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

Barbara Willekens, Silvia Presas-Rodríguez, M. J. Mansilla, Judith Derdelinckx, Wai Ping Lee, Griet Nijs, Maxime De Laere, Inez Wens, Patrick Cras, Paul Parizel, Wim Van Hecke, Annemie Ribbens, Thibo Billiet, Geert Adams, Marie Madeleine Couttenye, Juan Navarro-Barriuso, Aina Teniente-Serra, Bibiana Quirant-Sánchez, Ascensión Lopez-Diaz De Cerio, Susana InogésFelipe Prosper, Anke Kip, Herman Verheij, Catharina C. Gross, Heinz Wiendl, Marieke Van Ham, Anja Ten Brinke, Ana Maria Barriocanal, Anna Massuet-Vilamajó, Niel Hens, Zwi Berneman, Eva Martínez-Cáceres, Nathalie Cools, Cristina Ramo-Tello

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7 Citations (Scopus)

Abstract

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. 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.
Original languageEnglish
Article numbere030309
JournalBMJ Open
Volume9
DOIs
Publication statusPublished - 1 Sep 2019

Keywords

  • clinical trials
  • immunology
  • magnetic resonance imaging
  • multiple sclerosis

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