Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A "Negative"Dendritic Cell-based Vaccine for the Treatment of Multiple Sclerosis: a First-in-human Clinical Trial (MS-tolDC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02618902
Recruitment Status : Recruiting
First Posted : December 2, 2015
Last Update Posted : March 12, 2018
Sponsor:
Information provided by (Responsible Party):
Nathalie Cools, University Hospital, Antwerp

Tracking Information
First Submitted Date  ICMJE November 18, 2015
First Posted Date  ICMJE December 2, 2015
Last Update Posted Date March 12, 2018
Actual Study Start Date  ICMJE May 30, 2017
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 1, 2015)
  • Safety (Occurrence and severity of adverse events will be recorded) [ Time Frame: 6 months ]
    Occurrence and severity of adverse events will be recorded
  • Feasibility (Generation of GMP-grade cell product released according to QC) [ Time Frame: 6 months ]
    Generation of GMP-grade cell product released according to QC
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02618902 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
  • Expanded disability status scale (EDSS) [ Time Frame: 6 months ]
    The patients' disability level well be checked during every visit
  • 9 Hole Peg Test (9HPT) [ Time Frame: 6 months ]
    This is a brief, standardized, quantitative test of upper extremity function
  • 25 Foot walk test (T25FW) [ Time Frame: 6 months ]
    This is a quantitative mobility and leg function performance test based on a timed 25-walk.
  • Symbol Digit Modalities test (SDMT) [ Time Frame: 6 months ]
    This test quickly screens for organic cerebral dysfunction
  • Number of Gd-enhancing lesions on MRI [ Time Frame: 6 months ]
    By means of MRI Gd-enhancing lesions will be analysed
  • Number of new or enlarging T2 lesions on MRI [ Time Frame: 6 months ]
    By means of MRI new or enlarging T2 lesions will be analysed
Original Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2015)
  • Expanded disability status scale (EDSS) [ Time Frame: 6 months ]
  • 9 Hole Peg Test (9HPT) [ Time Frame: 6 months ]
  • 25 Foot walk test (T25FW) [ Time Frame: 6 months ]
  • Symbol Digit Modalities test (SDMT) [ Time Frame: 6 months ]
  • Number of Gd-enhancing lesions on MRI [ Time Frame: 6 months ]
  • Number of new or enlarging T2 lesions on MRI [ Time Frame: 6 months ]
Current Other Pre-specified Outcome Measures
 (submitted: March 9, 2018)
  • MSQOL-54 [ Time Frame: 6 months ]
    The MSQOL-54 is a multidimensional health-related quality of life measure that combines both generic and MS-specific items into a single instrument
  • whole-blood lymphocyte phenotyping - immunomonitoring [ Time Frame: 6 months ]
    Blood samples will be analysed into detail, before and after completion of the vaccination cycle
  • cytokine profiling - immunomonitoring [ Time Frame: 6 months ]
    Blood samples will be analysed into detail, before and after completion of the vaccination cycle
  • pathogenic T cell responses - immunomonitoring [ Time Frame: 6 months ]
    myelin-specific T cell reactivity will be determined before and after completion of the vaccination cycle
Original Other Pre-specified Outcome Measures
 (submitted: December 1, 2015)
  • MSQOL-54 [ Time Frame: 6 months ]
  • blood immunomonitoring studies [ Time Frame: 6 months ]
 
Descriptive Information
Brief Title  ICMJE A "Negative"Dendritic Cell-based Vaccine for the Treatment of Multiple Sclerosis: a First-in-human Clinical Trial
Official Title  ICMJE A "Negative"Dendritic Cell-based Vaccine for the Treatment of Multiple Sclerosis: a First-in-human Clinical Trial
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE Biological: tolerogenic dendritic cells (tolDC)
dose-escalation
Study Arms  ICMJE Experimental: tolerogenic dendritic cells (tolDC)
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.
Intervention: Biological: tolerogenic dendritic cells (tolDC)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 1, 2015)
9
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nathalie Cools, PhD +32-3-821 3584 nathalie.cools@uza.be
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02618902
Other Study ID Numbers  ICMJE CCRG15-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nathalie Cools, University Hospital, Antwerp
Study Sponsor  ICMJE University Hospital, Antwerp
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Nathalie Cools, PhD Universiteit Antwerpen
Study Director: Zwi Berneman, MD, PhD University Hospital, Antwerp
PRS Account University Hospital, Antwerp
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP