Clinical trial NCT01414634: Establish Tolerance In MS With Peptide-Coupled, Peripheral Blood Mononuclear Cells
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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
First posted: 2011-08-11
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: 12 months
measure: Number of Adverse Events
timeFrame: 3 months after treatment
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Department of Neurology, University Clinic Eppendorf (UKE)
name: Christoph Heesen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.