A Clinical Trial Evaluating the Safety and Efficacy of Myelin-peptide Loaded tolDC as Treatment for MS (MS-tolDC_2)

August 12, 2025 updated by: University Hospital, Antwerp

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Belgium
      • Edegem, Belgium, 2650
        • Antwerp University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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;
  • 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.

Exclusion Criteria:

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
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Intradermal arm: 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
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.
Active Comparator: Control arm: standard-of-care
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
Biological: Standard-of-care
Standard-of-care on first-line treatment such as interferon-beta, glatiramer acetate, teriflunomide, dimethylfumarate, ponesimod and ozanimod.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
18 months
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.
18 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Expanded disability status scale (EDSS)
Time Frame: 18 months
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.
18 months
9 Hole Peg Test (9HPT)
Time Frame: 18 months
This is a brief, standardized, quantitative test of upper extremity function
18 months
25 Foot walk test (T25FW)
Time Frame: 18 months
This is a quantitative mobility and leg function performance test based on a timed 25-walk.
18 months
Symbol Digit Modalities test (SDMT)
Time Frame: 18 months
This test quickly screens for organic cerebral dysfunction.
18 months
Non-clinical outcome measure (T2 lesion volume on MRI)
Time Frame: 18 months
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.
18 months
Non-clinical outcome measure (atrophy rate on MRI)
Time Frame: 18 months
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.
18 months
Non-clinical outcome measure (total brain volume on MRI)
Time Frame: 18 months
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.
18 months
Non-clinical outcome measure (fractional anisotropy on MRI)
Time Frame: 18 months
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.
18 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Immunological response
Time Frame: 18 months
In addition to (whole-blood) lymphocyte phenotyping and cytokine profiling before, during and after completion of the vaccination cycle, the ability of tolDC to suppress pathogenic T responses will be assessed. Therefore, myelin-specific T reactivity will be determined before, during and after completion of the vaccination cycle at specific timepoints.
18 months
Visual Analogic Scale (VAS)
Time Frame: 18 months
Measures pain intensity. The VAS consists of a 10cm line, with two end points representing 0 ('no pain') and 10 ('pain as bad as it could possibly be')
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Antwerp

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Hospital Germans Tríes i Pujol de Badalona

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Nathalie Cools, Universiteit Antwerpen
  • Study Director: Zwi Berneman, University Hospital, Antwerp

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 29, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 27, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 3, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 4, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 17, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CCRG22-002
  • 2024-512891-37-00 (Ctis)
  • 2022-003465-38 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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