Using tolerogenic dendritic cells to treat multiple sclerosis

Tolerance-Induction With Dendritic Cells Treated With Vitamin-D3 and Loaded With Myelin Peptides, in Multiple Sclerosis Patients (TOLERVIT-MS)

This study is testing if a new treatment using specially prepared immune cells can help people with multiple sclerosis feel better and manage their symptoms.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Fundació Institut Germans Trias i Pujol (other)
• Drugs / interventions: natalizumab, rituximab, alemtuzumab, methotrexate, cyclophosphamide
• Locations: 2 sites (Badalona, Barcelona and 1 other locations)
• Trial ID: NCT02903537 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety and tolerability of intranodal injections of autologous monocyte-derived dendritic cells that have been tolerized with Vitamin D3 and pulsed with myelin peptides in patients with multiple sclerosis. The trial will follow a dose-ascending design, starting with a low dose and increasing based on safety outcomes, with a total of six treatment cycles for each patient. The study will also evaluate preliminary proof of concept through clinical and radiological activity as well as immunological markers.

Who should consider this trial

Good fit: Ideal candidates include patients with active relapsing-remitting or progressive forms of multiple sclerosis who have not responded to or do not wish to pursue current therapies.

Not a fit: Patients with very advanced multiple sclerosis or those who have had the disease for more than 15 years may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a novel therapeutic option for patients with multiple sclerosis by promoting immune tolerance.

How similar studies have performed: While the use of dendritic cells in immunotherapy is a growing field, this specific approach is novel and has not been extensively tested in multiple sclerosis.

Eligibility criteria

Inclusion Criteria:

1. EDSS of 0.0 - 6.5.
2. Multiple Sclerosis according to 2010 revised Mc Donald criteria, and less than 15 years of evolution of disease.
3. Patients with:

   * Active relapsing remitting multiple sclerosis (RRMS) (more than 1 relapse in last year and/or occurrence of ≥3 new T2 lesions or Gd positive) who not wish to be treated with current therapies.
   * Low activity RRMS (1 relapse in last year or occurrence of 1 or 2 T2 lesions or Gd positive) without treatment.
   * Progressive forms of MS with activity (at least 1 relapse in last year or occurrence 1 or 2 T2 lesions or Gd positive).
   * RRMS treated with interferon beta (Additional group)
4. T cell proliferation to the pool of myelin peptides against which is to induce immune tolerance: Myelin basic protein (MBP)13-32, MBP83-99, MBP111-129, MBP146-170, proteolipid protein (PLP) 139-154, Myelin oligodendrocyte glycoprotein (MOG)1-20, MOG35 -55).
5. Adequate peripheral venous access.
6. Signed informed consent.

Exclusion Criteria:

1. Use of corticosteroids during the prior 4 weeks.
2. Use of interferon beta -in patients who is retired by inefficiency or other causes- and glatiramer acetate in the 4 weeks prior.
3. Use of fingolimod, dimethylfumarate, natalizumab, immunoglobulins or plasmapheresis at 12 weeks; and teriflunomide in the 15 weeks prior.
4. Use of azathioprine, mitoxantrone, rituximab, methotrexate, cyclophosphamide, cyclosporine, alemtuzumab or other immunosuppressive drug, except corticosteroids, at any time.
5. Bone marrow or stem cell transplant at any time.
6. Relapse during the month prior of starting treatment. If it appears and the patient meets the eligibility criteria, must wait long enough until the end of the 30 days free of relapse. If corticosteroids are administered, the MRI performed during this period should not be considered, and a new MRI will be performed at 4 weeks after administration of corticosteroids.
7. Pregnancy or planning pregnancy within the next 12 months and breastfeeding.
8. Fertile patients who are not using an appropriate method of contraception. If the patient is menopausal or sterile it must be documented in the medical record.
9. Abusing drugs or alcohol.
10. Inability to undergo MRI evaluations.
11. Seropositivity for HIV, hepatitis B or C and/or syphilis.
12. History of oncological disease.
13. Clinically relevant concomitant disease: cardiac, pulmonary, neurological, renal or other major illness.
14. Splenectomy.
15. Dementia, psychiatric problems or other comorbidities that might interfere protocol compliance.
16. To be participating in another clinical study or to have participated in one in the last 3 months.

Where this trial is running

Badalona, Barcelona and 1 other locations

• Hospital Universitari Germans Trias i Pujol — Badalona, Barcelona, Spain (RECRUITING)
• Clínica Universidad de Navarra — Pamplona, Navarra, Spain (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Cristina Ramo, MD.PhD.Neurologist — Badalona Hospital Germans Trias i Pujol. Neurology service. Multiple Sclerosis department
• Study coordinator: Cristina Ramo, MD.PhD. Neurologist

Conditions: Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Dendritic Cells, Immune Tolerance, Myelin Proteins, Tolerogenic dendritic cells