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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Biological: ETIMS

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: ETIMS; injection of peptide-coupled PBMC by i.v. infusion
Experimental: 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.	Biological: ETIMS; injection of peptide-coupled PBMC by i.v. infusion
Experimental: 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.	Biological: ETIMS; injection of peptide-coupled PBMC by i.v. infusion
Experimental: 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.	Biological: ETIMS; injection of peptide-coupled PBMC by i.v. infusion
Experimental: 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.	Biological: ETIMS; injection of peptide-coupled PBMC by i.v. infusion
Experimental: 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.	Biological: ETIMS; injection of peptide-coupled PBMC by i.v. infusion
Experimental: 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.	Biological: ETIMS; injection of peptide-coupled PBMC by i.v. infusion
Experimental: 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.	Biological: ETIMS; injection of peptide-coupled PBMC by i.v. infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Investigators: Principal Investigator: Christoph Heesen, MD, Department of Neurology, University Clinic Eppendorf (UKE)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: August 8, 2011
• First Submitted That Met QC Criteria: August 10, 2011
• First Posted (Estimate): August 11, 2011

Study Record Updates

• Last Update Posted (Estimate): May 4, 2015
• Last Update Submitted That Met QC Criteria: April 8, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: inims-oo1