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

NCT ID: NCT02618902

Last Updated: 2024-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-30
• Study Completion Date: 2022-02-03

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.

Conditions

Multiple Sclerosis

Keywords

patient safety; tolerogenic dendritic cells; tolDC

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

tolerogenic dendritic cells (tolDC)

Intervention Type: BIOLOGICAL

dose-escalation

Interventions

tolerogenic dendritic cells (tolDC)

dose-escalation

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Antwerp

OTHER

Sponsor Role: lead

Responsible Party

Zwi Berneman

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nathalie Cools, PhD

Role: PRINCIPAL_INVESTIGATOR

Universiteit Antwerpen

Zwi Berneman, MD, PhD

Role: STUDY_DIRECTOR

University Hospital, Antwerp

Locations

Antwerp University Hospital

Edegem, , Belgium

Countries

Belgium

References

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.

Reference Type: DERIVED

PMID: 31501122 (View on PubMed)

Other Identifiers

CCRG15-001

Identifier Type: -

Identifier Source: org_study_id