Cell Therapy for Chronic Traumatic Cervical Incomplete Spinal Cord Injury

Study Overview
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Brief Summary
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This is a double-blind, randomized, placebo-controlled, multicenter clinical trial in which 18 patients affected with chronic traumatic incomplete cervical spinal cord injury will be randomized to either the active treatment (2 doses of intrathecal WJ-MSC 3 months apart) or to placebo (2 intrathecal infusions, 3 months apart). Thereafter, patients will be followed-up for 12 months for safety and efficacy assessment.

Detailed Description
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Double-blind, randomized, placebo-controlled, multicenter clinical trial that will include 18 patients affected with chronic traumatic incomplete cervical spinal cord injury who will be randomized 1:1, stratified by center, to one of the 2 treatment arms of the study: WJ-MSC / WJ-MSC (at a dose of 1E6 ± 30% live cells / Kg of weight) or Placebo / placebo. Medication will be administered intrathecally at day 1 and at 3 months. The main objective of the trial is to assess safety at a 12-month follow-up. Secondary objectives include the evaluation of efficacy through clinical response, electrophysiological changes, questionnaires of functionality and quality of life, as well as the presence of anti-HLA antibodies and donor cellularity in the cerebrospinal fluid.

Official Title
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A Phase I/II, Randomized, Double-blind, Placebo-controlled, Parallel, 2-arms Clinical Trial to Assess the Safety and Efficacy of Intrathecal Administration of WJ-MSC in Chronic Traumatic Cervical Incomplete Spinal Cord Injury

Conditions
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Spinal Cord Injury Cervical

Intervention / Treatment
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* Drug: WJ-MSC (XCEL-UMC-BETA)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Single spinal cord injury lesion caused by trauma Affected cord segments between C1 and T1, confirmed by magnetic resonance Incomplete lesion (ASIA B, C or D) Chronic disease state (between 1 and 5 years after the injury) Patients from 18 to 70 years of age, both sexes Life expectancy > 2 years Residence near the center during study participation and confidence that the patient will attend the follow-up visits Given informed consent in writing Patient is able to understand the study and its procedures Exclusion Criteria: Mechanic ventilation Penetrating trauma affecting the spinal cord Pregnant woman or without proper anticonceptive measures according to the investigator, or breath feeding Planned spinal surgery within subsequent 12 month after entering the trial Neurodegenerative diseases Significant abnormal laboratory tests that contraindicates patient's participation in the study Neoplasia within the previous 5 years, or without complete remission Patient with communication difficulties Simultaneous participation in another clinical trial or treated with an investigational medicinal product the previous 30 days, that could interfere in the results of the study Previous treatment with and advanced Therapy Medicinal Product (cell therapy) Contraindication for lumbar punction Contraindication or inability to follow a rehabilitation program Other pathologic conditions or circumstances that difficult participation in the study according to medical criteria The patient does not accept to be followed-up for a period that could exceed the clinical trial length

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, randomized, placebo-controlled, 2-arms, multicenter clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WJ-MSC (XCEL-UMC-BETA)<br>Pre-filled syringe with 4 ± 1 mL containing WJ-MSC in a balanced saline solution supplemented with human albumin. | Drug: WJ-MSC (XCEL-UMC-BETA)<br>* Administration of 2 Intrathecal infusions of WJ-MSC at day 1 and at 3 months<br>* Other names: Tested product;|
| Placebo Comparator: Placebo<br>Pre-filled syringe with 4 ± 1 mL containing a balanced saline solution supplemented with human albumin | Drug: Placebo<br>* Administration of 2 Intrathecal infusions of placebo at day 1 and at 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Adverse events | At 12 month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American Spinal Injury Association (ASIA) impairment scale | Changes in ASIA score with respect to baseline value as detailed at https://asia-spinalinjury.org/international-standards-neurological-classification-sci-isncsci-worksheet/ | At 1, 3, 4, 6 and 12 month follow-up | 
| Motor evoked potentials | Changes in motor evoked potentials score with respect to baseline value. Higher scores mean a better outcome | At 6 and 12 month follow-up | 
| Somatosensory evoked potentials | Changes in somatosensory evoked potentials score with respect to baseline value. Higher scores mean a better outcome | At 6 and 12 month follow-up | 
| Electrical pain threshold perception | Changes in electrical pain threshold perception score with respect to baseline. Lower scores mean a better outcome | At 6 and 12 month follow-up | 
| Handgrip Strength | Will be assessed using a dynamometer. Changes in the score with respect to baseline values. Higher scores mean a better outcome | At 6 and 12 month follow-up | 
| Walking index for spinal cord injury (WISCI II) | Changes in the walk test WISCIII score with respect to baseline value. The score ranges from 0 (most severe impairment) to 20 (least severe impairment) | At 6 and 12 month follow-up | 
| Numerical scale for neuropathic pain assessment | Changes in the numerical scale for neuropathic pain score with respect to baseline value. Score ranges from 0 (no pain) to 10 (unbearable pain) | At 6 and 12 month follow-up | 
| Modified Ashworth scale for spasticity | Changes in the modified Ashworth scale score with respect to baseline value. It is a 5 point numerical scale that graded spasticity from 0 to 4, with 0 being no resistance and 4 being a limb rigid in flexion or extension, and includes a 1+ value. | At 6 and 12 month follow-up | 
| Spinal Cord Independence Measure III (SCIM III) | Changes in the SCIM III scale score with respect to baseline value. Score ranges from 0 to 20 with higher scores meaning better outcome. | At 6 and 12 month follow-up | 
| World Health Organization Quality of life questionnaire (WHOQOL-BREF) | Changes in the WHOQOL-BREF score with respect to baseline value. It contains contains 26 questions each punctuated from 1 to 5 and assesses the individual's overall perception of quality of life (1 to 5), overall perception of their health (1 to 5) and 4 domains of physical health, psychological, social relationships, environment (0-100 each domain). higher scores denote higher quality of life. | At 6 and 12 month follow-up | 
| Psychological general well-being index (PGWBI) | Changes in the PGWBI score with respect to baseline value. Score ranges from 0 to 132, with higher scores meaning a better outcome. | At 12 month follow-up | 
| Hospital Anxiety and Depression Scale (HADS) | Changes in the HADS score with respect to baseline value. This is a 14-item self-administered questionnaire containing 2 subscales (one for anxiety and one for depression), with a score range of each subscale from 0-21. Higher score indicates higher anxiety and depression. | At 12 month follow-up | 
| Community Integration Questionaire (CIQ-IG) | Changes in the CIQ-IG score with respect to baseline value. Score ranges from 0 to 25, with higher scores meaning a better outcome. | At 12 month follow-up | 
| AntiHLA antibodies in cerebrospinal fluid (CSF) | Presence or absence of antiHLA antibodies in the CSF after two WJ-MSC infusions | At 7 days and at 1 month follow-up after each infusion | 
| Detection of donor cells in CSF | Short tandem repeat (STR) analysis to detect permanence of donor cellularity (WJ-MsC) in the CSF | At 7 days after each infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal cord injury, Mesenchymal stromal cells, Wharton jelly, Cell therapy