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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Ziekenhuis Antwerpen, Hospital Germans Trias I Pujol

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2026-04-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

FWO TBM

External identifiers

EU CT number

2025-522040-40-01

ClinicalTrials.gov

NCT07020715

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To assess the safety and efficacy of administering myelin-derived peptide-pulsed tolDC, manufactured under Good Manufacturing Practice (GMP) conditions, in patients with progressive forms of MS, within a phase IIa clinical trial framework.

- To evaluate the safety of administering tolDC, the occurrence and severity of adverse events will be recorded.

- To evaluate the efficacy of tolDC administration, the change in Expanded Disability Severity Scale (EDSS) will be assessed.

Secondary objectives 4

1. Clinical outcomes, including number and severity of relapses, annualized relapse rate, 9 Hole Peg Test (9HPT), Symbol Digit Modalities Test (SDMT), and MRI outcome measures, including T2 lesion volume, brain whole brain volume, grey matter volume, will be evaluated to determine if administration of tolDC influences clinical and subclinical disease.
2. Change in Neurofilament Light Chain (NfL) serum and Glial Fibirallary Acidic Protein (GFAP) serum will be assessed as biomarkers.
3. Tertiary objective: To investigate the immunological effects of tolDC administration by analyzing: high-dimensional immune profiling at predefined timepoints before, during, and after the vaccination cycle, including: spectral flow cytometry of PBMCs (e.g., Tregs, Th1, Th17, activation markers), TCR sequencing to assess repertoire changes, scRNA- seq to uncover gene expression signatures of immune tolerance, and serum/plasma cytokine/chemokine analysis using Olink, at predefined timepoints.
4. Tertiary objective: For patient-reported outcomes, a Visual Analogue Scale (VAS) for pain will be assessed after every tolDC administration. Additionally, the Quality of Life (QoL) will be evaluated using the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) at V0, V3 and V12.

Conditions and MedDRA coding

Multiple Sclerosis

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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

Exclusion criteria 12

1. Previous treatment with alemtuzumab, autologous hematopoietic stem cell transplantation or cladribine in the past 3 years.
2. Prior treatment with any investigational agent within 3 months, or 5 half-lives, whichever is longer
3. Current and ongoing treatment with an approved DMT for MS
4. 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
5. Pregnancy or planning pregnancy in the next 12 months and breast feeding
6. Drug or alcohol abuse
7. Inability to undergo MRI assessments
8. History of or actual signs of immunodeficiency or malignancies (with the exception of treated basal cell carcinoma)
9. Concurrent clinically relevant cardiac, immunological, pulmonary, neurological, renal or other major disease that could impact safety or outcome measures.
10. Active or chronic infection with hepatitis B, C, HIV, syphilis or tuberculosis
11. Splenectomy
12. Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that could interfere with the compliance to the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Evaluate the efficacy of tolDC administration by assessing the change in Expanded Disability Severity Scale (EDSS) score.
2. 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.

Secondary endpoints 5

1. 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
2. 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.
3. Change in Neurofilament Light Chain (NfL) serum and Glial Fibirallary Acidic Protein (GFAP) serum will be assessed as biomarkers
4. 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.
5. Tertiary end point: Participants will report their pain experience using a VAS. Quality of life will be measured using the EQ-5D-5L questionnaire.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Ziekenhuis Antwerpen

Sponsor organisation

Universitair Ziekenhuis Antwerpen

Address

Drie Eikenstraat 655

City

Edegem

Postcode

2650

Country

Belgium

Scientific contact point

Organisation

Universitair Ziekenhuis Antwerpen

Contact name

Amber Dams

Public contact point

Organisation

Universitair Ziekenhuis Antwerpen

Contact name

Amber Dams

Hospital Germans Trias I Pujol

Sponsor organisation

Hospital Germans Trias I Pujol

Address

Carretera Canyet 1a Planta

City

Badalona

Postcode

08916

Country

Spain

Scientific contact point

Organisation

Hospital Germans Trias I Pujol

Contact name

Cristina Ramo Tello

Public contact point

Organisation

Hospital Germans Trias I Pujol

Contact name

Cristina Ramo Tello

Sponsor responsibilities

Article 77 compliance

Universitair Ziekenhuis Antwerpen

Contact point sponsor

Universitair Ziekenhuis Antwerpen

Article 77 implementation

Universitair Ziekenhuis Antwerpen

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications