Methylprednisolone During the Switch Between Natalizumab and Fingolimod (NTZ2TTY)

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)

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).

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Methylprednisolone; Drug: natalizumab (NTZ); Drug: fingolimob (FTY); Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 56
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • Recruiting
    • CHU Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methylprednisolone; 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).	Drug: Methylprednisolone; Included patients will receive either methylprednisolone (1 gramme, 1 day every 4 weeks for a total of 3 grammes) or undistinguishable capsules of placebo; Drug: natalizumab (NTZ); 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; Drug: fingolimob (FTY); 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.
Placebo Comparator: Placebo; Included patients will receive either methylprednisolone (1 gramme, 1 day every 4 weeks for a total of 3 grammes) or undistinguishable capsules of placebo	Drug: Placebo; Included patients will receive either methylprednisolone (1 gramme, 1 day every 4 weeks for a total of 3 grammes) or undistinguishable capsules of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy of high dose methylprednisolone compared to that of a placebo	To evaluate the efficacy of high dose methylprednisolone given once a month during the washout period for the switch between natalizumab and fingolimod, compared to that of a placebo, on multiple sclerosis inflammatory rebound evaluated using MRI, 16 to 18 weeks after natalizumab discontinuation and clinically at 6 months	at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
comparison of the number of new T2 or gadolinium enhanced lesions on MRI in the 2 treatment groups		at 4 months
comparison of the number of MS relapses during the 6 months after natalizumab discontinuation, in the 2 treatment groups		at 6 months
potential correlations between previous MS activity and the risk of relapse or inflammatory rebound on MRI after natalizumab discontinuation	To study the potential correlations between previous MS activity (annualised relapse rate during the year before natalizumab initiation) and the risk of relapse or inflammatory rebound on MRI after natalizumab discontinuation, in the whole group	at 6 months
adverse effects of high dose oral prednisolone		at 6 months
use of methylprednisolone once every 4 weeks during the switch between natalizumab and fingolimod in patients with MS	To perform a cost utility analysis in order to evaluate the use of methylprednisolone once every 4 weeks during the switch between natalizumab and fingolimod in patients with MS	at 6 months

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2019
• Primary Completion (Anticipated): June 20, 2024
• Study Completion (Anticipated): July 20, 2024

Study Registration Dates

• First Submitted: March 17, 2016
• First Submitted That Met QC Criteria: May 9, 2016
• First Posted (Estimate): May 12, 2016

Study Record Updates

• Last Update Posted (Estimate): January 9, 2023
• Last Update Submitted That Met QC Criteria: January 5, 2023
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Multiple sclerosis; Methylprednisolone; Natalizumab; Fingolimod
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Natalizumab
• Other Study ID Numbers: CHU-0259; 2015-003298-14 (Registry Identifier: 2015-003298-14)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No