Clinical trial NCT06592703: Allogenic Adipose Tissue-derived Mesenchymal Stromal Cells for the Treatment of Primary Progressive Multiple Sclerosis
Official title: Allogenic Adipose Tissue-derived Mesenchymal Stromal Cells for the Treatment of Primary Progressive Multiple Sclerosis: an Open-label Phase I Clinical Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Sclerosis
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
Collaborators: name: Etablissement Français du Sang
First posted: 2024-09-19
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study, we propose, for the first time, to test the safety and the potential efficacy of repeated allogenic Adipose tissue-derived Mesenchymal Stromal Cells IT injections in Primary Progressive Multiple Sclerosis patients.

Detailed description: In this study, the investigators propose, for the first time, to test the safety and the potential efficacy of repeated allogenic Adipose tissue-derived Mesenchymal Stromal Cells (ASCs) IT injections in Primary Progressive Multiple Sclerosis (PPMS) patients. In fact, even if autologous Bone Marrow-Mesenchymal Stromal Cells (BM-MSC) and ASCs have already been infused intrathecally in multiple sclerosis, repeated injections of allogenic ASCs have never been tested in this disease. The use of allogenic cells is driven by recent publications reporting decreased suppressive properties of autologous MSC from MS patients.

The hypothesis is that 3 repeated intrathecal (IT) injections of allogenic ASCs every 3 months will be safe and can lower disease progression in PPMS patients.

Preamble of infusing ASCs in the first patient, it's necessary to constitute and characterize the ASC bank. ASC will be obtained from Allogeneic human mesenchymal stromal cells derived from adipose tissue of a living donor.

Once the bank is available, MS patients will be screened and included in Rennes university hospital to received ASC's infusions.

MS patients will be followed for one year after inclusion

Eligibility criteria: Inclusion Criteria:

* Patient with Primary Progressive MS according to the criteria of Mc Donald 2017 (Thompson et al Lancet neurol, 2017)
* Age between 18 and 55 years
* EDSS score: 3 to 6 at inclusion
* Documented evidence of disability progression independent of relapse activity at any point in time over the 2 years prior to the screening visit
* Positive CSF with oligoclonal bands
* For women of childbearing potential (WOCBP), effective contraception as per the CFTG recommendations (version 1.1)
* Having signed a free, informed and written consent
* Affiliated to social security scheme

Exclusion Criteria:

* Inflammatory activity during the past year (relapses or new T2 MRI lesions)
* Disease Modifying Drugs during the past year
* Treatment with high dose corticosteroids during the 30 days preceding the inclusion
* Contra indication to lumbar puncture/intrathecal infusion: intracranial hypertension, puncture site infections, severe thrombocytopenia (\<50 G/L), anticoagulant or fibrinolytic treatment
* Participation in another therapeutic trial in the last 6 months
* Adults under legal protection (safeguard of justice, curatorship, guardianship), persons deprived of their liberty, pregnant or breastfeeding women, minors, persons unable to express their consent

Primary outcomes:
measure: Percentage of patients experiencing at least one adverse effect
timeFrame: 48 weeks
Secondary outcomes:
measure: Description of Adverse events related to experimental product
timeFrame: 48 weeks
measure: Clinical disease evolution at Week24 and Week48 after treatment : Confirmed Disability Progression using Expanded Disability Status Scale score
timeFrame: 3 months
measure: Clinical disease evolution at Week24 and Week48 after treatment : Expanded Disability Status Scale score
timeFrame: 48 weeks
measure: Clinical disease evolution at Week24 and Week48 after treatment : Expanded Disability Status Scale score
timeFrame: 48 weeks
measure: Clinical disease evolution at Week24 and Week48 after treatment : no evidence progression using 9HPT test
timeFrame: 48 weeks
measure: Clinical disease evolution at Week24 and Week48 after treatment : no evidence progression using T25-FW
timeFrame: 48 weeks
measure: Clinical disease evolution at Week24 and Week48 after treatment : MSFC mean changes
timeFrame: 48 weeks
measure: Quality of life disease evolution at Week24 and Week48 after treatment : Multiple Sclerosis International Quality Of Life (MusiQoL) questionnaire
timeFrame: 48 weeks
measure: Immunophenotyping
timeFrame: 48 weeks
measure: Detection of donor specific anti-HLA antibodies in the blood
timeFrame: 28 weeks
measure: MRI parameters : gadolinium (Gd) enhancing lesions
timeFrame: 48 weeks
measure: MRI parameters : new T2 lesions
timeFrame: 48 weeks
measure: MRI parameters : change in brain volume
timeFrame: 48 weeks
measure: MRI parameters : change in spinal cord volume
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Créteil
country: France
facility: APHP Henri Mondor
city: Rennes
country: France
facility: CHU Rennes
Study officials:
affiliation: CHU Rennes
name: Laure MICHEL, Pr
role: PRINCIPAL_INVESTIGATOR
References: