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    The EU Clinical Trials Register currently displays   38942   clinical trials with a EudraCT protocol, of which   6397   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2012-002357-35
    Sponsor's Protocol Code Number:CRO1959
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-07-26
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2012-002357-35
    A.3Full title of the trial
    Stem cells in Rapidly Evolving Active Multiple Sclerosis (STREAMS)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Bone marrow stem cells to treat multiple sclerosis
    A.3.2Name or abbreviated title of the trial where available
    Stem cells in Rapidly Evolving Active Multiple Sclerosis (STREAMS)
    A.4.1Sponsor's protocol code numberCRO1959
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01606215
    A.5.4Other Identifiers
    Name:Clinicaltrials.govNumber:NCT01606215
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorImperial College London
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportUK MS society
    B.4.2CountryUnited Kingdom
    B.4.1Name of organisation providing supportUK Stem Cell Foundation
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationImperial College London
    B.5.2Functional name of contact pointDr Paolo Muraro
    B.5.3 Address:
    B.5.3.1Street AddressCentre for Neuroscience, Division of Experimental Medicine Building 560/Burlington Danes Room E415
    B.5.3.2Town/ city160 Du Cane Road, London
    B.5.3.3Post codeW12 0NN
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02075946670
    B.5.5Fax number02075946548
    B.5.6E-mailp.muraro@imperial.ac.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAutologous Mesenchymal Cell Product
    D.3.4Pharmaceutical form Suspension for injection in cartridge
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.4EV Substance CodeAS4
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product Yes
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Yes
    D.3.11.3.5.1CAT classification and reference numberClassification: Somatic Cell Therapy by MHRA Reference: 2011/0752
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSuspension for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Multiple Sclerosis
    E.1.1.1Medical condition in easily understood language
    Multiple sclerosis
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    There are two co-primary objectives.

    The first is to assess the safety of intravenous therapy with autologous (derived from the individuals themselves) MSCs in MS patients.

    The second is to evaluate the activity of autologous MSCs in MS patients, quantified by the reduction in the number of new contrast-enhancing lesions on MRI scans over 24 weeks, the latter suggesting new inflammation.
    E.2.2Secondary objectives of the trial
    The secondary objectives of the study are to gather preliminary information about the efficacy of the experimental treatment in terms of combined MRI activity, MRI measures of remyelination (i.e. repair), clinical activity (incidence of relapses and disability progression in the MS patients), evaluating results of the Mantoux skin test (this is being used as a way of assessing the effect of the MSCs within the patient), and on immunological markers to be measured in blood and spinal fluid samples.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients with clinically and radiologically active multiple sclerosis as defined by:

    1. Diagnosis of MS:

    a. Relapsing remitting MS (RRMS): ≥1 moderate-severe relapse and ≥1 GEL in past 18 months or ≥1 moderate-severe relapse and ≥1 new T2 lesion in past 18 months.

    b. Secondary progressive MS (SPMS) with an increase of ≥1 EDSS point (if baseline EDSS ≤5) or 0.5 EDSS point (if baseline EDSS ≥5.5), in the previous 18 months and ≥1 GEL in past 18 months or ≥1 moderate-severe relapse and ≥1 new T2 lesion in past 18 months.

    c. Primary progressive MS (PPMS) patients with positive oligoclonal bands
    (OCBs) in the cerebrospinal fluid (CSF) and an increase of ≥1 EDSS point (if baseline EDSS is ≤5.0) or 0.5 EDSS point (if baseline EDSS is ≥5.5), or quantifiable, objective evidence of equivalent progression in the previous 18 months and ≥1 GEL in past 18 months or ≥1 new T2 lesion in past 18 months.

    2. Age 18 to 50 years.

    3. Disease duration 2 to 10 years from diagnosis (inclusive).

    4. EDSS 3.0 to 6.5 at screening evaluation.

    5. ≥1 GEL on MRI within 3 months prior to harvesting.

    6. Adequate culture of a subject’s MSCs and their release for clinical use.
    E.4Principal exclusion criteria
    1. RRMS without at least one severe relapse in the previous 18 months or without at least one GEL or one new T2 in the previous 18 months.
    2. SPMS without relapses and without new lesions (GEL or T2 positive) at MRI in the last 18 months.
    3. PPMS without positive CSF OCBs or without a GEL or new T2 lesion in the previous 18 months.
    4. No gadolinium enhancing lesion(s) in the 3 months prior to bone marrow harvesting.
    5. A previously ineligible patient who failed to meet the MRI requirements of the inclusion criteria will not be reviewed again even if further imaging, revealing ≥1 GEL, becomes available.
    6. Failure of BM sample to generate MSCs suitable for clinical use within a specified time frame (4 weeks).
    7. Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the last 3 months.
    8. Treatment with interferon-beta or glatiramer acetate within the last 1 month.
    9. Treatment with alemtuzumab (campath-1H) within the last 2 years.
    10. Prior treatment with total lymphoid irradiation and autologous or allogeneic hematopoietic stem cell transplantation.
    11. Participation in clinical trials of any experimental drugs in the 6 months before study entry.
    12. Corticosteroid treatment in the last 30 days.
    13. Presence of any active or chronic infection.
    14. Previous history of a malignancy other than basal cell carcinoma of the skin and carcinoma in situ that has been in remission for more than one year.
    15. Severely limited life expectancy by any other co-morbid illness.
    16. Abnormal blood counts, a history of myelodysplasia or other cytopenia.
    17. Known pregnancy, positive urine pregnancy test at screening or risk or pregnancy (this includes patients who are unwilling to practice active contraception during the duration of the study).
    18. Contraindication to MRI including but not limited to intracranial aneurysm clips (except Sugita), history of intra-orbital metal fragments that have not been removed by an MD (as confirmed by orbital X-Ray), pacemaker and non-MR compatible devices (e.g. heart valves, inner ear implants), history of claustrophobia or the inability of the subject to lie still on their back for a period of 1.5 hours in the MRI scanner.
    19. An estimated glomerular filtration rate (eGFR)< 60 mL/min/1.73m2 or history or presence of renal impairment (e.g. serum creatinine clearance less than 30ml/min).
    20. Inability to give written informed consent/comply with study procedures.
    21. Any significant organ dysfunction or co-morbidity that the Investigators consider would put the subject at unacceptable risk by participating in the study or that would interfere with the functional assessments.
    E.5 End points
    E.5.1Primary end point(s)
    There are two co-primary objectives:

    The first is to assess the safety of intravenous autologous MSCs in MS patients - hence the number, time-frame of occurrence and severity of adverse events in the MSC treatment group will be compared to the placebo group.

    The second is to evaluate the efficacy of autologous MSCs in MS patients, quantified by the reduction in the number of new contrast-enhancing lesions (GEL) on MRI scans over 24 weeks and the total number of GEL counted over months 1, 3 and 6 will be compared between treatment groups.

    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 0, 4, 12, 24, 28, 36 and 48 for MRI
    Safety will be evaluated at every visit throughout the 48 week study
    E.5.2Secondary end point(s)
    Secondary endpoints:
    • volume of GEL identified over months 1, 3 and 6 will be compared between treatment groups.
    • number of GEL counted over months 7, 9 and 12 (cross-over re-treatment) compared between treatment periods (placebo vs. active treatment) for each patient.
    • combined unique MRI activity (number of new or enlarging T2, or enhancing or re-enhancing lesions).
    • number of relapses in MSC treatment group vs. placebo group in the first 6 months and after cross-over re-treatment in the two groups (see below for the definition of a relapse).
    • time to sustained progression of disability (RRMS group) (see below for definition of sustained EDSS progression) and proportion of progression-free patients.
    • proportion of disease-free patients (i.e. patients without relapses) and progression of MRI activity in the two groups.
    • changes in the Multiple Sclerosis Functional Composite (MSFC) score in MSC treatment group compared to the placebo group.
    • effect of MSCs on the peripheral immune responses.
    • effect of MSCs on delayed type hypersensitivity (Type 1V hypersensitivity) reaction as measured by the Mantoux test
    E.5.2.1Timepoint(s) of evaluation of this end point
    Weeks 0, 4, 12, 24, 28, 36 and 48.
    The Mantoux test will be performed at weeks -8, 0 and 24 weeks and evaluated 48-72 hours thereafter.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 13
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state13
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Subjects will be continued to be monitored through the NHS service at Imperial Healthcare NHS Trust if they so wish and offered appropriate therapies in the future.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-10-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-09-25
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-05-23
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