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

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ClinicalTrials.gov Identifier: NCT03355365
Recruitment Status : Recruiting
First Posted : November 28, 2017
Last Update Posted : May 31, 2019
Sponsor:
Information provided by (Responsible Party):
Tisch Multiple Sclerosis Research Center of New York

Tracking Information
First Submitted Date  ICMJE November 14, 2017
First Posted Date  ICMJE November 28, 2017
Last Update Posted Date May 31, 2019
Actual Study Start Date  ICMJE September 21, 2018
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2019)
Expanded Disability Status Scale (EDSS) Plus [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 21, 2017)
Efficacy: Expanded Disability Status Scale (EDSS) Plus composite score [ Time Frame: 27 months from first treatment or placebo ]
Changes in disability assessed based 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, ≥20% improvement in T25FW, and ≥20% improvement in 9HPT in either dominant or non-dominant upper limb. Scores will be compared individually between baseline and post-treatment. Assessments will be made at baseline and 3 months after the 6th treatment/placebo in each crossover group (month 0, 13, and 27).
Change History Complete list of historical versions of study NCT03355365 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2019)
  • Multiple sclerosis functional composite (MSFC) [ Time Frame: 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 [ Time Frame: Month 27 from first treatment or placebo ]
    Degree of bladder dysfunction assessed by urodynamics testing at baseline, Month 13 and 27 in each group.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2017)
  • Safety: incidence and severity of adverse events [ Time Frame: 27 months from first treatment or placebo ]
    Incidence and severity of adverse events in MSC-NP treatment group compared to placebo group
  • Efficacy: bladder function [ Time Frame: 27 months from first treatment or placebo ]
    Degree of bladder dysfunction assessed by urodynamics assessment at baseline and 3 months after the 6th treatment placebo in each crossover group (month 0, 13, and 27).
  • Efficacy: Multiple sclerosis functional composite (MSFC) [ Time Frame: 27 months from first treatment or placebo ]
    Changes in disability assessed by MSFC assessed at baseline and 3 months after the 6th treatment/placebo in each crossover group (month 0, 13, and 27).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intrathecal Administration of Autologous Mesenchymal Stem Cell-derived Neural Progenitors (MSC-NP) in Progressive Multiple Sclerosis
Official Title  ICMJE Autologous, Bone Marrow-Derived Mesenchymal Stem Cell-Derived Neural Progenitor Cells (MSC-NP), Expanded Ex Vivo; Administered Intrathecally
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE
  • 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.
  • Other: Intrathecal saline injection
    Placebo
Study Arms  ICMJE
  • Experimental: Intrathecal MSC-NP injection
    Patients will receive six autologous stem cell injections through spinal taps every 2 months over a year.
    Intervention: Biological: Intrathecal MSC-NP injection
  • Placebo Comparator: Intrathecal saline injection
    Patients will receive six placebo injections through spinal taps every 2 months over a year.
    Intervention: Other: Intrathecal saline injection
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 21, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2023
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Saud A Sadiq, MD, FAAN 212 265 8070 atahir@tischms.org
Contact: Alifiya Tahir, BDS, MPH 212 265 8070 atahir@tischms.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03355365
Other Study ID Numbers  ICMJE TISCHMS-MSCNP-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tisch Multiple Sclerosis Research Center of New York
Study Sponsor  ICMJE Tisch Multiple Sclerosis Research Center of New York
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Saud A Sadiq, MD, FAAN Tisch MS Research Center of New York
PRS Account Tisch Multiple Sclerosis Research Center of New York
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP