Multiple Sclerosis
Conditions
Brief summary
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
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.
Interventions
UMSC01 cells will be IV infusion followed by IT infusion with 12 months of follow up after treatment.
BIOLOGICALControl group
Normal saline will be IV infusion followed by sham-IT infusion with 12 months of follow up after treatment.
Sponsors
Ever Supreme Bio Technology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients are willing to sign informed consent. 2. Male or female are age between 20 to 65 years old on date of consent. 3. 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) 4. MS diagnosis established between 2 to 15 years and EDSS score between 2.0 to 6.5 before enrollment 5. Patient has appropriated blood clotting function as assessed by the following laboratory requirements: PT, APTT ≤ 1.5X upper limit of normal (ULN). 6. 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 7. 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
1. 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. 2. Patients with uncontrolled diabetes (fasting blood glucose \> 250 mg/dL) 3. Patients with inadequate hepatic and renal function: AST and ALT \> 5X ULN; eGFR \< 30 mL/min. 4. Patients who are unable to undergo Brain MRI examination for any reason. 5. 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. 6. 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. 7. With active infection that required systemic treatment 8. Patients who are participating in other clinical trials with an investigational product within 1 month. 9. Patients who were treated with cytotoxic medications during the last 1 month prior to the infusion. 10. Relapse of MS within1 month before UMSC01 infusion. 11. With anti-CD20 therapy, such as rituximab 12. Patients not suitable to participate the trial as judged by the Investigator(s)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Endpoint for Phase I portion | from visit 2 to 12-month follow-up period | SAE, SUSAR, and AE incidences over the study period |
| Primary Endpoint for Phase IIa portion | from visit 2 to 12-month follow-up period | CFB of EDSS to Visit 10 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy endpoint for phase I portion | from visit 2 to 12-month follow-up period | CFB for EDSS of follow up visits (Visit 6-10) |
| Efficacy endpoints for phase IIa portion | from visit 2 to 6-month follow-up period | Time to onset of CDW confirmed by EDSS at least 6 months |
| The safety endpoints are listed below for both phase I and IIa portions | from visit 2 to 12-month follow-up period | SAE, SUSAR, and AE incidences over the study period |
Other
| Measure | Time frame | Description |
|---|---|---|
| The exploratory endpoints are listed below for both phase I and IIa portions | from visit 2 to 12-month follow-up period | Immunological markers, including CD3, CD4, CD8 surface markers, IgG, IgM, anti-HLA antibodies and Panel Reactive Antibody Assay in whole blood |
Countries
Taiwan
Contacts
Primary ContactSammi Hsu
Backup ContactJack Tsai
Outcome results
None listed