A Phase IIIb, Multinational, Multicenter, Open-Label Extension Study Assessing the Long-Term Safety of PRN Intravitreal Injections of DE-109 in Subjects With Non-Infectious Uveitis of the Posterior Segment of the Eye Who Have Participated in the SAKURA Development Program

Study Overview
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Brief Summary
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The objective of this extension study is to evaluate the long-term safety of treatment with DE-109 (440 μg) in subjects with non-infectious uveitis of the posterior segment of the eye who have participated in the SAKURA development program.

Detailed Description
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This is a multicenter, open-label, extension study of intravitreal injections of the 440 μg dose of DE-109 in subjects with non-infectious uveitis of the posterior segment who received any dose of DE-109 and exited the SAKURA program under Santen Protocol 32-007, Amendment 05. Subjects who were randomized and received at least two injections of DE-109 during the first five months of the SAKURA program and obtained clinical benefit from the study medication, as determined by the Investigator, may be considered for entry in this 12-month extension study. The minimum time lag from last injection in the SAKURA program to entry into the current protocol is 60 days.

Official Title
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A Phase IIIb, Multinational, Multicenter, Open-Label Extension Study Assessing the Long-Term Safety of PRN Intravitreal Injections of DE-109 in Subjects With Non-Infectious Uveitis of the Posterior Segment of the Eye Who Have Participated in the SAKURA Development Program

Conditions
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Non-Infectious Uveitis of the Posterior Segment of the Eye

Intervention / Treatment
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* Drug: DE-109 440 μg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participated in the SAKURA study Received clinical benefit from treatment in the SAKURA study Ability to sign informed consent and attend all study visits Exclusion Criteria: Uveitis of infectious etiology Implanted device Suspected or confirmed central nervous system or ocular lymphoma Uncontrolled glaucoma Significant ocular disease Intravitreal injections in the past 60 days Intraocular surgery or treatment Ocular or periocular infection History of herpetic infection Toxoplasmosis or toxoplasmosis scar Ocular malignancy Vitrectomy Allergy or hypersensitivity to study drug Participation in other uveitis device clinical trials within 30 days Any recent systemic condition/infection Immunosuppressive therapy or immunocomprimised Cytomegalovirus infection Malignancy in remission Females who are pregnant or lactating and who are not using adequate contraceptive Medical marijuana or illegal drug use Systemic saroidosis Therapeutic radiation to the head or neck

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DE-109 Sirolimus<br>DE-109 440 μg | Drug: DE-109 440 μg<br>* Medium Dose<br>* Other names: Sirolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 in the Study Eye | Best Corrected Visual Acuity (BCVA) measures the acuteness or clearness of best-corrected vision in ETDRS (Early Treatment of Diabetic Retinopathy Study) letters. An increase in BCVA indicates improvement in the best-corrected vision. A BCVA score of 85 ETDRS letters is equivalent to 20/20 vision, which is considered normal vision. | Day 1 (Baseline) and Month 12 or early termination visit | 
| Mean Change From Baseline in Intraocular Pressure at Month 12 in the Study Eye | Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg) with one decimal point. | Day 1 (Baseline) and Month 12 or early termination visit | 
| Number of Subjects With a Shift in Choroid Status at Month 12 in the Study Eye. | Ophthalmoscopy findings were reported as normal or abnormal. | Day 1 (Baseline) and Month 12 or early termination visit | 
| Changes From Baseline in Vitreous Haze (VH) Scores at Month 12 | Vitreous Haze (VH) scores were measured using the modified Standardized Uveitis Nomenclature Photographic Scale (SUN) : 0 No inflammation 0.5+ Trace Inflammation (slight blurring of the optic disc margins and or loss of nerve fiber layer reflex) Mild blurring of the retinal vessels and optic nerve 1.5+ Optic nerve head and posterior retina view obstruction greater than 1+ but less than 2+ Moderate blurring of the optic nerve head Marked blurring of the optic nerve head Optic Nerve head not visible | Day 1 (Baseline) and Month 12 or early termination visit | 
| Number of Subjects Who Receive Rescue Therapy. | Rescue therapy was defined as any treatment that would have a therapeutic effect on the uveitis in the posterior segment (e.g., systemic treatment with an immunosuppressant agent, or a corticosteroid injection in the study eye) other than intravitreal DE-109 determined by the Investigator. | By Month12 | 
| Number of Subjects With a Shift in Macula Status at Month 12 in the Study Eye. | Ophthalmoscopy findings were reported as normal or abnormal. | Day 1 (Baseline) and Month 12 or early termination visit | 
| Number of Subjects With a Shift in Optic Nerve Status at Month 12 in the Study Eye. | Ophthalmoscopy findings were reported as normal or abnormal. | Day 1 (Baseline) and Month 12 or early termination visit | 
| Number of Subjects With a Shift in Retina Status at Month 12 in the Study Eye. | Ophthalmoscopy findings were reported as normal or abnormal. | Day 1 (Baseline) and Month 12 or early termination visit |