Ifenprodil as a ReMyelinating repurpOsed Drug in Multiple Sclerosis

Prior treatment

• Patient with an acute NORB in the last 6 months prior to pre-inclusion visit
• Patient with a clinical relapse other than NORB in the last 6 months prior to pre-inclusion visit
• Patients having received methylprednisolone infusion in the last 4 weeks prior to pre-inclusion visit
• Inability to complete an MRI (contraindications for MRI include but are not restricted to weight ≥ 140 kg, pacemaker, cochlear implants, presence of foreign substances in the eye, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, contraindication to gadoteric acid etc.).
• Participation in another interventional trial evaluating a health product or any randomized trial or being in the exclusion period at the end of a previous study
• Inability to complete an MRI (contraindications for MRI include but are not restricted to weight ≥ 140 kg, pacemaker, cochlear implants, presence of foreign substances in the eye, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc).
• Impossibility to complete a PET scan: pregnancy, nuclear medicine irradiation for clinical research in the year preceding baseline visit.
• Participation in another interventional trial evaluating a health product or any randomized trial or being in the exclusion period at the end of a previous study

Other illness

• History or incidental discovery of significant cardiac conduction block
• Orthostatic hypotension Syndrome define as a drop of \> 20 mmHg in systolic, and/or \> 10 mmHg in diastolic between lying down and immediate standing
• Any uncontrolled general (cancer, infectious, hematologic, hepatic, immunologic, endocrinologic, neurologic, dermatologic, psychiatric, allergic, renal, or cardiovascular) disease.
• Patient treated for hypertension with the following drugs blocking the alpha-adrenergic system either in periphery (prazosine, urapidil, moxisylyte, labetalol) or centrally (clonidine, monoxidine, methyldopa)
  • Healthy Volunteers
• Known presence of any neurological disorders

Lab values

• Known long QT syndrome or long QT syndrome (the limit is defined at 450 ms on corrected QT) highlighted during the pre-inclusion visit
• Creatinine clearance \< 60 ml/min at pre-inclusion visit
• ASAT, ALAT of alkaline phosphatase \> 3-fold the upper limit normal at pre-inclusion visit
• Know Galactosemia, glucose malabsorption or lactase deficiency
• Thrombocytopenia with platelets \< 100 000/mm3
• Terminal renal insufficiency (Creatinin clearance \< 60 ml/min)

Other

• Patients
• Contraindications to investigational medicinal products (ifenprodil/placebo) and to auxiliary medicinal products (gadolinium, \[18F\]-florbetaben)
• PET imaging performed in the past 12 months as part of clinical research
• Known of lack of peripheral venous access or lack of peripheral venous access highlighted during the pre-inclusion visit
• Pregnancy and/or lactating women
• Legal protection (curatorship or tutorship)
• Deprive of freedom or under security measure
• Refusal to be informed in case of clinically significant incidental discovery after MRI
• Contraindication to auxiliary medicinal products (\[18F\]-florbetaben)
• Pregnancy and/or lactation
• Lack of peripheral venous access
• Legal protection (curatorship or tutorship)
• Deprive of freedom or under security measure
• Refusal to be informed in case of clinically significant incidental discovery after MRI

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• Patients:
• Signed informed consent form at pre-inclusion visit
• Age between 18 years and 55 years, inclusive, at time of pre-inclusion visit.
• Patient with a RR form of MS according McDonald criteria 2017 at pre-inclusion visit
• Able to comply with the study protocol and to understand the purpose and risks of the study, in the investigator's judgment
• Social security registration (AME excluded) at time of pre-inclusion visit
• At least one eye with a P100 latency \> 118ms on visual evoked potential at baseline (defining the qualifying eye) at time of pre-inclusion visit
• Retinal nerve fibre layer thickness on spectral-domain optical coherence tomography \[OCT\] \> 70 μm in the VEP qualifying eye (to increase the likelihood that the number of surviving axons is sufficient to provide the substrate for remyelination to occur) at time of pre-inclusion visit
• Patient under disease modifying therapy (first or second line approved immune active therapy) or patient without any DMT at time of pre-inclusion visit
• EDSS score ≤ 6 at time of pre-inclusion visit
• For women of childbearing potential : Efficient contraception include oral contraception, intrauterine devices hormonal device, intrauterine hormone-releasing system, sterilization method and other forms of contraception with failure rate \<1%)
  • Healthy Volunteers
  • 1\. Signed informed consent form 2. Age between 18 years and 55 years, inclusive 3. All female subjects of childbearing potential must practice effective contraception include oral contraception, intrauterine devices hormonal device, intrauterine hormone-releasing system, sterilization method and other forms of contraception with failure rate \<1%) 4. Able to comply with the study protocol, in the investigator's judgment 5. Social security registration (AME excluded)