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

University of California San Francisco (UCSF)

Status and phase: Invitation-only; Phase 2

Conditions: Traumatic Brain Injury

Treatments: Drug: Placebo; Drug: Cyclosporine (CsA)

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT06790095

PM-003

Details and patient eligibility

About

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.

Enrollment: 26 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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26 participants in 2 patient groups, including a placebo group

Cyclosporine (CsA)

Active Comparator group

Description:

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.

Treatment:

Drug: Cyclosporine (CsA)

Matching Placebo

Placebo Comparator group

Description:

Intravenous (IV) injection of 0.9% NaCl over 74 hours.

Treatment:

Drug: Placebo