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

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ClinicalTrials.gov Identifier: NCT00746941
Recruitment Status : Terminated (Primary endpoint not achieved)
First Posted : September 4, 2008
Results First Posted : July 31, 2014
Last Update Posted : July 31, 2014
Sponsor:
Collaborator:
Elan Pharmaceuticals
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE September 3, 2008
First Posted Date  ICMJE September 4, 2008
Results First Submitted Date  ICMJE January 3, 2013
Results First Posted Date  ICMJE July 31, 2014
Last Update Posted Date July 31, 2014
Study Start Date  ICMJE January 2009
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 2, 2014)
  • 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 Measures  ICMJE
 (submitted: September 3, 2008)
JC viral DNA levels in cerebrospinal fluid [ Time Frame: up to 24 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2014)
  • 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 Measures  ICMJE
 (submitted: September 3, 2008)
Neurological status and brain MRI. [ Time Frame: up to 24 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Explore the Effect of Mefloquine in Participants With Progressive Multifocal Leukoencephalopathy (PML)
Official Title  ICMJE 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 Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Progressive Multifocal Leukoencephalopathy
Intervention  ICMJE Drug: mefloquine
250 mg orally each day for 3 days and then weekly up to 6 months.
Other Names:
  • Lariam®
  • Mephaquin®
  • Mefliam®
Study Arms  ICMJE
  • 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
Publications * 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.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: December 8, 2011)
37
Original Estimated Enrollment  ICMJE
 (submitted: September 3, 2008)
40
Actual Study Completion Date  ICMJE November 2010
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Germany,   Italy,   Spain,   United States
Removed Location Countries Australia,   France,   Puerto Rico,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT00746941
Other Study ID Numbers  ICMJE 111JC101
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Elan Pharmaceuticals
Investigators  ICMJE Not Provided
PRS Account Biogen
Verification Date July 2014

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