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

Who is this study for? Patients with Multiple Sclerosis
What treatments are being studied? Cellular Therapy with EBV Specific Autologous CTL Infusion
Status: Recruiting
Location: See location...
Intervention Type: Biological
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 45
Healthy Volunteers: f
View:

• 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

Locations
Other Locations
France
University Hospital
RECRUITING
Nantes
Contact Information
Primary
David LAPLAUD, Doctor
david.laplaud@univ-nantes.fr
+ 33 (0)2 40 16 52 00
Time Frame
Start Date: 2021-01-26
Estimated Completion Date: 2028-11
Participants
Target number of participants: 7
Treatments
Experimental: Cellular therapy with EBV specific autologous CTL infusion
Related Therapeutic Areas
Sponsors
Leads: Nantes University Hospital

This content was sourced from clinicaltrials.gov

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