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

Sponsor

Tisch Multiple Sclerosis Research Center of New York (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03355365

Collaborator

(none)

Enrollment

Location

Arms

61.3

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Biological: Intrathecal MSC-NP injection Other: Intrathecal saline injection	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Autologous, Bone Marrow-Derived Mesenchymal Stem Cell-Derived Neural Progenitor Cells (MSC-NP), Expanded Ex Vivo; Administered Intrathecally

Actual Study Start Date :

Sep 21, 2018

Anticipated Primary Completion Date :

May 1, 2022

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intrathecal MSC-NP injection Patients will receive six autologous stem cell injections through spinal taps every 2 months over a year.	Biological: Intrathecal MSC-NP injection 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.
Placebo Comparator: Intrathecal saline injection Patients will receive six placebo injections through spinal taps every 2 months over a year.	Other: Intrathecal saline injection Placebo

Arm

Intervention/Treatment

Experimental: Intrathecal MSC-NP injection

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

Biological: Intrathecal MSC-NP injection

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.

Placebo Comparator: Intrathecal saline injection

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

Other: Intrathecal saline injection

Placebo

Outcome Measures

Primary Outcome Measures

Expanded Disability Status Scale (EDSS) Plus [Month 36 from first treatment or placebo]
Changes in disability assessed based on composite score of EDSS, timed 25-foot walk (T25FW), and nine hole peg test (9HPT) (EDSS-Plus). Improvement will be defined by at least one of the following three measures: ≥0.5 improvement in EDSS (if EDSS at entry is ≥ 6.0) or ≥ 1.0 improvement in EDSS (if EDSS at entry is ≤5.5), ≥20% improvement in T25FW, and ≥20% improvement in 9HPT in either dominant or non-dominant upper limb. Assessments will be made at baseline, Month 6, 13, 20, 27 & 36 in each group.

Secondary Outcome Measures

Multiple sclerosis functional composite (MSFC) [Month 36 from first treatment or placebo]
Changes in disability assessed by MSFC at baseline, Month 6, 13, 20, 27 & 36 in each group.
Bladder function [Month 27 from first treatment or placebo]
Degree of bladder dysfunction assessed by urodynamics testing at baseline, Month 13 and 27 in each group.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
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
History of central nervous system infection or immunodeficiency syndromes due to increased risk of CNS infection
Preexisting blood disease (such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia) due to invasive nature of bone-marrow aspiration
Previous or current history of a coagulation disorder
Any metal implant in the body, which is contraindicated for MRI studies
Patients with alcohol or other substance abuse problems that may affect stem cell growth; habitual drug (including marijuana and nicotine) abusers, will be excluded from the study
Other major disease that, in the opinion of the Principal Investigator, would preclude participation in the study
Patients with Hepatitis B (HBV), Hepatitis C (HCV), syphilis, HIV-1, or HIV-2.
Any evidence of significant cognitive dysfunction based on a screening history and physical examination because it would preclude giving a truly informed consent
Patients who are enrolled in another clinical trial for MS treatment or who have received any study drug/biologics within the last 6 months. Additionally, while in the trial, patients may not enroll in any other clinical trial for MS or any other condition.
Patients who are anticipated to have difficultly accessing the intrathecal space related to scoliosis, obesity, or any other relevant factors determined by the PI.