Autologous, Bone Marrow-Derived Mesenchymal Stem Cell-Derived Neural Progenitor Cells (MSC-NP), Expanded Ex Vivo; Administered Intrathecally
Overview
- Phase
- Phase 2
- Intervention
- Intrathecal MSC-NP injection
- Conditions
- Multiple Sclerosis
- Sponsor
- Tisch Multiple Sclerosis Research Center of New York
- Enrollment
- 54
- Locations
- 1
- Primary Endpoint
- Expanded Disability Status Scale (EDSS) Plus
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
This is a phase II, double-blinded, placebo-controlled, randomized, cross-over Study designed to determine the efficacy of multiple intrathecal administrations of autologous mesenchymal stem cell-derived neural progenitor cells (MSC-NP) compared to placebo in patients with progressive multiple sclerosis. Efficacy will be measured through assessment of disability outcomes. Study participants will receive six intrathecal injections of culture-expanded autologous MSC-NPs at two month intervals in one year and six lumbar punctures as placebo treatments in a second year.
Detailed Description
The IT-MSC-NP treatments and all clinical assessments will take place at a single center (Tisch MSRCNY). Study subjects will be assigned to blocks stratified by baseline EDSS score (3.0-4.0, 4.5-5.5, 6.0, and 6.5) and disease subtype (SPMS or PPMS). Study subjects are randomized in an equal fashion (1:1) to study treatment and placebo at initial randomization. Subjects in each block will be randomized into placebo or treatment group. In the second year, treated subjects will cross over to the placebo group and placebo subjects will cross over to the treated group. The total study duration will be 3 years upon enrollment. Each study subject will be required to attend up to 18 study visits, to include 1 screening visit, 1 bone marrow visit, 1 baseline visit, followed by study visits every 2 months during the treatment period of two years (12 treatment/LP procedure visits and 2 outcome visits), and an additional follow-up visit at the end of year 3.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of MS as defined by the McDonald criteria
- •Diagnosis of primary progressive or secondary progressive MS
- •Between the ages of 18-65 years
- •Significant disability shown by an Expanded Disability Status Score (EDSS) of greater than or equal to 3.0, and less than or equal to 6.5, that was not acquired within the last 12 months.
- •Stable disease state as evidenced by a lack of gadolinium-enhancing lesions on an MRI and by a stable MRI disease burden (number of T2 lesions and size of lesions) in the last six months and no significant change in EDSS (1 point or more) in the last 12 months
- •Must agree to undergo four MRIs: at the time of enrollment, after year 1, after year 2, and after year 3
- •Patients either within the geographical area or who are able to arrange reliable travel during the study period
Exclusion Criteria
- •EDSS greater than 6.5
- •Duration of Disease \>20 years at time of screening
- •Change of disease modifying agent \< 12 months prior to beginning treatment. Additionally, no changes in disease modifying agent will be made during the course of the study.
- •Change in MS symptom management treatment \< 6 months prior to beginning treatment. Additionally, no changes in MS symptom management treatments will be made during the course of the study, unless there has been clinical improvement, in which case, a patient may discontinue a medication.
- •Start of any new orthotic device or durable medical equipment \< 6 months prior to beginning treatment or during the course of the study (patients may discontinue use of these devices during the course of the study if they show clinical improvement).
- •All patients who have ever been on Lemtrada (alemtuzumab)
- •All patients who have had any prior stem cell treatments, including HSCT
- •Pregnant or nursing mothers, or any woman intending to become pregnant in the next three years
- •All patients will have screening blood tests done. Only patients whose values are in the normal range as determined by the laboratory norms based on age and sex will be allowed to participate. Exceptions may be made for borderline normal laboratory values manifesting no clinical symptoms at the discretion of the Principal Investigator.
- •Use of systemic chemotherapeutic or anti-mitotic medications within three months of study start date due to the possibility of interference with bone marrow procedure
Arms & Interventions
Intrathecal MSC-NP injection
Patients will receive six autologous stem cell injections through spinal taps every 2 months over a year.
Intervention: Intrathecal MSC-NP injection
Intrathecal saline injection
Patients will receive six placebo injections through spinal taps every 2 months over a year.
Intervention: Intrathecal saline injection
Outcomes
Primary Outcomes
Expanded Disability Status Scale (EDSS) Plus
Time Frame: Baseline and 13 months
Changes in disability assessed based on composite score of EDSS, timed 25-foot walk (T25FW), and nine hole peg test (9HPT) (EDSS-Plus). Improvement is defined by at least one of the following three measures: ≥0.5 decrease in EDSS (if EDSS at entry is ≥ 6.0) or ≥ 1.0 decrease in EDSS (if EDSS at entry is ≤5.5), ≥20% increase in T25FW, or ≥20% increase in 9HPT in either dominant or non-dominant hand. Assessments were made at baseline and month 13. The number of patients who improved in any of the 3 composite measures in month 13 compared to baseline is reported.
Secondary Outcomes
- Change in Multiple Sclerosis Functional Composite (MSFC) Z-Score From Baseline(Baseline and 13 months)
- Change in EDSS From Baseline(Baseline and 13 months)
- Percent Change in T25FW (Timed 25 Foot Walk) From Baseline(Baseline and 13 months)
- Percent Change in 6MWT (6 Minute Walk Test) From Baseline(Baseline and 13 months)
- Percent Change in 9HPT-D (9 Hole Peg Test in Dominant Hand) From Baseline(Baseline and 13 months)
- Percent Change in 9HPT-ND (9 Hole Peg Test in Non-Dominant Hand) From Baseline(Baseline and 13 months)
- Change in MSWS-12 (12 Item MS Walking Scale) Score From Baseline(Baseline and 13 months)
- Change in PASAT (Paced Auditory Serial Addition Test) Score From Baseline(Baseline and 13 months)