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Safety and Efficacy of ABX-101 in Participants Aged 18 to 50 Years of Age With Moderate to Severe Traumatic Brain Injury

Phase 2
Not yet recruiting
Conditions
Traumatic Brain Injury
Cerebral Edema
Interventions
Drug: ABX-101 1mg
Drug: ABX-101 2mg
Registration Number
NCT06096415
Lead Sponsor
Abalonex, LLC
Brief Summary

The purpose of this study is to investigate the clinical improvement measured by the Glasgow Outcome Scale Extended (GOS-E) with ABX-101 compared with Placebo intramuscular injection in participants with moderate to severe TBI.

Detailed Description

Study details include:

* The study duration will be up to 180 days per participant.

* The treatment duration will be up to 7 days.

* The visits post-treatment will be on day 30 and day 180 of the study.

Number of Participants:

A maximum of 45 participants will be enrolled into the study and randomized to each treatment arm in a ratio of 1:1:1. i.e., fifteen participants per arm.

Study Arms and Duration:

Participants will be screened, enrolled and receive the assigned treatment within 12 hours of the primary TBI insult. Enrolled participants will be stratified 1:1 (in each arm) by GCS score (GCS 4-8 in one group and GCS 9 - 12 in the other). The treatment period, which involves 6 hourly, i.e., quarter in die (QID), ABX-101 (1 mg OR 2 mg) intramuscular injections, is seven days. Enrolled participant will continue with the in-hospital standard of care, as decided by the external treating physician, and will be followed up by the study team on days 30 and days 180. The ABX-101 1 mg and 2 mg arm will be enrolled simultaneously.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
45
Inclusion Criteria
  • Written informed consent from patient, patient's legal guardian or legal representative, or deferred consent procedure, according to local requirements

  • 18 - 50 years of age, inclusive

  • Expected to survive more than 24 hours after admission

  • Clearly defined time of injury no more than 12 hours before administration of study drug/placebo

    o Subjects stratified 1:1 (in each arm) by treatment administered 0-12 hrs

  • TBI with Glasgow Coma Score (GCS) 4-12 requiring intracranial pressure (ICP) monitoring according to the assessment of the treating physician

    o Subjects stratified 1:1 (in each arm) by GCS 4-8 and GCS 9-12

  • Catheter placement (intraventricular or intraparenchymal, only) for monitoring and management of increased ICP

  • [Brain computed tomography (CT) showing intracranial parenchymal abnormality and hemodynamically stable]

Exclusion Criteria
  • Penetrating head injury (e.g. missile, stab wound)
  • Concurrent, but not pre-existing, spinal cord injury
  • Not expected to survive more than 24 hours after admission
  • Pregnant, or a positive pregnancy test
  • Coma due to an exclusive epidural hematoma (lucid interval and absence of structural brain damage on CT scan)
  • Patient pupils are unresponsive (dilation) in both eyes
  • The subject has a neurodegenerative disease or other neurological disorder including dementia, Parkinson's disease, multiple sclerosis, seizure disorder, or brain tumors.
  • Coma suspected to be primarily due to other causes than head injury (e.g. drug overdose intoxication, drowning/near drowning
  • Known or CT scan evidence of pre-existing major cerebral damage
  • Any severe concomitant condition (cancer; hematologic, renal, hepatic, coronary disease; major psychiatric disorder; alcohol or drug abuse), that can be ascertained at admission
  • Known to have received an experimental drug within 4 weeks prior to current injury
  • Patients who cannot be monitored with regard to their recovery (GOS-E and QOLIBRI)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Experimental: ABX-101 1mgABX-101 1mgParticipants will be screened, enrolled and receive the assigned treatment within 12 hours of the primary TBI insult (or estimated less than 12 hours if the exact time is unknown). Enrolled participants will be stratified 1:1 (in each arm) by GCS score (GCS 4-8 in one group and GCS 9 - 12 in the other). The treatment period, which involves 6 hourly, i.e., quarter in die (QID), ABX 101 (1 mg OR 2 mg) intramuscular injections, is seven days.
Experimental: ABX-101 1mgABX-101 2mgParticipants will be screened, enrolled and receive the assigned treatment within 12 hours of the primary TBI insult (or estimated less than 12 hours if the exact time is unknown). Enrolled participants will be stratified 1:1 (in each arm) by GCS score (GCS 4-8 in one group and GCS 9 - 12 in the other). The treatment period, which involves 6 hourly, i.e., quarter in die (QID), ABX 101 (1 mg OR 2 mg) intramuscular injections, is seven days.
Experimental: ABX-101 2mgABX-101 1mgParticipants will be screened, enrolled and receive the assigned treatment within 12 hours of the primary TBI insult (or estimated less than 12 hours if the exact time is unknown). Enrolled participants will be stratified 1:1 (in each arm) by GCS score (GCS 4-8 in one group and GCS 9 - 12 in the other). The treatment period, which involves 6 hourly, i.e., quarter in die (QID), ABX 101 (1 mg OR 2 mg) intramuscular injections, is seven days.
Experimental: ABX-101 2mgABX-101 2mgParticipants will be screened, enrolled and receive the assigned treatment within 12 hours of the primary TBI insult (or estimated less than 12 hours if the exact time is unknown). Enrolled participants will be stratified 1:1 (in each arm) by GCS score (GCS 4-8 in one group and GCS 9 - 12 in the other). The treatment period, which involves 6 hourly, i.e., quarter in die (QID), ABX 101 (1 mg OR 2 mg) intramuscular injections, is seven days.
Placebo Comparator: SalineABX-101 1mgPlacebo to the ABX-101 will be administered to patients.
Placebo Comparator: SalineABX-101 2mgPlacebo to the ABX-101 will be administered to patients.
Primary Outcome Measures
NameTimeMethod
Glasgow Outcome Scale-Extended (GOS-E)180 days

To demonstrate superiority of ABX-101 vs placebo on the Glasgow Outcome Scale-Extended (GOS-E) at 90-days in participants with TBI

Secondary Outcome Measures
NameTimeMethod
Glasgow Outcome Scale-Extended (GOS-E)30 days

To demonstrate superiority of ABX-101 vs placebo on the GOS-E at 30 days in participants with TBI

Glasgow Coma Score (GSC) improvement7 days

To demonstrate superiority of ABX-101 vs placebo on the GCS improvement (vs. baseline) at days 3 and 7 in participants with TBI

Quality of life- (QOLIBRI)180 days

To demonstrate superiority of ABX-101 vs placebo on the Quality of Life after Brain Injury at 90 days in participants with TBI

GFAP Inflammatory Biomarker Analysis7 days

To compare ABX-101 vs placebo on Glial fibrillary acidic protein (GFAP) levels at 1 day, 3 days, and 7 days in participants with TBI. The detection range for GFAP biomarker is 0.31 - 20 ng/ml using ELAB Science GFAP Kit.

ICP Maintenance7 days

To demonstrate superiority of ABX-101 vs placebo on the ICP maintenance at 3 days and 7 days in participants with TBI

Neuroworsening7 days

To demonstrate superiority of ABX-101 vs placebo on the Neuroworsening at 3 days and 7 days in participants with TBI

Mortality180 days

To demonstrate superiority of ABX-101 vs placebo on the mortality at 3 days, 7 days, 28 days, and 90 days in participants with TBI

Midline Shift3 days

To demonstrate superiority of ABX-101 vs placebo on the degree of midline shift as assessed by CT scan at 1 day and 3 days in participants with TBI

Adverse Events7 days

To compare ABX-101 vs placebo in terms of AEs assessed over 7 days of treatment and through the duration of follow-up in participants with TBI

Therapeutic Intensity Level7 days

To demonstrate superiority of ABX-101 vs placebo on the Therapeutic Intensity Level over 3 days and over 7 days in participants with TBI

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