Contributions
Abstract: EP1489
Type: ePoster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: In multiple sclerosis (MS) there is an established role for dendritic cells in the pathophysiology of the disease. Dendritic cells are capable of modulating the balance between immunity and tolerance. Animal studies have shown positive effects of tolerogenic dendritic cell (tolDC) treatment.
Methods: A single-center phase I dose-escalating clinical trial will be conducted to determine safety and feasability and to enable selection of a suitable dose regimen for phase II trials.
The primary objective is to determine whether myelin-derived peptide-loaded tolDC-based treatment is safe in active multiple sclerosis. Secondly, to establish the maximum tolerated dose as indicated by adverse events, clinical relapse rates, neurological disability and MRI endpoints, measured over 12 months.
Patients will be selected on the basis of having T-cell reactivity towards a mixture of 7 myelin-derived peptides. Furthermore, disease activity is required under the form of relapses and/or activity on brain magnetic resonance imaging (MRI), with the purpose of including a population of patients with inflammatory disease activity. A 3+3+3 design is used. The cell product will be injected intradermally at repeated intervals. Inclusion and exclusion criteria will be described in detail as well as the study plan and procedures.
Results: The primary outcome measures are the number and severity of adverse events as well as the feasability of the generation of a Good Manufacturing Practices (GMP)-grade cell product released according to quality control specifications.
Secondary outcome measures are Expanded Disability Status Scale (EDSS), Timed 25 Foot Walk test (T25FW), Symbol Digit Modalities Test (SDMT), brain MRI T2 and enhancing lesions at regular time points. Tertiary outcome measures are immunomonitoring and patient-reported outcome measures. Each patient is used as his/her own control, pre- and postintervention.
Discussion: In this phase I trial of a tolerogenic dendritic cell vaccination in active multiple sclerosis safety will be assessed in a selected population. The study protocol is presented here. Inclusion is expected to start in the second half of 2016. This study may lead to phase II trials investigating this patient-tailored treatment in multiple sclerosis.
Disclosure:
Source of funding: This work was supported by positive discussion through A FACTT network (Cost Action BM1305: www.afactt.eu). COST is supported by the EU Framework Programme Horizon 2020. Further support was provided by an applied biomedical research project of the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT-TBM 140191).
Barbara Willekens: nothing to disclose
Nathalie Cools: nothing to disclose
Zwi Berneman: nothing to disclose
Patrick Cras: nothing to disclose
Judith Derdelinckx: nothing to disclose
Annemie Ribbens: employee of Icometrix
Wim Van Hecke: shareholder of Icometrix
Eva-Martinez Caceres: nothing to disclose
Cristina-Ramo Tello: nothing to disclose
Paul Parizel: nothing to disclose
Abstract: EP1489
Type: ePoster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: In multiple sclerosis (MS) there is an established role for dendritic cells in the pathophysiology of the disease. Dendritic cells are capable of modulating the balance between immunity and tolerance. Animal studies have shown positive effects of tolerogenic dendritic cell (tolDC) treatment.
Methods: A single-center phase I dose-escalating clinical trial will be conducted to determine safety and feasability and to enable selection of a suitable dose regimen for phase II trials.
The primary objective is to determine whether myelin-derived peptide-loaded tolDC-based treatment is safe in active multiple sclerosis. Secondly, to establish the maximum tolerated dose as indicated by adverse events, clinical relapse rates, neurological disability and MRI endpoints, measured over 12 months.
Patients will be selected on the basis of having T-cell reactivity towards a mixture of 7 myelin-derived peptides. Furthermore, disease activity is required under the form of relapses and/or activity on brain magnetic resonance imaging (MRI), with the purpose of including a population of patients with inflammatory disease activity. A 3+3+3 design is used. The cell product will be injected intradermally at repeated intervals. Inclusion and exclusion criteria will be described in detail as well as the study plan and procedures.
Results: The primary outcome measures are the number and severity of adverse events as well as the feasability of the generation of a Good Manufacturing Practices (GMP)-grade cell product released according to quality control specifications.
Secondary outcome measures are Expanded Disability Status Scale (EDSS), Timed 25 Foot Walk test (T25FW), Symbol Digit Modalities Test (SDMT), brain MRI T2 and enhancing lesions at regular time points. Tertiary outcome measures are immunomonitoring and patient-reported outcome measures. Each patient is used as his/her own control, pre- and postintervention.
Discussion: In this phase I trial of a tolerogenic dendritic cell vaccination in active multiple sclerosis safety will be assessed in a selected population. The study protocol is presented here. Inclusion is expected to start in the second half of 2016. This study may lead to phase II trials investigating this patient-tailored treatment in multiple sclerosis.
Disclosure:
Source of funding: This work was supported by positive discussion through A FACTT network (Cost Action BM1305: www.afactt.eu). COST is supported by the EU Framework Programme Horizon 2020. Further support was provided by an applied biomedical research project of the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT-TBM 140191).
Barbara Willekens: nothing to disclose
Nathalie Cools: nothing to disclose
Zwi Berneman: nothing to disclose
Patrick Cras: nothing to disclose
Judith Derdelinckx: nothing to disclose
Annemie Ribbens: employee of Icometrix
Wim Van Hecke: shareholder of Icometrix
Eva-Martinez Caceres: nothing to disclose
Cristina-Ramo Tello: nothing to disclose
Paul Parizel: nothing to disclose