Multiple SclerosisPhase 2MS-tolDC_2aNCT07020715
A Phase IIa Study of Vitamin D3 Tolerogenic Dendritic Cells (tolDC) for Multiple Sclerosis
A Phase 2 study testing Tolerogenic dendritic cells (tolDC) in people with Multiple Sclerosis, run by University Hospital, Antwerp at 2 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Tolerogenic dendritic cells (tolDC)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Jul 2026to 30 Oct 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Belgium1 site
Universitair Ziekenhuis Antwerpen (UZA)
Edegem, 2650
Barbara Willekens, +3238213423, studies.neurologie@uza.be
Amber Dams, +32470011082, amber.dams@uantwerpen.be
Spain1 site
Germans Trias i Pujol Hospital (HUGTiP)
Badalona, 08916
Cristina Ramo Tello, 0034 93 497 84 33, cramrot@gmail.com
Silvia Presas Rodríguez, spresas.germanstrias@gencat.cat
About this study
Official title: An Autologous and Antigen-specific Cell-based Therapy of Vitamin D3-treated and Myelin-derived Peptide Loaded Tolerogenic Dendritic Cells in Subjects With Progressive Forms of Multiple Sclerosis: a Phase IIa, Open-label, Self-controlled, Multi-center Clinical Trial
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.
Read the 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 (using a surrogate primary outcome-change in EDSS score) and safe (the occurrence and severity of adverse events). Secondary evaluations will include the clinical outcomes (assessed using 9HPT, SDMT and number and severity of relapses) and MRI-based markers. Participants will serve as their own controls, with data from 24 weeks pre-treatment period (documented by their neurologist). Following six tolDC administrations, a 24-weeks follow-period will take place. Furthermore, participants can enroll voluntarily into an optional additional follow-up phase of 52 weeks. Completion of screening assessments and confirmation of eligibility criteria should take no longer than 8 weeks.
- Conditions
- Multiple Sclerosis
- Being tested
- Tolerogenic dendritic cells (tolDC)
- Keywords
- Tolerogenic dendritic cells, tolDC, Phase IIa, Multiple Sclerosis, MS, Patient Safety, Efficacy
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Tolerogenic dendritic cells (tolDC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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).
Measured: 62 weeks
Secondary outcomes (6)
9 Hole Peg Test (9HPT)
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.
Measured: 62 weeks
Symbol Digit Modalities test (SDMT)
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).
Measured: 62 weeks
T2 lesion volume on MRI
T2 lesion volume on MRI scans will be evaluated to determine if administration of tolDC influences clinical and subclinical disease evolution.
Measured: 62 weeks
Total Brain Volume on MRI
Total brain volume on MRI scans will be evaluated to determine if administration of tolDC influences clinical and subclinical disease evolution
Measured: 62 weeks
Brain Atrophy on MRI
Atrophy rate on MRI scans will be evaluated to determine if administration of tolDC influences clinical and subclinical disease evolution
Measured: 62 weeks
Biomarkers
Change in Neurofilament Light Chain (NfL) serum and Glial Fibirallary Acidic Protein (GFAP) serum will be assessed as biomarkers. NfL is a sensitive marker of neuroaxonal damage and has been associated with disease activity and treatment response in MS. GFAP reflects astrocytic activation and may provide insights into neuroinflammation and glial responses, particularly relevant in progressive MS. These biomarkers will be measured using ultrasensitive immunoassays, allowing for high-resolution monitoring of subclinical disease progression and treatment-related effects.
These will be measured in serum samples and biobanked for later analysis.
Measured: 62 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2025
- Study start1 Jul 2026 (estimated)
- Primary completion30 Sep 2029 (estimated)
- Study completion30 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University Hospital, AntwerpThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Participants will receive six administrations of the tolDC vaccine.
- Masking
- None (open label)
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Antwerp
- Sponsor type
- University, hospital or other
- Collaborators
- Fundació Institut Germans Trias i Pujol
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07020715
- Sponsor's protocol ID
- CCRG22-002 / FWO-TBM T002523N
- Other IDs
- T002523N, 2025-522040-40-01, 2025
- Acronym
- MS-tolDC_2a
- Status last verified
- Mar 2026
- First submitted
- 5 Jun 2025
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Autologous and Antigen-specific Cell-based Therapy of Vitamin D3-treated and Myelin-derived Peptide Loaded Tolerogenic Dendritic Cells in Subjects With Progressive Forms of Multiple Sclerosis: a Phase IIa, Open-label, Self-controlled, Multi-center Clinical Trial
- ClinicalTrials.gov ID
- NCT07020715
- Acronym / sponsor ID
- MS-tolDC_2a / CCRG22-002 / FWO-TBM T002523N
- Conditions
- Multiple Sclerosis
- Keywords
- Tolerogenic dendritic cells, tolDC, Phase IIa, Multiple Sclerosis, MS, Patient Safety, Efficacy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- University Hospital, AntwerpUniversity, hospital or other
- Collaborators
- Fundació Institut Germans Trias i Pujol
- Study start
- 1 Jul 2026 (estimated)
- Primary completion
- 30 Sep 2029 (estimated)
- Study completion
- 30 Oct 2029 (estimated)
- First posted
- 13 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 (using a surrogate primary outcome-change in EDSS score) and safe (the occurrence and severity of adverse events). Secondary evaluations will include the clinical outcomes (assessed using 9HPT, SDMT and number and severity of relapses) and MRI-based markers. Participants will serve as their own controls, with data from 24 weeks pre-treatment period (documented by their neurologist). Following six tolDC administrations, a 24-weeks follow-period will take place. Furthermore, participants can enroll voluntarily into an optional additional follow-up phase of 52 weeks. Completion of screening assessments and confirmation of eligibility criteria should take no longer than 8 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Participants will receive six administrations of the tolDC vaccine.
| Arm | Type | Receives |
|---|---|---|
| Intradermal Arm: tolerogenic dendritic cells (tolDC) | Experimental | Biological: Tolerogenic dendritic cells (tolDC)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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 allogeneic mixed leukocyte reaction (allo-MLR). | Biological | Intradermal Arm: tolerogenic dendritic cells (tolDC) |
Primary outcome
Efficacy (Change in EDSS score)
Time frame: 62 weeks
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
Incidence of treatment-emergent adverse events (safety and tolerability)
Time frame: 62 weeks
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).
6 secondary outcomes
9 Hole Peg Test (9HPT)
Time frame: 62 weeks
Symbol Digit Modalities test (SDMT)
Time frame: 62 weeks
T2 lesion volume on MRI
Time frame: 62 weeks
Total Brain Volume on MRI
Time frame: 62 weeks
Brain Atrophy on MRI
Time frame: 62 weeks
Biomarkers
Time frame: 62 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tolerogenic dendritic cells (tolDC) in people with Multiple Sclerosis, run by University Hospital, Antwerp at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Belgium, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amber Dams (+32470011082, amber.dams@uantwerpen.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy (Change in EDSS score) (time frame: 62 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.