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

Universitätsklinikum Hamburg-Eppendorf

Status and phase: Completed; Phase 2; Phase 1

Conditions: Multiple Sclerosis, Relapsing-Remitting

Treatments: Biological: ETIMS

Study type: Interventional

Funder types: Other

Identifiers

NCT01414634

inims-oo1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 9 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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9 participants in 8 patient groups

ETIMS 1x10^3

Experimental group

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.

Treatment:

Biological: ETIMS

ETIMS 1x10^5

Experimental group

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.

Treatment:

Biological: ETIMS

ETIMS 1x10^7

Experimental group

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.

Treatment:

Biological: ETIMS

ETIMS 1x10^8

Experimental group

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.

Treatment:

Biological: ETIMS

ETIMS 5x10^8

Experimental group

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.

Treatment:

Biological: ETIMS

ETIMS 1x10^9

Experimental group

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.

Treatment:

Biological: ETIMS

ETIMS 2.5x10^9

Experimental group

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.

Treatment:

Biological: ETIMS

ETIMS 3x10^9

Experimental group

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.

Treatment:

Biological: ETIMS