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

Overview

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.

Interventions

• 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).
• 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).

Primary outcome measures

• Change in Disability Rating Score (DRS) [Time frame: Baseline to Week 4 post-injury]

Secondary outcome measures (12)

• Change in Blood-based biomarker (Neurofilament light chain) [Time frame: Baseline to Week 2 post-injury]
• Change in Blood-based biomarker (GFAP) [Time frame: Baseline to Week 2 post-injury]
• Change in Blood-based biomarker (UCH-L1) [Time frame: Baseline to Week 2 post-injury]
• Post-TBI symptom outcome (CRSR-FAST) [Time frame: Baseline to Week 4 post-injury]
• Imaging biomarkers [Time frame: Week 2 to Month 6]
• Post-TBI functional outcomes (DRS) [Time frame: Baseline to Month 3 and Baseline to Month 6]
• Post-TBI functional outcomes (FSE) [Time frame: Week 2, Week 4, Month 3 and Month 6]
• Post-TBI functional outcomes (GOSE-TBI) [Time frame: Week 2, Week 4, Month 3 and Month 6]
• Post-TBI cognitive outcome (BTACT) [Time frame: Week 4, Month 3, and Month 6]
• Post-TBI quality of life and patient-reported outcomes (QOLIBRI) [Time frame: Month 3 and Month 6]
• Post-TBI quality of life and patient-reported outcomes (RPQ) [Time frame: Month 3 and Month 6]
• Post-TBI quality of life and patient-reported outcomes (Caregiver Burden) [Time frame: Week 2, Month 3, and Month 6]

Eligibility criteria

Inclusion criteria

• Adults (18-65 years of age, inclusive)
• 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.
• Able to receive investigational product within 24 hours of head injury.
• Closest, prior to randomization GCS score of 3 to 12 (motor score < 6)
• Evidence of TBI on imaging, confirmed by:

• Evidence of contusion and/or
• Evidence of traumatic axonal microvascular injury (TAMVI)
• Initial Glial Fibrillary Acidic Protein (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)
• Participants able to undergo Magnetic Resonance Imaging (MRI) scans, no contraindications
• Legally Authorized Representative (LAR) willing and able to provide informed consent
• Participant/LAR able to read, speak, and understand English

Exclusion criteria

• Isolated epidural hematoma
• Bilaterally fixed dilated pupils in the absence of paralytic medications, or evidence of herniation on cranial CT
• 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
• Order for comfort care placed prior to enrollment
• Current enrollment in another interventional study
• Currently pregnant or currently breastfeeding or planning on becoming pregnant in the next 6M
• Current incarceration or in custody
• On psychiatric hold (e.g. codes 5150, 5250)
• Ongoing pre-injury therapy with the Investigational Product (IP), currently receiving immunosuppressive therapy, chemotherapy, or any contraindicated medications (see CsA Drug contraindications/caution table in the Pharmacy Manual)
• Current or medical history of any allergic reactions and/or anaphylactic reactions towards cyclosporine (CsA) and cremophor (also known as kolliphor®)
• Severe polytrauma or previous conditions that would preclude conducting any study activities
• Any spinal cord injury of grade A to D on the American Spinal Injury Association (ASIA) Impairment Scale
• Primary diagnosis at the enrolling facility of ischemic or hemorrhagic stroke
• Body Mass Index (BMI) >35
• Hemodynamic instability, per participating site physician investigator clinical judgement
• Current or medical history of nephrectomy, 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
• Current or medical history of hepatic disease (e.g., liver laceration at time of injury with Abbreviated Injury Scale for Liver Lacerations > 1); cirrhosis), or serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >3 times the upper limit of normal lab value at the screening/baseline visit.
• Current or medical history of serious chronic viral or fungal infection.
• Current or medical history of active mycobacterial infection or anti-tuberculous treatment.
• Medical history of human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus antibody.
• 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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 3 centers

• University of California, San Francisco — San Francisco
• University of Pittsburgh — Pittsburgh
• University of Utah — Salt Lake City

Identifiers

NCT: NCT06790095 · PM-003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗