A Clinical Trial Evaluating the Safety and Efficacy of Myelin-peptide Loaded tolDC as Treatment for MS

NCT06715605 | Withdrawn Phase 2 DMC

• 3 other identifiers: CCRG22-0022024-512891-37-002022-003465-38
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose to design and conduct a phase II clinical trial to treat patients with multiple sclerosis (MS) by vaccination with tolerogenic dendtritic cells (tolDC), generated using Good Manufacturing Practices (GMP). Hereby, the investigators want to demonstrate the efficacy of administrating clinical-grade vitamin D3-treated tolDC loaded with myelin-derived peptides to treat a well-defined population of MS patients. In vitro generation of dedicated and stable immunomodulatory DC followed by in vitro loading of antigens to ensure tolerance and safety of DC-directed therapy is a promising strategy with the potential to induce long term tolerance

Conditions

Multiple Sclerosis

Keywords

patient safety; tolerogenic dendritic cells; tolDC; phase II; MS; Multiple sclerosis

Outcome Measures

Primary Outcomes (2)

• Efficacy (Number of new and/or enlarging T2 lesions on MRI)

  To evaluate the radiological efficacy of tolDC administration, number of new and/or enlarging T2 lesions on MRI scans

  18 months

• Safety (Occurrence and severity of adverse events will be recorded)

  To evaluate the safety of administering tolDC, the occurrence and severity of adverse events will be recorded.

  18 months

Secondary Outcomes (8)

• Expanded disability status scale (EDSS)

  18 months

• 9 Hole Peg Test (9HPT)

  18 months

• 25 Foot walk test (T25FW)

  18 months

• Symbol Digit Modalities test (SDMT)

  18 months

• Non-clinical outcome measure (T2 lesion volume on MRI)

  18 months

Other Outcomes (2)

• Immunological response

  18 months

• Visual Analogic Scale (VAS)

  18 months

Study Arms (2)

Intradermal arm: tolerogenic dendritic cells (tolDC)

EXPERIMENTAL

Each vaccine (15x106cells in 500 µL NaCl 0.9% solution supplemented with 5% human albumin) will be administered through intradermal injection at 5 sites (100 µL/site) in the posterior neck region to ensure lymphatic drainage to superficial and deep cervical lymph nodes (5-10 cm from the cervical lymph nodes). Injection sites will alternate between left and right sides

Biological: tolerogenic dendritic cells (tolDC)

Control arm: standard-of-care

ACTIVE COMPARATOR

Participants who receive standard-of-care, on first-line treatment (interferon-beta, glatiramer acetate, teriflunomide, dimethylfumarate, ponesimod, ozanimod). They will follow the same assessments as the interventional arms

Biological: Standard-of-care

Interventions

tolerogenic dendritic cells (tolDC) BIOLOGICAL

In brief, clinical-grade tolDC vaccines will be prepared from leukapheresis starting material of non-mobilized blood and subsequent immunomagnetic selection of CD14+ monocytes using a CliniMACS device. CD14+ monocytes will then be cultured in GMP-grade cell culture medium supplemented with 2% human AB serum, GM-CSF, IL-4 and 1 alpha,25 dihydroxyvitamin D3. At day 4, tolDC will be stimulated using a cytokine cocktail to induce a migratory phenotype. At day 6, tolDC will be harvested, loaded with antigen, resuspended, and cryopreserved. Separate aliquots of the cell product are prepared for final quality control and quality assurance (QC/QA) assessment. This includes cell count, viability, phenotypic analysis using flow cytometry, and induction of T cell hyporesponsiveness in allo-MLR.

Intradermal arm: tolerogenic dendritic cells (tolDC)

Standard-of-care BIOLOGICAL

Standard-of-care on first-line treatment such as interferon-beta, glatiramer acetate, teriflunomide, dimethylfumarate, ponesimod and ozanimod.

Control arm: standard-of-care

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• RIS, CIS or MS according to most recent Mc Donald's diagnostic criteria (1);
• Age 18-60 years;
• Expanded disability status scale (EDSS) of 0-6.0 inclusive;
• Active RIS, CIS, MS (relapsing and progressive forms): 1 relapse in the past year and/or at least 1 enhancing lesion on brain MRI in the past year and/or at least 1 new or enlarging T2 lesion in comparison with a reference scan from maximum 1 year before;
• RIS, CIS, MS patients already on first-line treatment or who will start first-line treatment (control arm)
• Untreated patients who do not want to be treated with currently available disease-modifying treatments or presence of treatment-related side effects; intervention arm;
• No evidence of relapse in the month prior to start of screening and throughout the screening phase;
• Only for the intervention arm: Normal total lymphocyte count above 800/mm3;
• Only for the intervention arm: Normal peripheral B cell count between 0.07x106 cells/ml and 0.53x106 cells/mL;
• Able to sign informed consent;
• Ability to comply with the protocol assessments;
• Appropriate venous access;
• Use of adequate contraceptive measures during the duration of the trial. Women and men of reproductive potential can only be included in the study following use of adequate contraceptive measures. Accepted methods of contraception include use of hormonal contraceptives (oral, intravaginal, intrauterine, or transdermal), intrauterine devices, sterilization or postmenopausal status, use of condoms with spermicide.

You may not qualify if:

• For tolDC intradermal arm:
• Previous use of severe immunosuppressive or cytostatic treatment, including cyclophosphamide, mitoxantrone, bone marrow transplantation or (hematopoietic or mesenchymal) stem cell transplantation (at any time) prior to enrolment;
• Previous use of cladribine with last course within last 2 years or alemtuzumab with last course within last 4 years; lymphocyte counts should be above 800/mm3
• Only for the intervention arm: Use of interferon beta and glatiramer acetate in the 4 previous weeks; use of teriflunomide in the previous 4 weeks with accelerated elimination procedure; use of dimethyl/diroximel fumarate in the previous 4 weeks with normal lymphocyte counts (above 800/mm3)
• Only for the intervention arm: Treatment with fingolimod, siponimod, ponesimod, ozanimod, natalizumab, intravenous or subcutaneous immunoglobulins or plasmapheresis in the past 3 months; teriflunomide in the previous 15 weeks without accelerated elimination; anti-CD20 monoclonal antibody (including ofatumumab, rituximab and ocrelizumab) within the past 6 months prior to the first administration and until confirmation of B cell count normalization; for S1P modulators lymphocyte counts should be above 800/mm3
• Use of another investigational product in the past 6 months or longer depending on the mode of action
• Previous use of azathioprine or methotrexate in the past 3 months; lymphocyte counts should be above 800/mm3
• Previous use of other immunosuppressive agents washout is at least 3 months or longer depending on the mode of action and half-life; lymphocyte counts should be above 800/mm3
• For intradermal and control arm:
• Relapse / use of corticosteroids for any reason in the previous month;
• Pregnancy or planning pregnancy in the next 18 months and breast feeding;
• Fertile patients, both men and women, who are not using an adequate method of contraception. If the patient is menopausal or sterile, it must be documented in the medical history;
• Drug or alcohol abuse;
• Inability to undergo MRI assessments or unwillingness to receive gadolinium administration;
• History of or actual signs of immunodeficiency (with the exception of treatment effects of patients on 1st line DMT) or malignancies;

Sponsors & Collaborators

• University Hospital, Antwerp: lead
• Hospital Germans Tríes i Pujol de Badalona: collaborator

Study Sites (1)

Antwerp University Hospital

Edegem, 2650, Belgium

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Nathalie Cools

  Universiteit Antwerpen

  PRINCIPAL INVESTIGATOR

• Zwi Berneman

  University Hospital, Antwerp

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2024
• First Posted: December 4, 2024
• Study Start: April 30, 2025
• Primary Completion: April 30, 2025
• Study Completion (Estimated): October 29, 2027
• Last Updated: August 17, 2025

Record last verified: 2024-11

Locations

BE (1)