A "negative"dendritic Cell-based Vaccine for the Treatment of Multiple Sclerosis: a First-in-human Clinical Trial

A phase I dose-escalating clinical trial will be conducted in a coordinated and comprehensive manner to determine safety and tolerability, and to enable selection of a suitable dose regimen for phase II trials. The primary objective of the phase I study will be to determine whether tolDC-based therapy is safe and well tolerated and to establish the dose-response, with clinical relapse rates, neurological disability (assessed using various scales) and MRI endpoints, measured over 12 months. Patients will serve as their own controls pre- and post-vaccination. Completion of screening assessments and confirmation of eligibility criteria should take no longer than 6 weeks. First-line treatments will be stopped 6 weeks before baseline at the latest.

Inclusion criteria

• MS according to 2010 revised McDonald criteria (76);
• Expanded disability status scale (EDSS) of 0-6.5 inclusive;
• Disease duration of maximum 15 years and first signs or symptoms at least 6 months prior to enrolment in the study;
• Active MS (relapsing and progressive): -1 relapse in the past year and/or

• at least 1 enhancing lesion on brain MRI in the past year
• new or enlarging T2 lesion(s) in comparison with a reference scan from maximum 1 year before
• Neurologically stable with no evidence of relapse for at least 30 days prior to start of screening and throughout during the screening phase;
• Positive T cell reactivity response to a mix of 7 myelin-derived peptides;
• Able to sign informed consent;
• Ability to comply with the protocol assessments;
• Appropriate venous access.
• Use of adequate contraceptive measures

Exclusion criteria

• Previous use of immunosuppressive or cytostatic treatment, including mitoxantrone, alemtuzumab or bone marrow transplantation or stem cell transplantation at any time prior to enrolment;
• Treatment with fingolimod or natalizumab or dimethylfumarate or teriflunomide within the last 3 months prior to study enrolment;
• Pregnancy or planning pregnancy in the next 12 months and breast feeding;
• Drug or alcohol abuse;
• Inability to undergo MRI assessments;
• History of or actual signs of immunodeficiency or malignancies;
• Concurrent clinically relevant cardiac, immunological, pulmonary, neurological, renal or other major disease;
• Hepatitis B, C, HIV, Syphilis or tuberculosis
• Splenectomy;
• Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that could interfere with the compliance to the protocol.