TY - JOUR
T1 - Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration
AU - RESTORE consortium
AU - Willekens, Barbara
AU - Presas-Rodríguez, Silvia
AU - Mansilla, M. J.
AU - Derdelinckx, Judith
AU - Lee, Wai-Ping
AU - Nijs, Griet
AU - de Laere, Maxime
AU - Wens, Inez
AU - Cras, Patrick
AU - Parizel, Paul
AU - van Hecke, Wim
AU - Ribbens, Annemie
AU - Billiet, Thibo
AU - Adams, Geert
AU - Couttenye, Marie-Madeleine
AU - Navarro-Barriuso, Juan
AU - Teniente-Serra, Aina
AU - Quirant-Sánchez, Bibiana
AU - Lopez-Diaz de Cerio, Ascensión
AU - Inogés, Susana
AU - Prosper, Felipe
AU - Kip, Anke
AU - Verheij, Herman
AU - Gross, Catharina C.
AU - Wiendl, Heinz
AU - van Ham, Marieke Sm
AU - ten Brinke, Anja
AU - Barriocanal, Ana Maria
AU - Massuet-Vilamajó, Anna
AU - Hens, Niel
AU - Berneman, Zwi
AU - Martínez-Cáceres, Eva
AU - Cools, Nathalie
AU - Ramo-Tello, Cristina
PY - 2019/9/1
Y1 - 2019/9/1
N2 - INTRODUCTION: Based on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk profile. Hence, the unmet need for safer and more selective treatments remains. Specifically restoring immune tolerance towards myelin antigens may provide an attractive alternative. In this respect, antigen-specific tolerisation with autologous tolerogenic dendritic cells (tolDC) is a promising approach. METHODS AND ANALYSIS: Here, we will evaluate the clinical use of tolDC in a well-defined population of MS patients in two phase I clinical trials. In doing so, we aim to compare two ways of tolDC administration, namely intradermal and intranodal. The cells will be injected at consecutive intervals in three cohorts receiving incremental doses of tolDC, according to a best-of-five design. The primary objective is to assess the safety and feasibility of tolDC administration. For safety, the number of adverse events including MRI and clinical outcomes will be assessed. For feasibility, successful production of tolDC will be determined. Secondary endpoints include clinical and MRI outcome measures. The patients' immune profile will be assessed to find presumptive evidence for a tolerogenic effect in vivo. ETHICS AND DISSEMINATION: Ethics approval was obtained for the two phase I clinical trials. The results of the trials will be disseminated in a peer-reviewed journal, at scientific conferences and to patient associations. TRIAL REGISTRATION NUMBERS: NCT02618902 and NCT02903537; EudraCT numbers: 2015-002975-16 and 2015-003541-26.
AB - INTRODUCTION: Based on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk profile. Hence, the unmet need for safer and more selective treatments remains. Specifically restoring immune tolerance towards myelin antigens may provide an attractive alternative. In this respect, antigen-specific tolerisation with autologous tolerogenic dendritic cells (tolDC) is a promising approach. METHODS AND ANALYSIS: Here, we will evaluate the clinical use of tolDC in a well-defined population of MS patients in two phase I clinical trials. In doing so, we aim to compare two ways of tolDC administration, namely intradermal and intranodal. The cells will be injected at consecutive intervals in three cohorts receiving incremental doses of tolDC, according to a best-of-five design. The primary objective is to assess the safety and feasibility of tolDC administration. For safety, the number of adverse events including MRI and clinical outcomes will be assessed. For feasibility, successful production of tolDC will be determined. Secondary endpoints include clinical and MRI outcome measures. The patients' immune profile will be assessed to find presumptive evidence for a tolerogenic effect in vivo. ETHICS AND DISSEMINATION: Ethics approval was obtained for the two phase I clinical trials. The results of the trials will be disseminated in a peer-reviewed journal, at scientific conferences and to patient associations. TRIAL REGISTRATION NUMBERS: NCT02618902 and NCT02903537; EudraCT numbers: 2015-002975-16 and 2015-003541-26.
UR - http://www.scopus.com/inward/record.url?scp=85071977960&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/bmjopen-2019-030309
DO - https://doi.org/10.1136/bmjopen-2019-030309
M3 - Article
C2 - 31501122
SN - 2044-6055
VL - 9
SP - e030309
JO - BMJ Open
JF - BMJ Open
IS - 9
M1 - e030309
ER -