Methylprednisolone During the Switch Between Natalizumab and Fingolimod (NTZ2TTY)

University Hospital, Clermont-Ferrand

Status and phase: Enrolling; Phase 4

Conditions: Multiple Sclerosis

Treatments: Drug: fingolimob (FTY); Drug: Methylprednisolone; Drug: natalizumab (NTZ); Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02769689

2015-003298-14 (Registry Identifier)

CHU-0259

Details and patient eligibility

About

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).

Full 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.

Enrollment: 56 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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56 participants in 2 patient groups, including a placebo group

Methylprednisolone

Experimental group

Description:

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).

Treatment:

Drug: natalizumab (NTZ)

Drug: Methylprednisolone

Drug: fingolimob (FTY)

Placebo

Placebo Comparator group

Description:

Included patients will receive either methylprednisolone (1 gramme, 1 day every 4 weeks for a total of 3 grammes) or undistinguishable capsules of placebo

Treatment:

Drug: Placebo