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

• Sponsor: Biogen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00746941
• Collaborator: Elan Pharmaceuticals (Industry)
• Enrollment: 37
• Locations: 12
• Arms: 2
• Duration (Months): 22
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Progressive Multifocal Leukoencephalopathy	Drug: mefloquine	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (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)
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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®

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 4 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF) [Day 0 (baseline), Week 4]

   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

2. Change From Baseline to Week 8 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF) [Day 0 (baseline), Week 8]

   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

1. Change From Baseline to Week 4 and Week 8 in the Expanded Disability Status Scale (EDSS) Score [Day 0 (baseline), Week 4 and 8]

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

2. Change From Baseline to Week 4 and Week 8 in Karnofsky Performance Status (KPS) Index Score [Day 0 (baseline), Week 4, Week 8]

   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.

3. Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT) [Day 0 (baseline), Week 4, Week 8]

   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.

4. Change From Baseline to Week 4 and Week 8 in Participants' Neurological Function Using a Visual Analog Scale (VAS) [Day 0 (baseline), Week 4, Week 8]

   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.

5. 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]

6. 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]

7. 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]

8. Participants Who Died Within 6 Months [Day 1 up to 6 months]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Chicago	Illinois	United States
2	Research Site	Baltimore	Maryland	United States
3	Research Site	Boston	Massachusetts	United States
4	Research Site	St. Louis	Missouri	United States
5	Research Site	New York	New York	United States
6	Research Site	Sao Paulo		Brazil
7	Research Site	Dusseldorf	North Rhine-Westphalia	Germany
8	Research Site	Berlin		Germany
9	Research Site	Hamburg		Germany
10	Research Site	Milano		Italy
11	Research Site	Barcelona		Spain
12	Research Site	Madrid		Spain

Sponsors and Collaborators

• Biogen
• Elan Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT00746941
• Other Study ID Numbers: 111JC101
• First Posted: Sep 4, 2008
• Last Update Posted: Jul 31, 2014
• Last Verified: Jul 1, 2014

• Keywords provided by Biogen: PML; Human Polyomavirus JC; HIV; Central Nervous System Disease; Mefloquine; JC Virus
• Additional relevant MeSH terms: Leukoencephalopathy, Progressive Multifocal; Leukoencephalopathies; Mefloquine

Study Results

Participant Flow

Recruitment Details	Twelve sites enrolled participants prior to study termination.
Pre-assignment Detail	Participants were initially randomized in a 1:1 ratio to the local standard of care arm (represented below as 3 treatment arms depending on Week 4 and Week 8 decisions) or the local standard of care plus mefloquine 250 mg arm.

Arm/Group Title	Local Standard of Care	Local Standard of Care; Mefloquine at Week 4	Local Standard of Care; Mefloquine at Week 8	Local Standard of Care Plus Mefloquine 250 mg
Arm/Group Description	Participants were randomized to receive 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. These participants received only local standard of care throughout the study; they did not choose to add 250 mg mefloquine at Week 4 (Day 28) or Week 8 (Day 56).	Participants were randomized to receive 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. These participants chose to add 250 mg mefloquine by mouth at Week 4 for 3 days and then weekly through Week 24 to their local standard of care treatment.	Participants were randomized to receive 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. These participants chose to add 250 mg mefloquine by mouth at Week 8 for 3 days and then weekly through Week 24 to their local standard of care treatment.	Participants were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.
Period Title: Overall Study
STARTED	7	5	5	20
COMPLETED	0	1	3	7
NOT COMPLETED	7	4	2	13

Baseline Characteristics

Arm/Group Title	Local Standard of Care	Local Standard of Care; Mefloquine at Week 4	Local Standard of Care; Mefloquine at Week 8	Local Standard of Care Plus Mefloquine 250 mg	Total
Arm/Group Description	Participants were randomized to receive 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. These participants received only local standard of care throughout the study; they did not choose to add 250 mg mefloquine at Week 4 (Day 28) or Week 8 (Day 56).	Participants were randomized to receive 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. These participants chose to add 250 mg mefloquine by mouth at Week 4 for 3 days and then weekly through Week 24 to their local standard of care treatment.	Participants were randomized to receive 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. These participants chose to add 250 mg mefloquine by mouth at Week 8 for 3 days and then weekly through Week 24 to their local standard of care treatment.	Participants were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.	Total of all reporting groups
Overall Participants	7	5	5	20	37
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.7 (20.56)	41.6 (11.37)	47.4 (10.06)	48.1 (9.4)	47.2 (12.16)
Sex: Female, Male (Count of Participants)
Female	1 14.3%	2 40%	2 40%	5 25%	10 27%
Male	6 85.7%	3 60%	3 60%	15 75%	27 73%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 14.3%	2 40%	2 40%	4 20%	9 24.3%
White	6 85.7%	3 60%	3 60%	16 80%	28 75.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Disease history (participants) [Number]
HIV positive: HAART Naive	3 42.9%	5 100%	3 60%	13 65%	24 64.9%
HIV positive: History of HAART	1 14.3%	0 0%	1 20%	3 15%	5 13.5%
HIV negative	3 42.9%	0 0%	1 20%	4 20%	8 21.6%
JVC Titer at Screening (participants) [Number]
<= 50 copies/mL	0 0%	0 0%	0 0%	4 20%	4 10.8%
> 50 copies/mL	7 100%	5 100%	5 100%	15 75%	32 86.5%
Missing	0 0%	0 0%	0 0%	1 5%	1 2.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Local standard of care participants who added mefloquine at Week 4 or Week 8 were counted as being dosed under both treatment arms. Participants with undetectable CSF JCV load at baseline were not included in the efficacy analysis. All other enrolled participants were included in the efficacy analysis if values for Week 4 were available.

Arm/Group Title	Local Standard of Care	Local Standard of Care Plus Mefloquine 250 mg
Arm/Group Description	Participants were randomized to receive 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 were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.
Measure Participants	13	14
Mean (Standard Deviation) [log10 copies/mL]	-0.2424 (0.83556)	-0.0675 (1.52685)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Local Standard of Care, Local Standard of Care Plus Mefloquine 250 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7132
	Comments
	Method	Student's t-test
	Comments

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Local standard of care participants who added mefloquine at Week 4 or Week 8 were counted as being dosed under both treatment arms. Participants with undetectable CSF JCV load at baseline were not included in the efficacy analysis. All other enrolled participants were included in the efficacy analysis if values for Week 8 were available.

Arm/Group Title	Local Standard of Care	Local Standard of Care Plus Mefloquine 250 mg
Arm/Group Description	Participants were randomized to receive 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 were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.
Measure Participants	4	10
Mean (Standard Deviation) [log10 copies/mL]	-0.2843 (0.68666)	-0.3455 (0.93960)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Local Standard of Care, Local Standard of Care Plus Mefloquine 250 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9086
	Comments
	Method	Student's t-test
	Comments

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants with values at the time frames being measured. EDSS was not required for participants who had physical or cognitive impairments that limited their ability to perform the assessment. Local standard of care participants who added mefloquine at Week 4 or Week 8 were counted as being dosed under both treatment arms.

Arm/Group Title	Local Standard of Care	Local Standard of Care Plus Mefloquine 250 mg
Arm/Group Description	Participants were randomized to receive 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 were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.
Measure Participants	17	30
Week 4 (n=12, 21)	0.79 (1.054)	0.50 (1.129)
Week 8 (n=7, 16)	0.71 (1.868)	0.88 (1.360)

4. Secondary Outcome

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	Day 0 (baseline), Week 4, Week 8

Outcome Measure Data

Analysis Population Description

Participants with values at the time frames being measured. Participants with undetectable CSF JCV load at baseline by the central laboratory were not included in the efficacy analysis. Local standard of care participants who added mefloquine at Week 4 or Week 8 were counted as being dosed under both treatment arms.

Arm/Group Title	Local Standard of Care	Local Standard of Care Plus Mefloquine 250 mg
Arm/Group Description	Participants were randomized to receive 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 were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.
Measure Participants	17	30
Week 4 (n=12, 21)	0.00 (14.771)	-8.10 (12.891)
Week 8 (n=7, 16)	-10.0 (26.46)	-10.6 (19.14)

5. Secondary Outcome

Title	Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT)
Description	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.
Time Frame	Day 0 (baseline), Week 4, Week 8

Outcome Measure Data

Analysis Population Description

Participants with values at the time frames being measured. SDMT was not required for participants who had physical or cognitive impairments that limited their ability to perform the assessment. Local standard of care participants who added mefloquine at Week 4 or Week 8 were counted as being dosed under both treatment arms.

Arm/Group Title	Local Standard of Care	Local Standard of Care Plus Mefloquine 250 mg
Arm/Group Description	Participants were randomized to receive 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 were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.
Measure Participants	17	30
Week 4 (n=6,8)	4.00 (6.723)	-1.50 (3.780)
Week 8 (n=3,6)	1.7 (10.12)	3.8 (6.43)

6. Secondary Outcome

Title	Change From Baseline to Week 4 and Week 8 in Participants' Neurological Function Using a Visual Analog Scale (VAS)
Description	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.
Time Frame	Day 0 (baseline), Week 4, Week 8

Outcome Measure Data

Analysis Population Description

Participants with values at the time frames being measured. VAS was not required for participants who had physical or cognitive impairments that limited their ability to perform the assessment. Local standard of care participants who added mefloquine at Week 4 or Week 8 were counted as being dosed under both treatment arms.

Arm/Group Title	Local Standard of Care	Local Standard of Care Plus Mefloquine 250 mg
Arm/Group Description	Participants were randomized to receive 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 were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.
Measure Participants	17	30
Week 4 (n=9,16)	8.9 (29.14)	-0.7 (33.71)
Week 8 (n=4,13)	26.3 (49.00)	3.5 (23.87)

7. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Participants with values at the time frames being measured. Participants with undetectable CSF JCV load at baseline by the central laboratory were not included in the efficacy analysis. Local standard of care participants who added mefloquine at Week 4 or Week 8 were counted as being dosed under both treatment arms.

Arm/Group Title	Local Standard of Care	Local Standard of Care Plus Mefloquine 250 mg
Arm/Group Description	Participants were randomized to receive 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 were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.
Measure Participants	17	30
Week 0 (n=15,21)	8 114.3%	8 160%
Week 4 (n=12,12)	5 71.4%	8 160%
Week 8 (n=5,11)	1 14.3%	7 140%

8. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Participants with values at the time frames being measured. Participants with undetectable CSF JCV load at baseline by the central laboratory were not included in the efficacy analysis. Local standard of care participants who added mefloquine at Week 4 or Week 8 were counted as being dosed under both treatment arms.

Arm/Group Title	Local Standard of Care	Local Standard of Care Plus Mefloquine 250 mg
Arm/Group Description	Participants were randomized to receive 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 were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.
Measure Participants	17	30
Week 4 (n=12,11)	0.1407 (0.20345)	0.1631 (0.22523)
Week 8 (n=5,11)	0.0248 (0.12425)	0.1029 (0.26502)

9. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Participants with values at the time frames being measured. Participants with undetectable CSF JCV load at baseline by the central laboratory were not included in the efficacy analysis. Local standard of care participants who added mefloquine at Week 4 or Week 8 were counted as being dosed under both treatment arms.

Arm/Group Title	Local Standard of Care	Local Standard of Care Plus Mefloquine 250 mg
Arm/Group Description	Participants were randomized to receive 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 were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.
Measure Participants	17	30
Week 4 (n=12,11)	0.1704 (0.22012)	0.1619 (0.17501)
Week 8 (n=5,10)	0.1738 (0.21454)	0.1050 (0.23429)

10. Secondary Outcome

Title	Participants Who Died Within 6 Months
Description	The death event is counted under the treatment arm relative to adding mefloquine to the treatment regimen.
Time Frame	Day 1 up to 6 months

Outcome Measure Data

Analysis Population Description

Safety population: All participants who enrolled in the study and were dosed, and who have at least 1 post-baseline safety assessment. The death event is counted under the treatment arm relative to adding mefloquine to the treatment regimen.

Arm/Group Title	Local Standard of Care	Local Standard of Care Plus Mefloquine 250 mg
Arm/Group Description	Participants were randomized to receive 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 were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24. Also includes participants who were randomized to receive local standard of care (only) and added mefloquine at Week 4 or Week 8.
Measure Participants	17	30
Number [participants]	2 28.6%	5 100%

Adverse Events

Time Frame	Day 1 to Month 6
Adverse Event Reporting Description	Because participants were primarily patients with HIV/Acquired Immunodeficiency Syndrome (AIDS), SAEs considered to be AIDS-Defining Events (ADEs) were exempt from SAE reporting and were collected on a specific case report form instead of being captured as SAEs. However, any ADE that resulted in death did not qualify for an SAE exemption.
Arm/Group Title	Local Standard of Care		Local Standard of Care; Mefloquine at Week 4		Local Standard of Care; Mefloquine at Week 8		Local Standard of Care Plus Mefloquine 250 mg
Arm/Group Description	Participants were randomized to receive 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 who chose to add mefloquine at Weeks 4 or 8 to their standard of care treatment are counted in this treatment arm until the time of switching to mefloquine treatment.		Participants were randomized to receive 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 who chose to add mefloquine at Week 4 to their standard of care treatment are counted in this treatment arm once mefloquine treatment started.		Participants were randomized to receive 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 who chose to add mefloquine at Week 8 to their standard of care treatment are counted in this treatment arm once mefloquine treatment started.		Participants were randomized to receive 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) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.
All Cause Mortality
	Local Standard of Care		Local Standard of Care; Mefloquine at Week 4		Local Standard of Care; Mefloquine at Week 8		Local Standard of Care Plus Mefloquine 250 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Local Standard of Care		Local Standard of Care; Mefloquine at Week 4		Local Standard of Care; Mefloquine at Week 8		Local Standard of Care Plus Mefloquine 250 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/17 (29.4%)		1/5 (20%)		3/5 (60%)		13/20 (65%)
Blood and lymphatic system disorders
Pancytopenia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
General disorders
Death	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Infections and infestations
Appendicitis	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Urinary tract infection	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Pneumonia	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Periorbital cellulitis	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Progressive multifocal leukoencephalopathy	2/17 (11.8%)		0/5 (0%)		1/5 (20%)		1/20 (5%)
Staphylococcal infection	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Urinary tract infection pseudomonal	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Osteomyelitis	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Meningitis	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Candida pneumonia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Injury, poisoning and procedural complications
Narcotic intoxication	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Metabolism and nutrition disorders
Marasmus	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Muscular weakness	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Nervous system disorders
Neurological decompensation	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Status epilepticus	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Convulsion	0/17 (0%)		0/5 (0%)		0/5 (0%)		3/20 (15%)
Psychiatric disorders
Delirium	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Cough	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Chronic obstructive pulmonary disease	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Pneumonia aspiration	0/17 (0%)		0/5 (0%)		0/5 (0%)		2/20 (10%)
Dyspnoea	1/17 (5.9%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Asphyxia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Respiratory failure	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Respiratory tract congestion	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Local Standard of Care		Local Standard of Care; Mefloquine at Week 4		Local Standard of Care; Mefloquine at Week 8		Local Standard of Care Plus Mefloquine 250 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/17 (70.6%)		4/5 (80%)		5/5 (100%)		19/20 (95%)
Blood and lymphatic system disorders
Lymphadenopathy	0/17 (0%)		0/5 (0%)		1/5 (20%)		1/20 (5%)
Pancytopenia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Anaemia	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Hilar lymphaedenopathy	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Neutropenia	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Splenomegaly	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Cardiac disorders
Arrhythmia supraventricular	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Tachycardia	1/17 (5.9%)		1/5 (20%)		0/5 (0%)		1/20 (5%)
Dilatation ventricular	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Sinus arrhythmia	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Sinus bradycardia	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Sinus tachycardia	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Ear and labyrinth disorders
Vertigo	0/17 (0%)		0/5 (0%)		0/5 (0%)		2/20 (10%)
Ear pain	0/17 (0%)		1/5 (20%)		0/5 (0%)		1/20 (5%)
Otorrhoea	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Eye disorders
Diplopia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Iridocyclitis	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Scotoma	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Visual impairment	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Eye discharge	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Eye irritation	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Eye pain	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Inflammation of lacrimal passage	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Periorbital oedema	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Photopsia	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Vision blurred	1/17 (5.9%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Gastrointestinal disorders
Dysphagia	1/17 (5.9%)		0/5 (0%)		1/5 (20%)		3/20 (15%)
Nausea	0/17 (0%)		0/5 (0%)		1/5 (20%)		3/20 (15%)
Constipation	0/17 (0%)		0/5 (0%)		1/5 (20%)		2/20 (10%)
Abdominal pain	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Ascites	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Gastrooesophageal reflux disease	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Glossitis	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Vomiting	0/17 (0%)		0/5 (0%)		1/5 (20%)		1/20 (5%)
Abdominal pain upper	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Cheilitis	1/17 (5.9%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Colitis	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Diarrhoea	1/17 (5.9%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Intestinal mucosal hypertrophy	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Rectal haemorrhage	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Tooth loss	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
General disorders
Asthenia	0/17 (0%)		0/5 (0%)		1/5 (20%)		2/20 (10%)
Pyrexia	1/17 (5.9%)		1/5 (20%)		0/5 (0%)		2/20 (10%)
Feeling hot	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Injection site reaction	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Irritability	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Local swelling	0/17 (0%)		0/5 (0%)		1/5 (20%)		1/20 (5%)
Mucosal membrane hyperplasia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Chest pain	1/17 (5.9%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Chills	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Extravasation	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Gait disturbance	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Infusion site haematoma	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Oedema peripheral	2/17 (11.8%)		2/5 (40%)		0/5 (0%)		0/20 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Immune system disorders
Immune reconstitution syndrome	2/17 (11.8%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Infections and infestations
Pneumonia	0/17 (0%)		0/5 (0%)		0/5 (0%)		3/20 (15%)
Progressive multifocal leukoencephalopathy	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		3/20 (15%)
Anogenital warts	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Bronchitis	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Campylobacter gastroenteritis	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Candidiasis	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Folliculitis	0/17 (0%)		1/5 (20%)		1/5 (20%)		1/20 (5%)
Genital herpes	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Helicobacter gastritis	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Herpes simplex	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Oral candidiasis	2/17 (11.8%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Sinusitis	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Urinary tract infection	2/17 (11.8%)		1/5 (20%)		0/5 (0%)		1/20 (5%)
Bacillus infection	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Bacterial disease carrier	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Cellulitis	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Conjunctivitis infection	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Enterobacter infection	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Escherichia infection	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Klebsiella infection	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Oral herpes	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Pelvic abscess	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Purulent discharge	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Pyomyositis	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Rash pustular	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Sepsis	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Tinea versicolour	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Injury, poisoning and procedural complications
Contusion	1/17 (5.9%)		1/5 (20%)		0/5 (0%)		2/20 (10%)
Limb injury	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Excoriation	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Fall	0/17 (0%)		1/5 (20%)		1/5 (20%)		0/20 (0%)
Fracture displacement	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Head injury	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Joint dislocation	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Mouth injury	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Investigations
Aspartate aminotransferase increased	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Blood lactate dehydrogenase increased	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Liver function test abnormal	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Skin turgor decreased	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Weight decreased	0/17 (0%)		0/5 (0%)		1/5 (20%)		1/20 (5%)
Blood bicarbonate decreased	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Blood bilirubin increased	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Blood glucose increased	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Blood potassium decreased	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Blood potassium increased	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Blood pressure increased	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Breath sounds abnormal	1/17 (5.9%)		2/5 (40%)		0/5 (0%)		0/20 (0%)
Eosinophil count increased	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Haematocrit decreased	1/17 (5.9%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Haemoglobin decreased	1/17 (5.9%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Neurological examination abnormal	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Prealbumin decreased	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Red blood cell count decreased	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Vitamin D decreased	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
White blood cell count decreased	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Metabolism and nutrition disorders
Hyponatraemia	0/17 (0%)		0/5 (0%)		0/5 (0%)		2/20 (10%)
Dehydration	0/17 (0%)		0/5 (0%)		1/5 (20%)		1/20 (5%)
Hypocalcaemia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Hypokalaemia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Magnesium deficiency	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Hyperlipidaemia	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Vitamin D deficiency	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/17 (0%)		1/5 (20%)		0/5 (0%)		2/20 (10%)
Back pain	0/17 (0%)		1/5 (20%)		0/5 (0%)		1/20 (5%)
Mobility decreased	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Muscle spasms	0/17 (0%)		0/5 (0%)		1/5 (20%)		1/20 (5%)
Arthralgia	1/17 (5.9%)		1/5 (20%)		1/5 (20%)		0/20 (0%)
Bursitis	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Coccydynia	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Joint effusion	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Joint swelling	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Muscle atrophy	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Muscular weakness	0/17 (0%)		1/5 (20%)		1/5 (20%)		0/20 (0%)
Musculoskeletal disorder	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Musculoskeletal pain	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Musculoskeletal stiffness	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Myalgia	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Myositis	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Nervous system disorders
Headache	0/17 (0%)		2/5 (40%)		1/5 (20%)		4/20 (20%)
Ataxia	0/17 (0%)		0/5 (0%)		0/5 (0%)		2/20 (10%)
Epilepsy	0/17 (0%)		0/5 (0%)		0/5 (0%)		2/20 (10%)
Hemianopia homonymous	0/17 (0%)		0/5 (0%)		1/5 (20%)		2/20 (10%)
Hemiparesis	0/17 (0%)		0/5 (0%)		0/5 (0%)		2/20 (10%)
Apallic syndrome	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Aphasia	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Cerebellar syndrome	2/17 (11.8%)		0/5 (0%)		1/5 (20%)		1/20 (5%)
Cognitive disorder	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Convulsion	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Extensor plantar response	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Hemiplegia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Hyperreflexia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Hypertonia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Hypoaesthesia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Hypokinesia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Lethargy	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Memory impairment	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Movement disorder	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Multiple sclerosis relapse	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Muscle spasticity	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Partial seizures	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Syncope	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Visual field defect	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Disarthria	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Nervous system disorder	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Neuropathy peripheral	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Nystagmus	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Sensory loss	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Tremor	1/17 (5.9%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Psychiatric disorders
Anxiety	0/17 (0%)		1/5 (20%)		0/5 (0%)		2/20 (10%)
Abnormal behaviour	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Confusional state	0/17 (0%)		1/5 (20%)		1/5 (20%)		1/20 (5%)
Depression	0/17 (0%)		1/5 (20%)		0/5 (0%)		1/20 (5%)
Insomnia	0/17 (0%)		1/5 (20%)		0/5 (0%)		1/20 (5%)
Sleep disorder	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Abnormal dreams	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Agitation	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Delusion	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Drug abuse	1/17 (5.9%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Drug dependence	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Dysphemia	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Hallucination, auditory	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Renal and urinary disorders
Pollakiuria	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Renal failure	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Urinary incontinence	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Micturition urgency	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Urinary retention	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Reproductive system and breast disorders
Cervical dysplasia	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Vaginal discharge	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Acquired diaphragmatic eventration	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Aspiration	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Atelectasis	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Chronic obstructive pulmonary disease	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Cough	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Dyspnoea	1/17 (5.9%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Dyspnoea exertional	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Hypoventilation	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Hypoxia	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Oropharyngeal pain	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Pleural effusion	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Pneumonitis	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Productive cough	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Respiratory distress	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Respiratory tract congestion	0/17 (0%)		0/5 (0%)		1/5 (20%)		0/20 (0%)
Tachypnoea	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Tonsillar hypertrophy	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Rash pruritic	0/17 (0%)		1/5 (20%)		0/5 (0%)		1/20 (5%)
Urticaria	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Blister	1/17 (5.9%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Decubitus ulcer	1/17 (5.9%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Dennie-Morgan fold	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Dry skin	1/17 (5.9%)		1/5 (20%)		1/5 (20%)		0/20 (0%)
Erythema	0/17 (0%)		2/5 (40%)		0/5 (0%)		0/20 (0%)
Exfoliative rash	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Petechiae	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Pruritus	1/17 (5.9%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Psoriasis	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Rash	0/17 (0%)		1/5 (20%)		1/5 (20%)		0/20 (0%)
Rash macular	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Rash papular	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Seborrhoeic dermatitis	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Skin exfoliation	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)
Skin hypertrophy	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Skin ulcer	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Vascular disorders
Hypertension	0/17 (0%)		1/5 (20%)		0/5 (0%)		1/20 (5%)
Hypotension	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Phlebitis	0/17 (0%)		0/5 (0%)		0/5 (0%)		1/20 (5%)
Deep vein thrombosis	1/17 (5.9%)		0/5 (0%)		0/5 (0%)		0/20 (0%)
Phlebolith	0/17 (0%)		1/5 (20%)		0/5 (0%)		0/20 (0%)

Limitations/Caveats

From ongoing analysis, it became clear, based on conditional power calculations, that the study would not reach its primary endpoint, a decrease of JC viral load in CSF with mefloquine treatment; therefore, the study was terminated early.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 45 to 60 days as agreed within their clinical trial agreement to review any manuscript for a proposed publication and must delay publication for up to an additional 60 to 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.