TRACK-TBI Precision Medicine Part 3 - Option II (PM-003)

Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Precision Medicine Part 3 - Option II

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Drug: Cyclosporine (CsA); Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • University of California, San Francisco
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cyclosporine (CsA); Intravenous (IV) injection, 2.5 mg/kg loading dose given over 2 hours, followed by a 3-day (72-hour) constant IV infusion of 5 mg/kg/day.	Drug: Cyclosporine (CsA); Intravenous (IV) injection, loading dose of 2.5 mg/kg (diluted in 0.9% NaCl to a final volume of 50 ml) given over 2 hours, immediately followed by a continuous IV infusion of of 5 mg/kg/day (diluted in 0.9% NaCl to a final volume of 250 ml) for 3 days (72-hour).; Other Names: Sandimmune®
Placebo Comparator: Matching Placebo; Intravenous (IV) injection of 0.9% NaCl over 74 hours.	Drug: Placebo; Intravenous (IV) injection of 0.9% NaCl with the same dosing strategy as CsA: "loading dose" given over 2 hours, immediately followed by a continuous IV infusion for 3 days (72-hour).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Disability Rating Score (DRS)	The primary outcome measure is to determine whether the intervention safely improves functional outcome in participants with TBI as compared to placebo, as measured by the change in the Disability Rating Score (DRS) score from Baseline to Week 4 post-injury.	Baseline to Week 4 post-injury

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Blood-based biomarker (Neurofilament light chain)	To determine whether the intervention lowers the rising plasma Neurofilament light chain (NfL) levels up to W2 post-injury in participants with TBI as compared to placebo.	Baseline to Week 2 post-injury
Change in Blood-based biomarker (GFAP)	To determine whether the intervention lowers the plasma GFAP levels up to W2 post-injury as compared to placebo.	Baseline to Week 2 post-injury
Change in Blood-based biomarker (UCH-L1)	To determine whether the intervention lowers the plasma UCH-L1 levels up to Week 2 post-injury in participants with TBI as completed to placebo.	Baseline to Week 2 post-injury
Post-TBI symptom outcome (CRSR-FAST)	To determine the effect of intervention on the change in the number of behavioral signs of consciousness present on the Coma Recovery Scale- Revised For Accelerated Standardized Testing (CRSR-FAST) from Baseline to W4 post-injury as compared to placebo.	Baseline to Week 4 post-injury
Imaging biomarkers	To determine whether the intervention results in improved imaging biomarkers compared to placebo measured by: 1) the change in white matter tract using MRI diffusion tensor imaging (DTI), and 2) change in total brain volumetrics using MRI T1 MPRAGE, from Week 2 to Month 6.	Week 2 to Month 6
Post-TBI functional outcomes (DRS)	To determine the effect of intervention on functional outcomes, as measured by: I. Change in the Disability Rating Scale (DRS) from Baseline to Month 3 and Baseline to Month 6	Baseline to Month 3 and Baseline to Month 6
Post-TBI functional outcomes (FSE)	To determine the effect of intervention on functional outcomes, as measured by: II. Functional Status Examination (FSE) score at Week 2, Week 4, Month 3 and Month 6	Week 2, Week 4, Month 3 and Month 6
Post-TBI functional outcomes (GOSE-TBI)	To determine the effect of intervention on functional outcomes, as measured by: III. Glasgow Outcome Scale Extended (TBI Version) (GOSE-TBI) score at Week 2, Week 4, Month 3 and Month 6.	Week 2, Week 4, Month 3 and Month 6
Post-TBI cognitive outcome (BTACT)	To determine the effect of the intervention on cognitive outcome, as measured by the Brief Test of Adult Cognition by Telephone (BTACT) Composite z-score at Week 4, Month 3 and Month 6.	Week 4, Month 3, and Month 6
Post-TBI quality of life and patient-reported outcomes (QOLIBRI)	To determine the effect of intervention on quality of life and other patient-reported outcomes (PRO), as measured by the Quality of Life Brain Injury (QOLIBRI) at Month 3 and Month 6.	Month 3 and Month 6
Post-TBI quality of life and patient-reported outcomes (RPQ)	To determine the effect of intervention on quality of life and other patient-reported outcomes (PRO), as measured by the Rivermead Post Concussion Symptoms Questionnaire (RPQ) at Month 3 and Month 6.	Month 3 and Month 6
Post-TBI quality of life and patient-reported outcomes (Caregiver Burden)	To determine the effect of intervention on quality of life and other patient-reported outcomes (PRO), as measured by the Caregiver Burden at Month 3 and Month 6.	Month 3 and Month 6

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: U.S. Army Medical Research and Development Command
• Investigators: Principal Investigator: Geoffrey Manley, MD, PhD, University of California, San Francisco

Publications and helpful links

Helpful Links

• Related Info
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Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: January 17, 2025
• First Submitted That Met QC Criteria: January 17, 2025
• First Posted (Actual): January 23, 2025

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Traumatic Brain Injury
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Peptides; Amino Acids, Peptides, and Proteins; Polycyclic Compounds; Macrocyclic Compounds; Peptides, Cyclic; Cyclosporins; Cyclosporine
• Other Study ID Numbers: PM-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be made available through the Federal Interagency TBI Research (FITBIR) Database.
• IPD Sharing Time Frame: Shared scientific data will be made accessible as soon as possible, and no later than the time of an associated publication, or the end of performance period, whichever comes first.
• IPD Sharing Access Criteria: FITBIR qualified investigators will be provided access

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No