MESENCHYMAL STROMAL CELLS, EX VIVO CULTURED for Traumatic brain injury

Inclusion criteria

• {"criterion_text":"- Age: 18-70 years (inclusive)"}
• {"criterion_text":"- Clinical frailty index (CFI) < 5"}
• {"criterion_text":"- Evidence of TBI confirmed by abnormalities consistent with trauma on CT scan upon admission (Marshall’s CT Classification >1)"}
• {"criterion_text":"- Study drug (MSC/placebo) administration within 48 hours from TBI"}
• {"criterion_text":"- Glasgow Coma Scale (GCS) ≤ 8 at recruitment (last valid neurological assessment before randomization) and at least one pupil reactive to light"}
• {"criterion_text":"- ICP monitoring, already inserted or planned for clinical indications"}
• {"criterion_text":"- Weight < 100 Kg and > 40 kg"}

Exclusion criteria

• {"criterion_text":"- Motor GCS > 5 at recruitment (last valid neurological assessment before randomization)"}
• {"criterion_text":"- High likelihood (>85%) of death in the first 48 h calculated by IMPACT (International Mission for Prognosis and Analysis of Clinical Trials in TBI) calculator128 on early admission data"}
• {"criterion_text":"- Bilateral unreactive mydriasis"}
• {"criterion_text":"- Opening ICP > 40 mmHg"}
• {"criterion_text":"- Known history of prior brain injury, psychiatric disorder, neurological impairment and/or deficit"}
• {"criterion_text":"- Brain penetrating injury"}
• {"criterion_text":"- Spinal cord injury"}
• {"criterion_text":"- Epilepsy requiring ongoing anti-convulsant therapy"}
• {"criterion_text":"- Severe organ failure (including PaO2/FiO2<200 and shock)"}
• {"criterion_text":"- Recent serious infectious process requiring ICU admission"}
• {"criterion_text":"- Cancer (ongoing)"}
• {"criterion_text":"- Immunosuppression"}
• {"criterion_text":"- Previous known history of immunodeficiency syndromes, or current signs/symptoms suggesting immunodeficiency"}
• {"criterion_text":"- Positive urine pregnancy test"}
• {"criterion_text":"- Known risk/history of coagulopathy and thromboembolism"}
• {"criterion_text":"- Pre-existing and severe ongoing: • lung disease (such as asthma, chronic obstructive pulmonary disease) • heart dysfunction (as heart failure and reduced cardiac output) • liver insufficiency (as cirrhosis) • kidney insufficiency • and other organ severe abnormalities"}
• {"criterion_text":"- Known hypersensitivity to excipients used in the formulation (Dimethyl sulfoxide, DMSO; Citratedextrose solution, ACD)"}
• {"criterion_text":"- Participation in a concurrent interventional study"}

Primary endpoints

• {"endpoint_text":"- 1. Safety. The number of patients experiencing at least one serious adverse drug reaction (SADR).\n- 2. Biological activity. a) The number of responder patients, defined as in paragraph ”Statistical design and sample size” b) The quantitative plasmatic NfL at Day 14 as measured by ultra-sensitive single-molecule array immunoassay (SIMOA). The plasmatic NfL levels, as well as all secondary outcomes, will be only analyzed if at least one of the treatment arms will be considered as safe.","definition_or_measurement_approach":"Safety: count of patients experiencing at least one serious adverse drug reaction (SADR). Biological activity: a) number of responder patients (as defined in 'Statistical design and sample size' in the protocol); b) quantitative plasmatic neurofilament light (NfL) at Day 14 measured by ultra-sensitive single-molecule array immunoassay (SIMOA). Analysis of plasmatic NfL and secondary outcomes contingent on at least one treatment arm being considered safe."}

Secondary endpoints

• {"endpoint_text":"- 1. Brain injury evolution and white matter damage by longitudinal advanced magnetic resonance imaging (MRI) (performed at 14 days +/- 3 days ,at 6 months +/- 15 days and 12 months +/- 15 days post-TBI).","definition_or_measurement_approach":"Longitudinal advanced MRI assessments at 14 days ±3 days, 6 months ±15 days, and 12 months ±15 days post-TBI to evaluate brain injury evolution and white matter damage."}
• {"endpoint_text":"- 2. Brain immunomodulatory changes by temporal profiling of circulating biomarkers of: a) structural damage: NfL, glial fibrillary acidic protein (GFAP) b) neuroinflammation: interleukin-6 (IL-6), IL-10, tumor necrosis factor alpha (TNFα) c) vascular integrity: matrix metallopeptidase 9 (MMP-9)","definition_or_measurement_approach":"Temporal profiling of circulating biomarkers including NfL and GFAP (structural damage), IL-6, IL-10, TNFα (neuroinflammation), and MMP-9 (vascular integrity)."}
• {"endpoint_text":"- 3. Clinical outcome by a structured clinical and neuropsychological outcome assessment at both 6 and 12 months, by: a) Glasgow Outcome Scale Extended (GOSE) b) quality of life after brain injury (QOLIBRI) test","definition_or_measurement_approach":"Structured clinical and neuropsychological assessments at 6 and 12 months using the Glasgow Outcome Scale Extended (GOSE) and QOLIBRI (quality of life after brain injury) test."}

Italy

Earliest CTIS Part Ii Submission Date

04-10-2024

Latest Decision Or Authorization Date

14-04-2026

Processing Time Days

557

Number Of Sites

4

Number Of Participants

78

Primary sponsor

Full Name

Fondazione IRCCS San Gerardo Dei Tintori

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy