E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Progressive Multifocal Leukoencephalopathy (PML) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036807 |
E.1.2 | Term | Progressive multifocal leukoencephalopathy |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To explore whether mefloquine can delay or stop progression of PML as measured by JCV levels in CSF |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 ≥30 kg. 4. Must have a diagnosis of PML confirmed by detection of JCV DNA in CSF. 5. Must have onset of PML symptoms within ≤3 months prior to signing the informed consent form (ICF). 6. Expected survival time of ≥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. |
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E.4 | Principal 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 × ULN) at Screening, and/or bilirubin >3 × ULN at Screening. 10. A calculated creatinine clearance <30 mL/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 randomization. 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To explore whether mefloquine can delay or stop progression of PML as measured by JCV DNA levels in CSF |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Chiusura del database per l`analisi finale. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |