E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-remitting multiple sclerosis already on interferon-beta therapy |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | Multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
The primary objective is to establish the safety and tolerability of bexarotene in the treatment of relapsing remitting multiple sclerosis. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess the efficacy of bexarotene in promoting myelin repair (remyelination) in relapsing remitting multiple sclerosis.
Exploratory objectives seek to assess bexarotene's effect on: -lesions of different ages and severities; -optic nerve function (giving a functional measure of whether a damaged (demyelinated) optic nerve may have remyelinated after bexarotene); -patients' level of disability; -immune markers in patient's bloods during and after treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Informed consent - Male or female aged between 30 and 50 years inclusive - Relapsing remitting multiple sclerosis as per the McDonald 2010 criteria, including an MRI satisfying the radiological criteria - At least five T2 lesions, attributable to MS, on baseline MRI brain scan - Kurtzke EDSS 3.0-6.0 - At least one relapse in the two years prior to screening - At the time of screening (and for at least the last 6 months) being treated with interferon-beta (any preparation) - Able and willing to comply with all study requirements
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E.4 | Principal exclusion criteria |
Patients who are: - Pregnant, lactating or planning pregnancy during course of trial - Female and male participants unwilling or unable to use two reliable non-hormonal methods of contraception during the course of the trial and for one month thereafter - Taking gemfibrozil - Taking disease-modifying therapy for multiple sclerosis, other than interferon-beta within the previous six months - Significant renal or hepatic impairment (Grade III or worse) - Known hypersensitivity to bexarotene or to any of the excipients of the product - Unwillingness to take a product containing gelatin - Known reaction to gadolinium (within the contrast agent used for MRI scans) - History of pancreatitis - Fasting triglycerides over 2.3 mmol/L or baseline dyslipidaemia requiring treatment - Known hypervitaminosis A - Uncontrolled thyroid disease - Excessive alcohol consumption (>24units/week for men, >14 units/week for women) - Uncontrolled diabetes mellitus - Biliary tract disease - Hereditary fructose intolerance - Use of CYP3A4-substrates (ketoconazole, itraconazole, protease inhibitors, clarithromycin and erythromycin) or CYP3A4-inducers (rifampicin, phenytoin, dexamethasone or phenobarbital), unless patients are willing to stop these (and it is safe to do so) - Any other significant disease, disability or investigation result which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is adverse events and withdrawals atributable to taking bexarotene. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of the 6 months of treatment. |
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E.5.2 | Secondary end point(s) |
The secondary endpoint is mean lesional Magnetisation Transfer Ratio (MTR) between month 0 and month 6 for lesions selected for each patient whose MTR lies below the within-patient median. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 6 months of treatment |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |