Multiple Sclerosis, Relapsing-Remitting
Conditions
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.
Interventions
BIOLOGICALETIMS
injection of peptide-coupled PBMC by i.v. infusion
Sponsors
Universitätsklinikum Hamburg-Eppendorf
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ETIMS Dose Escalation ETIMS: injection of peptide-coupled PBMC by i.v. infusion | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | ETIMS Dose Escalation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 42 years |
| Region of Enrollment Germany | 9 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 2 / 2 | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 2 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Number of Adverse Events
Time frame: 3 months after treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETIMS Dose Escalation | Number of Adverse Events | 14 Number of AE |
Primary
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: 12 months