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

NCT ID: NCT01414634

Last Updated: 2015-05-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2012-10-31

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.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ETIMS 1x10^3

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.

Group Type: EXPERIMENTAL

ETIMS

Intervention Type: BIOLOGICAL

injection of peptide-coupled PBMC by i.v. infusion

ETIMS 1x10^5

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.

Group Type: EXPERIMENTAL

ETIMS

Intervention Type: BIOLOGICAL

injection of peptide-coupled PBMC by i.v. infusion

ETIMS 1x10^7

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.

Group Type: EXPERIMENTAL

ETIMS

Intervention Type: BIOLOGICAL

injection of peptide-coupled PBMC by i.v. infusion

ETIMS 1x10^8

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.

Group Type: EXPERIMENTAL

ETIMS

Intervention Type: BIOLOGICAL

injection of peptide-coupled PBMC by i.v. infusion

ETIMS 5x10^8

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.

Group Type: EXPERIMENTAL

ETIMS

Intervention Type: BIOLOGICAL

injection of peptide-coupled PBMC by i.v. infusion

ETIMS 1x10^9

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.

Group Type: EXPERIMENTAL

ETIMS

Intervention Type: BIOLOGICAL

injection of peptide-coupled PBMC by i.v. infusion

ETIMS 2.5x10^9

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.

Group Type: EXPERIMENTAL

ETIMS

Intervention Type: BIOLOGICAL

injection of peptide-coupled PBMC by i.v. infusion

ETIMS 3x10^9

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.

Group Type: EXPERIMENTAL

ETIMS

Intervention Type: BIOLOGICAL

injection of peptide-coupled PBMC by i.v. infusion

Interventions

ETIMS

injection of peptide-coupled PBMC by i.v. infusion

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitätsklinikum Hamburg-Eppendorf

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christoph Heesen, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, University Clinic Eppendorf (UKE)

References

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.

Reference Type: RESULT

PMID: 23740901 (View on PubMed)

Other Identifiers

inims-oo1

Identifier Type: -

Identifier Source: org_study_id