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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A NegativeDendritic Cell-based Vaccine for the Treatment of Multiple Sclerosis: a First-in-human Clinical Trial

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Biological: tolerogenic dendritic cells (tolDC)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tolerogenic dendritic cells (tolDC)<br>Each vaccine (5x106, 10x106 , or 15x106cells in 500 µL NaCl 0.9% solution supplemented with 5% human albumin) will be administered through intradermal injection at 5 sites (100 µL/site) in the subclavicular region (5-10 cm from the cervical lymph nodes). Injection sites will alternate between left and right sides. | Biological: tolerogenic dendritic cells (tolDC)<br>* dose-escalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (Occurrence and severity of adverse events will be recorded) | Occurrence and severity of adverse events will be recorded | 6 months | 
| Feasibility (Generation of GMP-grade cell product released according to QC) | Generation of GMP-grade cell product released according to QC | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expanded disability status scale (EDSS) | The patients' disability level well be checked during every visit | 6 months | 
| 9 Hole Peg Test (9HPT) | This is a brief, standardized, quantitative test of upper extremity function | 6 months | 
| 25 Foot walk test (T25FW) | This is a quantitative mobility and leg function performance test based on a timed 25-walk. | 6 months | 
| Symbol Digit Modalities test (SDMT) | This test quickly screens for organic cerebral dysfunction | 6 months | 
| Number of Gd-enhancing lesions on MRI | By means of MRI Gd-enhancing lesions will be analysed | 6 months | 
| Number of new or enlarging T2 lesions on MRI | By means of MRI new or enlarging T2 lesions will be analysed | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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patient safety, tolerogenic dendritic cells, tolDC