E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062016 |
E.1.2 | Term | Immunosuppression |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10046851 |
E.1.2 | Term | Uveitis |
E.1.2 | System Organ Class | 10015919 - Eye 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 |
To determine whether the mean reduction in prednisolone dosage achieved at 12 months is greater in the simvastatin group compared to the placebo treated group?
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E.2.2 | Secondary objectives of the trial |
1. The mean reduction in prednisolone achieved at 24 months. 2. The number and dose of 2nd-line agents at 24 months 3. The number of disease relapses by 24 months 4. Blood cholesterol and lipid levels at 24 months as compared to baseline 5. Change in visual acuity at 12 and 24 months as compared to baseline 6. Treg and Th17 levels at 12 and 24 months as compared to baseline 7. Safety and tolerability of simvastatin
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients must be >18 years and under 80 years. 2. Both sexes may participate, but, because of possible teratogenicity of simvastatin women may do so only following counselling about the need for adequate contraception. 3. Women of child bearing potential will have to have a negative pregnancy test prior to enrolment. 4. Patients must have been previously diagnosed with intermediate, posterior or panuveitis (as defined by the standardization of uveitis nomenclature group). 5. Patients must be taking systemic prednisolone 10mg once daily or more. 6. Patients may be treated with or without a second line agent. 7. Patients must be willing and able to provide informed consent
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E.4 | Principal exclusion criteria |
1. Females who are pregnant, planning pregnancy or breastfeeding. 2. Patients concomitantly taking ciclosporin, fibrates, amiodarone, amlodipine, verapamil, CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, posaconazole, voriconazole), HIV protease inhibitors (e.g. nelfinavir), erythromycin, clarithromycin, telithromycin, nefazodone, gemfibrozil, danazol, fusidic acid, niacin, colchicine, rifampicin, diltiazem, statins or anti-coagulants. 3. Patients drinking grapefruit juice during the study. 4. Family history of hereditary muscle disorders. 5. Active Liver disease 6. Severe renal insufficiency. 7. Documented persistently elevated serum transaminases. 8. Allergies to excipients of IMP and placebo 9. Lactose intolerance 10. Active involvement in other clinical trials |
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E.5 End points |
E.5.1 | Primary end point(s) |
Does the addition of Simvastatin 80mg od to standard treatment result in a mean reduction in prednisolone dose at 12 months? We will document the dose of prednisolone at each follow-up visit and compare, at 12 months, the mean change in dose from baseline between the treatment groups. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The end point will be evaluated at 12 months from baseline. |
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E.5.2 | Secondary end point(s) |
1. The mean reduction in prednisolone achieved at 24 months. 2. The number and dose of 2nd-line agents at 24 months 3. The number of disease relapses by 24 months 4. Blood cholesterol and lipid levels at 24 months as compared to baseline 5. Change in visual acuity at 12 and 24 months as compared to baseline 6. Treg and Th17 levels at 12 and 24 months as compared to baseline 7. Safety and tolerability of simvastatin
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary end points will be evaluated at either 12 or 24 months. |
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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 | No |
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 | 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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 7 |
E.8.9.1 | In the Member State concerned days | 31 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 31 |