Abstract Details

Title Tolerogenic dendritic cell-based treatment in multiple sclerosis (MS): Interim results of two phase I clinical trials.

Topic Multiple Sclerosis

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-047

Objective To assess the safety, feasibility and clinical use of of autologous tolerogenic dendritic cells (tolDC) as a treatment option for MS patients in two clinical trials, comparing the intradermal (MS-tolDC) and intranodal (TOLERVIT-MS) route of administration.

Background

Although current treatments for MS reduce disease activity, they carry significant treatment-related risks. Hence, there still is an unmet need for treatments combining safety with efficacy.

Design/Methods Following a leukapheresis procedure, clinical-grade tolDC are differentiated from CD14+ monocytes in the presence of 1α,25-dihydroxyvitamin-D₃,loaded with 7 myelin-derived antigens (MBP_13-32, MBP_111-129, MBP_154-170, PLP_139-154, MOG_1-20, MOG_35-55and MBP_83-99), and cryopreserved. Six consecutive administrations are planned in 3 cohorts receiving incremental doses of tolDC (5x10⁶, 10x10⁶ and 15x10⁶ tolDC), according to a best-of-five design. For safety, number of adverse events (AE), relapses, neurological disability, and brain magnetic resonance imaging (MRI) endpoints are assessed. Other outcome measures include efficacy, immunomonitoring and quality of life.

Results To date, in both studies, six patients received tolDC and are in safety follow-up phase. Four of 6 patients have relapsing-remitting MS (1 male, 3 female), and 2 active primary-progressive MS. The age ranged between 30-43 years, the disease duration between 2-13 years. EDSS at baseline varied between 1.5-6.0. No serious AE have been reported. Mild-moderate local reactions and pain at the injection site were observed and considered treatment-related. Two patients experienced a mild relapse (not meeting protocol definition) following intradermal injection of tolDC. In 1 of these patients, a single new MRI lesion was detected before the onset of the relapse. Three patients with significant MRI activity before intranodal treatment with tolDC maintained high MRI activity during the study.

Conclusions The safety follow-up phase of the lowest dose cohort (n=6) is currently ongoing. Further follow-up is needed to demonstrate whether the observed disease activity on MRI is treatment related.

Authors/Disclosures
Silvia Presas PRESENTER	Silvia Presas has nothing to disclose.
Barbara Willekens, MD, PhD, FAAN (Antwerp University Hospital)	The institution of Dr. Willekens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Willekens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. The institution of Dr. Willekens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. The institution of Dr. Willekens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Willekens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. The institution of Dr. Willekens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. The institution of Dr. Willekens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. The institution of Dr. Willekens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Almirall . The institution of Dr. Willekens has received research support from Roche. The institution of Dr. Willekens has received research support from Janssen. Dr. Willekens has a non-compensated relationship as a Co-chair scientific panel of neuroimmunology with European Academy of Neurology that is relevant to AAN interests or activities.
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Aina Teniente-Serra	No disclosure on file
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Patrick Cras, MD, PhD (University of Antwerp)	The institution of Dr. Cras has received research support from Belgian Fund for Scientific Research. Dr. Cras has received personal compensation in the range of $0-$499 for serving as a member with National Bioethics Committee.
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Wim Van Hecke, PhD (University Hospital Brussels)	Dr. Van Hecke has received personal compensation for serving as an employee of icometrix.
Annemie Ribbens	Annemie Ribbens has received personal compensation for serving as an employee of icometrix. Annemie Ribbens has stock in icometrix. Annemie Ribbens has received intellectual property interests from a discovery or technology relating to health care.
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Heinz Wiendl, MD, FAAN (University of Freiburg)	Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Johnson&Johnson / Janssen. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Wiendl has received personal compensation in the range of $0-$499 for serving as a Consultant for Idorsia. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Immunic. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for LTS. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sangamo. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for INmune Bio_Syneos Health. Dr. Wiendl has received personal compensation in the range of $0-$499 for serving as a Consultant for Muna Therapeutics. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Myrobalan Therapeutics. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PSL Group. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Red Nucleus. Dr. Wiendl has received personal compensation in the range of $0-$499 for serving as a Consultant for Swiss Multiple Sclerosis Society. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teladoc Health. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Toleranzia . Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viatris. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz-Hexal. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cellerys. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Uniqure. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biocryst. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Galapagos. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Idorsia. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biontech. The institution of Dr. Wiendl has received research support from Biogen. The institution of Dr. Wiendl has received research support from Roche. The institution of Dr. Wiendl has received research support from Deutsche Forschungsgemeinschaft. The institution of Dr. Wiendl has received research support from European Union. The institution of Dr. Wiendl has received research support from Argenx. The institution of Dr. Wiendl has received research support from CSL Behring. The institution of Dr. Wiendl has received research support from Merck. The institution of Dr. Wiendl has received research support from UCB. Dr. Wiendl has received research support from Alexion Syneos Health iVH UK Ltd.. The institution of Dr. Wiendl has received research support from Deutsche Myasthenie-Gesellschaft. The institution of Dr. Wiendl has received research support from Winicker Norimed GmbH. The institution of Dr. Wiendl has received research support from Novartis. Dr. Wiendl has received publishing royalties from a publication relating to health care. Dr. Wiendl has received publishing royalties from a publication relating to health care. Dr. Wiendl has received publishing royalties from a publication relating to health care.
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Cristina M. Ramo, MD (Hospital Germans Trias I Pujol)	Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ALMIRALL . Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SANDOZ. Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Almirall. Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOGEN. Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen . Dr. Ramo has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of Dr. Ramo has received research support from HORIZON-2020. The institution of Dr. Ramo has received research support from fis (SPANISH GOVERNMENT). The institution of Dr. Ramo has received research support from BIOGEN. The institution of Dr. Ramo has received research support from MERCK. The institution of Dr. Ramo has received research support from ALMIRALL. The institution of Dr. Ramo has received research support from NOVARTIS. The institution of Dr. Ramo has received research support from RICORS (Spanish Government). The institution of Dr. Ramo has received research support from ROCHE. Dr. Ramo has received publishing royalties from a publication relating to health care.

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