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

Progressive Multifocal Leukoencephalopathy Clinical Trial

Official title:

A Randomized, Rater-Blinded Study to Explore the Effect of Mefloquine in Subjects With Progressive Multifocal Leukoencephalopathy (PML)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00746941
• Other study ID #: 111JC101
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: September 3, 2008
• Last updated: July 2, 2014
• Start date: January 2009
• Est. completion date: November 2010

Study information

• Verified date: July 2014
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Health Surveillance AgencyItaly: Ministry of HealthSpain: Spanish Agency of MedicinesGermany: Federal Institute for Drugs and Medical DevicesUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 37
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukoencephalopathies
• Leukoencephalopathy, Progressive Multifocal
• Progressive Multifocal Leukoencephalopathy

Intervention

Drug:
• mefloquine
250 mg orally each day for 3 days and then weekly up to 6 months.

Locations

Country	Name	City	State
Brazil	Research Site	Sao Paulo
Germany	Research Site	Berlin
Germany	Research Site	Dusseldorf	North Rhine-Westphalia
Germany	Research Site	Hamburg
Italy	Research Site	Milano
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
United States	Research Site	Baltimore	Maryland
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chicago	Illinois
United States	Research Site	New York	New York
United States	Research Site	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Biogen	Elan Pharmaceuticals

Countries where clinical trial is conducted

United States,  Brazil,  Germany,  Italy,  Spain, 

References & Publications (1)

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: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 4 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF)	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	No
Primary	Change From Baseline to Week 8 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF)	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	No
Secondary	Change From Baseline to Week 4 and Week 8 in the Expanded Disability Status Scale (EDSS) Score	EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death) was calculated. Negative change scores indicate improvement.	Day 0 (baseline), Week 4 and 8	No
Secondary	Change From Baseline to Week 4 and Week 8 in Karnofsky Performance Status (KPS) Index Score	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	No
Secondary	Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT)	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	No
Secondary	Change From Baseline to Week 4 and Week 8 in Participants' Neurological Function Using a Visual Analog Scale (VAS)	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	No
Secondary	Participants With Gadolinium (Gd)-Enhanced Lesions at Baseline, Week 4 and Week 8 as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains		Day 0 (baseline), Week 4, Week 8	No
Secondary	Change From Baseline to Week 4 and Week 8 in T1 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains		Day 0 (baseline), Week 4, Week 8	No
Secondary	Change From Baseline to Week 4 and Week 8 in T2 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains		Day 0 (baseline), Week 4, Week 8	No
Secondary	Participants Who Died Within 6 Months	The death event is counted under the treatment arm relative to adding mefloquine to the treatment regimen.	Day 1 up to 6 months	Yes