Clinical trial NCT00746941: Study to Explore the Effect of Mefloquine in Participants With Progressive Multifocal Leukoencephalopathy (PML)
Official title: A Randomized, Rater-Blinded Study to Explore the Effect of Mefloquine in Subjects With Progressive Multifocal Leukoencephalopathy (PML)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Progressive Multifocal Leukoencephalopathy
Keywords: PML
Human Polyomavirus JC
HIV
Central Nervous System Disease
Mefloquine
JC Virus
Lead sponsor: Biogen
Sponsor class: INDUSTRY
Collaborators: name: Elan Pharmaceuticals
First posted: 2008-09-04
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change From Baseline to Week 4 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF)
timeFrame: Day 0 (baseline), Week 4
measure: Change From Baseline to Week 8 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF)
timeFrame: Day 0 (baseline), Week 8
Secondary outcomes:
measure: Change From Baseline to Week 4 and Week 8 in the Expanded Disability Status Scale (EDSS) Score
timeFrame: Day 0 (baseline), Week 4 and 8
measure: Change From Baseline to Week 4 and Week 8 in Karnofsky Performance Status (KPS) Index Score
timeFrame: Day 0 (baseline), Week 4, Week 8
measure: Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT)
timeFrame: Day 0 (baseline), Week 4, Week 8
measure: Change From Baseline to Week 4 and Week 8 in Participants' Neurological Function Using a Visual Analog Scale (VAS)
timeFrame: Day 0 (baseline), Week 4, Week 8
measure: Participants With Gadolinium (Gd)-Enhanced Lesions at Baseline, Week 4 and Week 8 as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains
timeFrame: Day 0 (baseline), Week 4, Week 8
measure: Change From Baseline to Week 4 and Week 8 in T1 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains
timeFrame: Day 0 (baseline), Week 4, Week 8
measure: Change From Baseline to Week 4 and Week 8 in T2 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains
timeFrame: Day 0 (baseline), Week 4, Week 8
measure: Participants Who Died Within 6 Months
timeFrame: Day 1 up to 6 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Sao Paulo
country: Brazil
facility: Research Site
city: Dusseldorf
country: Germany
facility: Research Site
state: North Rhine-Westphalia
city: Berlin
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
Study officials:
References:
citation: 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.