drugset / Trial / NCT02903537
Tolerogenic Dendritic Cells as a Therapeutic Strategy for the Treatment of Multiple Sclerosis Patients (TOLERVIT-MS)
Phase 1
Unknown
16 enrolled
Germans Trias i Pujol Research Institute
Clinica Universidad de Navarra, Universidad de Navarra · collab
Non-randomizedParallel-groupOpen-labelTreatment
Summary
The purpose of this study is to determine the safety and tolerability of the intranodal administration of autologous monocyte-derived dendritic cells tolerised with Vitamin-D3 and pulsed with myelin peptides (tolDC-VitD3) in multiple sclerosis patients . To select the most appropriate regime for the development of future therapeutic trials. To evaluate the preliminary proof of concept by clinical and/or radiological activity and immunological markers.
Timeline
- Start
- 2017-07-06
- Primary completion
- 2023-12
- Completion
- 2023-12
Publications
- Background Lutterotti A, Yousef S, Sputtek A, Sturner KH, Stellmann JP, Breiden P, Reinhardt S, Schulze C, Bester M, Heesen C, Schippling S, Miller SD, Sospedra M, Martin R. Antigen-specific tolerance by autologous myelin peptide-coupled cells: a phase 1 trial in multiple sclerosis. Sci Transl Med. 2013 Jun 5;5(188):188ra75. doi: 10.1126/scitranslmed.3006168.
- Background Giannoukakis N, Phillips B, Finegold D, Harnaha J, Trucco M. Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. Diabetes Care. 2011 Sep;34(9):2026-32. doi: 10.2337/dc11-0472. Epub 2011 Jun 16.
- Background Benham H, Nel HJ, Law SC, Mehdi AM, Street S, Ramnoruth N, Pahau H, Lee BT, Ng J, Brunck ME, Hyde C, Trouw LA, Dudek NL, Purcell AW, O'Sullivan BJ, Connolly JE, Paul SK, Le Cao KA, Thomas R. Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients. Sci Transl Med. 2015 Jun 3;7(290):290ra87. doi: 10.1126/scitranslmed.aaa9301.
- Background Naranjo-Gomez M, Raich-Regue D, Onate C, Grau-Lopez L, Ramo-Tello C, Pujol-Borrell R, Martinez-Caceres E, Borras FE. Comparative study of clinical grade human tolerogenic dendritic cells. J Transl Med. 2011 Jun 9;9:89. doi: 10.1186/1479-5876-9-89.
- Background Raiotach-Regue D, Grau-Lopez L, Naranjo-Gomez M, Ramo-Tello C, Pujol-Borrell R, Martinez-Caceres E, Borras FE. Stable antigen-specific T-cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients. Eur J Immunol. 2012 Mar;42(3):771-82. doi: 10.1002/eji.201141835.
- Background Mansilla MJ, Selles-Moreno C, Fabregas-Puig S, Amoedo J, Navarro-Barriuso J, Teniente-Serra A, Grau-Lopez L, Ramo-Tello C, Martinez-Caceres EM. Beneficial effect of tolerogenic dendritic cells pulsed with MOG autoantigen in experimental autoimmune encephalomyelitis. CNS Neurosci Ther. 2015 Mar;21(3):222-30. doi: 10.1111/cns.12342. Epub 2014 Nov 18.
- Background Raich-Regue D, Naranjo-Gomez M, Grau-Lopez L, Ramo C, Pujol-Borrell R, Martinez-Caceres E, Borras FE. Differential effects of monophosphoryl lipid A and cytokine cocktail as maturation stimuli of immunogenic and tolerogenic dendritic cells for immunotherapy. Vaccine. 2012 Jan 5;30(2):378-87. doi: 10.1016/j.vaccine.2011.10.081. Epub 2011 Nov 12.
- Background Ten Brinke A, Hilkens CM, Cools N, Geissler EK, Hutchinson JA, Lombardi G, Lord P, Sawitzki B, Trzonkowski P, Van Ham SM, Martinez-Caceres EM. Clinical Use of Tolerogenic Dendritic Cells-Harmonization Approach in European Collaborative Effort. Mediators Inflamm. 2015;2015:471719. doi: 10.1155/2015/471719. Epub 2015 Dec 24.
- Background Bell GM, Anderson AE, Diboll J, Reece R, Eltherington O, Harry RA, Fouweather T, MacDonald C, Chadwick T, McColl E, Dunn J, Dickinson AM, Hilkens CM, Isaacs JD. Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis. Ann Rheum Dis. 2017 Jan;76(1):227-234. doi: 10.1136/annrheumdis-2015-208456. Epub 2016 Apr 26.
- Background Mansilla MJ, Contreras-Cardone R, Navarro-Barriuso J, Cools N, Berneman Z, Ramo-Tello C, Martinez-Caceres EM. Cryopreserved vitamin D3-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patients. J Neuroinflammation. 2016 May 20;13(1):113. doi: 10.1186/s12974-016-0584-9.
- Willekens B, Presas-Rodriguez S, Mansilla MJ, Derdelinckx J, Lee WP, Nijs G, De Laere M, Wens I, Cras P, Parizel P, Van Hecke W, Ribbens A, Billiet T, Adams G, Couttenye MM, Navarro-Barriuso J, Teniente-Serra A, Quirant-Sanchez B, Lopez-Diaz de Cerio A, Inoges S, Prosper F, Kip A, Verheij H, Gross CC, Wiendl H, Van Ham MS, Ten Brinke A, Barriocanal AM, Massuet-Vilamajo A, Hens N, Berneman Z, Martinez-Caceres E, Cools N, Ramo-Tello C; RESTORE consortium. 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. BMJ Open. 2019 Sep 9;9(9):e030309. doi: 10.1136/bmjopen-2019-030309.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides | Cell therapy | 5 cells | Other |
| Subject | Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides | Cell therapy | 10 cells | Other |
| Subject | Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides | Cell therapy | 15 cells | Other |
| Background | Interferon-beta | Protein / enzyme biologic | — | Subcutaneous |