A Randomized, Rater-Blinded Study to Explore the Effect of Mefloquine in Subjects with Progressive Multifocal Leukoencephalopathy (PML)

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-001314-24-GB
• Date of registration: 28/05/2008
• Prospective Registration: Yes
• Primary sponsor: Biogen Idec Ltd
• Public title: A Randomized, Rater-Blinded Study to Explore the Effect of Mefloquine in Subjects with Progressive Multifocal Leukoencephalopathy (PML)
• Scientific title: A Randomized, Rater-Blinded Study to Explore the Effect of Mefloquine in Subjects with Progressive Multifocal Leukoencephalopathy (PML)
• Date of first enrolment: 02/01/2009
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-001314-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Randomised, rater-blinded If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Local standard of care

Countries of recruitment

France, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Must give written informed consent and any authorizations required by local law (e.g., Protected Health Information).
2. Aged 18 to 75 years old, inclusive, at the time of informed consent.
3. Must weigh more or equal to 30 kg.
4. Must have a diagnosis of PML confirmed by detection of JCV DNA in CSF. JCV DNA detection in a CSF sample analysed by a local laboratory within 30 days prior to randomisation is acceptable, as long as a lumbar puncture is still performed at the Screening Visit for testing and confirmation by the central laboratory. However, the lumbar puncture at the Screening Visit may be waived if the positive CSF sample was analysed by a local laboratory within 14 days of randomisation and sufficient volume is available for testing and confirmation by the central laboratory.
5. Must have onset of PML symptoms within less or equal to 6 months of randomisation.
6. Expected survival time of more or equal to 2 months after baseline, as determined by the Investigator.
7. All male subjects and female subjects of child-bearing potential must practice effective contraception during the study and be willing and able to continue contraception for 14 weeks after their last dose of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Any current clinical or laboratory parameter assessed as Grade 4 in the AIDS Clinical Trial Group (ACTG) Grading System (Section 22). Asymptomatic Grade 4 laboratory abnormalities will be permitted, at the discretion of the Investigator, if the potential benefit of treatment outweighs the potential risk.
2. Concomitant opportunistic infection of the CNS.
3. Current severe illness or any other conditions that, in the opinion of the Investigator, would make the subject unsuitable for enrollment.
4. Any condition that precludes repeated lumbar punctures.
5. Active severe mental illness (e.g., depression, anxiety, psychosis, and schizophrenia).
6. Unexplained epileptic seizures within 6 months prior to randomization.
7. Hypersensitivity to mefloquine, quinine, or quinidine, or to any component of these drugs.
8. Known galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.
9. Alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT) and aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) greater than 5 times the upper limit of normal (> 5 x ULN) at Screening, and/or bilirubin >3 x ULN at Screening.
10. A calculated creatinine clearance <30mL/min at Screening.
11.A marked prolongation of QT/QTc interval (e.g., repeated demonstration of a QT/QTc interval >450 milliseconds [Msec]) at Screening or Baseline.
12. Vaccinations with live vaccines (even of attenuated viruses/bacteria) within 2 months prior to randomisation.
13. Participation in another study within 30 days prior to randomization.
14. Current treatment with quinine, quinidine, chloroquine, or halofantrine.
15. Current treatment with efavirenz, unless the subject has been on a stable dose for 30 days prior to randomization and is expected to remain on the same dose or on a lower dose throughout the study.
16. Female subjects who are pregnant or currently breastfeeding, or who plan to become pregnant during the study.
17. Inability to comply with study requirements.
18. Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Progressive Multifocal Leukoencephalopathy (PML)
MedDRA version: 9.1 Level: LLT Classification code 10036807 Term: Progressive multifocal leukoencephalopathy

Intervention(s)

Trade Name: Lariam
Product Name: Mefloquine
Product Code: 111JC101
Pharmaceutical Form: Tablet
INN or Proposed INN: MEFLOQUINE
CAS Number: 53230107
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Primary Outcome(s)

Secondary Objective: 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.

Main Objective: To explore whether mefloquine can delay or stop progression of PML as measured by JCV levels in CSF.

Primary end point(s): To explore whether mefloquine can delay or stop progression of PML as measured by JCV DNA levels in CSF.

Secondary ID(s)

111JC101