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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
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* Biological: ETIMS


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ETIMS 1x10^3<br>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. | Biological: ETIMS<br>* injection of peptide-coupled PBMC by i.v. infusion<br>|
| Experimental: ETIMS 1x10^5<br>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. | Biological: ETIMS<br>* injection of peptide-coupled PBMC by i.v. infusion<br>|
| Experimental: ETIMS 1x10^7<br>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. | Biological: ETIMS<br>* injection of peptide-coupled PBMC by i.v. infusion<br>|
| Experimental: ETIMS 1x10^8<br>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. | Biological: ETIMS<br>* injection of peptide-coupled PBMC by i.v. infusion<br>|
| Experimental: ETIMS 5x10^8<br>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. | Biological: ETIMS<br>* injection of peptide-coupled PBMC by i.v. infusion<br>|
| Experimental: ETIMS 1x10^9<br>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. | Biological: ETIMS<br>* injection of peptide-coupled PBMC by i.v. infusion<br>|
| Experimental: ETIMS 2.5x10^9<br>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. | Biological: ETIMS<br>* injection of peptide-coupled PBMC by i.v. infusion<br>|
| Experimental: ETIMS 3x10^9<br>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. | Biological: ETIMS<br>* injection of peptide-coupled PBMC by i.v. infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability |  | 12 months | 
| Number of Adverse Events |  | 3 months after treatment |