Clinical trial NCT01211665: Corticosteroids for Immune Reconstitution Inflammatory Syndrome (IRIS)
Official title: High-Dose Corticosteroids for Immune Reconstitution Inflammatory Syndrome in Patients Who Develop Progressive Multifocal Leukoencephalopathy on Natalizumab
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Immune Reconstitution Inflammatory Syndrome
Leukoencephalopathy, Progressive Multifocal
Keywords: IVMP
corticosteroids
IRIS
Progressive Multifocal Leukoencephalopathy
Immune reconstitution inflammatory syndrome
PML
Lead sponsor: Biogen
Sponsor class: INDUSTRY
Collaborators: name: Elan Pharmaceuticals
First posted: 2010-09-29
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Time Course Change in Functional Status Based on Karnofsky Performance Status Index Through 6 Months Following Completion of Plasma Exchange (PLEX)
timeFrame: Baseline up to 6 months
measure: Number of Participants Who Survived at 6 Months Following Completion of Plasma Exchange (PLEX)
timeFrame: 6 months
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: from the first dose of study treatment through the end of the treatment period (6 months) + a 4-week post-treatment period
measure: Severity of AEs and SAEs
timeFrame: from the first dose of study treatment through the end of the treatment period (6 months) + a 4-week post-treatment period
measure: Time Course Change in the Global Clinical Impression of Improvement (GCI-I) Scale
timeFrame: Screening to 6 months following completion of PLEX (participants began treatment with intravenous methylprednisolone (IVMP) within 2 weeks after PLEX [or equivalent]).
measure: Time Course Change in Cerebral Dysfunction Using the Symbol Digit Modalities Test (SDMT)
timeFrame: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]).
measure: Time Course Changes in Brain Magnetic Resonance Imaging (MRI)
timeFrame: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]).
measure: Time Course Change in Magnetoencephalography (MEG) Results
timeFrame: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]).
measure: Time Course Change in Clinical Laboratory Values
timeFrame: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]).
measure: Time Course Elimination of Serum Natalizumab Concentration Following Plasma Exchange (PLEX) or Equivalent
timeFrame: Baseline up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Hastings
country: United States
facility: Research Site
state: Nebraska
city: Bochum
country: Germany
facility: Research Site
city: Wurzburg
country: Germany
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: