improvement is defined as 1-point decrease on the mRS |
| Change from Baseline in the Montreal Cognitive Assessment (MoCA) Total Score | Baseline and at Days 29, 57, and 85 | 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. |
| 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 | — |
| Percentage of Participants with Clinically Significant Improvement on the National Institutes of Health Stroke Scale (NIHSS) | At Days 29, 57 and 85 | Clinically significant improvement is defined as a 4-point decrease on the NIHSS |
| 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 | Up to Day 141 | 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. |
| 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 | — |
| Number of Participants with Clinically Significant Vital Sign Values | Up to Day 141 | — |
Outcome results
None listed