Progressive Multifocal LeukoencephalopathyPhase 1/2NCT00746941
Study to Explore the Effect of Mefloquine in Participants With Progressive Multifocal Leukoencephalopathy (PML)
A Phase 1/2 study testing mefloquine in people with Progressive Multifocal Leukoencephalopathy, run by Biogen at 12 sites in 5 countries.
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Progressive Multifocal Leukoencephalopathy
- What is being tested?
- mefloquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 12 sitesin 5 countries
- Study dates
- Jan 2009to Nov 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of PML confirmed by detection of JCV DNA in CSF.
- Onset of PML symptoms within 6 months prior to study.
Who cannot join
- 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.
Trial locations and contacts
12 sites in 5 countries.
12 sites in 5 countries
United States5 sites
Research Site
Baltimore, Maryland
Research Site
Boston, Massachusetts
Research Site
Chicago, Illinois
Research Site
New York, New York
Research Site
St Louis, Missouri
Germany3 sites
Research Site
Berlin
Research Site
Düsseldorf, North Rhine-Westphalia
Research Site
Hamburg
About this study
Official title: A Randomized, Rater-Blinded Study to Explore the Effect of Mefloquine in Subjects With Progressive Multifocal Leukoencephalopathy (PML)
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.
- Being tested
- mefloquine
- Keywords
- PML, Human Polyomavirus JC, HIV, Central Nervous System Disease, Mefloquine, JC Virus
- Medical subject headings
- Leukoencephalopathy, Progressive Multifocal, Central Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mefloquineDrug
Also called Lariam®, Mephaquin®, Mefliam®
250 mg orally each day for 3 days and then weekly up to 6 months.
| Study group | Role | What they receive |
|---|---|---|
| Local standard of care | No intervention | 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. |
| Local standard of care plus mefloquine 250 mg | Experimental | 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. Receives: Drug: mefloquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Day 0 (baseline), Week 4
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
Measured: Day 0 (baseline), Week 8
Secondary outcomes (8)
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.
Measured: Day 0 (baseline), Week 4 and 8
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.
Measured: Day 0 (baseline), Week 4, Week 8
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.
Measured: Day 0 (baseline), Week 4, Week 8
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.
Measured: Day 0 (baseline), Week 4, Week 8
Participants With Gadolinium (Gd)-Enhanced Lesions at Baseline, Week 4 and Week 8 as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains
Measured: Day 0 (baseline), Week 4, Week 8
Change From Baseline to Week 4 and Week 8 in T1 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains
Measured: Day 0 (baseline), Week 4, Week 8
Change From Baseline to Week 4 and Week 8 in T2 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains
Measured: Day 0 (baseline), Week 4, Week 8
Participants Who Died Within 6 Months
The death event is counted under the treatment arm relative to adding mefloquine to the treatment regimen.
Measured: Day 1 up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2008 (estimated)
- Study startJan 2009
- Primary completionNov 2010
- Study completionNov 2010
Why it stopped: Primary endpoint not achieved
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Progressive Multifocal LeukoencephalopathyStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Elan Pharmaceuticals
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00746941
- Sponsor's protocol ID
- 111JC101
- Status last verified
- Jul 2014
- First submitted
- 3 Sep 2008
- Last updated
- 31 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Clifford DB, Nath A, Cinque P, Brew BJ, Zivadinov R, Gorelik L, Zhao Z, Duda P. A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes. J Neurovirol. 2013 Aug;19(4):351-8. doi: 10.1007/s13365-013-0173-y. Epub 2013 Jun 4.
PubMed 23733308
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Rater-Blinded Study to Explore the Effect of Mefloquine in Subjects With Progressive Multifocal Leukoencephalopathy (PML)
- ClinicalTrials.gov ID
- NCT00746941
- Acronym / sponsor ID
- 111JC101
- Keywords
- PML, Human Polyomavirus JC, HIV, Central Nervous System Disease, Mefloquine, JC Virus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Primary endpoint not achieved
- Enrolment
- 37 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Collaborators
- Elan Pharmaceuticals
- Study start
- Jan 2009
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 4 Sep 2008 (estimated)
- Results
- Posted 31 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Local standard of care | No intervention | –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. |
| Local standard of care plus mefloquine 250 mg | Experimental | Drug: mefloquineAll 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Diagnosis of PML confirmed by detection of JCV DNA in CSF.
- Onset of PML symptoms within 6 months prior to study.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mefloquineAlso: Lariam®, Mephaquin®, Mefliam®250 mg orally each day for 3 days and then weekly up to 6 months. | Drug | Local standard of care plus mefloquine 250 mg |
Primary outcome
Change From Baseline to Week 4 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF)
Time frame: 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)
Time frame: 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
8 secondary outcomes
Change From Baseline to Week 4 and Week 8 in the Expanded Disability Status Scale (EDSS) Score
Time frame: Day 0 (baseline), Week 4 and 8
Change From Baseline to Week 4 and Week 8 in Karnofsky Performance Status (KPS) Index Score
Time frame: Day 0 (baseline), Week 4, Week 8
Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT)
Time frame: Day 0 (baseline), Week 4, Week 8
Change From Baseline to Week 4 and Week 8 in Participants' Neurological Function Using a Visual Analog Scale (VAS)
Time frame: Day 0 (baseline), Week 4, Week 8
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
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
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
Participants Who Died Within 6 Months
Time frame: Day 1 up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23733308Clifford DB, Nath A, Cinque P, Brew BJ, Zivadinov R, Gorelik L, Zhao Z, Duda P. A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes. J Neurovirol. 2013 Aug;19(4):351-8. doi: 10.1007/s13365-013-0173-y. Epub 2013 Jun 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing mefloquine in people with Progressive Multifocal Leukoencephalopathy, run by Biogen at 12 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Germany, Spain, Brazil, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 4 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF) (time frame: Day 0 (baseline), Week 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00746941, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2014.