E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic non-infectious uveitis affecting the posterior segment of the eye |
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E.1.1.1 | Medical condition in easily understood language |
Uveitis in the back of the eye that is not caused by an infection |
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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 | 20.0 |
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 |
The primary objectives of this study are to evaluate the safety and efficacy of a FAI insert in the management of subjects with chronic non-infectious uveitis affecting the posterior segment of the eye. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or non-pregnant female at least 18 years of age at time of consent
• One or both eyes having a history of recurrent non-infectious uveitis affecting the posterior segment of the eye with or without anterior uveitis > 1 year duration.
• During the 12 months prior to enrollment (Day 1), the study eye has either received treatment:
o systemic corticosteroid or other systemic therapies given for at least 3 months, and/or
o at least 2 intra- or peri-ocular injections of corticosteroid for management of uveitis
OR the study eye has experienced recurrence:
o at least 2 separate recurrences of uveitis requiring systemic, intra- or peri-ocular injection of corticosteroid
• At the time of enrollment (Day1), study eye has < 10 anterior chamber cells/HPF and a vitreous haze ≤ grade 2.
• Visual acuity of study eye is at least 15 letters on the ETDRS chart
• Subject is not planning to undergo elective ocular surgery during the study
• Subject has ability to understand and sign the Informed Consent Form
• Subject is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures |
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E.4 | Principal exclusion criteria |
• Allergy to fluocinolone acetonide or any component of the FAI insert
• History of posterior uveitis only that is not accompanied by vitritis or macular edema
• History of iritis only and no vitreous cells, anterior chamber cells or vitreous haze
• Uveitis with infectious etiology
• Vitreous hemorrhage
• Intraocular inflammation associated with a condition other than noninfectious uveitis (e.g. intraocular lymphoma)
• Ocular malignancy in either eye, including choroidal melanoma
• Toxoplasmosis scar in study eye; or scar related to previous viral retinitis
• Previous viral retinitis
• Current viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, mycobacterial infections of the eye or fungal diseases of ocular structure
• Media opacity precluding evaluation of retina and vitreous
• Peripheral retinal detachment in area of insertion
• Diagnosis of any form of glaucoma or ocular hypertension in study eye at Screening, unless study eye has been previously treated with an incisional surgery procedure that has resulted in stable IOP in the normal range (10-21 mmHg) at Screening
• Intraocular pressure (IOP) > 21 mmHg or concurrent therapy at screening with any IOP-lowering pharmacologic agent in the study eye
• Chronic hypotony (< 6 mmHg)
• Ocular surgery on the study eye within 3 months prior to study Day 1
• Capsulotomy in study eye within 30 days prior to study Day 1
• Prior intravitreal treatment of study eye with Retisert within 36 months prior to study Day 1
• Prior intravitreal treatment of study eye with Ozurdex within 6 months prior to study Day 1
• Prior intravitreal treatment of study eye with Triesence or Trivaris within 3 months prior to study Day 1
• Prior peri-ocular or subtenon steroid treatment of study eye within 3 months prior to study Day 1
• Subjects requiring chronic systemic or inhaled corticosteroid therapy (>15mg prednisone daily) or chronic systemic immunosuppressive therapy
• Excluding certain skin cancers (specifically, basal cell carcinoma and squamous cell carcinoma), any malignancy receiving treatment, or in remission less than 5 years prior to study Day 1
• Subjects who have tested positive for human immune deficiency virus (HIV), tuberculosis or syphilis
•Mycobacterial uveitis or chorio-retinal changes of either eye which, in the opinion of the Investigator, result from infectious mycobacterial uveitis
• Systemic infection within 30 days prior to study Day 1
• Any severe acute or chronic medical or psychiatric condition that could increase the risk associated with study participation or could interfere with the interpretation of study results and, in the judgment of the investigator, could make the subject inappropriate for entry into this study
• Any other systemic or ocular condition which, in the judgment of the investigator, could make the subject inappropriate for entry into this study
• Treatment with an investigational drug or device within 30 days prior to study Day 1
• Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined in this protocol from at least 14 days prior to study Day 1 until the Month 12 Visit
• Subjects unlikely to comply with the study protocol or who are likely to be lost to follow-up within three years |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy:
Proportion of subjects who have a recurrence of uveitis in the study eye within 6 months after receiving study treatment.
Recurrence is defined as:
• A > 2 step increase in the number of cells in the anterior chamber per high powered field (1.6 X using a 1-mm beam), compared to any visit time point prior to Month 6
OR
• An increase in the vitreous haze of > 2 steps, compared to any visit time point prior to Month 6
OR
• A deterioration in visual acuity of at least 15 letters BCVA, compared to any visit time point prior to Month 6
Safety:
• Systemic adverse events
• Ocular adverse events, including IOP elevation; medications/procedures required to control elevated IOP; development or worsening of cataract; cataract-related procedures; clinically significant ocular changes; procedure related adverse events |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months after receiving study treatment |
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E.5.2 | Secondary end point(s) |
Exploratory Efficacy Endpoints:
• Proportion of subjects who have a recurrence of uveitis in the study eye within 12 months or 36 months
• Proportion of subjects who have a recurrence of uveitis in the fellow eye (within 6 months, 12 months and 36 months)
• Mean change from baseline in BCVA letter score in the study eye (at 6 months, 12 months and 36 months)
• Number of recurrences of uveitis (within 6 months, 12 months and 36 months)
• Time to recurrence of uveitis (within 6 months, 12 months and 36 months)
• Number of adjunctive treatments required to treat recurrences of uveitis (within 6 months, 12 months and 36 months)
• Resolution of macular edema, as measured by OCT imaging (at 6 months, 12 months and 36 months)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Within 6, 12 and/or 36 months after receiving study 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) | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
Germany |
Hungary |
India |
Israel |
Italy |
Turkey |
United Kingdom |
United States |
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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 | 4 |
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 | 4 |
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 |