Umbilical Cord Blood Cell (MC001) Transplant Into Injured Spinal Cord Followed by the Locomotor Training

Study Overview
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Brief Summary
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Umbilical cord blood mononuclear stem cells (UCBMSCs) transplant followed by the intensive locomotor training for up to 5±1 hours a day, 5±1 days a week, and for 3-6 months for treatment in patients with chronic, stable and complete spinal cord injury.

Detailed Description
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This study is a randomized controlled, Phase II, two-arm study of Umbilical Cord Blood Mononuclear Cell (MC001) transplant into the injured spinal cord followed by the locomotor training for up to 5±1 hours a day, 5±1 days a week, for 3-6 months. A total of 18 subjects with chronic complete spinal cord injury (SCI) will be randomized to one of the two groups. The subjects assigned to Group A will receive 6.4 million UCBMNC (MC001) transplanted into the dorsal root entry zones above and below the injury site exposed by a laminectomy. Subjects in Group B will not have MC001 transplant or surgery. All subjects will receive 3-6 months of intensive locomotor training.

Official Title
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A Randomized Controlled Phase II, Two-Arm Study of Umbilical Cord Blood Cell Transplant (MC001) Into Injured Spinal Cord Followed by the Locomotor Training for Patients With Chronic Complete Spinal Cord Injuries (SCI).

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Biological: Umbilical Cord Blood Mononuclear Cell
* Other: Locomotor Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects' ≥18 to ≤60 years. Traumatic SCI at a neurological level (the lowest contiguous spinal cord segmental level that has intact motor and sensory score) between C5 and T11 by MRI. Note: For the first three subjects at each study center, the neurological level of SCI will be limited to thoracic region (between T1 and T11). Subjects with chronic SCI (defined as ≥ 12 months post- initial SCI surgery) with stable neurologic findings for at least six months and be able stand at least 1 hour/day using a standing frame, tilt table, or equivalent device. Subjects with a current neurological status of ASIA impairment grade A (complete). The injured site of the spinal cord is within three vertebral levels as confirmed by MRI scan. Subject must be in good enough physical health to tolerate the surgery and participate in the intensive walking program. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator. Both male and female subjects and their partners of childbearing potential must agree to use medically accepted methods of contraception. Willing and able to participate in all aspects of the study, including completion of subjective evaluations, attendance at scheduled clinic visits, and compliance with all protocol requirements as evidenced by providing written informed consent. At least one frozen HLA-matched (≥4:6 to a specific patient) CBU identified for each subject. Exclusion Criteria: Clinically significant renal, cardiovascular, hepatic and psychiatric diseases or other conditions that may increase risk of complications during or after surgery or may reduce the ability of the patient to participate in intense locomotor training based on the medical judgment of the investigator. Presence of any clinically significant medical condition(s) or infection (including but not limited to the carrier of hepatitis B virus or HIV) that, in the opinion of the Investigator, could interfere with the treatment or participation in the study. Subjects with flaccid paralysis with absence of deep tendon reflexes in the legs, severe atrophy of the lower limbs, or other evidence of lumbosacral injury, peripheral nerve injury, and motoneuronal loss. Fracture of weight-bearing bones and joints. These include fractures of femur, tibia, and fibula, as well as the ankle, knee, or hip joints. If such fractures have healed, the patient can be included in the trial. Injury to brain, peripheral nerve, or muscle that may interfere with neurologic or walking assessment. Pregnant or lactating woman. Unavailability of HLA-matched umbilical cord blood cells. Any contraindication of laminectomy operation or locomotor training includes: Patient with active infection diseases. Patient with wound infection on or near the implantation site. Patient with severe deformity of spine on or near the implantation site. Patient has immuno-compromised condition, or is with known autoimmune conditions or is human immunodeficiency virus (HIV) seropositive. Patient has on-going moderate to severe organ impairment other than study. Subject with abnormal renal function, cardiovascular disease, depression at screening will be excluded, if considered clinically significant and unstable by the Principal Investigator. Subject who is currently participating in another investigational study or has been taking any investigational drug within the last 4 weeks before screening for this study. Any other criteria, which, in the opinion of the investigator, suggests that the subject would not be compliant with the study protocol and/or would not be suitable to participate in this study. Subject with low bone density (DEXA scan resulted T score < -4).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MC001<br>UCBMNC (MC001) transplant+Locomotor training | Biological: Umbilical Cord Blood Mononuclear Cell<br>* Active ingredients: Monocytes, CD34+, CD133+ cells Dose: 4 injections of 16-μliter (100,000 cells/μliter)<br>* Other names: MC001;Other: Locomotor Training<br>* Locomotor training for up to 6 hours a day, 6 days a week, and for 3-6 months<br>|
| Other: No treatment<br>No surgery, no transplant, locomotor training only | Other: Locomotor Training<br>* Locomotor training for up to 6 hours a day, 6 days a week, and for 3-6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Walking Index of Spinal Cord Injury (WISCI II) Overall Measure | The primary endpoint for this study is mean change from baseline of the Walking Index of Spinal Cord Injury (WISCI II). | At Week 48. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Walking Index of Spinal Cord Injury Measure (WISCI II) at Week 6 and 28 | Mean change from baseline of the Walking Index of Spinal Cord Injury (WISCI II). | At Week 6 and 28. | 
| Spinal Cord Independence Measure (SCIM III) | Mean change from baseline of Spinal Cord Independence Measure (SCIM III) | At Week 6, 28, and 48. | 
| Measure of American Spinal Injury Association (ASIA) Motor and Sensory Scores and AIS Grade | American Spinal Injury Association (ASIA) score has three components: (1) Sensory scores: There is a maximum total of 56 points each for light touch and pin prick (sharp/dull discrimination) modalities, for a total of 112 points per side of the body. (2) Motor scores: There is a maximum score of 25 for each extremity, totaling 50 for the upper limbs and 50 for the lower limbs. (3) ASIA Impairment Scale: Injuries are classified in general terms of being neurologically complete or incomplete based upon the sacral sparing definition. | At Week 2, 6, 28, and 48. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal Cord Injury, Umbilical Cord Blood, Injured Spinal Cord, MC001