A Trial for Evaluating Both Safety and Preliminary Efficacy of a Single Infusion of Stimulated Autologous CD4+T Cells in Patients With Relapsing- Remitting Multiple Sclerosis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the safety and the preliminary efficacy of a single infusion of stimulated autologous CD4+ T cells in patients with Relapsing-Remitting Multiple Sclerosis. The study duration for the patients (from start of baseline to end of follow-up) is 270 days.

Official Title
-----------------
A Clinical Trial to Document Safety and Radiological Disease Activity in Patients With Relapsing-remitting Multiple Sclerosis Treated With Autologous CD4+ T Cells, Stimulated and Expanded ex Vivo by a Myelin Oligodendrocyte Glycoprotein Peptide Modified by the Introduction of a Thioreductase Motif Into the Flanking Residues of the Cell Epitope - A First-in-human Trial (SCLEROLYM TRIAL)

Conditions
-----------------
Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
-----------------
* Biological: Autologous CD4+T cells stimulated and expanded ex vivo by a MOG peptide modified by the introduction of a thioreductase motif into the flanking residues of the T cell epitope


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females 18 to 60 years of age Patients closely followed up for at least one year prior to inclusion (i.e. prior to the start of the baseline phase) if the diagnosis of the disease was made more than one year ago, to ensure that all possible episodes of clinical relapses which occurred during this interval of time were recorded and documented Multiple sclerosis that meets the 2010 revised McDonald criteria Relapsing/remitting type of multiple sclerosis (which includes clinically isolated syndromes if imaging shows brain lesions disseminated in space and time) Radiologically active disease defined by at least one gadolinium-enhancing lesion on a T1-weighted magnetic resonance imaging brain scan performed recently (i.e. within 3 months prior to inclusion) Disease-modifying drug naïve patients or patients with stable and adequately taken disease-modifying therapy (interferon β-1, glatiramer acetate, or dimethyl fumarate) for at least six months before inclusion (NOTE: Other disease modifying drugs might be added at a later date, depending on the results of current investigations) EDSS Score <= 5.5 Positive predictive test in vitro for patient's CD4+ cell reactivity to immunogenic peptide Women of childbearing age must have a negative pregnancy test and must use adequate contraception during the treatment and follow-up phase of the study (three pregnancy tests will be required prior to and during the study: (1) during the screening phase, (2) about one week prior to leukapheresis, and (3) about one week prior to re-infusion of autologous cells) Fully informed written consent obtained Exclusion Criteria: Positive only for the HLA DRB1*0101, DRB1*0102, DRB1*0401, DRB1*0426 alleles or for the combination of the previous alleles. Evidence of clinical relapse and use of intravenous or oral corticosteroids within 30 days prior to inclusion Therapeutic escalation anticipated (including change of disease modifying drug), other than the cell-based immunotherapy of this study, within the next six months Significant coexisting systemic disease including renal insufficiency Positive serology for hepatitis B and C, AIDS and syphilis Participation in another interventional clinical study, currently or during the past three months

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMP<br> | Biological: Autologous CD4+T cells stimulated and expanded ex vivo by a MOG peptide modified by the introduction of a thioreductase motif into the flanking residues of the T cell epitope<br>* 1 administration comprising 5 - 50 millions of cells<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the cell based immunotherapy (Adverse events) | Adverse events | 6 months | 
| Safety of the cell based immunotherapy (Vital signs) | Vital signs | 6 hours | 
| Safety of the cell based immunotherapy (Physical examination) | Physical examination | 6 months | 
| Safety of the cell based immunotherapy (Laboratory parameters) | Laboratory parameters | 6 months | 
| Safety of the cell based immunotherapy (MRI) | MRI | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI derived parameters | Cumulative number and mean number per scan of active inflammatory lesions Cumulative number and mean number per scan of new lesions Cumulative number and mean number per scan of enlarged lesions | 3 months before the day of administration of the investigational medicinal product, the day of administration, 45, 90, 135 and 180 days after the administration | 
| Expanded Disability Status Scale (EDSS) |  | 3 months before the day of administration of the investigational medicinal product, the day of administration, 45, 90, 135 and 180 days after the administration | 
| Clinical relapses |  | 3 months before the day of administration of the investigational medicinal product, the day of administration, 45, 90, 135 and 180 days after the administration | 
| Circulating MOG specific cytolytic CD4+ cells |  | 3 months before the day of administration of the investigational medicinal product, the day of administration, 45, 90, 135 and 180 days after the administration | 
| Circulating anti-MOG antibodies |  | 3 months before the day of administration of the investigational medicinal product, the day of administration, 45, 90, 135 and 180 days after the administration |