Cell Therapy for Chronic Traumatic Cervical Incomplete Spinal Cord Injury

Sponsor

Banc de Sang i Teixits (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05054803

Collaborator

Institut Guttmann (Other), Academic Research Organization (ARO) - VHIR (Other), Complexo Hospitalario Universitario de A Coruña (Other)

Enrollment

Locations

Arms

47.6

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Spinal Cord Injury Cervical	Drug: WJ-MSC (XCEL-UMC-BETA) Drug: Placebo	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double-blind, randomized, placebo-controlled, 2-arms, multicenter clinical trialDouble-blind, randomized, placebo-controlled, 2-arms, multicenter clinical trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Active treatment and placebo will be released using the same syringe and blinded in a way that it is no possible to distinguish one to the other.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 13, 2021

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Incidence of adverse events [At 12 month follow-up]
Adverse events

Secondary Outcome Measures

American Spinal Injury Association (ASIA) impairment scale [At 1, 3, 4, 6 and 12 month follow-up]
Changes in ASIA score with respect to baseline value as detailed at https://asia-spinalinjury.org/international-standards-neurological-classification-sci-isncsci-worksheet/
Motor evoked potentials [At 6 and 12 month follow-up]
Changes in motor evoked potentials score with respect to baseline value. Higher scores mean a better outcome
Somatosensory evoked potentials [At 6 and 12 month follow-up]
Changes in somatosensory evoked potentials score with respect to baseline value. Higher scores mean a better outcome
Electrical pain threshold perception [At 6 and 12 month follow-up]
Changes in electrical pain threshold perception score with respect to baseline. Lower scores mean a better outcome
Handgrip Strength [At 6 and 12 month follow-up]
Will be assessed using a dynamometer. Changes in the score with respect to baseline values. Higher scores mean a better outcome
Walking index for spinal cord injury (WISCI II) [At 6 and 12 month follow-up]
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)
Numerical scale for neuropathic pain assessment [At 6 and 12 month follow-up]
Changes in the numerical scale for neuropathic pain score with respect to baseline value. Score ranges from 0 (no pain) to 10 (unbearable pain)
Modified Ashworth scale for spasticity [At 6 and 12 month follow-up]
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.
Spinal Cord Independence Measure III (SCIM III) [At 6 and 12 month follow-up]
Changes in the SCIM III scale score with respect to baseline value. Score ranges from 0 to 20 with higher scores meaning better outcome.
World Health Organization Quality of life questionnaire (WHOQOL-BREF) [At 6 and 12 month follow-up]
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.
Psychological general well-being index (PGWBI) [At 12 month follow-up]
Changes in the PGWBI score with respect to baseline value. Score ranges from 0 to 132, with higher scores meaning a better outcome.
Hospital Anxiety and Depression Scale (HADS) [At 12 month follow-up]
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.
Community Integration Questionaire (CIQ-IG) [At 12 month follow-up]
Changes in the CIQ-IG score with respect to baseline value. Score ranges from 0 to 25, with higher scores meaning a better outcome.
AntiHLA antibodies in cerebrospinal fluid (CSF) [At 7 days and at 1 month follow-up after each infusion]
Presence or absence of antiHLA antibodies in the CSF after two WJ-MSC infusions
Detection of donor cells in CSF [At 7 days after each infusion]
Short tandem repeat (STR) analysis to detect permanence of donor cellularity (WJ-MsC) in the CSF

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital de Neurorehabilitació Institut Guttmann	Badalona	Barcelona	Spain	08916
2	Complexo Hospitalario Universitario A Coruña (CHUAC)	A Coruña		Spain	15006