E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Infectious Intermediate, Posterior or Pan-uveitis |
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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.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to assess the safety and efficacy of voclosporin as therapy in subjects with active noninfectious uveitis involving the intermediate and/or posterior ocular segments. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to obtain voclosporin blood concentration data for inclusion in a Population Pharmacokinetic analysis. These data, in combination with data from Phase 1 studies of voclosporin in normal volunteers and Phase 2/3 studies in subjects with plaque psoriasis, will be used to assess the impact of demographics on the exposure to voclosporin and to assess the role of exposure as it relates to efficacy and adverse events. The results of this analysis will be provided in a separate report. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
I.1. Active noninfectious uveitis involving the intermediate and/or posterior segment (i.e., anterior +
intermediate-, intermediate-, posterior- or pan-uveitis) in at least one eye as evidenced by a vitreous haze grade of at least 2+ at the baseline visit (Visit 1). Subjects who also have anterior segment involvement need not be excluded if otherwise qualified.
I.2. Uveitis therapy
Current therapy must conform to one of the following:
- Prednisone monotherapy at a dose of ≥ 10 mg/day and ≤ 40 mg/day (or equivalent dose of another corticosteroid) for at least 2 weeks prior to the baseline visit (Visit 1).
- Prednisone, at any dose ≤ 40 mg/day (or equivalent dose of another corticosteroid), in addition to one immunosuppressive agent from among cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mycophenolic acid or methotrexate for at least 2 weeks prior to the baseline visit (Visit 1).
- N.B: All immunosuppressive therapy (excluding systemic corticosteroids) must be discontinued by the evening prior to the baseline visit (Visit 1).
I.3. Considered by the Investigator to require systemic immunosuppressive therapy.
I.4. A minimum ability to count fingers at a distance of 30 cm (1 foot) with each eye at the baseline visit (Visit 1).
I.5. At least 18 years of age.
I.6. Subjects, whether male or female, with reproductive potential and who are sexually active must agree to use double-barrier contraception methods BEFORE beginning study drug therapy, for the duration of the study (minimum of 24 weeks), and for 6 weeks following completion of study drug.
I.7. Women of childbearing potential must have a negative urine pregnancy test within 48 hours prior to subject’s assignment to study treatment at the baseline visit (Visit 1). All female subjects (including those with tubal ligations) will be considered to be of childbearing potential unless one or more of the following criteria are met:
- Over the age of 60 years.
- Amenorrheic for at least 2 years if age 45-60 years.
- Have had a hysterectomy and/or bilateral oophorectomy.
I.8. Subjects must be:
- Capable of understanding the purpose and risks of the study.
- Able to give written informed consent.
- Able to comply with all study requirements. |
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E.4 | Principal exclusion criteria |
E1.1. Uveitis limited to only the anterior segment of the study eye.
E1.2. Confirmed or suspected infectious uveitis in either eye, including but not limited to infectious uveitis due to tuberculosis, cytomegalovirus, Lyme disease, toxoplasmosis, Human T-Lymphotropic Virus Type 1 (HTLV-1), Whipple’s disease, herpes zoster virus (HZV), and herpes simplex virus (HSV) or history of other ocular herpetic infection; Fuchs heterochromic iridocyclitis.
E1.3. Presence of an ocular toxoplasmosis scar or suspected active infection in either eye.
E1.4. Active infection (i.e. bacterial, viral, parasitic or fungal) in either eye.
E1.5. Serpiginous choroidopathy in either eye.
E1.6. Active inflammatory lesions or vasculitis involving the central macula within 1,000 microns of the fovea (either eye).
E1.7. History of central serous chorioretinopathy in either eye.
E1.8. Proliferative or severe non-proliferative diabetic retinopathy in either eye.
E1.9. Neovascular/exudative/wet age-related macular degeneration in either eye.
E1.10. Abnormality of vitreoretinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) thought by the Investigator to interfere with measurement of macular thickness or with the potential for macular structural damage independent of the inflammatory process in the study eye.
E1.11. Clinically suspected or confirmed ocular lymphoma (either eye).
E1.12. Obscured ocular media (e.g., corneal scars, lens opacities, vitreous abnormalities, etc.) in the study eye at baseline (Visit 1) such that reliable evaluations and grading of either the intermediate or posterior segment cannot be performed.
E1.13. Any other ocular disease in the study eye that can interfere with the diagnosis or assessment of disease progression.
E1.14. Monocular (anophthalmic fellow eye).
E1.15. Intraocular pressure of < 6 mmHg or > 21 mmHg in either eye at the baseline visit (Visit 1).
E1.16. Chronic hypotony (intraocular pressure less than 6 mmHg or clinical signs such as choroidals, choroidal, or corneal folds) or pre-phthisical state (e.g., scleral thickening on ultrasonography, decreasing globe size) in either eye.
E1.17. Contraindication to pupil dilation in either eye.
E1.18. A likely need for ocular surgery (e.g., cataract extraction, laser treatment) in the study eye during the period of study participation.
E2. Specific Prior and Current Treatments (for details please refer to protocol).
E3. Specific Extra-ocular Conditions (for details please refer to protocol).
E4. Specific Laboratory, Blood Pressure and ECG Evaluations (for details please refer to protocol). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in graded vitreous haze in the study eye at 12 weeks of therapy or at time of treatment failure, if earlier. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary objective of this study is to obtain voclosporin blood concentration data for inclusion in a Population Pharmacokinetic analysis. These data, in combination with data from Phase 1 studies of voclosporin in normal volunteers and Phase 2/3 studies in subjects with plaque psoriasis, will be used to assess the impact of demographics on the exposure to voclosporin and to assess the role of exposure as it relates to efficacy and adverse events. The results of this analysis will be provided in a separate report. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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
| 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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | No |
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 |
Austria |
Brazil |
Canada |
France |
Germany |
Italy |
Netherlands |
Spain |
Turkey |
United States |
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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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Possible reasons for termination of a study site include, but are not limited to:
• Unsatisfactory enrollment with respect to quantity or quality
• Inaccurate or incomplete data collection
• Falsification of records
• Failure to adhere to the protocol
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |