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

NCT00746941 | Terminated Phase 1 Results

• 1 other identifier: 111JC101
• Study Type: interventional
• Target: 37
• Locations: 5 countries
• Sites: 12

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.

Conditions

Progressive Multifocal Leukoencephalopathy

Keywords

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

Outcome Measures

Primary Outcomes (2)

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

  Change from baseline to Week 4 in JC viral load in CSF is expressed as log10 copies/mL. Negative values indicate a reduction in viral load. Only participants with measurable baseline values are included. Post-baseline values of 'Below the Limit of Quantification' or 'Below Limit of Detection' or 'Negative' were set to 50. Log10 (50) = 1.699

  Day 0 (baseline), Week 4

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

  Change from baseline to Week 8 in JC viral load in CSF is expressed as log10 copies/mL. Negative values indicate a reduction in viral load. Only participants with measurable baseline values are included. Post-baseline values of 'Below the Limit of Quantification' or 'Below Limit of Detection' or 'Negative' were set to 50. Log10 (50) = 1.699

  Day 0 (baseline), Week 8

Secondary Outcomes (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

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

  Day 0 (baseline), Week 4, Week 8

• Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT)

  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)

  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

  Day 0 (baseline), Week 4, Week 8

Study Arms (2)

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.

Drug: mefloquine

Interventions

mefloquine DRUG

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

Also known as: Lariam®, Mephaquin®, Mefliam®

Local standard of care plus mefloquine 250 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of PML confirmed by detection of JCV DNA in CSF.
• Onset of PML symptoms within 6 months prior to study.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead
• Elan Pharmaceuticals: collaborator

Study Sites (12)

Research Site

Chicago, Illinois, United States

Location

Research Site

Baltimore, Maryland, United States

Location

Research Site

Boston, Massachusetts, United States

Location

Research Site

St Louis, Missouri, United States

Location

Research Site

New York, New York, United States

Location

Research Site

São Paulo, Brazil

Location

Research Site

Düsseldorf, North Rhine-Westphalia, Germany

Location

Research Site

Berlin, Germany

Location

Research Site

Hamburg, Germany

Location

Research Site

Milan, Italy

Location

Research Site

Barcelona, Spain

Location

Research Site

Madrid, Spain

Location

Related Publications (1)

• Clifford DB, Nath A, Cinque P, Brew BJ, Zivadinov R, Gorelik L, Zhao Z, Duda P. A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes. J Neurovirol. 2013 Aug;19(4):351-8. doi: 10.1007/s13365-013-0173-y. Epub 2013 Jun 4.

  PMID: 23733308 RESULT

MeSH Terms

Conditions

Leukoencephalopathy, Progressive Multifocal; Central Nervous System Diseases

Interventions

Mefloquine

Condition Hierarchy (Ancestors)

Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Virus Diseases; Polyomavirus Infections; DNA Virus Infections; Slow Virus Diseases; Encephalitis; Brain Diseases; Nervous System Diseases; Leukoencephalopathies; Demyelinating Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and 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.

Results Point of Contact

• Title: Biogen Idec Study Medical Director
• Organization: Biogen Idec

clinicaltrials@biogenidec.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2008
• First Posted: September 4, 2008
• Study Start: January 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: July 31, 2014
• Results First Posted: July 31, 2014

Record last verified: 2014-07

Locations

BR (1); ES (2); US (5); DE (3); IT (1)