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
  Purpose

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.


Condition Intervention Phase
Progressive Multifocal Leukoencephalopathy
Drug: mefloquine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Rater-Blinded Study to Explore the Effect of Mefloquine in Subjects With Progressive Multifocal Leukoencephalopathy (PML)

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • 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



Secondary Outcome Measures:
  • 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.


Enrollment: 37
Study Start Date: January 2009
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: mefloquine
250 mg orally each day for 3 days and then weekly up to 6 months.
Other Names:
  • Lariam®
  • Mephaquin®
  • Mefliam®

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  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: NCT00746941

Locations
United States, Illinois
Research Site
Chicago, Illinois, United States
United States, Maryland
Research Site
Baltimore, Maryland, United States
United States, Massachusetts
Research Site
Boston, Massachusetts, United States
United States, Missouri
Research Site
St. Louis, Missouri, United States
United States, New York
Research Site
New York, New York, United States
Brazil
Research Site
Sao Paulo, Brazil
Germany
Research Site
Dusseldorf, North Rhine-Westphalia, Germany
Research Site
Berlin, Germany
Research Site
Hamburg, Germany
Italy
Research Site
Milano, Italy
Spain
Research Site
Barcelona, Spain
Research Site
Madrid, Spain
Sponsors and Collaborators
Biogen Idec
Elan Pharmaceuticals
  More Information

Publications:
Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT00746941     History of Changes
Other Study ID Numbers: 111JC101
Study First Received: September 3, 2008
Results First Received: January 3, 2013
Last Updated: July 2, 2014
Health Authority: Brazil: National Health Surveillance Agency
Italy: Ministry of Health
Spain: Spanish Agency of Medicines
Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Keywords provided by Biogen Idec:
PML
Human Polyomavirus JC
HIV
Central Nervous System Disease
Mefloquine
JC Virus

Additional relevant MeSH terms:
Leukoencephalopathy, Progressive Multifocal
Leukoencephalopathies
Encephalitis, Viral
Encephalitis
Central Nervous System Viral Diseases
Virus Diseases
Polyomavirus Infections
DNA Virus Infections
Slow Virus Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Infections
Demyelinating Diseases
Mefloquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014