The aim of this project is to assess properly the clinical efficacy of TolDec therapy by imaging, clinical and surrogate end-points related with the activity of the disease.
Our working hypothesis is to make a combination therapy with low-moderate efficacy immunomodulatory drugs with the aim of increasing efficacy without causing serious adverse effects such as those associated with the available high-efficacy therapies. Cellular therapies represent a highly specific treatment aimed to target selective "pathogenic" cells subsets. Tol-Dec loaded with immunogenic peptides interacts with Ag-specific T lymphocytes inducing regulatory T cells without affecting other cell subsets leading to a antinflammatory shift of immunological responses.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
45
The infusion of the cells / placebo will take place at the Hospital Clínic de Barcelona (weeks 0, 2 and 4).
The infusion of the cells / placebo will take place at the Hospital Clínic de Barcelona (weeks 0, 2 and 4).
Hospital Moisés Broggi
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Clínic de Barcelona
Barcelona, Spain
Hospital de Sant Pau
Barcelona, Spain
Changes from baseline in the number of CUA lesion (mean number of the sum at week 12, 18 and 24).
Time frame: week 12, 18 and 24
Proportion of patients with any Grade 3 -4 adverse events related to product administration during the study period.
Time frame: week 24
Proportion of patients with any Grade 3 -4 adverse events related to study product.
Time frame: week 24
Proportion of patients with any Grade 3 -4 adverse events related to study product.
Time frame: week 24
Proportion of patients with any SAE events related to study product.
Time frame: week 24
Proportion of patients with at least one MS relapse during the study period.
Time frame: week 24
Total number of MS relapse at 24 weeks.
Time frame: week 24
Time to first MS relapse during the study period.
Time frame: week 24
Changes from baseline in the disability progression by Expanded Disability Status Scale (EDSS) at week 24.
Time frame: week 24
Changes from baseline in the disability progression by Multiple Sclerosis Functional Composite (MSFC) at week 24.
Time frame: week 24
Changes from baseline in the number of CUA lesion at week 24.
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Hospital del Mar
Barcelona, Spain
Time frame: week 24
Proportion of patients free from CUA lesion, gadolinium-enhancing lesions on T1 MRI and new or enlarged lesions on T2-MRI thought the 24 weeks of study.
Time frame: week 24
Changes from baseline in the number of Gd-enhancing T1 lesions by scan (mean number of the sum at week 12, 18 and 24) and at week 24.
Time frame: week 24
Changes from baseline in number of new or enlarging T2 lesions by scan (mean number of the sum at week 12, 18 and 24) and at week 24.
Time frame: week 24
Changes from baseline in brain global, white and gray matter volume and cervical cord volume on MRI at 24 weeks.
Time frame: week 24
Changes from baseline in the number of cortical lesions on MRI at 24 weeks.
Time frame: week 24
Changes from baseline in MR measurements of diffuse damage of brain tissue by MTR at 24 weeks
Time frame: week 24
Changes from baseline in MR measurements of relaxation times of T1 and T2 by MTR at 24 weeks.
Time frame: week 24
Changes in DTI measures as mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (Dr) and axial diffusivity (Da) at 24 weeks.
Time frame: week 24
Changes from baseline in cytokine production (including IFNgamma, IL-17, IL-4 and IL-10) in response to specific peptide stimulation in peripheral blood mononuclear cells (PBMCs) culture supernatants at 12 and 24 weeks.
Time frame: week 24
Changes from baseline in T cell proliferation to immunogenic peptides at 12 and 24 weeks.
Time frame: week 24
Changes from baseline in immune cell subsets in PBMCs including PBMC subtypes, T lymphocytes subpopulations and Treg subsets, CD4 and CD8 GM-CSF 'encephalitogenic' T cells and T cell subtypes by activation memory phenotype at 12 and 24 weeks.
Time frame: week 24