Clinical trial NCT07020715: A Phase IIa Study of Vitamin D3 Tolerogenic Dendritic Cells (tolDC) for Multiple Sclerosis
Official title: An Autologous Vitamin D3 Tolerogenic Dendritic Cell-based Therapy in Subjects With Progressive Forms of Multiple Sclerosis: a Phase IIa, Open-label, Self-controlled, Multi-center Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: Tolerogenic dendritic cells
tolDC
Phase IIa
Multiple Sclerosis
MS
Patient Safety
Efficacy
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
Collaborators: name: Fundació Institut Germans Trias i Pujol
First posted: 2025-06-13
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Participants will receive six administrations of the tolDC vaccin.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy (Change in EDSS score)
timeFrame: 62 weeks
measure: Safety (Occurrence and severity of adverse events will be recorded)
timeFrame: 62 weeks
Secondary outcomes:
measure: 9 Hole Peg Test (9HPT)
timeFrame: 62 weeks
measure: Symbol Digit Modalities test (SDMT)
timeFrame: 62 weeks
measure: T2 lesion volume on MRI
timeFrame: 62 weeks
measure: Total Brain Volume on MRI
timeFrame: 62 weeks
measure: Brain Atrophy on MRI
timeFrame: 62 weeks
measure: Biomarkers
timeFrame: 62 weeks
Other outcomes:
measure: Immunological response
timeFrame: 62 weeks
measure: Patient Reported Outcomes - Visual Analog Scale (VAS)
timeFrame: 62 weeks
measure: Patient Reported Outcomes - EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L)
timeFrame: 62 weeks
Locations:
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (UZA)
city: Badalona
country: Spain
facility: Germans Trias i Pujol Hospital (HUGTiP)
Study officials:
References: