Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With Multiple Sclerosis

Study Overview
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Brief Summary
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This study is to identify the safety and efficacy of repeat IV(Intravenous) and IT(Intrathecal) administrations of UMSC01 in patients with MS. While anti-inflammatory drugs are routinely used for the treatment of MS by inhibiting immune responses, their effects on axon remyelination or neuroregeneration are limited. The combined systemic delivery of UCMSCs via intravenous injection and local administration of the cells by IT was to have safety and therapeutic efficacy for patients with MS.

Detailed Description
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There is single arm in Phase I part: 6 patients will be enrolled sequentially for safety considerations. The patient will receive UMSC01 via IV followed by IT at day 28 as described in above. After all patients in Phase I complete the safety assessment by SMC without any major safety issue 4 weeks after the last UMSC01 administration, the Phase IIa part will be initiated. There are 2 arms in Phase IIa part: Sham-controlled with conventional treatment control and administration of UMSC01 with conventional treatment.

Official Title
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A Seamless Phase I/IIa Clinical Study to Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Biological: Allogeneic umbilical cord mesenchymal stem cells
* Biological: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients are willing to sign informed consent. Male or female are age between 20 to 65 years old on date of consent. Diagnosis of Relapsing-Remitting MS (RRMS) (≥1 clinically documented relapse in the past 12 months, ≥2 clinically documented relapses in the last 24 months or ≥ 1 gadolinium enhanced lesion or T2 new lesion in the last 12 months) or Secondary Progressive MS (SPMS) (EDSS increase ≥1.0 point (baseline EDSS ≤ 5.0) or ≥ 0.5 point (baseline EDSS ≥5.5), and ≥1 clinical relapse or ≥1 gadolinium enhanced lesion in the last 12 months) MS diagnosis established between 2 to 15 years and EDSS score between 2.0 to 6.5 before enrollment Patient has appropriated blood clotting function as assessed by the following laboratory requirements: PT, APTT ≤ 1.5X upper limit of normal (ULN). Treatment failure (either ≥ 1 relapse, ≥ 1 new T2 lesion, ≥ one gadolinium enhanced lesion or EDSS deterioration) with at least one of MS disease modifying therapy as Interferon-β, Glatiramer acetate (Copaxone), Dimethyl fumarate (Tecfidera), Teriflunomide (Aubagio), Fingolimod (Gilenya), Ozanimod (Zeposia), Cladribine (Mavenclad), Siponimod (Mayzent), Ofatumumab (Kesimpta), or Natalizumab (Tysabri) for more than 6 months All male patients and female patients with child-bearing potential (between puberty and 2 years after menopause) should use appropriate contraception method(s) for at least 4 weeks after UMSC01 treatment Exclusion Criteria: Pregnancy, lactation, and those who are not pregnant but did not, or unwilling to, take effective contraceptives measures 4 weeks before and after the treatment. Patients with uncontrolled diabetes (fasting blood glucose > 250 mg/dL) Patients with inadequate hepatic and renal function: AST and ALT > 5X ULN; eGFR < 30 mL/min. Patients who are unable to undergo Brain MRI examination for any reason. Patients who have medical history or current clinically active malignant tumor, peripheral neuropathy, myopathy or other clinically significant neurological diseases that will confound the evaluation of this study. Patients who have immuno-compromised condition or is with known clinically significantly autoimmune conditions other than MS or is receiving immunosuppressive treatments other than MS treatment within 6 months. With active infection that required systemic treatment Patients who are participating in other clinical trials with an investigational product within 1 month. Patients who were treated with cytotoxic medications during the last 1 month prior to the infusion. Relapse of MS within1 month before UMSC01 infusion. With anti-CD20 therapy, such as rituximab Patients not suitable to participate the trial as judged by the Investigator(s)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UMSC01<br>UMSC01 cells mixed with normal saline will be administered to patients after the onset of diagnosis of multiple sclerosis. | Biological: Allogeneic umbilical cord mesenchymal stem cells<br>* UMSC01 cells will be IV infusion followed by IT infusion with 12 months of follow up after treatment.<br>|
| Sham Comparator: Placebo<br>For IV administration, normal saline will be administered to patients after the onset of diagnosis of multiple sclerosis. For IT administration, sham puncture procedure will partially penetrate without reaching subarachnoid space, and no spinal fluid will be drawn. | Biological: Control group<br>* Normal saline will be IV infusion followed by sham-IT infusion with 12 months of follow up after treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoint for Phase I portion | SAE, SUSAR, and AE incidences over the study period | from visit 2 to 12-month follow-up period | 
| Primary Endpoint for Phase IIa portion | CFB of EDSS to Visit 10 | from visit 2 to 12-month follow-up period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy endpoint for phase I portion | CFB for EDSS of follow up visits (Visit 6-10) | from visit 2 to 12-month follow-up period | 
| Efficacy endpoint for phase I portion | CFB for brain MRI parameters of follow-up visits (Visit 6 -10) | from visit 2 to 12-month follow-up period | 
| Efficacy endpoint for phase I portion | Quality of life: CFB for MSQoL-54 questionnaire score of follow-up visits (Visit 6 -10) | from visit 2 to 12-month follow-up period | 
| Efficacy endpoint for phase I portion | CFB of T25FW scores of follow-up visits (Visit 6-10) | from visit 2 to 12-month follow-up period | 
| Efficacy endpoint for phase I portion | CFB of 9-HPT scores of follow-up visits (Visit 6-10) | from visit 2 to 12-month follow-up period | 
| Efficacy endpoint for phase I portion | CFB of PASAT scores of follow-up visits (Visit 6-10) | from visit 2 to 12-month follow-up period | 
| Efficacy endpoint for phase I portion | CFB of SDMT scores of follow-up visits (Visit 6-10) | from visit 2 to 12-month follow-up period | 
| Efficacy endpoint for phase I portion | CFB of RNFL thickness, measured by OCT of follow-up visits (Visit 6-10) | from visit 2 to 12-month follow-up period | 
| Efficacy endpoint for phase I portion | CFB of MSFC of follow-up visits (Visit 6-10) | from visit 2 to 12-month follow-up period | 
| Efficacy endpoints for phase IIa portion | Time to onset of CDW confirmed by EDSS at least 6 months | from visit 2 to 6-month follow-up period | 
| Efficacy endpoints for phase IIa portion | ARR (Annualized relapse rate), where relapse is defined as new or worsening neurological symptoms lasting for >24 hours | from visit 2 to 12-month follow-up period | 
| Efficacy endpoints for phase IIa portion | CFB of follow-up visits (Visit 6 -10) for EDSS | from visit 2 to 12-month follow-up period | 
| Efficacy endpoints for phase IIa portion | CFB of follow up visits (Visit 6-10) for brain MRI parameters | from visit 2 to 12-month follow-up period | 
| Efficacy endpoints for phase IIa portion | Quality of life: CFB of follow up visits (Visit 6-10) for MSQoL-54 questionnaire score | from visit 2 to 12-month follow-up period | 
| Efficacy endpoints for phase IIa portion | CFB of follow up visits (Visit 6-10) for T25FW scores | from visit 2 to 12-month follow-up period | 
| Efficacy endpoints for phase IIa portion | CFB of follow up visits (Visit 6-10) for 9-HPT scores | from visit 2 to 12-month follow-up period | 
| Efficacy endpoints for phase IIa portion | CFB of follow up visits (Visit 6-10) for PASAT scores | from visit 2 to 12-month follow-up period | 
| Efficacy endpoints for phase IIa portion | CFB of follow up visits (Visit 6-10) for SDMT scores | from visit 2 to 12-month follow-up period | 
| Efficacy endpoints for phase IIa portion | CFB of follow up visits (Visit 6-10) for RNFL thickness, measured by OCT | from visit 2 to 12-month follow-up period | 
| Efficacy endpoints for phase IIa portion | CFB of follow up visits (Visit 6-10) for MSFC | from visit 2 to 12-month follow-up period | 
| The safety endpoints are listed below for both phase I and IIa portions | SAE, SUSAR, and AE incidences over the study period | from visit 2 to 12-month follow-up period | 
| The safety endpoints are listed below for both phase I and IIa portions | CFB of laboratory data to subsequent visits | from visit 2 to 12-month follow-up period | 
| The safety endpoints are listed below for both phase I and IIa portions | CFB of physical examination to subsequent visits | from visit 2 to 12-month follow-up period | 
| The safety endpoints are listed below for both phase I and IIa portions | CFB of vital signs to subsequent visits | from visit 2 to 12-month follow-up period | 
| The safety endpoints are listed below for both phase I and IIa portions | CFB of AFP, CEA, CA199, SCC, IgA, anti-EBV, β-HCG, CA125, CA153, and PSA to Visit 6 (Phase I) or Visit 10 (Phase IIa) | from visit 2 to 12-month follow-up period |