Safety and Preliminary Efficacy of FAB117-HC in Patients With Acute Traumatic Spinal Cord Injury
Safety and Preliminary Efficacy of FAB117-HC in Patients With Acute Traumatic Spinal Cord Injury
The main objective of the study is the evaluation of the safety and tolerability of FAB117-HC
 (a medicinal product containing human allogeneic adipose derived adult mesenchymal stem cells
 expanded and pulsed with H2O2, HC016 cells) administered at a single-time point to patients
 with acute thoracic traumatic spinal cord injury (SCI). The study will also include initial
 exploration of potential clinical efficacy. Dose levels of 20 million and 40 million cells
 will be administered.
FAB117-HC is an investigational medicinal product whose active substance is HC016, allogeneic
 adipose-derived adult mesenchymal stem cells expanded and pulsed with H2O2.

 The main purpose of this study is to evaluate the safety and tolerability of a single
 administration of FAB117-HC using: a) two sequential escalating doses administered between 72
 and 120 hours post-injury, to patients with acute traumatic SCI with ASIA Impairment Scale
 (AIS) grade A; and b) the determined maximum tolerated dose administered up to 96 h
 post-injury to patients with AIS grading of A or B. The study includes also initial
 exploration of efficacy.

 Treatment is administered by intramedullary injection into the injured spinal cord, during
 the decompression and stabilization surgery (DSS) of the fracture. DSS is routinely performed
 on almost all SCI patients.

 The study has been divided into two phases:

 Phase 1 (open label): 8 AIS A patients with lesion located between D1 and D12 will be
 included in 2 sequential cohorts.

 Phase 2 (randomized, controlled, double-blind): 40 AIS A or B patients with lesion located
 between D1 and D12, will be randomly divided into two groups (control and treated) that will
 be balanced in AIS grade.
Inclusion Criteria:

 Phase 1 (2 Cohorts)

 1. Male or female subjects ≥ 16 to ≤ 70 years.

 2. ASIA impairment grade A.

 3. Either a level of injury between D1-D12 both inclusive (cohorts 1 and 2).

 4. Single traumatic spinal cord injury as defined by MRI.

 5. Injury occurred between 72 and 120h before undergoing DSS and treatment.

 6. Clinically and haemodynamically stable, under medical criteria, enough to undergo DSS.

 7. Able to give informed consent either in writing or orally in the presence of a
 witness.

 Phase 2 (2 Groups)

 1. Male or female subjects ≥ 16 to ≤ 70 years.

 2. ASIA impairment grade A or B.

 3. An injury between D1 and D12, both inclusive.

 4. Single traumatic spinal cord injury as defined by MRI.

 5. Injury occurring up to 96 h before undergoing DSS and treatment.

 6. Clinically and haemodynamically stable enough, under medical criteria, to undergo DSS.

 7. Able to give informed consent either in writing or orally in the presence of a
 witness.

 Exclusion Criteria:

 1. Participated in a previous clinical study and received an investigational product
 within 28 days of SCI (within 5 years of SCI if the investigational product is a
 cell-based medicine).

 2. Radiological or MRI or DSS evidence of complete or partial spinal cord transection.

 3. Inability to unequivocally identify the injection sites.

 4. Multiple injuries to the neurological spinal cord at different levels.

 5. Patients with any of these additional conditions:

 1. Penetrating spinal cord injuries.

 2. Associated trauma or injury to the brachial and / or lumbosacral plexus.

 6. Active infection in the surgical area.

 7. Haemodynamic instability contraindicating DSS procedure in the time frame defined for
 inclusion in the trial.

 8. Multiple organ failure.

 9. Severe multiple trauma that hampers the stabilization procedure in the defined term
 for the inclusion in the trial.

 10. Significant head injury (Score on the Glasgow scale less than or equal to 13 and / or
 abnormal MRI/CT, meaning oedema, axonal lesion and/or haemorrhage) or other injury
 that in the investigator's opinion is sufficient to interfere with the assessment of
 spinal cord function or compromise the validity of patient data.

 11. Patients undergoing mechanical ventilation that does not allow a prior clinical
 examination.

 12. Inability to communicate with the neurological examiner so that the validity of
 patient data could be unreliable.

 13. Coma or significant impairment in the level of consciousness, including
 unconsciousness due to sedative-analgesic medications, that interferes with the
 performance or interpretation of assessments specific in the protocol.

 14. Preexisting or current significant diseases such as hepatitis C, HIV, epilepsy,
 neoplastic disease or other diseases that could cause neurological deficits including
 syphilis, myelopathy, and polyneuropathy.

 15. Background or acute episode of Guillain-Barre syndrome.

 16. History of meningitis or meningoencephalitis.

 17. Current autoimmune disease treated with immunosuppressant therapy.

 18. Patients with history of severe thrombophilia or under anticoagulant pharmacological
 therapy which long elimination half-live prevents a rapid transition to heparin (like
 dabigatran and rivaroxaban).

 19. Presence of any psychiatric illness, as defined by the DSM-IV-TR, or medically
 unstable illness that means a hindrance to the adherence to rehabilitation and/or to
 the informed consent signature.

 20. Pregnant women or women of childbearing age who are not using an appropriate method of
 contraception and, moreover, are not willing to continue to use it for the duration of
 the trial. If the patient is menopausal or sterile, it must be documented in the
 medical record.

 21. Women who are breastfeeding if unwilling to stop at the time of recruitment.

 22. History of allergy with anaphylactic shock.

 23. Patients with known hypersensitivity to any of the excipients of FAB117-HC.

 24. Patients with known hypersensitivity to penicillin, streptomycin, enzymes (trypsin or
 collagenase), bovine serum or DMSO.