Clinical Trial: Corticosteroids for Immune Reconstitution Inflammatory Syndrome (IRIS)

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: High-Dose Corticosteroids for Immune Reconstitution Inflammatory Syndrome in Patients Who Develop Progressive Multifocal Leukoencephalopathy on Natalizumab

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.

Detailed Summary:
Sponsor: Biogen

Current Primary Outcome:

  • Time Course Change in Functional Status Based on Karnofsky Performance Status Index Through 6 Months Following Completion of Plasma Exchange (PLEX) [ Time Frame: Baseline up to 6 months ]
    The Karnofsky Performance Status Index (KPSI) is an assessment tool intended to assist clinicians and caretakers in gauging a patient's functional status and ability to carry out activities of daily living. A KPSI of 100=normal, no complaints, no evidence of disease; 90=able to carry on normal activity, minor signs or symptoms of disease; 80=normal activity with effort, some signs or symptoms of disease; 70=cares for self, unable to carry on normal activity or do active work; 60=requires occasional assistance but is able to care for most personal needs; 50=requires considerable assistance and frequent medical care; 40=disabled, requires special care and assistance; 30=severely disabled, hospitalization is indicated, although death is not imminent; 20=very sick, hospitalization is necessary, active support treatment is necessary; 10=moribund, fatal processes progressing rapidly; 0=dead.
  • Number of Participants Who Survived at 6 Months Following Completion of Plasma Exchange (PLEX) [ Time Frame: 6 months ]
    Following the completion of rapid removal of natalizumab using PLEX or equivalent.
  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: from the first dose of study treatment through the end of the treatment period (6 months) + a 4-week post-treatment period ]
    AE=any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal rel

    Original Primary Outcome:

    • Time course change in functional status based on Karnofsky Performance Status Scale through 6 months following the completion of PLEX or Equivalent [ Time Frame: 6 months ]
    • Survival at 6 months following the completion of PLEX or equivalent [ Time Frame: 6 months ]
    • Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability [ Time Frame: 6 months ]
    • Measure of symptom severity, treatment response and the efficacy of treatments using the Global Clinical Impression of Improvement (GCI-I) [ Time Frame: 6 months ]
    • Measure cerebral dysfunction using Symbol Digit Modalities Test (SDMT) [ Time Frame: 6 months ]
    • Measure Gadolinium enhancing lesions using Brain Magnetic Resonance Imaging (MRI) [ Time Frame: 6 months ]
    • Mapping of brain activity using Magnetoencephalography (MEG) [ Time Frame: 6 months ]
    • Laboratories (Chemokines, Cytokines, C-reactive protein, JCV load and cell count in cerebral fluid (CSF)) [ Time Frame: 6 months ]


    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: Biogen

    Dates:
    Date Received: July 29, 2010
    Date Started: September 2010
    Date Completion:
    Last Updated: August 26, 2014
    Last Verified: August 2014