Tolerogenic Dendritic Cells as a Therapeutic Strategy for the Treatment of Multiple Sclerosis Patients (TOLERVIT-MS) (TOLERVIT-MS)

July 6, 2023 updated by: Fundació Institut Germans Trias i Pujol

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

The purpose of this study is to determine the safety and tolerability of the intranodal administration of autologous monocyte-derived dendritic cells tolerised with Vitamin-D3 and pulsed with myelin peptides (tolDC-VitD3) in multiple sclerosis patients . To select the most appropriate regime for the development of future therapeutic trials.

To evaluate the preliminary proof of concept by clinical and/or radiological activity and immunological markers.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Phase I dose ascending ("best of five") clinical trial.

First group will start by intranodal injection in cervical lymph nodes of 5*10^6 tolDC-VitD3.

Up titration depending on security outcomes to 10*10^6 tolDC-VitD3, same route in second cohort dose and next uptitration to 15*10^6 tolDC-VitD3.

Six cycles per patient with the following schema: for the first four cycles the administration will be each 2 weeks, for the remaining 2 cycles administration each 4 weeks.

A last cohort with the dose identified in the previous groups, administered in patients treated with beta interferon, same route, same dose schema.

Study Type

Interventional

Enrollment (Estimated)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Ana M Barriocanal, MD.PhD.Clinical Pharmacologist
  • Phone Number: +34934978488
  • Email: ambarrioocanal@igtp.cat

Study Locations

  • Spain
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Recruiting
        • Hospital Universitari Germans Trias I Pujol
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Eva Martínez-Cáceres, MD.PhD.Immunology
        • Sub-Investigator:
          • Silvia Presas, MD.Neurology
        • Sub-Investigator:
          • Magí Farré, MD.PhD.Clinical Pharmacology
        • Sub-Investigator:
          • Ana M Barriocanal, MD.PhD.Clinical Pharmacology
        • Sub-Investigator:
          • María J Mansilla, MD.Immunology
        • Sub-Investigator:
          • Bibiana Quirant, MD.Immunology
        • Sub-Investigator:
          • Aina Teniente, MD.Immunology
        • Sub-Investigator:
          • Juan Navarro, MD.Immunology
        • Sub-Investigator:
          • Josep Munuera, MD.Radiology
        • Sub-Investigator:
          • Anna Massuet, MD.Radiology
        • Sub-Investigator:
          • Jordi Reverter, MD.Endocrine Intervention
        • Sub-Investigator:
          • Anna Suñol, RN
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Not yet recruiting
        • Clinica Universidad de Navarra
        • Contact:
          • Jaime Gállego, MD.PhD
          • Phone Number: 3594 +34948255400
          • Email: jgallego@unav.es
        • Contact:
          • Amaya Izal
          • Phone Number: 2724 +34948255400
          • Email: aizal@unav.es
        • Principal Investigator:
          • Jaime Gallego, MD.PhD. Neurology
        • Sub-Investigator:
          • Purificación De Castro, MD.Neurology
        • Sub-Investigator:
          • Felipe Prosper, MD.Haematology
        • Sub-Investigator:
          • Susana Inogés, MD.Immunology
        • Sub-Investigator:
          • Ascensión López, MD.Immunology
        • Sub-Investigator:
          • Enrique Andreu, MD.Cell therapy
        • Sub-Investigator:
          • Javier Larrache, MD.Radiology
        • Sub-Investigator:
          • Carmen Azcona, RN

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 5 * 10 ^6 tolDC-VitD3
5 million autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3)
Drug: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3)
Intranodal administration
Other Names:
  • tolDC-VitD3
Experimental: 10 * 10 ^6 tolDC-VitD3
10 million autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3).
Drug: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3)
Intranodal administration
Other Names:
  • tolDC-VitD3
Experimental: 15 * 10 ^6 tolDC-VitD3
15 million autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3).
Drug: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3)
Intranodal administration
Other Names:
  • tolDC-VitD3
Experimental: Interferon-beta
Additional group (patients treated with beta-interferon) will receive the selected dose of those 3 previously cohorts studied
Drug: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3)
Intranodal administration
Other Names:
  • tolDC-VitD3
Drug: Interferon-beta
Subcutaneous administration interferon-beta
Other Names:
  • beta-interferon

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety as assessed by the occurrence and severity of adverse events
Time Frame: 24 months
Occurence and severity of adverse events will be recorded
24 months
Neurologic changes
Time Frame: 24 months
New relapse. Disability progression on Expanded Disability Status Scale (EDSS)
24 months
Radiologic changes
Time Frame: 24 months
Number of new or enlarging T2 lesions on brain MRI. Number of Gadolinium (Gd)-enhancing T1 lesions on brain MRI
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annual relapse rate (ARR)
Time Frame: 24 months
24 months
Expanded Disability Status Scale (EDSS)
Time Frame: 24 months
24 months
9-Hole Peg Test (9HPT)
Time Frame: 24 months
24 months
25-Foot Walking Test (T25FW)
Time Frame: 24 months
24 months
Symbol Digit Modalities Test (SDMT)
Time Frame: 24 months
24 months
Radiologic preliminary efficacy
Time Frame: 24 months
Number of new or enlarging T2 lesions on brain MRI. Number of Gadolinium (Gd)-enhancing T1 lesions on brain MRI
24 months
Lymphocyte proliferation to myelin peptides
Time Frame: 24 months
24 months
Blood Immunomonitoring studies
Time Frame: 24 months
24 months
Feasibility
Time Frame: 6 months
Generation of Good Manufacturing Practices (GMP)-grade cell product released according to Quality Control. Feasibility of cellular product injection.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundació Institut Germans Trias i Pujol

Collaborators

Clinica Universidad de Navarra, Universidad de Navarra

Investigators

  • Principal Investigator: Cristina Ramo, MD.PhD.Neurologist, Badalona Hospital Germans Trias i Pujol. Neurology service. Multiple Sclerosis department
  • Study Director: Eva Martínez-Cáceres, MD.PhD.Immunology, Badalona Hospital Germans Trias i Pujol. Immunology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 6, 2017

Primary Completion (Estimated)

December 1, 2023

Study Completion (Estimated)

December 1, 2023

Study Registration Dates

First Submitted

July 21, 2016

First Submitted That Met QC Criteria

September 15, 2016

First Posted (Estimated)

September 16, 2016

Study Record Updates

Last Update Posted (Actual)

July 7, 2023

Last Update Submitted That Met QC Criteria

July 6, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TOLERVIT-MS
  • 2015-003541-26 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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