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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Biological: tolerogenic dendritic cells (tolDC)

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: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Antwerp University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Biological: tolerogenic dendritic cells (tolDC); dose-escalation

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MSQOL-54	The MSQOL-54 is a multidimensional health-related quality of life measure that combines both generic and MS-specific items into a single instrument	6 months
whole-blood lymphocyte phenotyping - immunomonitoring	Blood samples will be analysed into detail, before and after completion of the vaccination cycle	6 months
cytokine profiling - immunomonitoring	Blood samples will be analysed into detail, before and after completion of the vaccination cycle	6 months
pathogenic T cell responses - immunomonitoring	myelin-specific T cell reactivity will be determined before and after completion of the vaccination cycle	6 months

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Investigators: Principal Investigator: Nathalie Cools, PhD, Universiteit Antwerpen

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2017
• Primary Completion (Anticipated): November 30, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: November 18, 2015
• First Submitted That Met QC Criteria: December 1, 2015
• First Posted (Estimate): December 2, 2015

Study Record Updates

• Last Update Posted (Actual): May 13, 2021
• Last Update Submitted That Met QC Criteria: May 10, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: patient safety; tolerogenic dendritic cells; tolDC
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: CCRG15-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No