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

Phase 2

Not yet recruiting

• Conditions: Multiple Sclerosis
• Interventions: Biological: Tolerogenic dendritic cells (tolDC)

• Registration Number: NCT07020715
• Lead Sponsor: University Hospital, Antwerp

Brief Summary

The investigators propose to design and conduct a phase IIa 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 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.

Detailed Description

This is an open-label, self-controlled, multi-center phase IIa clinical trial designed to evaluate the proof-of-concept for both efficacy and safety of tolDC-based therapy. The primary objective is to determine whether treatment with tolDC is effective and safe, using a surrogate primary outcome-change in EDSS score. Secondary evaluations will include the incidence of adverse events neurological disability (assessed using various clinical scales) and MRI-based markers. Participants will serve as their own controls, with data from 24 weeks pre-treatment period (documented by their neurologist) compared to outcomes during the 62 weeks follow up after initiating treatment. Completion of screening assessments and confirmation of eligibility criteria should take no longer than 8 weeks.

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-06-05
• Study First Submitted QC: 2025-06-12
• Last Update Submitted: 2025-06-12
• Study First Posted: 2025-06-13
• Last Update Posted: 2025-06-13
• Study Start: 2025-12-01
• Primary Completion: 2025-12-01
• Study Completion: 2027-10-29

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• 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

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intradermal Arm: tolerogenic dendritic cells (tolDC)	Tolerogenic dendritic cells (tolDC)	Each vaccine (15x10E6cells 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

Primary Outcome Measures

Name	Time	Method
Efficacy (Change in EDSS score)	62 weeks	Evaluate the efficacy of tolDC administration by assessing the change in Expanded Disability Severity Scale (EDSS) score. 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.
Safety (Occurrence and severity of adverse events will be recorded)	62 weeks	Tolerability of tolDC administration will be assessed by recording the incidence, severity, and relationship to study treatment of adverse events throughout the trial.

Secondary Outcome Measures

Name	Time	Method
9 Hole Peg Test (9HPT)	62 weeks	The 9-HPT is a quantitative assessment of upper limb (arm and hand) function. The test device consists of a container containing nine pegs and a wooden or plastic board with nine empty holes. The participant is required to pick up each peg individually and place them as quickly as possible in the nine holes. Once all the pegs are placed in the holes, the participant must remove them one by one, again as quickly as possible and return them to the container. The total time to complete the task is recorded.
Symbol Digit Modalities test (SDMT)	62 weeks	The SDMT is a useful tool for identifying cognitive impairment as well as monitoring changes in cognitive functioning over time or in response to treatment. The SDMT is quick and easy to administer, typically taking about five minutes. The test involves a basic substitution exercise that is easily manageable for adults. Using a reference key, participants are given 90 seconds to match specific numbers with corresponding geometric figures and verbally provide their answers. A study nurse or another appropriately trained individual records the responses in writing. The final outcome is calculated by the total number of answers given minus the incorrect answers (N numbers in 90 seconds).
T2 lesion volume on MRI	62 weeks	T2 lesion volume on MRI scans will be evaluated to determine if administration of tolDC influences clinical and subclinical disease evolution.
Total Brain Volume on MRI	62 weeks	Total brain volume on MRI scans will be evaluated to determine if administration of tolDC influences clinical and subclinical disease evolution
Brain Atrophy on MRI	62 weeks	Atrophy rate on MRI scans will be evaluated to determine if administration of tolDC influences clinical and subclinical disease evolution
Biomarkers	62 weeks	Change in Neurofilament Light Chain (NfL) serum and Glial Fibirallary Acidic Protein (GFAP) serum will be assessed as biomarkers. These will be measured in serum samples and biobanked for later analysis.

Trial Locations

Locations (2)

Universitair Ziekenhuis Antwerpen (UZA); 🇧🇪 Edegem, Belgium

Germans Trias i Pujol Hospital (HUGTiP); 🇪🇸 Badalona, Spain