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Establish Tolerance In MS With Peptide-Coupled, Peripheral Blood Mononuclear Cells (ETIMS)

Primary Purpose

Multiple Sclerosis, Relapsing-Remitting

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
ETIMS
Sponsored by
Universitätsklinikum Hamburg-Eppendorf
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis, Relapsing-Remitting

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Between the ages of 18 and 55 years.
  2. Patients with relapsing-remitting (Phase I/II) or secondary progressive MS (Phase I) according to published criteria
  3. EDSS score between 1 and 5.5.
  4. Patients are off-treatment for standard therapies (interferon-beta, glatiramer acetate, natalizumab, mitoxantrone)
  5. Patients are able to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care.
  6. Disease duration ≤ 5 years (Only Phase II)

Exclusion Criteria:

  1. Diagnosis of secondary-progressive (Phase II) or primary-progressive MS, as defined by published diagnostic criteria.
  2. Abnormal screening/baseline blood tests exceeding any of the limits defined
  3. Pregnant or breast-feeding female.
  4. History or signs of immunodeficiency.
  5. Concurrent clinically significant (as determined by the investigators) cardiac, immunological, pulmonary, neurological, renal or other major disease.
  6. Splenectomy
  7. History of HIV or positive HIV antibody testing
  8. Serology indicating active Hepatitis B or C infection.
  9. Patients with cognitive impairments who are unable to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm 8

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    ETIMS 1x10^3

    ETIMS 1x10^5

    ETIMS 1x10^7

    ETIMS 1x10^8

    ETIMS 5x10^8

    ETIMS 1x10^9

    ETIMS 2.5x10^9

    ETIMS 3x10^9

    Arm Description

    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 1x10^3 cells.

    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 1x10^5 cells.

    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 1x10^7 cells.

    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 1x10^8 cells.

    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 5x10^8 cells.

    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 1x10^9 cells.

    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 2.5x10^9 cells.

    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 3x10^9 cells.

    Outcomes

    Primary Outcome Measures

    Number of Participants With Adverse Events as a Measure of Safety and Tolerability
    Number of Adverse Events

    Secondary Outcome Measures

    Full Information

    First Posted
    August 8, 2011
    Last Updated
    April 8, 2015
    Sponsor
    Universitätsklinikum Hamburg-Eppendorf
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01414634
    Brief Title
    Establish Tolerance In MS With Peptide-Coupled, Peripheral Blood Mononuclear Cells
    Acronym
    ETIMS
    Official Title
    Establish Tolerance in Multiple Sclerosis With Peptide-coupled, Peripheral Blood Mononuclear Cells - A MRI-controlled, Single Center, Phase I Trial in Relapsing-remitting MS Patients
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    February 2010 (undefined)
    Primary Completion Date
    October 2012 (Actual)
    Study Completion Date
    October 2012 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Universitätsklinikum Hamburg-Eppendorf

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Open-label, single center, phase I clinical trial to assess the safety, tolerability and preliminary efficacy and in vivo mechanisms of action of i.v. administration of autologous peripheral blood mononuclear cell (PBMC) chemically coupled with a cocktail containing seven immunodominant myelin peptides to which T cell responses are demonstrable in early RR MS patients.
    Detailed Description
    Open-label, single center, phase I dose-escalation study to assess the safety, tolerability and preliminary efficacy and in vivo mechanisms of action of a single infusion of autologous peripheral blood mononuclear cells chemically coupled with seven myelin peptides (MOG1-20, MOG35-55, MBP13-32, MBP83-99, MBP111-129, MBP146-170, and PLP139-154) in Multiple Sclerosis patients who were off-treatment for standard therapies. Neurological, magnetic resonance imaging, laboratory, and immunological examinations were performed to assess the safety, tolerability, and in vivo mechanisms of action of this regimen.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Multiple Sclerosis, Relapsing-Remitting

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    9 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    ETIMS 1x10^3
    Arm Type
    Experimental
    Arm Description
    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 1x10^3 cells.
    Arm Title
    ETIMS 1x10^5
    Arm Type
    Experimental
    Arm Description
    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 1x10^5 cells.
    Arm Title
    ETIMS 1x10^7
    Arm Type
    Experimental
    Arm Description
    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 1x10^7 cells.
    Arm Title
    ETIMS 1x10^8
    Arm Type
    Experimental
    Arm Description
    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 1x10^8 cells.
    Arm Title
    ETIMS 5x10^8
    Arm Type
    Experimental
    Arm Description
    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 5x10^8 cells.
    Arm Title
    ETIMS 1x10^9
    Arm Type
    Experimental
    Arm Description
    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 1x10^9 cells.
    Arm Title
    ETIMS 2.5x10^9
    Arm Type
    Experimental
    Arm Description
    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 2.5x10^9 cells.
    Arm Title
    ETIMS 3x10^9
    Arm Type
    Experimental
    Arm Description
    The drug product consists of autologous peripheral blood mononuclear cells that have been chemically coupled with seven myelin peptides and resuspended in autologous plasma. This patient receives 3x10^9 cells.
    Intervention Type
    Biological
    Intervention Name(s)
    ETIMS
    Intervention Description
    injection of peptide-coupled PBMC by i.v. infusion
    Primary Outcome Measure Information:
    Title
    Number of Participants With Adverse Events as a Measure of Safety and Tolerability
    Time Frame
    12 months
    Title
    Number of Adverse Events
    Time Frame
    3 months after treatment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Between the ages of 18 and 55 years. Patients with relapsing-remitting (Phase I/II) or secondary progressive MS (Phase I) according to published criteria EDSS score between 1 and 5.5. Patients are off-treatment for standard therapies (interferon-beta, glatiramer acetate, natalizumab, mitoxantrone) Patients are able to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care. Disease duration ≤ 5 years (Only Phase II) Exclusion Criteria: Diagnosis of secondary-progressive (Phase II) or primary-progressive MS, as defined by published diagnostic criteria. Abnormal screening/baseline blood tests exceeding any of the limits defined Pregnant or breast-feeding female. History or signs of immunodeficiency. Concurrent clinically significant (as determined by the investigators) cardiac, immunological, pulmonary, neurological, renal or other major disease. Splenectomy History of HIV or positive HIV antibody testing Serology indicating active Hepatitis B or C infection. Patients with cognitive impairments who are unable to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Christoph Heesen, MD
    Organizational Affiliation
    Department of Neurology, University Clinic Eppendorf (UKE)
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    23740901
    Citation
    Lutterotti A, Yousef S, Sputtek A, Sturner KH, Stellmann JP, Breiden P, Reinhardt S, Schulze C, Bester M, Heesen C, Schippling S, Miller SD, Sospedra M, Martin R. Antigen-specific tolerance by autologous myelin peptide-coupled cells: a phase 1 trial in multiple sclerosis. Sci Transl Med. 2013 Jun 5;5(188):188ra75. doi: 10.1126/scitranslmed.3006168.
    Results Reference
    result

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    Establish Tolerance In MS With Peptide-Coupled, Peripheral Blood Mononuclear Cells

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