Dendritic Cells Therapy Combined With Immunomodulatory Treatment in Multiple Sclerosis (TolDecCOMBINEM)

Judit Pich

Status and phase: Enrolling; Phase 2

Conditions: Relapsing-Remitting Multiple Sclerosis

Treatments: Other: Placebo; Other: Autologous peripheral blood differentiated adult tolerogenic dendritic cells expanded

Study type: Interventional

Funder types: Other

Identifiers

NCT04530318

2020-000737-41 (EudraCT Number)

TolDec-COMBINEM

Details and patient eligibility

About

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.

Full 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.

Enrollment: 45 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age between 18-65 years old.
2. Patients diagnosed with RRMS according to 2017 McDonald criteria.
3. MS disease duration < 10 years.
4. Expanded disability status scale (EDSS) from 0 to < 5.5.
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).
6. Able to sign informed consent.
7. 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

1. Presence of a relapse or use of steroids 30 days prior to screening visit.
2. Concomitant use of any type of immunomodulatory / immunosuppressive therapy.
3. 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.
4. Patients unable or unwilling to undergo MRI scans.
5. Severe systemic diseases or history of cancer or hereditary familiar cancer.
6. Clinically relevant concomitant disease: cardiac, gastrointestinal, hepatic, pulmonary, neurological, renal or other major disease.
7. Impossibility to proceed to the leukapheresis (e.g. absence of peripheral venous access).
8. Pregnant or breastfeeding women.
9. Drug or alcohol abuse.
10. Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS or to test positive for HIV antibody at screening.
11. 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.
12. 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).
13. Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that may interfere with the compliance to the protocol.
14. 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.
15. Participation in other experimental studies within the previous 90 days prior to screening visit.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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45 participants in 2 patient groups, including a placebo group

TolDec

Experimental group

Description:

Autologous peripheral blood differentiated adult tolerogenic dendritic cells expanded

Treatment:

Other: Autologous peripheral blood differentiated adult tolerogenic dendritic cells expanded

Placebo

Placebo Comparator group

Description:

Placebo of dendritic cells

Treatment:

Other: Placebo