Overview
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.
Description
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.
Eligibility
Inclusion Criteria:
- Age between 18-65 years old.
- Patients diagnosed with RRMS according to 2017 McDonald criteria.
- MS disease duration < 10 years.
- Expanded disability status scale (EDSS) from 0 to < 5.5.
- Patients eligible to start or already are in on treatment with first line immunomodulatory treatment (interferon beta 1a, interferon beta 1b, glatiramer acetate, teriflunomide or dymethyl-fumarate).
- Able to sign informed consent.
- Women of child-bearing potential must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include: intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence.
Exclusion Criteria:
- Presence of a relapse or use of steroids 30 days prior to screening visit.
- Concomitant use of any type of immunomodulatory / immunosuppressive therapy.
- Use of previous immunosuppressive or cytotoxic therapy in the last 6 months. Use of previous alemtuzumab, cladribine or bone marrow or stem cell transplant at any time.
- Patients unable or unwilling to undergo MRI scans.
- Severe systemic diseases or history of cancer or hereditary familiar cancer.
- Clinically relevant concomitant disease: cardiac, gastrointestinal, hepatic, pulmonary, neurological, renal or other major disease.
- Impossibility to proceed to the leukapheresis (e.g. absence of peripheral venous access).
- Pregnant or breastfeeding women.
- Drug or alcohol abuse.
- Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS or to test positive for HIV antibody at screening.
- Ongoing known bacterial, viral or fungal infection (with the exception of onychomycosis and dermatomycosis), positive hepatitis B surface antigen or hepatitis C antibody tests at screening.
- Patients with a known history of syphilis or tuberculosis or test positive for syphilis (positive rapid plasma reagin, RPR) or tuberculosis (positive skin test) at screening. Active or latent tuberculosis (TB).
- Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that may interfere with the compliance to the protocol.
- Any other clinically relevant medical or surgical condition, which, in the opinion of the investigator, would put the subject at risk by participating in the study.
- Participation in other experimental studies within the previous 90 days prior to screening visit.