Trial record 9 of 24 for:    Progressive Multifocal Leukoencephalopathy

Corticosteroids for Immune Reconstitution Inflammatory Syndrome (IRIS)

This study has been terminated.
(This study was stopped prematurely due to lack of enrollment within a 1-5-year period.)
Sponsor:
Collaborator:
Elan Pharmaceuticals
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT01211665
First received: July 29, 2010
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Immune Reconstitution Inflammatory Syndrome
Leukoencephalopathy, Progressive Multifocal
Drug: Methylprednisolone
Drug: Prednisolone
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High-Dose Corticosteroids for Immune Reconstitution Inflammatory Syndrome in Patients Who Develop Progressive Multifocal Leukoencephalopathy on Natalizumab

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    AE=any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above.

  • Severity of AEs and 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 ] [ Designated as safety issue: Yes ]
    AEs and SAEs were categorized as mild, moderate or severe according to the following criteria: Mild=barely noticeable to participant or does not make participant uncomfortable; does not influence performance or functioning; prescription drug not ordinarily needed for relief of symptom(s) but may be given because of personality of participant. Moderate=of a sufficient severity to make participant uncomfortable; performance of daily activity is influenced; participant is able to continue in study; treatment for symptom(s) may be needed. Severe=symptoms cause severe discomfort; symptoms cause incapacity or significant impact on participant's daily life; severity may cause cessation of treatment with study treatment; treatment for symptom(s) may be given and/or participant hospitalized. Please see Outcome Measure 3 for AE and SAE definitions.

  • Time Course Change in the Global Clinical Impression of Improvement (GCI-I) Scale [ Time Frame: Screening to 6 months following completion of PLEX (participants began treatment with intravenous methylprednisolone (IVMP) within 2 weeks after PLEX [or equivalent]). ] [ Designated as safety issue: No ]
    The GCI-I scale is a 7-point scale that assesses how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention, and rates it as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.

  • Time Course Change in Cerebral Dysfunction Using the Symbol Digit Modalities Test (SDMT) [ Time Frame: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]). ] [ Designated as safety issue: No ]
    The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution.

  • Time Course Changes in Brain Magnetic Resonance Imaging (MRI) [ Time Frame: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]). ] [ Designated as safety issue: No ]
    The brain MRI data collected included: progressive multifocal leukoencephalopathy (PML) lesion localization, T2 hyperintense lesion volume, and signs of cerebral edema.

  • Time Course Change in Magnetoencephalography (MEG) Results [ Time Frame: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]). ] [ Designated as safety issue: No ]
    MEG was used to map brain activity.

  • Time Course Change in Clinical Laboratory Values [ Time Frame: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]). ] [ Designated as safety issue: Yes ]
    Clinical laboratory values included chemokines, cytokines, C-reactive protein (CRP), John Cunningham (JC) virus load, and cell count in cerebrospinal fluid.

  • Time Course Elimination of Serum Natalizumab Concentration Following Plasma Exchange (PLEX) or Equivalent [ Time Frame: Baseline up to 6 months ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: September 2010
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pulsed IVMP
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.
Drug: Methylprednisolone
In intravenous form (for a daily dose of 1 g/day on treatment days).
Other Names:
  • Medrol
  • Solu-Medrol
Experimental: IVMP with oral prednisolone taper
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.
Drug: Methylprednisolone
In intravenous form (for a daily dose of 1 g/day on treatment days).
Other Names:
  • Medrol
  • Solu-Medrol
Drug: Prednisolone
Oral prednisolone used as a taper, with suggested dosages starting at 80 mg and tapering to 5 mg.
Other Names:
  • Orapred
  • Prelone

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01211665

Locations
United States, Nebraska
Research Site
Hastings, Nebraska, United States
Germany
Research Site
Bochum, Germany
Research Site
Wurzburg, Germany
Sponsors and Collaborators
Biogen Idec
Elan Pharmaceuticals
Investigators
Study Director: Medical Director Biogen Idec
  More Information

No publications provided

Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT01211665     History of Changes
Other Study ID Numbers: 101JC404, 2010-020369-26
Study First Received: July 29, 2010
Results First Received: July 23, 2014
Last Updated: August 26, 2014
Health Authority: United States: Institutional Review Board
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Keywords provided by Biogen Idec:
IVMP
corticosteroids
IRIS
Progressive Multifocal Leukoencephalopathy
Immune reconstitution inflammatory syndrome
PML

Additional relevant MeSH terms:
Leukoencephalopathies
Leukoencephalopathy, Progressive Multifocal
Syndrome
Immune Reconstitution Inflammatory Syndrome
Disease
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Encephalitis, Viral
Encephalitis
Central Nervous System Viral Diseases
Virus Diseases
Polyomavirus Infections
DNA Virus Infections
Slow Virus Diseases
Central Nervous System Infections
Demyelinating Diseases
Immune System Diseases
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics

ClinicalTrials.gov processed this record on September 22, 2014