Multiple SclerosisPhase 2MS-tolDC_2NCT06715605
A Clinical Trial Evaluating the Safety and Efficacy of Myelin-peptide Loaded tolDC as Treatment for MS
A Phase 2 study testing tolerogenic dendritic cells (tolDC) and Standard-of-care in people with Multiple Sclerosis, run by University Hospital, Antwerp at 1 site in Belgium.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- tolerogenic dendritic cells (tolDC) and Standard-of-care
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteBelgium
- Study dates
- 30 Apr 2025to 29 Oct 2027
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- RIS, CIS or MS according to most recent Mc Donald's diagnostic criteria (1);
- Age 18-60 years;
- Expanded disability status scale (EDSS) of 0-6.0 inclusive;
- Active RIS, CIS, MS (relapsing and progressive forms): 1 relapse in the past year and/or at least 1 enhancing lesion on brain MRI in the past year and/or at least 1 new or enlarging T2 lesion in comparison with a reference scan from maximum 1 year before;
- RIS, CIS, MS patients already on first-line treatment or who will start first-line treatment (control arm)
- Untreated patients who do not want to be treated with currently available disease-modifying treatments or presence of treatment-related side effects; intervention arm;
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- No evidence of relapse in the month prior to start of screening and throughout the screening phase;
- Only for the intervention arm: Normal total lymphocyte count above 800/mm3;
- Only for the intervention arm: Normal peripheral B cell count between 0.07x106 cells/ml and 0.53x106 cells/mL;
- Able to sign informed consent;
- Ability to comply with the protocol assessments;
- Appropriate venous access;
- Use of adequate contraceptive measures during the duration of the trial. Women and men of reproductive potential can only be included in the study following use of adequate contraceptive measures. Accepted methods of contraception include use of hormonal contraceptives (oral, intravaginal, intrauterine, or transdermal), intrauterine devices, sterilization or postmenopausal status, use of condoms with spermicide.
Who cannot join
- For tolDC intradermal arm:
- Previous use of severe immunosuppressive or cytostatic treatment, including cyclophosphamide, mitoxantrone, bone marrow transplantation or (hematopoietic or mesenchymal) stem cell transplantation (at any time) prior to enrolment;
- Previous use of cladribine with last course within last 2 years or alemtuzumab with last course within last 4 years; lymphocyte counts should be above 800/mm3
- Only for the intervention arm: Use of interferon beta and glatiramer acetate in the 4 previous weeks; use of teriflunomide in the previous 4 weeks with accelerated elimination procedure; use of dimethyl/diroximel fumarate in the previous 4 weeks with normal lymphocyte counts (above 800/mm3)
- Only for the intervention arm: Treatment with fingolimod, siponimod, ponesimod, ozanimod, natalizumab, intravenous or subcutaneous immunoglobulins or plasmapheresis in the past 3 months; teriflunomide in the previous 15 weeks without accelerated elimination; anti-CD20 monoclonal antibody (including ofatumumab, rituximab and ocrelizumab) within the past 6 months prior to the first administration and until confirmation of B cell count normalization; for S1P modulators lymphocyte counts should be above 800/mm3
- Use of another investigational product in the past 6 months or longer depending on the mode of action
Show all 22Show fewer
- Previous use of azathioprine or methotrexate in the past 3 months; lymphocyte counts should be above 800/mm3
- Previous use of other immunosuppressive agents washout is at least 3 months or longer depending on the mode of action and half-life; lymphocyte counts should be above 800/mm3
- For intradermal and control arm:
- Relapse / use of corticosteroids for any reason in the previous month;
- Pregnancy or planning pregnancy in the next 18 months and breast feeding;
- Fertile patients, both men and women, who are not using an adequate method of contraception. If the patient is menopausal or sterile, it must be documented in the medical history;
- Drug or alcohol abuse;
- Inability to undergo MRI assessments or unwillingness to receive gadolinium administration;
- History of or actual signs of immunodeficiency (with the exception of treatment effects of patients on 1st line DMT) or malignancies;
- History of oncological diseases, with the exception of completely removed local basal cell carcinoma
- Concurrent clinically relevant cardiac, immunological, pulmonary, neurological, renal or other major disease;
- Positive hepatitis B or C, HIV serology, syphilis or tuberculosis indicating an active of chronic infection;
- Splenectomy;
- Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that could interfere with the compliance to the protocol;
- Participating in another interventional clinical trial, assessing an IMP, or having participated in one, in the last 6 months.
- Previous treatment in the phase I clinical trial with tolDC.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Controlled Phase II Clinical Trial Evaluating the Safety and Efficacy of Myelin-peptide Loaded tolDC as Treatment for Multiple Sclerosis
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
Read the 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
- Being tested
- tolerogenic dendritic cells (tolDC), Standard-of-care
- Keywords
- patient safety, tolerogenic dendritic cells, tolDC, phase II, MS, Multiple sclerosis
- 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 allo-MLR.
Standard-of-careBiological
Standard-of-care on first-line treatment such as interferon-beta, glatiramer acetate, teriflunomide, dimethylfumarate, ponesimod and ozanimod.
| Study group | Role | What they receive |
|---|---|---|
| Intradermal arm: tolerogenic dendritic cells (tolDC) | Experimental | Each vaccine (15x106cells 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 Receives: Biological: tolerogenic dendritic cells (tolDC) |
| Control arm: standard-of-care | Active comparator | Participants who receive standard-of-care, on first-line treatment (interferon-beta, glatiramer acetate, teriflunomide, dimethylfumarate, ponesimod, ozanimod). They will follow the same assessments as the interventional arms Receives: Biological: Standard-of-care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy (Number of new and/or enlarging T2 lesions on MRI)
To evaluate the radiological efficacy of tolDC administration, number of new and/or enlarging T2 lesions on MRI scans
Measured: 18 months
Safety (Occurrence and severity of adverse events will be recorded)
To evaluate the safety of administering tolDC, the occurrence and severity of adverse events will be recorded.
Measured: 18 months
Secondary outcomes (8)
Expanded disability status scale (EDSS)
The patients' 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.
Measured: 18 months
9 Hole Peg Test (9HPT)
This is a brief, standardized, quantitative test of upper extremity function
Measured: 18 months
25 Foot walk test (T25FW)
This is a quantitative mobility and leg function performance test based on a timed 25-walk.
Measured: 18 months
Symbol Digit Modalities test (SDMT)
This test quickly screens for organic cerebral dysfunction.
Measured: 18 months
Non-clinical outcome measure (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 in comparison to standard of care.
Measured: 18 months
Non-clinical outcome measure (atrophy rate on MRI)
Atrophy rate on MRI scans will be evaluated to determine if administration of tolDC influences clinical and subclinical disease evolution in comparison to standard of care.
Measured: 18 months
Non-clinical outcome measure (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 in comparison to standard of care.
Measured: 18 months
Non-clinical outcome measure (fractional anisotropy on MRI)
Fractional anisotropy on MRI scans will be evaluated to determine if administration of tolDC influences clinical and subclinical disease evolution in comparison to standard of care.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2024
- Study start30 Apr 2025 (estimated)
- Primary completion30 Apr 2025 (estimated)
- Study completion29 Oct 2027 (estimated)
Why it stopped: Feasibility issues, insufficient funding, delays due transition to CTIS.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Antwerp
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Germans Tríes i Pujol de Badalona
- Responsible party
- Sponsor
- Investigators
- Nathalie Cools, Principal investigator, Universiteit AntwerpenZwi Berneman, Study director, University Hospital, Antwerp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06715605
- Sponsor's protocol ID
- CCRG22-002
- Other IDs
- 2024-512891-37-00, 2022-003465-38
- Acronym
- MS-tolDC_2
- Status last verified
- Nov 2024
- First submitted
- 27 Nov 2024
- Last updated
- 17 Aug 2025
- 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 17 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Controlled Phase II Clinical Trial Evaluating the Safety and Efficacy of Myelin-peptide Loaded tolDC as Treatment for Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT06715605
- Acronym / sponsor ID
- MS-tolDC_2 / CCRG22-002
- Conditions
- Multiple Sclerosis
- Keywords
- patient safety, tolerogenic dendritic cells, tolDC, phase II, MS, Multiple sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Feasibility issues, insufficient funding, delays due transition to CTIS.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospital, AntwerpUniversity, hospital or other
- Collaborators
- Hospital Germans Tríes i Pujol de Badalona
- Study start
- 30 Apr 2025 (estimated)
- Primary completion
- 30 Apr 2025 (estimated)
- Study completion
- 29 Oct 2027 (estimated)
- First posted
- 4 Dec 2024 (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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intradermal arm: tolerogenic dendritic cells (tolDC) | Experimental | Biological: tolerogenic dendritic cells (tolDC)Each vaccine (15x106cells 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 |
| Control arm: standard-of-care | Active comparator | Biological: Standard-of-careParticipants who receive standard-of-care, on first-line treatment (interferon-beta, glatiramer acetate, teriflunomide, dimethylfumarate, ponesimod, ozanimod). They will follow the same assessments as the interventional arms |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- RIS, CIS or MS according to most recent Mc Donald's diagnostic criteria (1);
- Age 18-60 years;
- Expanded disability status scale (EDSS) of 0-6.0 inclusive;
- Active RIS, CIS, MS (relapsing and progressive forms): 1 relapse in the past year and/or at least 1 enhancing lesion on brain MRI in the past year and/or at least 1 new or enlarging T2 lesion in comparison with a reference scan from maximum 1 year before;
- RIS, CIS, MS patients already on first-line treatment or who will start first-line treatment (control arm)
Key exclusion criteria (22 listed)
- Previous use of severe immunosuppressive or cytostatic treatment, including cyclophosphamide, mitoxantrone, bone marrow transplantation or (hematopoietic or mesenchymal) stem cell transplantation (at any time) prior to enrolment;
- Previous use of cladribine with last course within last 2 years or alemtuzumab with last course within last 4 years; lymphocyte counts should be above 800/mm3
- Only for the intervention arm: Use of interferon beta and glatiramer acetate in the 4 previous weeks; use of teriflunomide in the previous 4 weeks with accelerated elimination procedure; use of dimethyl/diroximel fumarate in the previous 4 weeks with normal lymphocyte counts (above 800/mm3)
- Only for the intervention arm: Treatment with fingolimod, siponimod, ponesimod, ozanimod, natalizumab, intravenous or subcutaneous immunoglobulins or plasmapheresis in the past 3 months; teriflunomide in the previous 15 weeks without accelerated elimination; anti-CD20 monoclonal antibody (including ofatumumab, rituximab and ocrelizumab) within the past 6 months prior to the first administration and until confirmation of B cell count normalization; for S1P modulators lymphocyte counts should be above 800/mm3
- Use of another investigational product in the past 6 months or longer depending on the mode of action
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 allo-MLR. | Biological | Intradermal arm: tolerogenic dendritic cells (tolDC) |
| Standard-of-careStandard-of-care on first-line treatment such as interferon-beta, glatiramer acetate, teriflunomide, dimethylfumarate, ponesimod and ozanimod. | Biological | Control arm: standard-of-care |
Primary outcome
Efficacy (Number of new and/or enlarging T2 lesions on MRI)
Time frame: 18 months
To evaluate the radiological efficacy of tolDC administration, number of new and/or enlarging T2 lesions on MRI scans
Safety (Occurrence and severity of adverse events will be recorded)
Time frame: 18 months
To evaluate the safety of administering tolDC, the occurrence and severity of adverse events will be recorded.
8 secondary outcomes
Expanded disability status scale (EDSS)
Time frame: 18 months
9 Hole Peg Test (9HPT)
Time frame: 18 months
25 Foot walk test (T25FW)
Time frame: 18 months
Symbol Digit Modalities test (SDMT)
Time frame: 18 months
Non-clinical outcome measure (T2 lesion volume on MRI)
Time frame: 18 months
Non-clinical outcome measure (atrophy rate on MRI)
Time frame: 18 months
Non-clinical outcome measure (total brain volume on MRI)
Time frame: 18 months
Non-clinical outcome measure (fractional anisotropy on MRI)
Time frame: 18 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2025.
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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. This study is not recruiting at the moment.
Nathalie Cools principal investigator
Universiteit Antwerpen
Zwi Berneman study director
University Hospital, Antwerp
1 site in 1 country: 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) and Standard-of-care in people with Multiple Sclerosis, run by University Hospital, Antwerp at 1 site in Belgium.
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 13 inclusion and 22 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: withdrawn, as of the sponsor's last update on 17 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. 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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy (Number of new and/or enlarging T2 lesions on MRI) (time frame: 18 months). 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 17 Aug 2025.