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

• ClinicalTrials.gov Identifier: NCT05156827
• Recruitment Status: Withdrawn
• First Posted: December 14, 2021
• Last Update Posted: January 12, 2024
• Sponsor: TrueBinding, Inc.
• Information provided by (Responsible Party): TrueBinding, Inc.

Tracking Information

• First Submitted Date: December 1, 2021
• First Posted Date: December 14, 2021
• Last Update Posted Date: January 12, 2024
• Actual Study Start Date: July 26, 2022
• Actual Primary Completion Date: December 18, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 14, 2023)

Percentage of Participants with Recovery Success Measured by modified Rankin Scale (mRS) score of 0-1 on the final mRS assessment. [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: December 1, 2021): Change From Baseline in Neurological Function on the National Institutes of Health Stroke Scale (NIHSS) through Day 104 [ Time Frame: Baseline through Day 104 ]

Current Secondary Outcome Measures (submitted: March 14, 2023)

• Percentage of Participants with Clinically Significant Improvement on the National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: At Days 29, 57 and 85 ]
  Clinically significant improvement is defined as a 4-point decrease on the NIHSS
• Change from Baseline in Neurological Function on the NIHSS [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Up to Day 141 ]
• Number of Participants with Clinically Significant Clinical Laboratory Parameter Values [ Time Frame: Up to Day 141 ]
• Number of Participants with Clinically Significant Vital Sign Values [ Time Frame: Up to Day 141 ]
• Number of Participants with Clinically Significant 12-Lead Electrocardiogram Findings [ Time Frame: Up to Day 141 ]
• Number of participants with Columbia Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: 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 [ Time Frame: Up to Day 141 ]
• Number of Participants with Anti-drug Antibodies [ Time Frame: Up to Day 141 ]
• Plasma concentration of TB006 [ Time Frame: Pre-dose and post-dose on Days 1, 29, 57, 85 and 141 ]

Original Secondary Outcome Measures (submitted: December 1, 2021)

• Number of Participants with Clinically Significant Improvement on the NIHSS at Day 36 and Sustained through Day 104 [ Time Frame: Day 36 through Day 104 ]
• Change from Baseline in Neurological Function on the NIHSS at Day 36 [ Time Frame: Baseline; up to Day 36 ]
• Number of Participants with Clinically Significant Improvement on the Modified Rankin Scale (mRS) at Day 36 and Sustained through Day 104 [ Time Frame: Day 36 through Day 104 ]
• Change from Baseline in the Fugl-Meyer Assessment (FMA) Total Score at Day 36 and Day 104 [ Time Frame: Baseline; Day 36 and Day 104 ]
• Change from Baseline in the Montreal Cognitive Assessment (MoCA) Total Score at Day 36 and Day 104 [ Time Frame: Baseline; Day 36 and Day 104 ]
• Number of Participants with Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events [ Time Frame: up to Day 104 ]
• Number of Participants with Clinically Significant Clinical Laboratory Parameter Values [ Time Frame: up to Day 104 ]
• Number of Participants with Clinically Significant Vital Sign Values [ Time Frame: up to Day 104 ]
• Number of Participants with Clinically Significant 12-Lead Electrocardiogram Findings [ Time Frame: up to Day 104 ]
• Change from Baseline in the Columbia Suicide Severity Rating Scale (C-SSRS) Score at Day 104 [ Time Frame: Baseline; Day 104 ]
• Number of Participants with Clinically Significant Physical Examination Findings [ Time Frame: up to Day 104 ]
• Number of Participants with Clinically Significant Neurological Examination Findings [ Time Frame: up to Day 104 ]
• Number of Participants with Anti-drug Antibodies at Day 1, Day 36, and Day 104 [ Time Frame: Day 1, Day 36, and Day 104 ]
• Mean Area Under the Concentration Time Curve over a Dosing Interval (AUC0-tau) at Steady State [ Time Frame: Day 1 (Predose), Day 29 (Predose), Day 36, Day 64, and Day 104 ]
• Mean Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day 1 (Predose), Day 29 (Predose), Day 36, Day 64, and Day 104 ]
• Mean Concentration at the End of a Dosing Interval (Ctrough) [ Time Frame: Day 1 (Predose), Day 29 (Predose), Day 36, Day 64, and Day 104 ]
• Median Terminal Elimination Phase Half-life (t1/2) [ Time Frame: Day 1 (Predose), Day 29 (Predose), Day 36, Day 64, and Day 104 ]
• Median Time to Cmax (tmax) [ Time Frame: Day 1 (Predose), Day 29 (Predose), Day 36, Day 64, and Day 104 ]
• Mean Clearance (CLss) at Steady State [ Time Frame: Day 1 (Predose), Day 29 (Predose), Day 36, Day 64, and Day 104 ]
• Mean Volume at Steady State (Vss) [ Time Frame: Day 1 (Predose), Day 29 (Predose), Day 36, Day 64, and Day 104 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess the Efficacy, Safety, and Pharmacokinetics of TB006 in Participants With Acute Ischemic Stroke
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Acute Ischemic Stroke

Intervention

• Drug: TB006
  TB006 diluted in normal saline, administered through IV infusion over an hour
• Drug: Placebo
  Normal saline administered through IV infusion over an hour

Study Arms

• Experimental: TB006
  Participants will receive intravenous (IV) 3 infusions of 4000 milligrams (mg) TB006, one every 28 days (Q28D).
  Intervention: Drug: TB006
• Placebo Comparator: Placebo
  Participants will receive an IV infusion of normal saline 500 milliliters (mL) Q28D.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: January 10, 2024): 0
• Original Estimated Enrollment (submitted: December 1, 2021): 112
• Actual Study Completion Date: December 18, 2023
• Actual Primary Completion Date: December 18, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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/Exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT05156827
• Other Study ID Numbers: TB006AIS2103
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: TrueBinding, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: TrueBinding, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: TrueBinding, Inc.; TrueBinding, Inc.

• PRS Account: TrueBinding, Inc.
• Verification Date: January 2024