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

• DE-109 Intravitreal Injections (Drug): 440 ug of DE-109 Injectable Solution
• Sham Procedure (Other): The sham procedure mimics an intravitreal injection without penetrating the eye.
• DE-109 Intravitreal Injections (Drug): Undisclosed Fixed Dose of DE-109 Injectable Solution (range of 44 ug to 880 ug)
• DE-109 Intravitreal Injections (Open Label) (Drug): 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)

Primary outcomes

• Vitreous Haze (VH) of Zero Response at Month 5 [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

Secondary outcomes

• Mean Composite Score at Month 3 and Month 5 [Month 3, 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
• Vitreous Haze (VH) of Zero Response at Month 3 [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.

Sex: All, ages: 18 Years to any

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

Participant flow

Outcome results

• Vitreous Haze (VH) of Zero Response at Month 5 (Primary), Number, percentage response of study eyes: Test Arm: DE-109 Injectable Solution 15.7; Control Arm: Sham Procedure 12.2; Dummy Arm: DE-109 Injectable Solution 28.7
• Mean Composite Score at Month 3 and Month 5 (Secondary), Mean, score on a scale: Test Arm: DE-109 Injectable Solution 0.4 +/- 1.10; Control Arm: Sham Procedure 0.3 +/- 0.80; Dummy Arm: DE-109 Injectable Solution 0.4 +/- 0.98
• Vitreous Haze (VH) of Zero Response at Month 3 (Secondary), Number, percentage response of study eyes: Test Arm: DE-109 Injectable Solution 14.7; Control Arm: Sham Procedure 5.5; Dummy Arm: DE-109 Injectable Solution 15.4

Adverse events

Time frame: Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both periods: 6-month Double-Masked Treatment Period at Month 6; and 6-month Open-Label Treatment Period at Month 12.

Serious adverse events by term

Other adverse events by term

• Results publication: Hashida N, Nishida K. Recent advances and future prospects: Current status and challenges of the intraocular injection of drugs for vitreoretinal diseases. Adv Drug Deliv Rev. 2023 Jul;198:114870. doi: 10.1016/j.addr.2023.114870. Epub 2023 May 10. PMID 37172783

• Study Protocol (PDF, 2021-07-14)
• Statistical Analysis Plan (PDF, 2022-08-16)