Intrathecal Administration of Autologous Mesenchymal Stem Cell-derived Neural Progenitors (MSC-NP) in Progressive Multiple Sclerosis

NCT03355365 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: TISCHMS-MSCNP-002
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Keywords

Mesenchymal Stem Cells; Neural Progenitors; Autologous; Bone Marrow; Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Expanded Disability Status Scale (EDSS) Plus

  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.

  Baseline and 13 months

Secondary Outcomes (8)

• 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

Study Arms (2)

Intrathecal MSC-NP injection

EXPERIMENTAL

Patients will receive six autologous stem cell injections through spinal taps every 2 months over a year.

Biological: Intrathecal MSC-NP injection

Intrathecal saline injection

PLACEBO COMPARATOR

Patients will receive six placebo injections through spinal taps every 2 months over a year.

Other: Intrathecal saline injection

Interventions

Intrathecal MSC-NP injection BIOLOGICAL

MSC-NPs represent a neural subpopulation of MSCs from bone marrow with reduced pluripotency and minimized risk of ectopic differentiation, thus are likely to be more suitable for CNS delivery. Importantly, characterization of MSC-NPs demonstrated their immunoregulatory and trophic properties, and MSC-NPs derived from MS and non-MS patients alike were therapeutically viable.

Intrathecal MSC-NP injection

Intrathecal saline injection OTHER

Placebo

Intrathecal saline injection

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Any patients with a history of or with active malignancy
• Use of steroids within three months of the study start date, as this would suggest an active disease state
• History of cirrhosis due to increased risk of central nervous system (CNS) infection
• Significantly uncontrolled hypertension because of increased risk for stroke or CNS hemorrhage.
• Patients with active thyroid disease resulting in hyperthyroidism or hypothyroidism (Only well controlled patients with labs in the normal range will be included) because of hormone influence on cell growth

Sponsors & Collaborators

• Tisch Multiple Sclerosis Research Center of New York: lead

Study Sites (1)

Tisch MS Research Center of New York

New York, New York, 10019, United States

Location

Related Publications (2)

• Harris VK, Stark J, Vyshkina T, Blackshear L, Joo G, Stefanova V, Sara G, Sadiq SA. Phase I Trial of Intrathecal Mesenchymal Stem Cell-derived Neural Progenitors in Progressive Multiple Sclerosis. EBioMedicine. 2018 Mar;29:23-30. doi: 10.1016/j.ebiom.2018.02.002. Epub 2018 Feb 3.

  PMID: 29449193 BACKGROUND

• Harris VK, Stark J, Williams A, Roche M, Malin M, Kumar A, Carlson AL, Kizilbash C, Wollowitz J, Andy C, Gerber LM, Sadiq SA. Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: results from a phase II, randomized, placebo-controlled clinical trial. Stem Cell Res Ther. 2024 May 23;15(1):151. doi: 10.1186/s13287-024-03765-6.

  PMID: 38783390 RESULT

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Saud Sadiq
• Organization: Tisch MS Research Center of New York

ssadiq@tischms.org

212-265-8070

Study Officials

• Saud A Sadiq, MD, FAAN

  Tisch MS Research Center of New York

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Compassionate crossover design

Study Record Dates

• First Submitted: November 14, 2017
• First Posted: November 28, 2017
• Study Start: September 21, 2018
• Primary Completion: February 9, 2023
• Study Completion: April 17, 2023
• Last Updated: June 11, 2025
• Results First Posted: June 11, 2025

Record last verified: 2025-05

Locations

US (1)