- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00746941
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)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Sao Paulo, Brazil
- Research Site
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Berlin, Germany
- Research Site
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Hamburg, Germany
- Research Site
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North Rhine-Westphalia
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Dusseldorf, North Rhine-Westphalia, Germany
- Research Site
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Milano, Italy
- Research Site
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Barcelona, Spain
- Research Site
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Madrid, Spain
- Research Site
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Illinois
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Chicago, Illinois, United States
- Research Site
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Maryland
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Baltimore, Maryland, United States
- Research Site
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Massachusetts
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Boston, Massachusetts, United States
- Research Site
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Missouri
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St. Louis, Missouri, United States
- Research Site
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New York
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New York, New York, United States
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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. |
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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. |
250 mg orally each day for 3 days and then weekly up to 6 months.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline to Week 4 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF)
Time Frame: Day 0 (baseline), Week 4
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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 |
Day 0 (baseline), Week 4
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Change From Baseline to Week 8 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF)
Time Frame: Day 0 (baseline), Week 8
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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 |
Day 0 (baseline), Week 8
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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
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EDSS assesses disability in 8 functional systems.
An overall score ranging from 0 (normal) to 10 (death) was calculated.
Negative change scores indicate improvement.
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Day 0 (baseline), Week 4 and 8
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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
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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. |
Day 0 (baseline), Week 4, Week 8
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Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT)
Time Frame: Day 0 (baseline), Week 4, Week 8
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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. |
Day 0 (baseline), Week 4, Week 8
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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
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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. |
Day 0 (baseline), Week 4, Week 8
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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
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Day 0 (baseline), Week 4, Week 8
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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
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Day 0 (baseline), Week 4, Week 8
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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
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Day 0 (baseline), Week 4, Week 8
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Participants Who Died Within 6 Months
Time Frame: Day 1 up to 6 months
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The death event is counted under the treatment arm relative to adding mefloquine to the treatment regimen.
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Day 1 up to 6 months
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Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Virus Diseases
- Infections
- Demyelinating Diseases
- Encephalitis, Viral
- Central Nervous System Viral Diseases
- Central Nervous System Infections
- Infectious Encephalitis
- DNA Virus Infections
- Slow Virus Diseases
- Encephalitis
- Polyomavirus Infections
- Leukoencephalopathy, Progressive Multifocal
- Leukoencephalopathies
- Anti-Infective Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Mefloquine
Other Study ID Numbers
- 111JC101
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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