Multiple SclerosisPhase 2MODIF-MSNCT06330077
Ifenprodil as a ReMyelinating repurpOsed Drug in Multiple Sclerosis
A Phase 2 study testing Ifenprodil in people with Multiple Sclerosis and Remitting Relapsing Multiple Sclerosis, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial summary
Multiple sclerosis (MS) is the most frequently acquired demyelinating disease and the first cause of non-traumatic chronic disability in young adults. Major progress has been achieved in the treatment of MS through the development of therapies targeting the adaptative immune system, which drastically reduce the… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis, Remitting Relapsing Multiple Sclerosis
- What is being tested?
- Ifenprodil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesFrance
- Study dates
- Mar 2024to Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- -
- 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
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- 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)
Who cannot join
- Patients
- 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
- Contraindications to investigational medicinal products (ifenprodil/placebo) and to auxiliary medicinal products (gadolinium, [18F]-florbetaben)
- 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.).
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- PET imaging performed in the past 12 months as part of clinical research
- 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
- Known long QT syndrome or long QT syndrome (the limit is defined at 450 ms on corrected QT) highlighted during the pre-inclusion visit
- Any uncontrolled general (cancer, infectious, hematologic, hepatic, immunologic, endocrinologic, neurologic, dermatologic, psychiatric, allergic, renal, or cardiovascular) disease.
- 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
- Known of lack of peripheral venous access or lack of peripheral venous access highlighted during the pre-inclusion visit
- Thrombocytopenia with platelets < 100 000/mm3
- Pregnancy and/or lactating women
- Legal protection (curatorship or tutorship)
- Deprive of freedom or under security measure
- 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
- Refusal to be informed in case of clinically significant incidental discovery after MRI
- 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
- 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.
- Contraindication to auxiliary medicinal products ([18F]-florbetaben)
- Known presence of any neurological disorders
- Pregnancy and/or lactation
- Lack of peripheral venous access
- Terminal renal insufficiency (Creatinin clearance < 60 ml/min)
- Legal protection (curatorship or tutorship)
- Deprive of freedom or under security measure
- 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
- Refusal to be informed in case of clinically significant incidental discovery after MRI
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France2 sites
Hôpital Neurologique Pierre WERTHEIMER - HCL
Bron, 69677
Françoise DURAND DUBIEF, MD, 04 72 35 75 22, françoise.durand-dubief@chu-lyon.fr
Groupe Hospitalier Pitié Salpêtrière - APHP
Paris, 75013
Bruno STANKOFF, MD, bruno.stankoff@aphp.fr
About this study
Official title: A Phase 2 Trial Assessing Ifenprodil as a ReMyelinating repurpOsed Drug in Multiple Sclerosis
Multiple sclerosis (MS) is the most frequently acquired demyelinating disease and the first cause of non-traumatic chronic disability in young adults. Major progress has been achieved in the treatment of MS through the development of therapies targeting the adaptative immune system, which drastically reduce the relapse rate, with various efficiency and safety profiles (Ontaneda, 2015). However, these drugs generally fail to prevent disability worsening along the disease course, and we are now assisting to a shift in therapeutic objectives from the development of new immune drugs towards the identification of therapeutic strategies that could prevent neurodegeneration by promoting myelin regeneration (Stangel, 2017; Stankoff, 2016), in order to prevent neurological disability in MS (Irvine and Blakemore, 2008; Patrikios, 2006; Duncan I, 2017, Bodini, 2016).
Among the first candidate compounds developed to promote remyelination was the anti Lingo1 antibody, which enhance remyelination (Mi, 2009). Medium and large throughput screening of drug libraries subsequently identified several chemical classes of compounds with strong promyelinating properties, such as the antifongic drug miconazole (Najm, 2015) or the muscarinic antagonist clemastine (Wei, 2014). A recent innovative trial has investigated the effect of clemastine, compared to placebo, in a small sample of subjects (25 patients per group) and showed that clemastine could significantly improve the optic nerve conduction speed which reflecting myelin integrity and functionality (Green, 2017).
Our preclinical research has allowed us to identify ifenprodil as a powerful drug to promote myelin repair in vitro and in vivo across species. In parallel our team recently pioneered and optimized a PET imaging approach for quantifying remyelination in the whole brain, that allowed to enhance the sensitivity to detect the myelin repair process, and showed that patients are characterized by heterogeneous profiles of spontaneous remyelination profiles that are closely linked to disability accrual (Bodini, 2016).
- Being tested
- Ifenprodil, Placebo
- Keywords
- Multiple Sclerosis, Ifenprofil, Combination of magnetic resonance imaging (MRI) and positron emission tomography (PET), 18f-Florbetaben, Remyelination
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IfenprodilDrug
Treatment administration
PlaceboDrug
Treatment administration
| Study group | Role | What they receive |
|---|---|---|
| Ifenprodil | Experimental | Ifenprodil : 20mg three time a day (60mg/day). Patients will have an escalation of dose over 48 hours (from Day 1) in order to achieve at the end of the 144 hours (6 days, Day 6) a dose of 60mg/day. Receives: Drug: Ifenprodil |
| Placebo | Placebo comparator | Placebo of ifenprodil : 20mg three time a day (60mg/day). Patients will have an escalation of dose over 48 hours (from Day 1) in order to achieve at the end of the 144 hours (6 days, Day 6) a dose of 60mg/day. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in P100 latency according to visual evoked potential.
Assess the efficacy of ifenprodil on the remyelination of the optic nerve measured as the improvement of P100 latency, assessed using full field visual evoked potentials.
Measured: Between months 6 and months 12
Secondary outcomes (9)
Proportion of voxels within white matter lesions classified as remyelinating
Change in remyelination potential measured by PET-MR Between M6 (end of run-in, calculation of pre-treatment remyelination potential, randomization) and M12 (end of follow-up, calculation of post-treatment remyelination potential) in each group.
Measured: Between 6 months and 12 months
Proportion of remyelinating voxels extracted in cortical regions from magnetization transfer imaging (MTR) acquisitions
Change in the proportion of remyelinating voxels extracted in cortical regions from MTR acquisitions (as cortical myelin in not assessed by PET) between M6 and M12 in each group
Measured: Between 6 months and 12 months
Change in amplitude of P100 on to visual evoked potential
- determine whether the treatment by ifenprodil could influence axonal damage in the visual pathway assessed by the amplitude of P100
Measured: Between 6 months and 12 months
Change in retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) thickness on OCT
To determine whether the treatment by ifenprodil could influence neurodegeneration measured by optical coherence tomography (OCT) parameters in each group
Measured: Between 6 months and 12 months
Change in blood concentration of NfL fragments
To determine whether the treatment by ifenprodil could influence axonal damage assessed by the blood concentration of neurofilament light chain (NfL) in each group
Measured: From Pre-inclusion visit to 6 months and from 6 months to 9 months and 6 months to 12 months
Change in the brain atrophy rate
To determine whether the treatment by ifenprodil could influence white matter lesions load or brain atrophy rate in each group
Measured: From baseline to 6 months and 6 months to 12 months
The correlation between the change in the proportion of remyelinating voxels extracted in white matter lesions from [18F]florbetaben PET acquisitions
To determine whether the efficacy of ifenprodil is influenced by endogenous remyelination profiles assessed in the run-in period, and to describe the profile of optimal responders
Measured: Between 6 months and 12 months and the pre-treatment individual remyelination profiles as determined during the Run-in period
The comparison of the proportion of remyelinating voxels extracted in white matter lesions from [18F]florbetaben PET acquisitions
To assess whether the disease modifying therapies received during the study influence the remyelination level and/or the ifenprodil effect on remyelination
Measured: Between 6 months and 12 months
Incidence of adverse drug reactions
Measured: Between inclusion and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2024
- Study startMar 2024 (estimated)
- Primary completionMar 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06330077
- Sponsor's protocol ID
- APHP200027
- Other IDs
- 2021-003584-99
- Acronym
- MODIF-MS
- Status last verified
- Sep 2023
- First submitted
- 12 Mar 2024
- Last updated
- 26 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial Assessing Ifenprodil as a ReMyelinating repurpOsed Drug in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT06330077
- Acronym / sponsor ID
- MODIF-MS / APHP200027
- Keywords
- Multiple Sclerosis, Ifenprofil, Combination of magnetic resonance imaging (MRI) and positron emission tomography (PET), 18f-Florbetaben, Remyelination
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Mar 2024 (estimated)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 26 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multiple sclerosis (MS) is the most frequently acquired demyelinating disease and the first cause of non-traumatic chronic disability in young adults. Major progress has been achieved in the treatment of MS through the development of therapies targeting the adaptative immune system, which drastically reduce the relapse rate, with various efficiency and safety profiles (Ontaneda, 2015). However, these drugs generally fail to prevent disability worsening along the disease course, and we are now assisting to a shift in therapeutic objectives from the development of new immune drugs towards the identification of therapeutic strategies that could prevent neurodegeneration by promoting myelin regeneration (Stangel, 2017; Stankoff, 2016), in order to prevent neurological disability in MS (Irvine and Blakemore, 2008; Patrikios, 2006; Duncan I, 2017, Bodini, 2016).
Among the first candidate compounds developed to promote remyelination was the anti Lingo1 antibody, which enhance remyelination (Mi, 2009). Medium and large throughput screening of drug libraries subsequently identified several chemical classes of compounds with strong promyelinating properties, such as the antifongic drug miconazole (Najm, 2015) or the muscarinic antagonist clemastine (Wei, 2014). A recent innovative trial has investigated the effect of clemastine, compared to placebo, in a small sample of subjects (25 patients per group) and showed that clemastine could significantly improve the optic nerve conduction speed which reflecting myelin integrity and functionality (Green, 2017).
Our preclinical research has allowed us to identify ifenprodil as a powerful drug to promote myelin repair in vitro and in vivo across species. In parallel our team recently pioneered and optimized a PET imaging approach for quantifying remyelination in the whole brain, that allowed to enhance the sensitivity to detect the myelin repair process, and showed that patients are characterized by heterogeneous profiles of spontaneous remyelination profiles that are closely linked to disability accrual (Bodini, 2016).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ifenprodil | Experimental | Drug: IfenprodilIfenprodil : 20mg three time a day (60mg/day). Patients will have an escalation of dose over 48 hours (from Day 1) in order to achieve at the end of the 144 hours (6 days, Day 6) a dose of 60mg/day. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo of ifenprodil : 20mg three time a day (60mg/day). Patients will have an escalation of dose over 48 hours (from Day 1) in order to achieve at the end of the 144 hours (6 days, Day 6) a dose of 60mg/day. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- -
- 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
Key exclusion criteria (34 listed)
- Patients
- 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
- Contraindications to investigational medicinal products (ifenprodil/placebo) and to auxiliary medicinal products (gadolinium, [18F]-florbetaben)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IfenprodilTreatment administration | Drug | Ifenprodil |
| PlaceboTreatment administration | Drug | Placebo |
Primary outcome
Change in P100 latency according to visual evoked potential.
Time frame: Between months 6 and months 12
Assess the efficacy of ifenprodil on the remyelination of the optic nerve measured as the improvement of P100 latency, assessed using full field visual evoked potentials.
9 secondary outcomes
Proportion of voxels within white matter lesions classified as remyelinating
Time frame: Between 6 months and 12 months
Proportion of remyelinating voxels extracted in cortical regions from magnetization transfer imaging (MTR) acquisitions
Time frame: Between 6 months and 12 months
Change in amplitude of P100 on to visual evoked potential
Time frame: Between 6 months and 12 months
Change in retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) thickness on OCT
Time frame: Between 6 months and 12 months
Change in blood concentration of NfL fragments
Time frame: From Pre-inclusion visit to 6 months and from 6 months to 9 months and 6 months to 12 months
Change in the brain atrophy rate
Time frame: From baseline to 6 months and 6 months to 12 months
The correlation between the change in the proportion of remyelinating voxels extracted in white matter lesions from [18F]florbetaben PET acquisitions
Time frame: Between 6 months and 12 months and the pre-treatment individual remyelination profiles as determined during the Run-in period
The comparison of the proportion of remyelinating voxels extracted in white matter lesions from [18F]florbetaben PET acquisitions
Time frame: Between 6 months and 12 months
Incidence of adverse drug reactions
Time frame: Between inclusion and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ifenprodil in people with Multiple Sclerosis and Remitting Relapsing Multiple Sclerosis, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 26 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bruno STANKOFF, MD (0171970659, bruno.stankoff@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in P100 latency according to visual evoked potential. (time frame: Between months 6 and months 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2024.