Cell Therapy for Chronic Traumatic Cervical Incomplete Spinal Cord Injury

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

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.

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injury Cervical
• Intervention / Treatment: Drug: WJ-MSC (XCEL-UMC-BETA); Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • A Coruña, Spain, 15006
    • Complexo Hospitalario Universitario A Coruña (CHUAC)
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital de Neurorehabilitació Institut Guttmann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Single spinal cord injury lesion caused by trauma
2. Affected cord segments between C1 and T1, confirmed by magnetic resonance
3. Incomplete lesion (ASIA B, C or D)
4. Chronic disease state (between 1 and 5 years after the injury)
5. Patients from 18 to 70 years of age, both sexes
6. Life expectancy > 2 years
7. Residence near the center during study participation and confidence that the patient will attend the follow-up visits
8. Given informed consent in writing
9. Patient is able to understand the study and its procedures

Exclusion Criteria:

1. Mechanic ventilation
2. Penetrating trauma affecting the spinal cord
3. Pregnant woman or without proper anticonceptive measures according to the investigator, or breath feeding
4. Planned spinal surgery within subsequent 12 month after entering the trial
5. Neurodegenerative diseases
6. Significant abnormal laboratory tests that contraindicates patient's participation in the study
7. Neoplasia within the previous 5 years, or without complete remission
8. Patient with communication difficulties
9. 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
10. Previous treatment with and advanced Therapy Medicinal Product (cell therapy)
11. Contraindication for lumbar punction
12. Contraindication or inability to follow a rehabilitation program
13. Other pathologic conditions or circumstances that difficult participation in the study according to medical criteria
14. The patient does not accept to be followed-up for a period that could exceed the clinical trial length

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Banc de Sang i Teixits
• Collaborators: Complexo Hospitalario Universitario de A Coruña; Institut Guttmann; Academic Research Organization (ARO) - VHIR
• Investigators: Principal Investigator: Joan VIDAL, MD, PhD, Institut Guttmann

Publications and helpful links

General Publications

• Albu S, Kumru H, Coll R, Vives J, Valles M, Benito-Penalva J, Rodriguez L, Codinach M, Hernandez J, Navarro X, Vidal J. Clinical effects of intrathecal administration of expanded Wharton jelly mesenchymal stromal cells in patients with chronic complete spinal cord injury: a randomized controlled study. Cytotherapy. 2021 Feb;23(2):146-156. doi: 10.1016/j.jcyt.2020.08.008. Epub 2020 Sep 25.

Helpful Links

• Blood and tissue bank of Catalonia, cell producer and sponsor of the trial
• Hospital specialized in spinal cord injury
• Hospital specialized in spinal cord injury

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2021
• Primary Completion (Actual): January 20, 2024
• Study Completion (Actual): January 20, 2024

Study Registration Dates

• First Submitted: September 14, 2021
• First Submitted That Met QC Criteria: September 14, 2021
• First Posted (Actual): September 23, 2021

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cell therapy; spinal cord injury; Mesenchymal stromal cells; Wharton jelly
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Wounds and Injuries; Spinal Cord Injuries
• Other Study ID Numbers: BST-SCI-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No