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

NCT02618902 | Completed Phase 1 DMC

• 1 other identifier: CCRG15-001
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Keywords

patient safety; tolerogenic dendritic cells; tolDC

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Expanded disability status scale (EDSS)

  6 months

• 9 Hole Peg Test (9HPT)

  6 months

• 25 Foot walk test (T25FW)

  6 months

• Symbol Digit Modalities test (SDMT)

  6 months

• Number of Gd-enhancing lesions on MRI

  6 months

Other Outcomes (4)

• MSQOL-54

  6 months

• whole-blood lymphocyte phenotyping - immunomonitoring

  6 months

• cytokine profiling - immunomonitoring

  6 months

Study Arms (1)

tolerogenic dendritic cells (tolDC)

EXPERIMENTAL

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)

Interventions

tolerogenic dendritic cells (tolDC) BIOLOGICAL

dose-escalation

tolerogenic dendritic cells (tolDC)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Antwerp: lead

Study Sites (1)

Antwerp University Hospital

Edegem, 2650, Belgium

Location

Related Publications (1)

• 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.

  PMID: 31501122 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Nathalie Cools, PhD

  Universiteit Antwerpen

  PRINCIPAL INVESTIGATOR

• Zwi Berneman, MD, PhD

  University Hospital, Antwerp

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 18, 2015
• First Posted: December 2, 2015
• Study Start: May 30, 2017
• Primary Completion: February 3, 2022
• Study Completion: February 3, 2022
• Last Updated: December 9, 2024

Record last verified: 2024-12

Locations

BE (1)