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

This study has been terminated.
(Primary endpoint not achieved)
Sponsor:
Collaborator:
Elan Pharmaceuticals
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00746941
First received: September 3, 2008
Last updated: July 2, 2014
Last verified: July 2014

September 3, 2008
July 2, 2014
January 2009
November 2010   (final data collection date for primary outcome measure)
  • Change From Baseline to Week 4 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF) [ Time Frame: Day 0 (baseline), Week 4 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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

JC viral DNA levels in cerebrospinal fluid [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00746941 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Participants Who Died Within 6 Months [ Time Frame: Day 1 up to 6 months ] [ Designated as safety issue: Yes ]
    The death event is counted under the treatment arm relative to adding mefloquine to the treatment regimen.
Neurological status and brain MRI. [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study to Explore the Effect of Mefloquine in Participants With Progressive Multifocal Leukoencephalopathy (PML)
A Randomized, Rater-Blinded Study to Explore the Effect of Mefloquine in Subjects With Progressive Multifocal Leukoencephalopathy (PML)

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.

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Progressive Multifocal Leukoencephalopathy
Drug: mefloquine
250 mg orally each day for 3 days and then weekly up to 6 months.
Other Names:
  • Lariam®
  • Mephaquin®
  • Mefliam®
  • No Intervention: Local standard of care

    All participants received local standard of care, which may have included any treatment or procedure that the Investigator would normally use in the treatment of a PML patient at their study site or hospital.

    Participants in this treatment arm had the option of adding 250 mg mefloquine by mouth at Week 4 (Day 28) or Week 8 (Day 56) daily for 3 days, and then weekly through Week 24.

  • Experimental: Local standard of care plus mefloquine 250 mg

    All participants received local standard of care, which may have included any treatment or procedure that the Investigator would normally use in the treatment of a PML patient at their study site or hospital.

    Participants received 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.

    Intervention: Drug: mefloquine
Clifford DB, Nath A, Cinque P, Brew BJ, Zivadinov R, Gorelik L, Zhao Z, Duda P. A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes. J Neurovirol. 2013 Aug;19(4):351-8. doi: 10.1007/s13365-013-0173-y. Epub 2013 Jun 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
37
November 2010
November 2010   (final data collection date for primary outcome measure)

Key Inclusion Criteria:

  • Diagnosis of PML confirmed by detection of JCV DNA in CSF.
  • Onset of PML symptoms within 6 months prior to study.

Key Exclusion Criteria:

  • Other opportunistic infection of the central nervous system.
  • Current severe illness or any other conditions that, in the opinion of the Investigator, would make the subject unsuitable for enrollment.
  • Active severe mental illness (e.g., depression, anxiety, psychosis, and schizophrenia).
  • Hypersensitivity to mefloquine, quinine, or quinidine, or to any component of these drugs.
  • Current treatment with quinine, quinidine, chloroquine, or halofantrine.

Note: Other protocol-defined criteria may also apply.

Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Brazil,   Germany,   Italy,   Spain
 
NCT00746941
111JC101
No
Biogen Idec
Biogen Idec
Elan Pharmaceuticals
Not Provided
Biogen Idec
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP