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

Back to results

Primary Purpose

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

mefloquine

About this trial

This is an interventional treatment trial for Progressive Multifocal Leukoencephalopathy focused on measuring PML, Human Polyomavirus JC, HIV, Central Nervous System Disease, Mefloquine, JC Virus

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Local standard of care

Local standard of care plus mefloquine 250 mg

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome Measures

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.

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.

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.

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.

Participants With Gadolinium (Gd)-Enhanced Lesions at Baseline, Week 4 and Week 8 as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains

Change From Baseline to Week 4 and Week 8 in T1 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains

Change From Baseline to Week 4 and Week 8 in T2 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains

Participants Who Died Within 6 Months

The death event is counted under the treatment arm relative to adding mefloquine to the treatment regimen.

Full Information

NCT ID

NCT00746941

First Posted

September 3, 2008

Last Updated

July 2, 2014

Sponsor

Biogen

Collaborators

Elan Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00746941

Brief Title

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

2. Study Status

Record Verification Date

July 2014

Overall Recruitment Status

Terminated

Why Stopped

Primary endpoint not achieved

Study Start Date

January 2009 (undefined)

Primary Completion Date

November 2010 (Actual)

Study Completion Date

November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Biogen

Collaborators

Elan Pharmaceuticals

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Progressive Multifocal Leukoencephalopathy

Keywords

PML, Human Polyomavirus JC, HIV, Central Nervous System Disease, Mefloquine, JC Virus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Local standard of care

Arm Type

No Intervention

Arm Description

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.

Arm Title

Local standard of care plus mefloquine 250 mg

Arm Type

Experimental

Arm Description

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 Type

Drug

Intervention Name(s)

mefloquine

Other Intervention Name(s)

Lariam®, Mephaquin®, Mefliam®

Intervention Description

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

Primary Outcome Measure Information:

Title

Change From Baseline to Week 4 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF)

Description

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

Time Frame

Day 0 (baseline), Week 4

Title

Change From Baseline to Week 8 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF)

Description

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

Time Frame

Day 0 (baseline), Week 8

Secondary Outcome Measure Information:

Title

Change From Baseline to Week 4 and Week 8 in the Expanded Disability Status Scale (EDSS) Score

Description

EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death) was calculated. Negative change scores indicate improvement.

Time Frame

Day 0 (baseline), Week 4 and 8

Title

Change From Baseline to Week 4 and Week 8 in Karnofsky Performance Status (KPS) Index Score

Description

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.

Time Frame