Corticosteroids for Immune Reconstitution Inflammatory Syndrome (IRIS)

Biogen

Status and phase: Terminated; Phase 4

Conditions: Leukoencephalopathy, Progressive Multifocal; Immune Reconstitution Inflammatory Syndrome

Treatments: Drug: Prednisolone; Drug: Methylprednisolone

Study type: Interventional

Funder types: Industry

Identifiers

NCT01211665

2010-020369-26 (EudraCT Number)

101JC404

Details and patient eligibility

About

The objectives of this study are to explore the effects of administering high-dose corticosteroids to participants who developed progressive multifocal leukoencephalopathy (PML) while on natalizumab as measured by time-course change in functional status based on Karnofsky Performance Status Index through 6 months following the completion of plasma exchange (PLEX; or equivalent), survival at 6 months following the completion of PLEX (or equivalent), and incidence and severity of adverse events (AEs) and serious adverse events (SAEs); to characterize the evolution of immune reconstitution inflammatory syndrome (IRIS) as measured by time course changes in Global Clinical Impression of Improvement (GCI-I), Symbol Digit Modalities Test (SDMT), brain magnetic resonance imaging (MRI), magnetoencephalography (MEG), chemokines, cytokines, C-reactive protein (CRP), John Cunningham virus (JCV) load and cell count in cerebrospinal fluid (CSF); and to characterize the time course elimination of serum natalizumab concentrations in the study population following the last PLEX (or equivalent) procedure.

Enrollment: 3 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Must have been receiving natalizumab for multiple sclerosis (MS) prior to the diagnosis or suspicion of Progressive multifocal leukoencephalopathy (PML).
• Subject must be willing to undergo or have completed plasma exchange (PLEX) prior to initiating study treatment.

Key Exclusion Criteria:

• History of severe allergic or anaphylactic reactions or known hypersensitivity to any drug including hypersensitivity to corticosteroids.

NOTE: Other protocol defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3 participants in 2 patient groups

Pulsed IVMP

Experimental group

Description:

Intravenous methylprednisolone (IVMP) 1 g/day administered the first 3 days of each weekly cycle, and repeated for 3 additional cycles (totaling 4 cycles). If necessary, 2 additional weekly cycles of 1 g IVMP daily for 3 days can be administered at the discretion of the investigator.

Treatment:

Drug: Methylprednisolone

IVMP with oral prednisolone taper

Experimental group

Description:

Intravenous methylprednisolone (IVMP) 1g/day for 6 days followed by an oral taper of prednisolone over 2 months (suggested dosages starting at 80 mg and tapering to 5 mg). If necessary, additional cycles of 1 g IVMP daily for 3 to 5 days can be administered at any time.

Treatment:

Drug: Methylprednisolone

Drug: Prednisolone