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

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

A first-in-human clinical trial to treat patients with multiple sclerosis by vaccination with tolerogenic dendritic cells (tolDC), generated using Good Manufacturing Practice (GMP) will be conducted. In doing so, the feasibility and safety of administering myelin-derived peptide-pulsed tolDC in patients with MS will be assessed.

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.