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

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.

• DE-109 440 μg (Drug), also known as Sirolimus: Medium Dose

Primary outcomes

• Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 in the Study Eye [Day 1 (Baseline) and Month 12 or early termination visit]: 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.
• Mean Change From Baseline in Intraocular Pressure at Month 12 in the Study Eye [Day 1 (Baseline) and Month 12 or early termination visit]: Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg) with one decimal point.
• Number of Subjects With a Shift in Choroid Status at Month 12 in the Study Eye. [Day 1 (Baseline) and Month 12 or early termination visit]: Ophthalmoscopy findings were reported as normal or abnormal.
• Changes From Baseline in Vitreous Haze (VH) Scores at Month 12 [Day 1 (Baseline) and Month 12 or early termination visit]: 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) 1. 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+ 2. Moderate blurring of the optic nerve head 3. Marked blurring of the optic nerve head 4. Optic Nerve head not visible
• Number of Subjects Who Receive Rescue Therapy. [By Month12]: 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.
• Number of Subjects With a Shift in Macula Status at Month 12 in the Study Eye. [Day 1 (Baseline) and Month 12 or early termination visit]: Ophthalmoscopy findings were reported as normal or abnormal.
• Number of Subjects With a Shift in Optic Nerve Status at Month 12 in the Study Eye. [Day 1 (Baseline) and Month 12 or early termination visit]: Ophthalmoscopy findings were reported as normal or abnormal.
• Number of Subjects With a Shift in Retina Status at Month 12 in the Study Eye. [Day 1 (Baseline) and Month 12 or early termination visit]: Ophthalmoscopy findings were reported as normal or abnormal.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Participated in the SAKURA study
2. Received clinical benefit from treatment in the SAKURA study
3. Ability to sign informed consent and attend all study visits

Exclusion Criteria:

1. Uveitis of infectious etiology
2. Implanted device
3. Suspected or confirmed central nervous system or ocular lymphoma
4. Uncontrolled glaucoma
5. Significant ocular disease
6. Intravitreal injections in the past 60 days
7. Intraocular surgery or treatment
8. Ocular or periocular infection
9. History of herpetic infection
10. Toxoplasmosis or toxoplasmosis scar
11. Ocular malignancy
12. Vitrectomy
13. Allergy or hypersensitivity to study drug
14. Participation in other uveitis device clinical trials within 30 days
15. Any recent systemic condition/infection
16. Immunosuppressive therapy or immunocomprimised
17. Cytomegalovirus infection
18. Malignancy in remission
19. Females who are pregnant or lactating and who are not using adequate contraceptive
20. Medical marijuana or illegal drug use
21. Systemic saroidosis
22. Therapeutic radiation to the head or neck

Participant flow

Outcome results

• Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 in the Study Eye (Primary), Mean, ETDRS Letters: DE-109 440 μg 2.1 +/- 11.35
• Mean Change From Baseline in Intraocular Pressure at Month 12 in the Study Eye (Primary), Mean, mmHg: DE-109 440 μg 0.3 +/- 4.16
• Number of Subjects With a Shift in Choroid Status at Month 12 in the Study Eye. (Primary), Number, Subjects: DE-109 440 μg 36
• Changes From Baseline in Vitreous Haze (VH) Scores at Month 12 (Primary), Mean, score on a scale: DE-109 440 μg -0.09 +/- 0.847
• Number of Subjects Who Receive Rescue Therapy. (Primary), Count of participants, Participants: DE-109 440 μg 9
• Number of Subjects With a Shift in Macula Status at Month 12 in the Study Eye. (Primary), Number, Subjects: DE-109 440 μg 20
• Number of Subjects With a Shift in Optic Nerve Status at Month 12 in the Study Eye. (Primary), Number, Subjects: DE-109 440 μg 39
• Number of Subjects With a Shift in Retina Status at Month 12 in the Study Eye. (Primary), Number, Subjects: DE-109 440 μg 34

Adverse events

Time frame: An on-study Adverse Events (AEs) were collected after the date of the written informed consent until the Last Study Visit at Month 12 or early termination visit.

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2014-06-30)
• Statistical Analysis Plan (PDF, 2017-11-15)

• Lanita Scott, MD, Study director, Santen Inc.