Clinical Trial: Study to Explore the Effect of Mefloquine in Participants With Progressive Multifocal Leukoencephalopathy (PML)

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

Official Title: A Randomized, Rater-Blinded Study to Explore the Effect of Mefloquine in Subjects With Progressive Multifocal Leukoencephalopathy (PML)

Brief Summary: The primary objective of the study was to explore whether mefloquine can delay or stop progression of progressive multifocal leukoencephalopathy (PML) as measured by JC virus (human polyomavirus or JCV) deoxyribonucleic acid (DNA) levels in cerebrospinal fluid (CSF). The secondary objective of the study was to explore whether mefloquine can delay or stop progression of PML based on neurological deterioration, magnetic resonance imaging (MRI) measures of brain lesion evolution or the formation of new lesions, and mortality.

Detailed Summary:
Sponsor: Biogen

Current Primary Outcome:

  • Change From Baseline to Week 4 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF) [ Time Frame: Day 0 (baseline), Week 4 ]

    Change from baseline to Week 4 in JC viral load in CSF is expressed as log10 copies/mL. Negative values indicate a reduction in viral load.

    Only participants with measurable baseline values are included. Post-baseline values of 'Below the Limit of Quantification' or 'Below Limit of Detection' or 'Negative' were set to 50. Log10 (50) = 1.699

  • Change From Baseline to Week 8 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF) [ Time Frame: Day 0 (baseline), Week 8 ]

    Change from baseline to Week 8 in JC viral load in CSF is expressed as log10 copies/mL. Negative values indicate a reduction in viral load.

    Only participants with measurable baseline values are included. Post-baseline values of 'Below the Limit of Quantification' or 'Below Limit of Detection' or 'Negative' were set to 50. Log10 (50) = 1.699



Original Primary Outcome: JC viral DNA levels in cerebrospinal fluid [ Time Frame: up to 24 weeks ]

Current Secondary Outcome:

  • Change From Baseline to Week 4 and Week 8 in the Expanded Disability Status Scale (EDSS) Score [ Time Frame: Day 0 (baseline), Week 4 and 8 ]
    EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death) was calculated. Negative change scores indicate improvement.
  • Change From Baseline to Week 4 and Week 8 in Karnofsky Performance Status (KPS) Index Score [ Time Frame: Day 0 (baseline), Week 4, Week 8 ]

    The KPS Index classifies participants' functional impairment. KPS can be used to compare effectiveness of different therapies and to assess the prognosis in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the KPS score, the worse the survival for most serious illnesses. The KPS index is subdivided into 3 categories: incapacitated (0 to 40), self-care (50 to 70), and normal activity (80 to 100).

    Negative change from baseline scores indicate improved prognosis.

  • Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT) [ Time Frame: Day 0 (baseline), Week 4, Week 8 ]

    The SDMT is a simple substitution task. The test gives participants 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The total score is the total number of correctly completed boxes in the time allowed. The test score range is from 0 (worst outcome) to 110 (best outcome).

    Negative change from baseline scores indicates a worsening outcome.

  • Change From Baseline to Week 4 and Week 8 in Participants' Neurological Function Using a Visual Analog Scale (VAS) [ Time Frame: Day 0 (baseline), Week 4, Week 8 ]

    Participants rate their neurological function on a scale of 100 mm line, where the 0 end of the scale indicates poor neurological function and 100 indicates excellent neurological function. VAS was not required for participants who had physical or cognitive impairments that limited their ability to perform the assessment.

    Negative change from baseline scores indicates a worsening outcome.

  • Participants With Gadolinium (Gd)-Enhanced Lesions at Baseline, Week 4 and Week 8 as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains [ Time Frame: Day 0 (baseline), Week 4, Week 8 ]
  • Change From Baseline to Week 4 and Week 8 in T1 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains [ Time Frame: Day 0 (baseline), Week 4, Week 8 ]
  • Change From Baseline to Week 4 and Week 8 in T2 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains [ Time Frame: Day 0 (baseline), Week 4, Week 8 ]
  • Participants Who Died Within 6 Months [ Time Frame: Day 1 up to 6 months ]
    The death event is counted under the treatment arm relative to adding mefloquine to the treatment regimen.


Original Secondary Outcome: Neurological status and brain MRI. [ Time Frame: up to 24 weeks ]

Information By: Biogen

Dates:
Date Received: September 3, 2008
Date Started: January 2009
Date Completion:
Last Updated: July 2, 2014
Last Verified: July 2014