Safety and Efficacy of an Injectable Fluocinolone Acetonide Intravitreal Insert

Study Overview
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Brief Summary
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A study to evaluate the safety and efficacy of an FAI insert for the management of subjects with non-infectious uveitis affecting the posterior segment of the eye.

Detailed Description
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This is a phase 3, multi-national, multi-center, randomized, masked, controlled study to evaluate the safety and efficacy of an injectable fluocinolone acetonide intravitreal (FAI) insert for the management of subjects with non-infectious uveitis affecting the posterior segment of the eye. Patients will be randomized to receive either a sham injection or the FAI insert and will be observed for three years following treatment.

Official Title
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A Phase III, Multi-National, Multi-Center, Randomized, Masked, Controlled, Safety and Efficacy Study of a Fluocinolone Acetonide Intravitreal Insert in Subjects With Chronic Non-Infectious Uveitis Affecting the Posterior Segment of the Eye

Conditions
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Non-Infectious Uveitis

Intervention / Treatment
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* Drug: FAI insert
* Drug: Sham injection


Participation Criteria
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Eligibility Criteria
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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: systemic corticosteroid or other systemic therapies given for at least 3 months, and/or at least 2 intra- or peri-ocular injections of corticosteroid for management of uveitis OR the study eye has experienced recurrence: at least 2 separate recurrences of uveitis requiring systemic, intra- or peri-ocular injection of corticosteroid At the time of enrollment (Day 1), 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 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) 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 test positive for human immune deficiency virus (HIV) or syphilis during screening 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: sham injection<br>sham injection | Drug: Sham injection<br> <br> * Other names: Sham Comparator;|
| Experimental: FAI insert<br>FAI insert (0.18 mg fluocinolone acetonide) | Drug: FAI insert<br> <br> * Other names: Active Drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With Recurrence of Uveitis in the Study Eye and Overall Summary of Number of Participants With Ocular Treatment-Emergent Adverse Events for the Study Eye Through Month 36 Visit | Safety: 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 Primary Efficacy Endpoint: Proportion of subjects who have a recurrence of uveitis in the study eye within 6 months after receiving study treatment. | 36 months |