Clinical trial NCT02769689: Methylprednisolone During the Switch Between Natalizumab and Fingolimod
Official title: Once a Month High-dose Methylprednisolone During Wash-out Period Between Natalizumab and Fingolimod Treatments in Patients With Multiple Sclerosis: a Randomised, Controlled, Double-blind Trial (NTZ2FTY)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Multiple Sclerosis
Keywords: Multiple sclerosis
Natalizumab
Fingolimod
Methylprednisolone
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2016-05-12
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Progressive multifocal leukoencephalopathy (PML) is the most feared complication when natalizumab (NTZ) is used in the treatment of relapsing multiple sclerosis (MS). The risk of PML increases after 18 months of treatment. When switching from NTZ to another disease modifying treatment (DMT) in these MS patients with an active disease, there is a high risk of inflammatory reactivation. Nonetheless, a washout period of several weeks is necessary before initiating a new DMT.

The primary purpose of this protocol is to investigate the impact of high dose of oral methylprednisolone, given once a month during the washout period between NTZ and Fingolimod (FTY).

Detailed description: Patients with MS receiving NTZ for at least 18 months and without any disease activity during the previous year will be eligible. Included patients will receive either methylprednisolone (1 gramme, 1 day every 4 weeks for a total of 3 grammes) or undistinguishable capsules of placebo.

Every patient will initiate a treatment with FTY 7 weeks after the last NTZ perfusion. Methylprednisolone or placebo will be taken 4, 8 and 12 weeks (W4, W8 and W12) after NTZ discontinuation.

A spinal and brain MRI will be performed at baseline (last NTZ perfusion, noted W0) and 16 to 18 weeks after. The last clinical follow-up will be made after 24 weeks.

Eligibility criteria: Inclusion Criteria:

* Relapsing-Remitting Multiple Sclerosis (Mc Donald's 2010 criteria)
* EDSS\<6.0
* At least18 natalizumab infusions
* Planned switch from natalizumab to fingolimod
* Aged between 18 and 65
* Patients must have received high dose IV methylprednisolone during the 5 previous years

Exclusion Criteria:

* Progressive MS
* Uncontrolled MS with natalizumab (existence of a relapse during the previous 12 months or existence of a gadolinium enhancing lesion on a MRI performed during the last 12 months)
* SEP de forme progressive
* Contra-indication to the use of high dose oral methylprednisolone
* Marked cognitive impairment altering protocole understanding
* Switch from natalizumab to a disease modifying treatment different from fingolimod
* Contra-indication to fingolimod use
* Existence of a disease or condition that could alter study completion
* Chronic treatment with steroids
* Acute treatment with steroids (more than 300mg during the month prior to inclusion)
* Contra-indication to gadolinium containing products injection
* Pregnancy

Primary outcomes:
measure: efficacy of high dose methylprednisolone compared to that of a placebo
timeFrame: at 6 months
Secondary outcomes:
measure: comparison of the number of new T2 or gadolinium enhanced lesions on MRI in the 2 treatment groups
timeFrame: at 4 months
measure: comparison of the number of MS relapses during the 6 months after natalizumab discontinuation, in the 2 treatment groups
timeFrame: at 6 months
measure: potential correlations between previous MS activity and the risk of relapse or inflammatory rebound on MRI after natalizumab discontinuation
timeFrame: at 6 months
measure: adverse effects of high dose oral prednisolone
timeFrame: at 6 months
measure: use of methylprednisolone once every 4 weeks during the switch between natalizumab and fingolimod in patients with MS
timeFrame: at 6 months
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Pierre CLAVELOU
role: PRINCIPAL_INVESTIGATOR
References: