Progressive Multifocal Leukoencephalopathy
Conditions
Keywords
PML, Human Polyomavirus JC, HIV, Central Nervous System Disease, Mefloquine, JC Virus
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.
Interventions
DRUGmefloquine
250 mg orally each day for 3 days and then weekly up to 6 months.
Sponsors
Elan Pharmaceuticals
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 | — |
| 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. |
| 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 | — |
| 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. |
| 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 | — |
| 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. |
Countries
Brazil, Germany, Italy, Spain, United States
Participant flow
Recruitment details
Twelve sites enrolled participants prior to study termination.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Local Standard of Care 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). | 7 |
| Local Standard of Care; Mefloquine at Week 4 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. | 5 |
| Local Standard of Care; Mefloquine at Week 8 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. | 5 |
| Local Standard of Care Plus Mefloquine 250 mg 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. | 20 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Death | 2 | 0 | 0 | 6 |
| Overall Study | Other, reason not provided | 2 | 4 | 0 | 4 |
| Overall Study | Physician Decision | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Local Standard of Care Plus Mefloquine 250 mg | Local Standard of Care; Mefloquine at Week 8 | Local Standard of Care; Mefloquine at Week 4 | Local Standard of Care |
|---|---|---|---|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 12.16 | 48.1 years STANDARD_DEVIATION 9.4 | 47.4 years STANDARD_DEVIATION 10.06 | 41.6 years STANDARD_DEVIATION 11.37 | 48.7 years STANDARD_DEVIATION 20.56 |
| Disease history HIV negative | 8 participants | 4 participants | 1 participants | 0 participants | 3 participants |
| Disease history HIV positive: HAART Naive | 24 participants | 13 participants | 3 participants | 5 participants | 3 participants |
| Disease history HIV positive: History of HAART | 5 participants | 3 participants | 1 participants | 0 participants | 1 participants |
| JVC Titer at Screening <= 50 copies/mL | 4 participants | 4 participants | 0 participants | 0 participants | 0 participants |
| JVC Titer at Screening > 50 copies/mL | 32 participants | 15 participants | 5 participants | 5 participants | 7 participants |
| JVC Titer at Screening Missing | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 4 Participants | 2 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 16 Participants | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Female | 10 Participants | 5 Participants | 2 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 27 Participants | 15 Participants | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 17 | 4 / 5 | 5 / 5 | 19 / 20 |
| serious Total, serious adverse events | 5 / 17 | 1 / 5 | 3 / 5 | 13 / 20 |
Outcome results
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
Time frame: Day 0 (baseline), Week 4
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Local Standard of Care | Change From Baseline to Week 4 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF) | -0.2424 log10 copies/mL | Standard Deviation 0.83556 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF) | -0.0675 log10 copies/mL | Standard Deviation 1.52685 |
p-value: 0.7132Student's t-test
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
Time frame: Day 0 (baseline), Week 8
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Local Standard of Care | Change From Baseline to Week 8 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF) | -0.2843 log10 copies/mL | Standard Deviation 0.68666 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 8 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF) | -0.3455 log10 copies/mL | Standard Deviation 0.9396 |
p-value: 0.9086Student's t-test
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.
Time frame: Day 0 (baseline), Week 4, Week 8
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Local Standard of Care | Change From Baseline to Week 4 and Week 8 in Karnofsky Performance Status (KPS) Index Score | Week 4 (n=12, 21) | 0.00 units on a scale | Standard Deviation 14.771 |
| Local Standard of Care | Change From Baseline to Week 4 and Week 8 in Karnofsky Performance Status (KPS) Index Score | Week 8 (n=7, 16) | -10.0 units on a scale | Standard Deviation 26.46 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 and Week 8 in Karnofsky Performance Status (KPS) Index Score | Week 4 (n=12, 21) | -8.10 units on a scale | Standard Deviation 12.891 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 and Week 8 in Karnofsky Performance Status (KPS) Index Score | Week 8 (n=7, 16) | -10.6 units on a scale | Standard Deviation 19.14 |
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.
Time frame: Day 0 (baseline), Week 4, Week 8
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Local Standard of Care | Change From Baseline to Week 4 and Week 8 in Participants' Neurological Function Using a Visual Analog Scale (VAS) | Week 4 (n=9,16) | 8.9 units on a scale | Standard Deviation 29.14 |
| Local Standard of Care | Change From Baseline to Week 4 and Week 8 in Participants' Neurological Function Using a Visual Analog Scale (VAS) | Week 8 (n=4,13) | 26.3 units on a scale | Standard Deviation 49 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 and Week 8 in Participants' Neurological Function Using a Visual Analog Scale (VAS) | Week 4 (n=9,16) | -0.7 units on a scale | Standard Deviation 33.71 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 and Week 8 in Participants' Neurological Function Using a Visual Analog Scale (VAS) | Week 8 (n=4,13) | 3.5 units on a scale | Standard Deviation 23.87 |
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.
Time frame: Day 0 (baseline), Week 4, Week 8
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Local Standard of Care | Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT) | Week 4 (n=6,8) | 4.00 units on a scale | Standard Deviation 6.723 |
| Local Standard of Care | Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT) | Week 8 (n=3,6) | 1.7 units on a scale | Standard Deviation 10.12 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT) | Week 4 (n=6,8) | -1.50 units on a scale | Standard Deviation 3.78 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT) | Week 8 (n=3,6) | 3.8 units on a scale | Standard Deviation 6.43 |
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
Time frame: Day 0 (baseline), Week 4, Week 8
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Local Standard of Care | Change From Baseline to Week 4 and Week 8 in T1 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 4 (n=12,11) | 0.1407 log10 mm^3 | Standard Deviation 0.20345 |
| Local Standard of Care | Change From Baseline to Week 4 and Week 8 in T1 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 8 (n=5,11) | 0.0248 log10 mm^3 | Standard Deviation 0.12425 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 and Week 8 in T1 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 4 (n=12,11) | 0.1631 log10 mm^3 | Standard Deviation 0.22523 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 and Week 8 in T1 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 8 (n=5,11) | 0.1029 log10 mm^3 | Standard Deviation 0.26502 |
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
Time frame: Day 0 (baseline), Week 4, Week 8
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Local Standard of Care | Change From Baseline to Week 4 and Week 8 in T2 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 4 (n=12,11) | 0.1704 log10 mm^3 | Standard Deviation 0.22012 |
| Local Standard of Care | Change From Baseline to Week 4 and Week 8 in T2 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 8 (n=5,10) | 0.1738 log10 mm^3 | Standard Deviation 0.21454 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 and Week 8 in T2 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 4 (n=12,11) | 0.1619 log10 mm^3 | Standard Deviation 0.17501 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 and Week 8 in T2 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 8 (n=5,10) | 0.1050 log10 mm^3 | Standard Deviation 0.23429 |
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.
Time frame: Day 0 (baseline), Week 4 and 8
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Local Standard of Care | Change From Baseline to Week 4 and Week 8 in the Expanded Disability Status Scale (EDSS) Score | Week 4 (n=12, 21) | 0.79 units on a scale | Standard Deviation 1.054 |
| Local Standard of Care | Change From Baseline to Week 4 and Week 8 in the Expanded Disability Status Scale (EDSS) Score | Week 8 (n=7, 16) | 0.71 units on a scale | Standard Deviation 1.868 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 and Week 8 in the Expanded Disability Status Scale (EDSS) Score | Week 4 (n=12, 21) | 0.50 units on a scale | Standard Deviation 1.129 |
| Local Standard of Care Plus Mefloquine 250 mg | Change From Baseline to Week 4 and Week 8 in the Expanded Disability Status Scale (EDSS) Score | Week 8 (n=7, 16) | 0.88 units on a scale | Standard Deviation 1.36 |
Secondary
Participants Who Died Within 6 Months
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Local Standard of Care | Participants Who Died Within 6 Months | 2 participants |
| Local Standard of Care Plus Mefloquine 250 mg | Participants Who Died Within 6 Months | 5 participants |
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
Time frame: Day 0 (baseline), Week 4, Week 8
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Local Standard of Care | Participants With Gadolinium (Gd)-Enhanced Lesions at Baseline, Week 4 and Week 8 as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 0 (n=15,21) | 8 participants |
| Local Standard of Care | Participants With Gadolinium (Gd)-Enhanced Lesions at Baseline, Week 4 and Week 8 as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 4 (n=12,12) | 5 participants |
| Local Standard of Care | Participants With Gadolinium (Gd)-Enhanced Lesions at Baseline, Week 4 and Week 8 as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 8 (n=5,11) | 1 participants |
| Local Standard of Care Plus Mefloquine 250 mg | Participants With Gadolinium (Gd)-Enhanced Lesions at Baseline, Week 4 and Week 8 as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 0 (n=15,21) | 8 participants |
| Local Standard of Care Plus Mefloquine 250 mg | Participants With Gadolinium (Gd)-Enhanced Lesions at Baseline, Week 4 and Week 8 as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 4 (n=12,12) | 8 participants |
| Local Standard of Care Plus Mefloquine 250 mg | Participants With Gadolinium (Gd)-Enhanced Lesions at Baseline, Week 4 and Week 8 as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains | Week 8 (n=5,11) | 7 participants |