Multiple Sclerosis
Conditions
Keywords
patient safety, tolerogenic dendritic cells, tolDC
Brief summary
A first-in-human clinical trial to treat patients with multiple sclerosis by vaccination with tolerogenic dendritic cells (tolDC), generated using Good Manufacturing Practice (GMP) will be conducted. In doing so, the feasibility and safety of administering myelin-derived peptide-pulsed tolDC in patients with MS will be assessed.
Detailed description
A phase I dose-escalating clinical trial will be conducted in a coordinated and comprehensive manner to determine safety and tolerability, and to enable selection of a suitable dose regimen for phase II trials. The primary objective of the phase I study will be to determine whether tolDC-based therapy is safe and well tolerated and to establish the dose-response, with clinical relapse rates, neurological disability (assessed using various scales) and MRI endpoints, measured over 12 months. Patients will serve as their own controls pre- and post-vaccination. Completion of screening assessments and confirmation of eligibility criteria should take no longer than 6 weeks. First-line treatments will be stopped 6 weeks before baseline at the latest.
Interventions
BIOLOGICALtolerogenic dendritic cells (tolDC)
dose-escalation
Sponsors
University Hospital, Antwerp
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* MS according to 2010 revised McDonald criteria (76); * Expanded disability status scale (EDSS) of 0-6.5 inclusive; * Disease duration of maximum 15 years and first signs or symptoms at least 6 months prior to enrolment in the study; * Active MS (relapsing and progressive): -1 relapse in the past year and/or * at least 1 enhancing lesion on brain MRI in the past year * new or enlarging T2 lesion(s) in comparison with a reference scan from maximum 1 year before * Neurologically stable with no evidence of relapse for at least 30 days prior to start of screening and throughout during the screening phase; * Positive T cell reactivity response to a mix of 7 myelin-derived peptides; * Able to sign informed consent; * Ability to comply with the protocol assessments; * Appropriate venous access. * Use of adequate contraceptive measures
Exclusion criteria
* Previous use of immunosuppressive or cytostatic treatment, including mitoxantrone, alemtuzumab or bone marrow transplantation or stem cell transplantation at any time prior to enrolment; * Treatment with fingolimod or natalizumab or dimethylfumarate or teriflunomide within the last 3 months prior to study enrolment; * Pregnancy or planning pregnancy in the next 12 months and breast feeding; * Drug or alcohol abuse; * Inability to undergo MRI assessments; * History of or actual signs of immunodeficiency or malignancies; * Concurrent clinically relevant cardiac, immunological, pulmonary, neurological, renal or other major disease; * Hepatitis B, C, HIV, Syphilis or tuberculosis * Splenectomy; * Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that could interfere with the compliance to the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety (Occurrence and severity of adverse events will be recorded) | 6 months | Occurrence and severity of adverse events will be recorded |
| Feasibility (Generation of GMP-grade cell product released according to QC) | 6 months | Generation of GMP-grade cell product released according to QC |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 25 Foot walk test (T25FW) | 6 months | This is a quantitative mobility and leg function performance test based on a timed 25-walk. |
| 9 Hole Peg Test (9HPT) | 6 months | This is a brief, standardized, quantitative test of upper extremity function |
| Symbol Digit Modalities test (SDMT) | 6 months | This test quickly screens for organic cerebral dysfunction |
| Number of Gd-enhancing lesions on MRI | 6 months | By means of MRI Gd-enhancing lesions will be analysed |
| Number of new or enlarging T2 lesions on MRI | 6 months | By means of MRI new or enlarging T2 lesions will be analysed |
| Expanded disability status scale (EDSS) | 6 months | The patients' disability level well be checked during every visit |
Other
| Measure | Time frame | Description |
|---|---|---|
| pathogenic T cell responses - immunomonitoring | 6 months | myelin-specific T cell reactivity will be determined before and after completion of the vaccination cycle |
| whole-blood lymphocyte phenotyping - immunomonitoring | 6 months | Blood samples will be analysed into detail, before and after completion of the vaccination cycle |
| cytokine profiling - immunomonitoring | 6 months | Blood samples will be analysed into detail, before and after completion of the vaccination cycle |
| MSQOL-54 | 6 months | The MSQOL-54 is a multidimensional health-related quality of life measure that combines both generic and MS-specific items into a single instrument |
Countries
Belgium
Outcome results
None listed