Macular Edema due to Retinal Vein Occlusion (RVO)

Part 1: • To characterize the dose-limiting toxicity(ies) (DLT[s]) of TLC399 (ProDex) in patients with macular edema due to retinal vein occlusion (RVO) Part 2 • To evaluate the safety, tolerability, and efficacy of the selected TLC399 (ProDex) strength administered as a single dose in patients with macular edema due to RVO for up to 1 year

TLC399 (ProDex)

Dexamethasone Sodium Phosphate (DSP)

Injection

13.2

Determination of Maximum Tolerated Dose and Dose Limiting Toxicities Maximum Tolerated Dose: The MTD will be defined either as the dose that was one level below the dose cohort which elicited a DLT in at least 2 patients or as the highest dose cohort with ≦1/6 DLTs. During the dose escalation period, only the subjects receiving the correct dose
administration are considered evaluable and will be include in DLT analysis. The MTD must be confirmed with 6 patients.

Signed informed consent must be obtained prior to participation in the study.
• Patients ≥ 20 years of age at Screening.Participant cooperation sufficient for adequate fundus photographs and retinal images.
• Patients diagnosed with diabetes mellitus (DM) type 1 or 2, and HbA1c ≤ 12% at Screening.
• Any medication administered for the management of diabetes should be stable within 3 months prior to randomization and is expected to remain stable during the course of the study, as medically acceptable.
• PDR in the study eye as assessed by the investigator using standard or wide-field color fundus photography (CFP) and fluorescein angiography (FA), with no evidence of previous PRP, and that requires treatment with either anti-Vascular Endothelial Growth Factor (VEGF) agent or PRP in the opinion of the investigator.
• BCVA ≥ 34 ETDRS letters (Snellen equivalent 20/200) in the study eye at Screening and Baseline.

1. Macular edema due to diabetic retinopathy or other etiologies at Screening visit.
2. Brisk afferent pupillary defect (i.e., obvious and unequivocal) at Screening visit.
3. Stroke or myocardial infarction within 3 months prior to the Screening visit.
4. Uncontrolled systemic disease, or poorly controlled hypertension (defined as systolic blood pressure [BP]
>160 mm Hg and/or diastolic BP >90 mm Hg), or poorly controlled diabetes (defined as hemoglobin A1c
level > 9.5%) at Screening visit.
5. Any ocular condition that in the opinion of the Investigator would prevent a 15-letter gain in visual acuity
(e.g., severe macular ischemia).
6. Presence of an epiretinal membrane in the study eye which, in the opinion of the Investigator, is the
primary cause of macular edema, or is severe enough to prevent gain in visual acuity despite reduction in
macular edema.
7. History of clinically significant IOP elevation in response to steroid treatment.
8. History of glaucoma or optic nerve head change consistent with glaucoma damage, and/or typical
glaucomatous visual field loss in both eyes.
9. Active ocular hypertension ≥ 21 mm Hg or history of treated ocular hypertension in the study eye.
10. Aphakia or presence of anterior chamber intraocular lens in the study eye.
11. Active retinal neovascularization in the study eye at the Screening visit.
12. Active or history of choroidal neovascularization in the study eye.
13. History of central serous chorioretinopathy in either eye.
14. Presence of rubeosis iridis in the study eye at the Screening visit.
15. Any active ocular infection (i.e., bacterial, viral, parasitic, or fungal) in either eye at the Screening visit.
16. History of herpetic ocular infection in the study eye or adnexa.
17. Presence of active or inactive toxoplasmosis in either eye at the Screening visit.
18. Presence of visible scleral thinning or ectasia in the study eye at the Screening visit.
19. Media opacity in the study eye at the Screening visit that precludes clinical and photographic evaluation
(including but not limited to preretinal or vitreous hemorrhage, lens opacity).20. Intraocular surgery, including cataract surgery, in the study eye within 6 months prior to the Screening
visit.
21. History of pars plana vitrectomy, radial optic neurotomy, or sheathotomy in the study eye.
22. Anticipated need for ocular surgery in the study eye during the 12-month study period.
23. Use of hemodilution for the treatment of RVO within 3 months prior to the Screening visit.
24. Use of any intraocular anti-VEGF therapy in the study eye, including aflibercept within 56 days,
ranibizumab within 28 days and bevacizumab within 28 days, and has satisfied improvement prior to the
Screening visit.
25. Use of laser of any type in the study eye within 3 months prior to the Screening visit.
26. Previous use of intravitreal steroids in the study eye within 6 months prior to the Screening visit. Prior
use of Iluvien® is not allowed.
27. Periocular depot of steroids to the study eye within 1 month prior to the Screening visit.
28. Use of systemic steroids, or warfarin/heparin within 1 month prior to the Screening visit or anticipated
use at any time during the study.29. Use of immunosuppressants, immunomodulators, antimetabolites, and/or alkylating agents within
6 months prior to the Screening visit or anticipated use at any time during the study.
30. BCVA score < 34 letters (approximately 20/200 Snellen equivalent) in the non-study eye using the chart
ETDRS method at the Screening visit.
31. Known allergy or hypersensitivity to the study medication or its components.
32. Known allergy or contraindication to the use of fluorescein or povidone iodine or contraindication to
pupil dilation in either eye.
33. Female patients who are pregnant, nursing, or planning a pregnancy, or who are of childbearing potential
and not using a reliable means of contraception.
34. Current enrollment in an investigational drug or device study or participation in such a study within
90 days prior to the Screening visit.
35. Patient has a condition or is in a situation which, in the Investigator’s opinion, will interfere with the
patient’s ability to comply with the dosing and visit schedules and the protocol evaluations or m