NCT06715605

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

A Controlled Phase II Clinical Trial Evaluating the Safety and Efficacy of Myelin-peptide Loaded tolDC as Treatment for Multiple Sclerosis

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University Hospital, Antwerp · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

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

Detailed description

A two-arm non-randomized controlled phase II clinical trial will be conducted in a coordinated and comprehensive manner to provide proof-of-concept for efficacy and safety. The primary objective of the phase II study is to determine whether tolDC-based therapy is effective and safe based on a surrogate outcome measure as primary outcome (i.e. brain MRI). Adverse events, clinical relapse rates, neurological disability (assessed using various scales) and MRI endpoints will be followed and measured over the course of 18 months. Participants who receive the tolDC treatment will be compared to MS patients, who receive standard-of-care (control group). Completion of screening assessments and confirmation of eligibility criteria should take no longer than 8 weeks. Furthermore, patients for the two arms will be recruited simultaneously and at the same pace.

Conditions

• Multiple Sclerosis

Interventions

Type	Name	Description
BIOLOGICAL	tolerogenic dendritic cells (tolDC)	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.
BIOLOGICAL	Standard-of-care	Standard-of-care on first-line treatment such as interferon-beta, glatiramer acetate, teriflunomide, dimethylfumarate, ponesimod and ozanimod.

Timeline

• Start date: 2025-04-30
• Primary completion: 2025-04-30
• Completion: 2027-10-29
• First posted: 2024-12-04
• Last updated: 2025-08-17

Locations

1 site across 1 country: Belgium