LUMINA Phase III Study Assessing the Efficacy and Safety of Intravitreal Injections of 440 ug DE-109 Sirolimus for the Treatment of Active, Non-Infectious Uveitis of the Posterior Segment of the Eye

Study Overview
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Brief Summary
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This is a Phase III study to assess the efficacy and safety of DE-109 440 µg every 2 months in subjects with active, non-infectious uveitis of the posterior segment of the eye (NIU-PS). There is a 6-month, single-arm, open-label period after completion of the 6-month double- masked, controlled period allows the evaluation of the efficacy and safety of intravitreal injection of DE-109 440 µg every 2 months for longer duration than appropriate for a placebo or sham control.

Official Title
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LUMINA: A Phase III, Multicenter, Sham-Controlled, Randomized, Double-Masked Study Assessing the Efficacy and Safety of Intravitreal Injections of 440 ug DE-109 for the Treatment of Active, Non-Infectious Uveitis of the Posterior Segment of the Eye.

Conditions
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Non Infectious Uveitis

Intervention / Treatment
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* Drug: DE-109 Intravitreal Injections
* Other: Sham Procedure
* Drug: DE-109 Intravitreal Injections
* Drug: DE-109 Intravitreal Injections (Open Label)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-Infectious Active Uveitis of the Posterior Segment Exclusion Criteria: Females who are pregnant, nursing, or planning a pregnancy Confirmed or suspected infectious uveitis

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Arm: DE-109 Injectable Solution<br>Intravitreal injection of DE-109 440 µg in the study eye(s) every 2 months (Day 1, Month 2, and Month 4). | Drug: DE-109 Intravitreal Injections<br>* 440 ug of DE-109 Injectable Solution<br>|
| Sham Comparator: Control Arm: Sham Procedure<br>Sham procedure administered to the study eye(s) every 2 months (Day 1, Month 2, and Month 4). The sham procedure mimics an intravitreal injection without penetrating the eye. | Other: Sham Procedure<br>* The sham procedure mimics an intravitreal injection without penetrating the eye.<br>|
| Other: Dummy Arm: DE-109 Injectable Solution<br>Dummy Arm: Intravitreal injection of DE-109 at an undisclosed, fixed dose (within the range of 44 µg to 880 µg) in the study eye(s) every 2 months (Day 1, Month 2, and Month 4). | Drug: DE-109 Intravitreal Injections<br>* Undisclosed Fixed Dose of DE-109 Injectable Solution (range of 44 ug to 880 ug)<br>|
| Experimental: Open-label:DE-109 Injectable Solution<br>Subjects completing the Month 6 pre-dose evaluations (the final evaluations in the double-masked period) began the open-label period of the study, in which all subjects received intravitreal injection of DE-109 440 μg in the study eye(s) every 2 months for an additional 6 months of dosing. | Drug: DE-109 Intravitreal Injections (Open Label)<br>* After double-masked treatment period (injections every 2 months), eligible subjects would enter the open-labeled period and had DE-109 440 ug injections every 2 months (Month 6, Month 8, and Month 10)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitreous Haze (VH) of Zero Response at Month 5 | Vitreous Haze (VH) was assessed during slit-lamp biomicroscopy and scored using the modified Standardized Uveitis Nomenclature (SUN) scale as follows: Score = 0: No inflammation Score = 0.5+: Trace inflammation (slight blurring if the optic disc margins and/or loss of nerve fiber layer reflex) Score = 1+: Mild blurring of the retinal vessels and optic nerve Score = 1.5+: Optic nerve had and posterior retina view obstruction greater than 1+ but less than 2+ Score = 2+: Moderate blurring of the optic nerve head Score = 3+: Marked blurring of the optic nerve head Score = 4+: Optic nerve head not visible VH 0 response (resolution of inflammation) is defined as a VH score of 0 in the study eye at a specified follow up visit based on the modified SUN scale. The response as a percentage is calculated as the proportion of study eyes which achieved a VH score of zero at Month 5 | Month 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Composite Score at Month 3 and Month 5 | Composite score scale is defined as follows. Each study eye was assigned one of the following scores: Score = 3 if a study eye achieved Vitreous Haze (VH) score of 0 at the specified visit without taking any rescue therapies that could affect VH score prior to the specified visit. Score = 2 if a study eye had at least improved (decreased) by 2 units (i.e., 2+ to 0, 3+ to 1+, or 4+ to 2+) in VH (compared to baseline) at the specified visit without taking any rescue therapies that could affect VH score prior to the specified visit. Score = 1 if a study eye achieved VH score of 0.5+ at the specified visit without taking any rescue therapies that could affect VH score prior to the specified visit. Score = -1 if a study eye got rescued due to worsening of uveitis or discontinued from the study due to lack of efficacy or due to adverse event prior to the specified visit. Score = 0 if otherwise | Month 3, Month 5 | 
| Vitreous Haze (VH) of Zero Response at Month 3 | Vitreous Haze (VH) was assessed during slit-lamp biomicroscopy and scored using the modified Standardized Uveitis Nomenclature (SUN) scale as follows: Score = 0: No inflammation Score = 0.5+: Trace inflammation (slight blurring if the optic disc margins and/or loss of nerve fiber layer reflex) Score = 1+: Mild blurring of the retinal vessels and optic nerve Score = 1.5+: Optic nerve had and posterior retina view obstruction greater than 1+ but less than 2+ Score = 2+: Moderate blurring of the optic nerve head Score = 3+: Marked blurring of the optic nerve head Score = 4+: Optic nerve head not visible VH 0 response (resolution of inflammation) is defined as a VH score of 0 in the study eye at a specified follow up visit based on the modified SUN scale. The response as a percentage is calculated as the proportion of study eyes which achieved a VH score of zero at Month 3. | Month 3 |