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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: TB006; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: TrueBinding, Inc.
• Investigators: Study Director: Truebinding, Inc., TrueBinding, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2022
• Primary Completion (Actual): December 18, 2023
• Study Completion (Actual): December 18, 2023

Study Registration Dates

• First Submitted: December 1, 2021
• First Submitted That Met QC Criteria: December 1, 2021
• First Posted (Actual): December 14, 2021

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: safety; stroke; pharmacokinetics; efficacy; ischemia; TB006; Acute Ischemic Stroke (AIS)
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: TB006AIS2103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No