Clinical Trials Logo

Clinical Trial Summary

STUDY OBJECTIVES:

Primary Objective: Assessment of treatment safety based on incidence of any treatment emergent/treatment associated adverse events prior to discharge and at 1, 3, 6 and 12 months post treatment.

Secondary objective: Assessment of efficacy at baseline, prior to discharge, 1 month, 3 months, 6 months and 12 months after treatment based on the following: EDSS and 29-item Multiple Sclerosis Impact Scale (MSIS-29), MS Functional Composite (MSFC) consisting of (1) Timed 25-Foot Walk, (2) 9 Hole Peg Test, and (3) Paced Auditory Serial Addition Test and gadolinium-enhanced magnetic resonance imaging (MRI)


Clinical Trial Description

STUDY TREATMENT:

Investigational therapy product: Wharton Jelly derived allogeneic MSCs.

Method of administration and dose: Super selective intravenous administration of 50 million Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSC) and intrathecal administration of UC-MSCs in dose of 100 million along with liberation therapy (when associated with CCSVI).

SAFETY AND EFFICACY EVALUATION:

The proposed study will assess safety and primary and secondary efficacy endpoints after super selective intravenous and intrathecal administration of allogeneic umbilical cord mesenchymal stem cells (UC-MSC) in 69 patients with Relapsing Remitting Multiple Sclerosis.

Safety Evaluation:

Assessment of treatment safety based on incidence of any treatment emergent/treatment associated adverse events prior to discharge and at 1, 3, 6 and 12 months post treatment.

Efficacy evaluation:

Clinical evaluations, including EDSS and 29-item Multiple Sclerosis Impact Scale (MSIS-29) will be performed at baseline before stem cell mobilization, prior to discharge at 1, 3, 6 and 12 months after stem cell therapy.

The MS Functional Composite (MSFC) consists of the (a) Timed 25-Foot Walk, (b) 9 Hole Peg Test, and (c) Paced Auditory Serial Addition Test will be performed at baseline before stem cell mobilization and at 12 months after stem cell therapy.

Gadolinium enhanced MRI scans of the brain will be performed at baseline before therapy and then 12 months after stem cell therapy. Follow-up scans will be performed on the same type of scanner used at baseline. Scans will be analyzed centrally. The 'baseline MRI scan' will be the reference for brain volume changes.

DATA COLLECTION AND STATISTICAL ANALYSIS:

Descriptive analyses of the adverse events will be performed. Proportion of adverse events at each visit will be calculated using frequency distribution. The frequency, severity, timing and the potential relationship to the intervention will be assessed in order to characterize the safety of the intervention.

The probability of overall event-free survival (as well as progression-free, relapse-free, or MRI event-free survival) at baseline through 1 year will be calculated. The end point of progression is defined as increased Expanded Disability Status Scale (EDSS) score greater than 0.5 from baseline. Analyses will be conducted using Kaplan-Meier estimates with Wald-type 90% CIs based on Greenwood's formula for SE.

Descriptive analyses of all primary and secondary efficacy endpoints will be performed using descriptive statistics. Proportion of patients with clinically significant change in this efficacy measurement scales (EDSS, MSIS, MSFC, MSFC-25 foot walking test, MSFC-Nine Hole Peg Test, MSFC-Paced Auditory Serial Addition Test) and change in gadolinium enhancing lesions, new T2 lesions from previous visit will be presented as a proportion.

The percentage of change in brain volume will be calculated from screening and analyzed by end point status at month 12 with an exact Wilcoxon rank sum test using mean scores when the results are identical.The null hypothesis tests whether the median percentage of change in brain volume among participants who met the endpoint by month 12 is equal to the median of those who have not met the end point by month 12.

Other primary and secondary efficacy endpoints (EDSS, MSIS, MSFC, MSFC-25 foot walking test, MSFC-Nine Hole Peg Test, MSFC-Paced Auditory Serial Addition Test) will be analyzed using a Wilcoxon signed rank test. Change from baseline outcomes for all the endpoints will be calculated for each patient who underwent stem cell transplant as the post transplant value minus the baseline value. The null hypothesis tests whether the median difference from baseline measurement in the values at the month 1, month 3, month 6 and month 12 visits was significantly different from zero,with baseline measurement defined as the screening assessment for the percentage of change in brain volume and the baseline visit for all other end points.

To calculate MSFC, results from each of the 3 components will be transformed into a z score and averaged to yield a composite for each patient at each timepoint. The z scores that compose the MSFC score will be calculated using the reference population from the National Multiple Sclerosis Society Task Force database. ;


Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT02418325
Study type Interventional
Source Genesis Limited
Contact
Status Terminated
Phase Phase 1/Phase 2
Start date February 2015
Completion date February 2017

See also
  Status Clinical Trial Phase
Completed NCT02861014 - A Study of Ocrelizumab in Participants With Relapsing Remitting Multiple Sclerosis (RRMS) Who Have Had a Suboptimal Response to an Adequate Course of Disease-Modifying Treatment (DMT) Phase 3
Terminated NCT01435993 - Multiple Doses of Anti-NOGO A in Relapsing Forms of Multiple Sclerosis Phase 1
Recruiting NCT05964829 - Impact of the Cionic Neural Sleeve on Mobility in Multiple Sclerosis N/A
Completed NCT03653585 - Cortical Lesions in Patients With Multiple Sclerosis
Completed NCT02410200 - Study of the Effect of BG00012 on MRI Lesions and Pharmacokinetics in Pediatric Subjects With RRMS Phase 2
Completed NCT03975413 - Fecal Microbiota Transplantation (FMT) in Multiple Sclerosis
Completed NCT05080270 - Feasibility Study of Tolerogenic Fibroblasts in Patients With Refractory Multiple Sclerosis Early Phase 1
Completed NCT01116427 - A Cooperative Clinical Study of Abatacept in Multiple Sclerosis Phase 2
Completed NCT01108887 - An Observational Study for the Assessment of Adherence, Effectiveness and Convenience of Rebif® Treatment in Relapsing Multiple Sclerosis Patients Using RebiSmartâ„¢. N/A
Completed NCT01141751 - An Observational Study Comparing Multiple Sclerosis International Quality of Life Questionnaire (MusiQoL) and Multiple Sclerosis Quality of Life-54 Instrument (MSQOL-54) in Relapsing Multiple Sclerosis (RMS) Patients on Long-term Rebif® Therapy N/A
Completed NCT00097331 - Three Months Treatment With SB683699 In Patients With Relapsing Multiple Sclerosis Phase 2
Completed NCT01909492 - Measurement of Relaxin Peptide in Multiple Sclerosis (MS)
Completed NCT04121221 - A Study to Asses Efficacy, Safety and Tolerability of Monthly Long-acting IM Injection of GA Depot in Subjects With RMS Phase 3
Not yet recruiting NCT05290688 - Cellular microRNA Signatures in Multiple Sclerosis N/A
Withdrawn NCT04880577 - Tenofovir Alafenamide for Treatment of Symptoms and Neuroprotection in Relapsing Remitting Multiple Sclerosis Phase 2
Completed NCT04528121 - Effect of CoDuSe Balance Training and Step Square Exercises on Risk of Fall in Multiple Sclerosis N/A
Recruiting NCT04002934 - Bazedoxifene Acetate as a Remyelinating Agent in Multiple Sclerosis Phase 2
Recruiting NCT05019248 - Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine
Completed NCT04580381 - Real World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort
Completed NCT00071838 - Zenapax (Daclizumab) to Treat Relapsing Remitting Multiple Sclerosis Phase 2