Diagnosis of multiple sclerosis, according to the most recent diagnostic criteria MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: LLT Classification code 10046859 Term: Vaccination System Organ Class: 100000004865
Conditions
Interventions
Product Name: cryopreserved myelin-derived peptide-loaded tolerogenic dendritic cells
Product Code: tolDC - intradermal
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Autologous my
Sponsors
Antwerp University Hospital
Hospital Universitari Germans Trias i Pujol
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age 18-60 years; • Expanded disability status scale (EDSS) of 0.0 - 6.0 inclusive; • Active MS (relapsing remitting and progressive): 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; • MS patients already on first-line treatment or who will start first-line treatment (control arm) or untreated patients (no wish to be treated with currently available disease-modifying treatments or presence of treatment-related side effects; intervention arms); • No evidence of relapse in the month prior to start of screening and throughout the screening phase; • Normal total lymphocyte count; • Normal peripheral B cell count; • Able to sign informed consent; • Ability to comply with the protocol assessments; • Appropriate venous access; • Appropriate cervical node mapping (only applicable for intranodal injection, in Spain) • Use of adequate contraceptive measures in female and male patients of reproductive potential, for the duration of the trial. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 72 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: For the tolDC intervention groups only: • Previous use of 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; • Use of interferon beta and glatiramer acetate in the 4 previous weeks; • Treatment with fingolimod, natalizumab, immunoglobulins or plasmapheresis in the past 3 months; teriflunomide in the previous 15 weeks; 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 all participants: • Relapse / use of corticosteroids for any reason in the previous month; • Pregnancy or planning pregnancy in the next 12 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, this has to be documented in the medical history. • Drug or alcohol abuse; • Inability to undergo MRI assessments; • History of or actual signs of immunodeficiency or malignancies; • History of oncological diseases unless local basal cell carcinoma • Concurrent clinically relevant cardiac, immunological, pulmonary, neurological, renal or other major disease; • Hepatitis B or C, HIV serology, syphilis or tuberculosis; • 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, or having participated in one, in the last 3 months; • Previous treatment with tolDC.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the phase II study is to determine whether intradermal (in Belgium) or intranodal (in Spain) injection of tolDC is effective and safe. Adverse events, clinical relapse rates, neurological disability (assessed using various scales) and magnetic resonance imaging (MRI) endpoints will be measured over 18 months. Patients, receiving the tolDC intervention, will be compared to a standard-of-care control group - primairy endpoints: safety (reporting of adverse events) and efficacy (the number of new and/or enlarging T2 lesions on MRI scans) - secondary endpoints: (i) clinical: relapse rate, EDSS, 9HPT, T25FW and SDMT, and (ii) non-clinical: all other MRI outcomes - Tertiary and exploratory endpoints: immunological responses and patient-reported quality of life (MS-QoL54);Secondary Objective: not applicable;Primary end point(s): - Efficacy (the number of new and/or enlarging T2 lesions on MRI scans) - Safety (reporting of adverse events) ;Timepoint(s) of evaluation of this end point: - trial entry, defined as the day that the patient signs the informed consent form - at each vaccination visit (V1 to V6) - at follow up visits (F1, F3, F6 and F12) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - clinical: relapse rate, EDSS, 9HPT, T25FW and SDMT - non-clinical: T2 lesion volume, atrophy rate, total brain volume and fractional anisotropy (FA) on MRI scans;Timepoint(s) of evaluation of this end point: CLINICAL: - trial entry, defined as the day that the patient signs the informed consent form - at each vaccination visit (V1 to V6) - at follow up visits (F1, F3, F6 and F12) NON-CLINICAL: - at screening, V1, V4, V6, F1, F6 and F12 | — |
Countries
Belgium, Spain
Contacts
Public ContactNathalie Cools
University of Antwerp
Outcome results
None listed