Clinical trial NCT06790095: TRACK-TBI Precision Medicine Part 3 - Option II
Official title: Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Precision Medicine Part 3 - Option II
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Traumatic Brain Injury
Keywords: Traumatic Brain Injury
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: U.S. Army Medical Research and Development Command
First posted: 2025-01-23
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if experimental drug treatment improves recovery after TBI as compared to a control (placebo) group. Changes in recovery will be measured throughout the study. The study drug listed below is approved by the U.S. Food and Drug Administration (FDA) but is being used "off-label" in this study. This means that the drug is not currently approved to treat TBI.


Eligibility criteria: Inclusion Criteria:

1. Adults (18-65 years of age, inclusive)
2. Presents to a participating enrollment site and is able to receive treatment within 24 hours of head injury warranting clinical evaluation with a non- contrast cranial CT based on American College of Emergency Physicians (ACEP) Centers for Disease Control and Prevention (CDC) clinical policy for TBI imaging.
3. Closest, prior to randomization GCS score of 3 to 8
4. Evidence of TBI on cranial CT, confirmed by:

   * Evidence of contusion and/or
   * Evidence of traumatic axonal microvascular injury (TAMVI)
5. Initial GFAP blood level \>1000 pg/mL ≤ 15000 pg/mL determined using a for Research Use Only (RUO) assay(s) or an Investigation Use Only (IUO) assay(s)
6. Participants able to undergo Magnetic Resonance Imaging (MRI) scans, no contraindications
7. Legally Authorized Representative (LAR) willing and able to provide informed consent
8. Participant/LAR able to read, speak, and understand English or Spanish (participating site dependent, where available), including the Informed Consent Form (ICF)

Exclusion Criteria:

1. Isolated epidural hematoma
2. Bilaterally fixed dilated pupils in the absence of paralytic medications, or evidence of herniation on cranial CT
3. Pre-existing conditions including disabling developmental, neurologic, psychiatric, medical disorder that continues to produce functional disability up to the time of injury; or imminent death based on clinical judgement
4. Order for comfort care placed prior to enrollment
5. Current enrollment in another interventional study
6. Currently pregnant or currently breastfeeding or planning on becoming pregnant in the next 6M
7. Current incarceration or in custody
8. On psychiatric hold (e.g. Codes 5150, 5250)
9. Ongoing pre-injury therapy with the Investigational Product (IP), currently receiving immunosuppressive therapy or any contraindicated medications (see CsA Drug contraindications/caution table in Manual of Procedures)
10. Current or medical history of any allergic reactions and/or anaphylactic reactions towards CsA and cremophor (also known as kolliphor®)
11. Severe polytrauma or previous conditions that would preclude conducting any study activities
12. Any spinal cord injury of grade A to D on the American Spinal Injury Association (ASIA) Impairment Scale
13. Primary diagnosis at the enrolling facility of ischemic or hemorrhagic stroke
14. Body Mass Index (BMI) \>35
15. Hemodynamic instability, per participating site physician investigator clinical judgement
16. Current or medical history of renal dysfunction, significant renal failure, or high-risk for renal failure, defined as:

    * Creatinine Clearance (CrCl) or estimated Glomerular Filtration Rate (eGFR) (\<60 mL/minute/1.73 m2)
    * Major rhabdomyolysis with creatine kinase \> 5,000 IU/L
17. Current or medical history of hepatic disease or serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \>3 times the upper limit of normal lab value at the screening/baseline visit
18. Current or medical history of serious chronic viral or fungal infection
19. Current or medical history of active mycobacterial infection or anti- tuberculous treatment
20. Medical history of human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus antibody
21. Any significant disease or disorder (including abnormal laboratory tests) which, in the opinion of the participating site investigator, may either put the patient at risk because of participation in the study, or may influence the results of the study
22. Low likelihood of follow up or study compliance, or any other reason, in the opinion of the participating site investigator, the participants should not participate in the study

Primary outcomes:
measure: Change in Disability Rating Score (DRS)
timeFrame: Baseline to Week 4 post-injury
Secondary outcomes:
measure: Change in Blood-based biomarker (Neurofilament light chain)
timeFrame: Baseline to Week 2 post-injury
measure: Change in Blood-based biomarker (GFAP)
timeFrame: Baseline to Week 2 post-injury
measure: Change in Blood-based biomarker (UCH-L1)
timeFrame: Baseline to Week 2 post-injury
measure: Post-TBI symptom outcome (CRSR-FAST)
timeFrame: Baseline to Week 4 post-injury
measure: Imaging biomarkers
timeFrame: Week 2 to Month 6
measure: Post-TBI functional outcomes (DRS)
timeFrame: Baseline to Month 3 and Baseline to Month 6
measure: Post-TBI functional outcomes (FSE)
timeFrame: Week 2, Week 4, Month 3 and Month 6
measure: Post-TBI functional outcomes (GOSE-TBI)
timeFrame: Week 2, Week 4, Month 3 and Month 6
measure: Post-TBI cognitive outcome (BTACT)
timeFrame: Week 4, Month 3, and Month 6
measure: Post-TBI quality of life and patient-reported outcomes (QOLIBRI)
timeFrame: Month 3 and Month 6
measure: Post-TBI quality of life and patient-reported outcomes (RPQ)
timeFrame: Month 3 and Month 6
measure: Post-TBI quality of life and patient-reported outcomes (Caregiver Burden)
timeFrame: Month 3 and Month 6
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Geoffrey Manley, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: