Methylprednisolone During the Switch Between Natalizumab and Fingolimod

NCT02769689 | Unknown Phase 4

• 2 other identifiers: CHU-02592015-003298-14
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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).

Conditions

Multiple Sclerosis

Keywords

Multiple sclerosis; Natalizumab; Fingolimod; Methylprednisolone

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

  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

  at 6 months

Study Arms (2)

Methylprednisolone

EXPERIMENTAL

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; Drug: natalizumab (NTZ); Drug: fingolimob (FTY)

Placebo

PLACEBO COMPARATOR

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

Interventions

Methylprednisolone DRUG

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

Methylprednisolone

Placebo DRUG

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

Placebo

natalizumab (NTZ) DRUG

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

Methylprednisolone

fingolimob (FTY) DRUG

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.

Methylprednisolone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Contra-indication to gadolinium containing products injection
• Pregnancy

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (1)

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Methylprednisolone; Natalizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pierre CLAVELOU

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrick LACARIN

CONTACT

04 73 75 11 95; placarin@chu-clermontferrand.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2016
• First Posted: May 12, 2016
• Study Start: June 12, 2019
• Primary Completion: June 20, 2024
• Study Completion: July 20, 2024
• Last Updated: January 9, 2023

Record last verified: 2022-08

Locations

FR (1)