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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ETIMS 1x10^3 | Experimental | 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. |
|
| ETIMS 1x10^5 | Experimental | 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. |
|
| ETIMS 1x10^7 | Experimental | 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. |
|
| ETIMS 1x10^8 | Experimental | 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. |
|
| ETIMS 5x10^8 | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ETIMS | Biological | injection of peptide-coupled PBMC by i.v. infusion |
|
| Measure | Description | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christoph Heesen, MD | Department of Neurology, University Clinic Eppendorf (UKE) | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23740901 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | ETIMS 1x10^3 | ETIMS: injection of peptide-coupled peripheral blood mononuclear cell (PBMC) by i.v. infusion |
| FG001 | ETIMS 1x10^5 | ETIMS: injection of peptide-coupled peripheral blood mononuclear cell (PBMC) by i.v. infusion |
| FG002 | ETIMS 1x10^7 | ETIMS: injection of peptide-coupled peripheral blood mononuclear cell (PBMC) by i.v. infusion |
| FG003 | ETIMS 1x10^8 | ETIMS: injection of peptide-coupled peripheral blood mononuclear cell (PBMC) by i.v. infusion |
| FG004 | ETIMS 5x10^8 | ETIMS: injection of peptide-coupled peripheral blood mononuclear cell (PBMC) by i.v. infusion |
| FG005 | ETIMS 1x10^9 | ETIMS: injection of peptide-coupled peripheral blood mononuclear cell (PBMC) by i.v. infusion |
| FG006 | ETIMS 2.5x10^9 | ETIMS: injection of peptide-coupled peripheral blood mononuclear cell (PBMC) by i.v. infusion |
| FG007 | ETIMS 3x10^9 | ETIMS: injection of peptide-coupled peripheral blood mononuclear cell (PBMC) by i.v. infusion |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ETIMS Dose Escalation | ETIMS: injection of peptide-coupled PBMC by i.v. infusion |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Not Posted | 12 months | |||||||||||||
| Primary | Number of Adverse Events | Posted | Number | Number of AE | 3 months after treatment |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ETIMS 1x10^3 | ETIMS: injection of peptide-coupled PBMC by i.v. infusion |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| diverticulitis of sigma | Gastrointestinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| metallic flavor during infusion of study drug | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Roland Martin | Neuroimmunology and MS Research, Department of Neurology, University Hospital Zürich, 8091 Zürich, Switzerland | 044 255 11 25 | roland.martin@usz.ch |
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| ID | Term |
|---|---|
| D020529 | Multiple Sclerosis, Relapsing-Remitting |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
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| ETIMS 1x10^9 | Experimental | 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. |
|
| ETIMS 2.5x10^9 | Experimental | 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. |
|
| ETIMS 3x10^9 | Experimental | 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. |
|
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | ETIMS Dose Escalation | ETIMS: injection of peptide-coupled PBMC by i.v. infusion |
|
|
| 1 |
| 1 |
| 1 |
| 1 |
| EG001 | ETIMS 1x10^5 | ETIMS: injection of peptide-coupled PBMC by i.v. infusion | 0 | 1 | 1 | 1 |
| EG002 | ETIMS 1x10^7 | ETIMS: injection of peptide-coupled PBMC by i.v. infusion | 0 | 1 | 1 | 1 |
| EG003 | ETIMS 1x10^8 | ETIMS: injection of peptide-coupled PBMC by i.v. infusion | 0 | 1 | 1 | 1 |
| EG004 | ETIMS 5x10^8 | ETIMS: injection of peptide-coupled PBMC by i.v. infusion | 0 | 1 | 1 | 1 |
| EG005 | ETIMS 1x10^9 | ETIMS: injection of peptide-coupled PBMC by i.v. infusion | 0 | 2 | 2 | 2 |
| EG006 | ETIMS 2.5x10^9 | ETIMS: injection of peptide-coupled PBMC by i.v. infusion | 0 | 1 | 0 | 1 |
| EG007 | ETIMS 3x10^9 | ETIMS: injection of peptide-coupled PBMC by i.v. infusion | 0 | 1 | 0 | 1 |
| Headache | Nervous system disorders | Systematic Assessment |
|
| Common cold | Infections and infestations | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Irritation of punctured vein | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Migraine | Nervous system disorders | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Vision disturbance | Nervous system disorders | Systematic Assessment |
|
| Dysaesthesia/pain in one hand | Nervous system disorders | Systematic Assessment |
|
| Gastric pain | Gastrointestinal disorders | Systematic Assessment |
|
| Syncope | Cardiac disorders | Systematic Assessment |
|
| Paravertebral dysaesthesia | Nervous system disorders | Systematic Assessment |
|
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| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |