A Phase IIa Study of Vitamin D3 Tolerogenic Dendritic Cells (tolDC) for Multiple Sclerosis

NCT07020715 | Not Yet Recruiting Phase 2 DMC

• 3 other identifiers: CCRG22-002 / FWO-TBM T002523NT002523N2025-522040-40-01
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 2

Brief Summary

The investigators propose to design and conduct a phase IIa clinical trial to treat patients with progressive forms of multiple sclerosis (MS) by vaccination with tolerogenic dendritic cells (tolDC), generated using Good Manufacturing Practices (GMP). Hereby, the investigators want to demonstrate the efficacy and safety of administrating clinical-grade vitamin D3-treated tolDC loaded with myelin-derived peptides to patients with progressive forms of MS. 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

Tolerogenic dendritic cells; tolDC; Phase IIa; Multiple Sclerosis; MS; Patient Safety; Efficacy

Outcome Measures

Primary Outcomes (2)

• Efficacy (Change in EDSS score)

  To evaluate the efficacy of tolDC administration, the change in Expanded Disability Severity Scale (EDSS) will be employed. The participants' disability level well be checked during every visit. The EDSS consists of a 10-point scale of disease severity ranging from 0, i.e. no disability, to 10, i.e. death from MS. The impact on disability progression will be analyzed by the proportion of participants free from confirmed disability progression, defined by sustained changes in the EDSS score. Disease progression criteria: * 1.0 point in participants with a screening EDSS of 0-5.0 * 0.5 point in those with a screening EDSS of 5.5-6.0

  62 weeks

• Incidence of treatment-emergent adverse events (safety and tolerability)

  Tolerability and safety of tolDC administration will be assessed by recording the incidence, severity, and relationship to study treatment of adverse events throughout the trial. Participants will be monitored by the treating neurologist for the occurrence and outcomes of AEs, SAEs, relapses and study discontinuations. Full physical examinations, vital signs, and blood and urine samples (only in case of women of childbearing age for pregnancy test) will be recorded at screening, during tolDC administration and during follow-up. An assessment of severity grading of AEs will follow the WHO toxicity grading scale (1= mild, 2= moderate, 3= severe, 4= potentially life threatening).

  62 weeks

Secondary Outcomes (6)

• 9 Hole Peg Test (9HPT)

  62 weeks

• Symbol Digit Modalities test (SDMT)

  62 weeks

• T2 lesion volume on MRI

  62 weeks

• Total Brain Volume on MRI

  62 weeks

• Brain Atrophy on MRI

  62 weeks

Other Outcomes (3)

• Immunological response

  62 weeks

• Patient Reported Outcomes - Visual Analog Scale (VAS)

  62 weeks

• Patient Reported Outcomes - EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L)

  62 weeks

Study Arms (1)

Intradermal Arm: tolerogenic dendritic cells (tolDC)

EXPERIMENTAL

Each vaccine (15x10E6cells in 500 µL solution with 5% human albumin supplemented with 10% DMSO and 4% glucose) will be administered through intradermal injection at 5 sites (100 µL/site) in the posterior cervical region, targeting lymphatic drainage into both superficial and deep cervical lymph nodes (5-10 cm from the cervical lymph nodes). Injection sites will alternate between left and right sides of the neck for each administration timepoint.

Biological: Tolerogenic dendritic cells (tolDC)

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 allogeneic mixed leukocyte reaction (allo-MLR).

Intradermal Arm: tolerogenic dendritic cells (tolDC)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is ≥ 18 years old, and ≤65 years of age, at time of screening visit
• Diagnosis of MS according to the 2017 McDonald Criteria or more recent criteria
• Progressive MS by 2014 Lublin MS phenotypic criteria
• EDSS 2,0 - ≤7,5
• No clinical evidence of relapses in the past 2 years
• Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial.
• Appropriate venous access
• Use of adequate contraceptive measures or not of childbearing potential

You may not qualify if:

• Previous treatment with alemtuzumab, autologous hematopoietic stem cell transplantation or cladribine in the past 3 years.
• Prior treatment with any investigational agent within 3 months, or 5 half-lives, whichever is longer.
• Current and ongoing treatment with an approved DMT for MS
• Treatment with S1P receptor modulators, natalizumab, dimethylfumarate, teriflunomide within the last 3 months prior to study enrolment; last treatment with B cell depleting monoclonal antibodies at least 6 months prior to enrollment and normal CD19 B cell counts at time of enrollment
• Pregnancy or planning pregnancy in the next 12 months and breast feeding
• Drug or alcohol abuse
• Inability to undergo MRI assessments
• History of or actual signs of immunodeficiency or malignancies (with the exception of treated basal cell carcinoma)
• Concurrent clinically relevant cardiac, immunological, pulmonary, neurological, renal or other major disease that could impact safety or outcome measures.
• Active or chronic infection with hepatitis B, C, HIV, syphilis or tuberculosis
• Splenectomy
• Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that could interfere with the compliance to the protocol.

Sponsors & Collaborators

• University Hospital, Antwerp: lead
• Fundació Institut Germans Trias i Pujol: collaborator

Study Sites (2)

Universitair Ziekenhuis Antwerpen (UZA)

Edegem, 2650, Belgium

Location

Germans Trias i Pujol Hospital (HUGTiP)

Badalona, 08916, Spain

Location

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Amber Dams

CONTACT

+32470011082; amber.dams@uantwerpen.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will receive six administrations of the tolDC vaccine.

Study Record Dates

• First Submitted: June 5, 2025
• First Posted: June 13, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): October 30, 2029
• Last Updated: May 5, 2026

Record last verified: 2026-03

Locations

BE (1); ES (1)