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

Primary Purpose

Multiple Sclerosis

Status
Unknown status
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
tolerogenic dendritic cells (tolDC)
Sponsored by
University Hospital, Antwerp
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring patient safety, tolerogenic dendritic cells, tolDC

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Antwerp University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

tolerogenic dendritic cells (tolDC)

Arm Description

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.

Outcomes

Primary Outcome Measures

Safety (Occurrence and severity of adverse events will be recorded)
Occurrence and severity of adverse events will be recorded
Feasibility (Generation of GMP-grade cell product released according to QC)
Generation of GMP-grade cell product released according to QC

Secondary Outcome Measures

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

Full Information

First Posted
November 18, 2015
Last Updated
May 10, 2021
Sponsor
University Hospital, Antwerp
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1. Study Identification

Unique Protocol Identification Number
NCT02618902
Brief Title
A "Negative"Dendritic Cell-based Vaccine for the Treatment of Multiple Sclerosis: a First-in-human Clinical Trial
Acronym
MS-tolDC
Official Title
A "Negative"Dendritic Cell-based Vaccine for the Treatment of Multiple Sclerosis: a First-in-human Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Unknown status
Study Start Date
May 30, 2017 (Actual)
Primary Completion Date
November 30, 2021 (Anticipated)
Study Completion Date
December 31, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Antwerp

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
patient safety, tolerogenic dendritic cells, tolDC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
tolerogenic dendritic cells (tolDC)
Arm Type
Experimental
Arm Description
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 Type
Biological
Intervention Name(s)
tolerogenic dendritic cells (tolDC)
Intervention Description
dose-escalation
Primary Outcome Measure Information:
Title
Safety (Occurrence and severity of adverse events will be recorded)
Description
Occurrence and severity of adverse events will be recorded
Time Frame
6 months
Title
Feasibility (Generation of GMP-grade cell product released according to QC)
Description
Generation of GMP-grade cell product released according to QC
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Expanded disability status scale (EDSS)
Description
The patients' disability level well be checked during every visit
Time Frame
6 months
Title
9 Hole Peg Test (9HPT)
Description
This is a brief, standardized, quantitative test of upper extremity function
Time Frame
6 months
Title
25 Foot walk test (T25FW)
Description
This is a quantitative mobility and leg function performance test based on a timed 25-walk.
Time Frame
6 months
Title
Symbol Digit Modalities test (SDMT)
Description
This test quickly screens for organic cerebral dysfunction
Time Frame
6 months
Title
Number of Gd-enhancing lesions on MRI
Description
By means of MRI Gd-enhancing lesions will be analysed
Time Frame
6 months
Title
Number of new or enlarging T2 lesions on MRI
Description
By means of MRI new or enlarging T2 lesions will be analysed
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
MSQOL-54
Description
The MSQOL-54 is a multidimensional health-related quality of life measure that combines both generic and MS-specific items into a single instrument
Time Frame
6 months
Title
whole-blood lymphocyte phenotyping - immunomonitoring
Description
Blood samples will be analysed into detail, before and after completion of the vaccination cycle
Time Frame
6 months
Title
cytokine profiling - immunomonitoring
Description
Blood samples will be analysed into detail, before and after completion of the vaccination cycle
Time Frame
6 months
Title
pathogenic T cell responses - immunomonitoring
Description
myelin-specific T cell reactivity will be determined before and after completion of the vaccination cycle
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nathalie Cools, PhD
Organizational Affiliation
Universiteit Antwerpen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zwi Berneman, MD, PhD
Organizational Affiliation
University Hospital, Antwerp
Official's Role
Study Director
Facility Information:
Facility Name
Antwerp University Hospital
City
Edegem
ZIP/Postal Code
2650
Country
Belgium

12. IPD Sharing Statement

Citations:
PubMed Identifier
31501122
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.
Results Reference
derived

Learn more about this trial

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

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