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NCT Number: NCT02912897

Trial to Assess the Safety and Feasibility of Adoptive Cell Therapy with Autologous EBV-specific Cytotoxic T Lymphocytes (CTL) in Patients with a First Clinical Episode Highly Suggestive of Multiple Sclerosis

The etiologic mechanisms involved in multiple sclerosis (MS) are not yet fully understood. Indeed MS is a multifactorial disease involving genetic and environmental factors and Epstein-Barr-Virus (EBV) could be one of these factors. However the link between EBV infection and the immunological mechanisms underlying MS is not clear. Robust sero-epidemiological evidences support an association between EBV infection and MS, and immunological data suggest an altered/deficient immune response against this virus. In healthy individuals EBV produces a persistent infection that is tightly controlled by the immune system. In patients with MS, cellular and humoral immune studies demonstrate an altered response against the virus with a T-cell abnormal reactivity against the EBV-infected autologous B-cells, elevated humoral immune response to Epstein Barr Nuclear Antigen-1, and in the case of children, an increased EBV shedding, demonstrating frequent EBV reactivations. Thus, it has been proposed, that patients with MS present a partially inefficient control of the EBV infection. Some experimental data support the hypothesis suggesting that the presence of autoreactive EBV-B cells in the meninges of patients, probably due to an insufficient clearance of these cells by the immune system, lead to the infiltration of autoreactive T cells. Another hypothesis also suggests a deficient control of the virus, in that case during the inactive phase of the disease. Together, the above data and hypotheses lead to the notion that an immune intervention capable of restoring the host-EBV balance could be beneficial to MS patients In this project, we will assess the feasibility and safety of autologous transfer of several amounts of CD8 T cells directed against autologous EBV transformed B cell lines, in order to finally restore an efficient control of EBV in MS patients. The main objective of the project is to test the feasibility and safety of the process, while efficacy parameters will be also assessed in secondary objectives.

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Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Nervous System Diseases

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 18<Age≤45 years
  • Patients with :
  • A clinically isolated syndrome (first acute or sub acute neurological event consistent with demyelination [i.e. optic neuritis, spinal cord syndrome, brainstem/ cerebellar syndrome])
  • And a MRI scan showing dissemination of MRI lesions in space based on 2017 McDonald criteria At least 1 lesion detected in 2 or more following locations (sites) periventricular, cortical or juxtacortical, infratentorial, spinal cord
  • With a possible dissemination in time based on the revised McDonald cirteria and evicenced on simultaneous detection of one Gadolinium (Gd) enhancing and non-Gd enhancing lesions
  • Or demonstration of CSF-specific oligoclonal bands (OCBs)
  • EDSS Score <3
  • Patients covered by health care insurance (social security)
  • Written informed consent obtained.
  • Onset of symptoms occurring within 60 days of inclusion
  • Patients with HIV, HTLV, Hepatitis B, C Syphilis testing negative within 30 days
  • Positive EBV serology
  • White blood cell count (Leukocytes) > 750/mm3
  • Negative pregnancy test

Exclusion criteria

  • Patients with clinically definite multiple sclerosis
  • Patients known to have HIV, HTLV Hepatitis A, B, C or Syphilis infections or patient with active uncontrolled systemic bacterial, viral, parasitic or fungal infections.
  • Patients with white blood cell count (Leukocytes) < 750/mm3
  • Pregnant or breast feeding women
  • Patient with childbearing potentiel refusing efficient contraceptive method
  • Patients wishing to be pregnant during the course of the study
  • Patients under legal guardianship
  • Concomitant participation of any other trial
  • Patients with mental or psychiatry condition unable to understand the trial
  • Patients with any medically unstable condition or any health conditions that may impact the safety of the patient as determined by the investigator or patient with any stable condition treated with immunotherapy
  • Patients with a history of cancer within 5 years or progressive cancer except for basal or cell skin lesions surgically excised and cured, in situ cervical cancer
  • Patients unable to comply with protocol.
  • Contraindication for MRI or/and any known history of hypersensitivity to contrast medium
  • Patients currently treated with immunosuppressive drugs including oral or systemic corticosteroids

Treatment and study plan

Cellular therapy with EBV specific autologous CTL infusion

Biological

CTL infusions at D0, M3 and M6

Primary outcomes

  1. Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE

    Time frame: 2 years

Study contacts

Contact information is provided by the study sponsor or research team.

David LAPLAUD, Doctor

CONTACT

[email protected]

+ 33 (0)2 40 16 52 00

Sponsors and collaborators

Lead sponsor

Nantes University Hospital

Other

Registry information

Official study title

An Open Single-center, Phase I Proof of Concept Trial to Assess the Safety and Feasibility of Adoptive Cell Therapy with Autologous EBV-specific Cytotoxic T Lymphocytes (CTL) in Patients with a First Clinical Episode Highly Suggestive of Multiple Sclerosis

Acronym: MS and EBV-CTL

Important dates

Study start
2021
Primary completion
2028
Study completion
2028
First posted
Sep 23, 2016
Registry last updated
Feb 19, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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