TOLDC for Multiple sclerosis|Progressive multiple sclerosis

Inclusion criteria

• {"criterion_text":"- Patient is ≥ 18 years old, and ≤65 years of age, at time of screening visit"}
• {"criterion_text":"- Diagnosis of MS according to the 2017 McDonald Criteria or more recent criteria"}
• {"criterion_text":"- Progressive MS by 2014 Lublin MS phenotypic criteria"}
• {"criterion_text":"- EDSS 2,0 - ≤7,5"}
• {"criterion_text":"- No clinical evidence of relapses in the past 2 years"}
• {"criterion_text":"- Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial."}
• {"criterion_text":"- Appropriate venous access"}
• {"criterion_text":"- Use of adequate contraceptive measures or not of childbearing potential"}

Exclusion criteria

• {"criterion_text":"- Previous treatment with alemtuzumab, autologous hematopoietic stem cell transplantation or cladribine in the past 3 years."}
• {"criterion_text":"- Active or chronic infection with hepatitis B, C, HIV, syphilis or tuberculosis"}
• {"criterion_text":"- Splenectomy"}
• {"criterion_text":"- Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that could interfere with the compliance to the protocol."}
• {"criterion_text":"- Prior treatment with any investigational agent within 3 months, or 5 half-lives, whichever is longer"}
• {"criterion_text":"- Current and ongoing treatment with an approved DMT for MS"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Pregnancy or planning pregnancy in the next 12 months and breast feeding"}
• {"criterion_text":"- Drug or alcohol abuse"}
• {"criterion_text":"- Inability to undergo MRI assessments"}
• {"criterion_text":"- History of or actual signs of immunodeficiency or malignancies (with the exception of treated basal cell carcinoma)"}
• {"criterion_text":"- Concurrent clinically relevant cardiac, immunological, pulmonary, neurological, renal or other major disease that could impact safety or outcome measures."}

Primary endpoints

• {"endpoint_text":"- Evaluate the efficacy of tolDC administration by assessing the change in Expanded Disability Severity Scale (EDSS) score.","definition_or_measurement_approach":"Change in Expanded Disability Severity Scale (EDSS) score will be assessed to evaluate efficacy."}
• {"endpoint_text":"- To assess the safety the tolerability of tolDC administration will be assessed by recording the incidence, severity, and relationship to study treatment of adverse events throughout the trial.","definition_or_measurement_approach":"Safety/tolerability assessed by recording incidence, severity and relationship to study treatment of adverse events throughout the trial."}

Secondary endpoints

• {"endpoint_text":"- Neurological examinations will be complemented with two validated functional tests: the 9-HPT for arm dexterity and the SDMT for cognitive performance. The impact on disability progression will be analyzed by the proportion of participants free from confirmed disability progression","definition_or_measurement_approach":"Functional tests: 9-Hole Peg Test (9-HPT) for arm dexterity; Symbol Digit Modalities Test (SDMT) for cognitive performance; proportion free from confirmed disability progression will be analysed."}
• {"endpoint_text":"- Various MRI measures will be followed for safety and efficacy via the number of new and/or enlarging T2 lesions, total brain volume and brain atrophy.","definition_or_measurement_approach":"MRI measures: number of new/enlarging T2 lesions, total brain volume and measures of brain atrophy."}
• {"endpoint_text":"- Change in Neurofilament Light Chain (NfL) serum and Glial Fibirallary Acidic Protein (GFAP) serum will be assessed as biomarkers","definition_or_measurement_approach":"Biomarker assessment: serum NfL and GFAP measured and compared over time."}
• {"endpoint_text":"- Tertiary end point: To comprehensively assess therapy-related immunological changes and the induction of antigen-specific tolerance, we will perform high-dimensional immune profiling using cryopreserved peripheral blood mononuclear cells (PBMCs) and matched serum/plasma samples collected at predefined time points throughout the trial.","definition_or_measurement_approach":"High-dimensional immune profiling on cryopreserved PBMCs and matched serum/plasma at predefined timepoints (e.g., spectral flow cytometry, TCR sequencing, scRNA-seq, cytokine/chemokine analysis)."}
• {"endpoint_text":"- Tertiary end point: Participants will report their pain experience using a VAS. Quality of life will be measured using the EQ-5D-5L questionnaire.","definition_or_measurement_approach":"Patient-reported outcomes: Visual Analogue Scale (VAS) for pain after each administration; EQ-5D-5L at V0, V3 and V12 for quality of life."}

Belgium

Earliest CTIS Part Ii Submission Date

14-03-2026

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

37

Number Of Sites

1

Number Of Participants

8

Spain

Earliest CTIS Part Ii Submission Date

27-03-2026

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

28

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

Universitair Ziekenhuis Antwerpen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium

Third parties

• {"country":"","full_name":"FWO TBM","duties_or_roles":"Monetary support","organisation_type":""}

Co-sponsors

• Hospital Germans Trias I Pujol