Clinical trial NCT02618902: A "negative"dendritic Cell-based Vaccine for the Treatment of Multiple Sclerosis: a First-in-human Clinical Trial
Official title: A "negative"dendritic Cell-based Vaccine for the Treatment of Multiple Sclerosis: a First-in-human Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Sclerosis
Keywords: patient safety
tolerogenic dendritic cells
tolDC
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
First posted: 2015-12-02
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety (Occurrence and severity of adverse events will be recorded)
timeFrame: 6 months
measure: Feasibility (Generation of GMP-grade cell product released according to QC)
timeFrame: 6 months
Secondary outcomes:
measure: Expanded disability status scale (EDSS)
timeFrame: 6 months
measure: 9 Hole Peg Test (9HPT)
timeFrame: 6 months
measure: 25 Foot walk test (T25FW)
timeFrame: 6 months
measure: Symbol Digit Modalities test (SDMT)
timeFrame: 6 months
measure: Number of Gd-enhancing lesions on MRI
timeFrame: 6 months
measure: Number of new or enlarging T2 lesions on MRI
timeFrame: 6 months
Other outcomes:
measure: MSQOL-54
timeFrame: 6 months
measure: whole-blood lymphocyte phenotyping - immunomonitoring
timeFrame: 6 months
measure: cytokine profiling - immunomonitoring
timeFrame: 6 months
measure: pathogenic T cell responses - immunomonitoring
timeFrame: 6 months
Locations:
city: Edegem
country: Belgium
facility: Antwerp University Hospital
Study officials:
affiliation: Universiteit Antwerpen
name: Nathalie Cools, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Antwerp
name: Zwi Berneman, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.