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A Study of Allogeneic Human UC-MSC and Liberation Therapy (When Associated With CCSVI) in Patients With RRMS

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ClinicalTrials.gov Identifier: NCT02587715
Recruitment Status : Unknown
Verified October 2015 by Novo Cellular Medicine Institute LLP.
Recruitment status was:  Recruiting
First Posted : October 27, 2015
Last Update Posted : October 28, 2015
Sponsor:
Information provided by (Responsible Party):
Novo Cellular Medicine Institute LLP

Tracking Information
First Submitted Date  ICMJE October 26, 2015
First Posted Date  ICMJE October 27, 2015
Last Update Posted Date October 28, 2015
Study Start Date  ICMJE February 2015
Estimated Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 27, 2015)
Proportion of patients with clinical improvement in EDSS score compared to baseline [ Time Frame: Up to 12 months ]
Proportion of patients with clinical improvement in EDSS score compared to baseline. Clinical improvement is defined as decrease in Expanded Disability Status Scale (EDSS) score greater than 0.5 from baseline.
Original Primary Outcome Measures  ICMJE
 (submitted: October 26, 2015)
  • Proportion of patients with clinical improvement in EDSS score compared to baseline [ Time Frame: Up to 12 months ]
  • Proportion of patients with clinical improvement in EDSS score compared to baseline [ Time Frame: up to 12 months ]
    Clinical improvement is defined as decrease in Expanded Disability Status Scale (EDSS) score greater than 0.5 from baseline.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2015)
  • Proportion of patients with a change in either gadolinium enhancing or new T2-weighted lesions on brain MRI [ Time Frame: 12 months ]
  • Proportion of patients with reduction in T2 lesion volume on brain MRI [ Time Frame: 12 months ]
  • Proportion of patients with reduction in brain volume on MRI [ Time Frame: 12 months ]
  • Proportion of patients with clinical improvement in EDSS score compared to baseline [ Time Frame: 3 months and 6 months ]
  • Proportion of patients with clinical improvement in MSIS score compared to baseline [ Time Frame: 3 months, 6 months and 12 months ]
  • Proportion of patients with clinical improvement in MSFC score compared to baseline [ Time Frame: 3 months, 6 months and 12 months ]
  • Proportion of patients with a change in mobility and leg function as measured by the 25 foot walking test [ Time Frame: 12 months ]
  • Proportion of patients with a change in upper extremity function as measured by the Nine Hole Peg Test [ Time Frame: 12 months ]
  • Proportion of patients with a change in cognitive function as measured by the Paced Auditory Serial Addition Test (PASAT) [ Time Frame: 12 months ]
  • Proportion of patients with reduced number of relapses or freedom from progression of disease [ Time Frame: 3 months, 6 months and 12 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Allogeneic Human UC-MSC and Liberation Therapy (When Associated With CCSVI) in Patients With RRMS
Official Title  ICMJE An Open-label, Non-randomized, Phase I/II Study of Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSC) and Liberation Therapy (When Associated With Chronic Cerebrovascular Venous Insufficiency) in Patients With Relapsing Remitting Multiple Sclerosis (RRMS)
Brief 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)

Detailed 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis, Relapsing-Remitting
Intervention  ICMJE
  • Biological: Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells
    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)
  • Other: Liberation therapy
Study Arms  ICMJE Experimental: AllogeneicHumanUmbilicalCordTissue-DerivedMesenchymalStemCells
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)
Interventions:
  • Biological: Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells
  • Other: Liberation therapy
Publications *

*   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 Unknown status
Estimated Enrollment  ICMJE
 (submitted: October 26, 2015)
69
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2017
Estimated Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main inclusion criteria: Males and Females between age 18 and 60 years with confirmed diagnosis of Relapsing Remitting Multiple Sclerosis made by a neurology expert/MS expert with lesions demonstrated on brain MRI that are consistent with MS and having an EDSS (Kurtzke Expanded Disability Status Scale) score between 3.5 & 6

Inclusion Criteria:

  • Males and Females between age 18 and 60 years
  • Diagnosis of Relapsing Remitting Multiple Sclerosis made by a neurology expert/MS expert with lesions demonstrated on brain MRI that are consistent with MS
  • Duration of disease: >5 years
  • Having an EDSS (Kurtzke Expanded Disability Status Scale) score between 3.5 & 6
  • History of 2 or more relapses within last 2 years with increase in EDSS scale of > 0.5 sustained for > 4 weeks
  • Failure to respond or intolerance to the currently available Multiple Sclerosis (MS) immunomodulatory treatments): the lack of response to these treatments will be determined/defined by history of 2 or more relapses within last 2 years with increase in EDSS scale of > 0.5 sustained for > 4 weeks
  • Must have proof of health insurance in country of residence

Exclusion Criteria:

  • Primary progressive, secondary progressive or progressive relapsing MS as defined by Lublin and Reingold, 1996. These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Subjects with these conditions may also have superimposed relapses but are distinguished from relapsing remitting subjects by the lack of clinically stable periods of clinical improvement.
  • Unable to perform Timed 25-Foot Walk, 9 Hole Peg Test (HPT) (with both upper extremities) and Paced Auditory Serial Addition Test (PASAT 3)
  • Females who are pregnant or nursing or females of childbearing potential who are unwilling to maintain contraceptive therapy for the duration of the study
  • Life expectancy < 6 months due to concomitant illnesses
  • Exposure to any investigational drug or procedure within 1 month prior to study entry or enrolled in a concurrent study that may confound results of this study.
  • Active infectious disease: For patients who have tested positive, an expert will be consulted as to patient eligibility based on the patient's infectious status
  • Any illness which, in the Investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of the study results
  • Patients on chronic immunosuppressive transplant therapy
  • Patients with unstable cardiac status (unstable angina, attack of myocardial infarction within last 6 months, uncontrolled high blood pressure, hypotension, cardiomyopathy)
  • Cerebrovascular accident within 6 months prior to study entry
  • Patients with poorly controlled diabetes mellitus
  • Patients with renal insufficiency (Creatinine> 2.5) or failure
  • Known drug or alcohol dependence or any other factors which will interfere with the study conduct or interpretation of the results or who in the opinion of the investigator is not suitable to participate.
  • History of cancer (other than non-melanoma skin cancer or in-situ cervical cancer) in the last five years
  • Unwilling and/or not able to give written informed consent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Trinidad and Tobago
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02587715
Other Study ID Numbers  ICMJE PRT/NOVO/2015/001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novo Cellular Medicine Institute LLP
Study Sponsor  ICMJE Novo Cellular Medicine Institute LLP
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dr. Bill Brashier, M.D. Novo Cellular Medicine Institute LLP
PRS Account Novo Cellular Medicine Institute LLP
Verification Date October 2015

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