Use of stem cells for the treatment of traumatic brain injury. Multicenter, doubleblind, randomized with placebo phase II clinical trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione IRCCS San Gerardo Dei Tintori

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

27 Jan 2025 → ongoing

Decision date (initial)

2025-01-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ministero della Salute (Progetto RF-2021-12372642) · Fondazione Regionale per la Ricerca Biomedica (FRRB)

External identifiers

EU CT number

2024-516510-38-00

EudraCT number

2022-000680-49

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The study is meant:
i) to define if MSCs, administered at dosage of 80 or 160 x 106 cells are safe in patients with severe TBI;
ii) to define if MSCs, administered at the dosage found to be safe and more promising in terms of activity as revealed by the interim analysis, decrease the plasmatic NFfL biomarker of brain damage at 14 days post-TBI.

Secondary objectives 3

1. To assess: i) brain injury evolution and white matter damage by longitudinal neuroimaging (at 14 days +/- 3 days, 6 months +/- 15 days and 12 months +/- 15 days);
2. To assess: ii) brain immunomodulatory changes by temporal profiling of circulating biomarkers of brain damage and neuroinflammation;
3. To assess: iii) clinical outcome by a structured clinical and neuropsychological assessments at both 6 and 12 months.

Conditions and MedDRA coding

Traumatic Brain Injury

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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

Exclusion criteria 18

1. Motor GCS > 5 at recruitment (last valid neurological assessment before randomization)
2. 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
3. Bilateral unreactive mydriasis
4. Opening ICP > 40 mmHg
5. Known history of prior brain injury, psychiatric disorder, neurological impairment and/or deficit
6. Brain penetrating injury
7. Spinal cord injury
8. Epilepsy requiring ongoing anti-convulsant therapy
9. Severe organ failure (including PaO2/FiO2<200 and shock)
10. Recent serious infectious process requiring ICU admission
11. Cancer (ongoing)
12. Immunosuppression
13. Previous known history of immunodeficiency syndromes, or current signs/symptoms suggesting immunodeficiency
14. Positive urine pregnancy test
15. Known risk/history of coagulopathy and thromboembolism
16. 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
17. Known hypersensitivity to excipients used in the formulation (Dimethyl sulfoxide, DMSO; Citratedextrose solution, ACD)
18. Participation in a concurrent interventional study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Safety. The number of patients experiencing at least one serious adverse drug reaction (SADR). 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.

Secondary endpoints 3

1. 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).
2. 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)
3. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione IRCCS San Gerardo Dei Tintori

Sponsor organisation

Fondazione IRCCS San Gerardo Dei Tintori

Address

Via Giovanni Battista Pergolesi 33

City

Monza

Postcode

20900

Country

Italy

Scientific contact point

Organisation

Fondazione IRCCS San Gerardo Dei Tintori

Contact name

Scientific coordinator

Public contact point

Organisation

Fondazione IRCCS San Gerardo Dei Tintori

Contact name

Scientific coordinator

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications